Pharmeuropa bio & scientific notes最新文献

{"title":"Calibration of pertussis toxin BRP batch 1 in a standardised CHO cell-based clustering assay.","authors":"K Markey,&nbsp;A Douglas-Bardsley,&nbsp;J Hockley,&nbsp;D Le Tallec,&nbsp;A Costanzo","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The European Pharmacopoeia (Ph. Eur.) pertussis toxin (PT) Biological Reference Preparation (BRP) is used as a working standard for safety testing of acellular pertussis vaccines as prescribed in the Ph. Eur. monographs 1356 \"Pertussis vaccine (acellular, component, adsorbed)\" and 1595 \"Pertussis vaccine (acellular, co-purified, adsorbed)\". The BRP was calibrated in 2006 in the murine histamine sensitisation test (HIST) against the World Health Organization (WHO) 1^st International Standard (IS) for PT. In recent years, there have been increasing efforts to replace the <i>in vivo</i> test with <i>in vitro</i> methods. The Chinese hamster ovary (CHO) cell clustering assay has been used for many years by manufacturers to monitor residual PT activity in detoxified non-adjuvanted bulks. More recently a standardised protocol has been developed for this assay and a PT reference preparation was needed. Due to low stocks, the WHO 1^st International Standard for Pertussis Toxin (JNIH-5) needed to be replaced and therefore a joint study between the European Directorate for the Quality of Medicines & HealthCare (EDQM) and WHO was initiated to calibrate the PT BRP for the CHO clustering assay and to replace the IS. The collaborative study involved 14 laboratories from Europe, North America and Asia. The outcome of the study confirmed that the BRP is suitable for use as a reference preparation in the CHO clustering assay. The material was assigned a potency of 1360 IU per vial for the CHO clustering assay.</p>","PeriodicalId":39192,"journal":{"name":"Pharmeuropa bio & scientific notes","volume":"2018 ","pages":"112-123"},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36535210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Establishment of the Ph. Eur. Hepatitis A virus RNA for NAT testing BRP batch 1.","authors":"M Chudy,&nbsp;C M Nübling,&nbsp;J Blümel,&nbsp;A Daas,&nbsp;A Costanzo","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Detection of viral contamination in plasma donations is critical to prevent transmission of infectious diseases. The European Pharmacopoeia (Ph. Eur.) monograph 1646 'Human plasma (pooled and treated for virus inactivation)', requires that plasma pools used for the manufacture of this product be tested, among others, for the presence of hepatitis A virus RNA by nucleic acid testing (NAT) using a positive control containing 100 International Units (IU) of hepatitis A virus (HAV) RNA per mL. To this end, the European Directorate for the Quality of Medicines & HealthCare (EDQM, Council of Europe) organised an international collaborative study under the aegis of the Biological Standardisation Programme, for the establishment of the 1^st Biological Reference Preparation (BRP) for HAV RNA for NAT testing. A freeze-dried candidate material was thus prepared and calibrated against the WHO 2^nd International Standard for HAV for NAT (00/562) in a study in which thirteen European and North American laboratories including Official Medicines Control Laboratories (OMCLs), manufacturers of plasma-derived products, producers of <i>in vitro</i> diagnostic kits and a blood transfusion centre participated. Based on the outcome of the study, an HAV RNA content of 40 000 IU/vial (corresponding approximately to 4.6 log₁₀ IU/vial) was assigned to the BRP, which was adopted by the Ph. Eur. Commission in March 2016 as Ph. Eur. hepatitis A virus RNA for NAT testing BRP batch 1.</p>","PeriodicalId":39192,"journal":{"name":"Pharmeuropa bio & scientific notes","volume":"2017 ","pages":"29-43"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35492701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validation of ELISA methods for quantification of the major birch allergen Bet v 1 (BSP090).","authors":"S Kaul,&nbsp;J Zimmer,&nbsp;O Dehus,&nbsp;A Constanzo,&nbsp;A Daas,&nbsp;K-H Buchheit,&nbsp;J Asturias,&nbsp;M C Arilla,&nbsp;D Barber,&nbsp;A Bertocchi,&nbsp;B Brunetto,&nbsp;J A Carnes,&nbsp;M Chapman,&nbsp;G Chaudemanche,&nbsp;J Dayan-Kenigsberg,&nbsp;S Döring,&nbsp;F Führer,&nbsp;M T Gallego,&nbsp;P Iacovacci,&nbsp;K M Hanschmann,&nbsp;T Holzhauser,&nbsp;M Hrabina,&nbsp;A Ledesma,&nbsp;P Moingeon,&nbsp;E Nony,&nbsp;C Pini,&nbsp;G Plunkett,&nbsp;M Raulf,&nbsp;G Reese,&nbsp;E Sandberg,&nbsp;I Sander,&nbsp;B Smith,&nbsp;D Strecker,&nbsp;C Valerio,&nbsp;R van Ree,&nbsp;B Weber,&nbsp;S Vieths","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>To date, the potency of allergen products in Europe is expressed in manufacturer-specific units relative to a product-specific in-house reference. Consequently, cross-product comparability of allergen products from different manufacturers with respect to strength and efficacy is impossible. The Biological Standardisation Programme (BSP) project BSP090 addresses this issue via the establishment of reference standards in conjunction with ELISA methods for the quantification of major allergens in allergen products. Since the initiation of BSP090, the recombinant major allergen Bet v 1 has been adopted by the European Pharmacopoeia Commission as a Chemical Reference Substance (CRS). In parallel, two sandwich ELISA systems for quantification of Bet v 1 were found suitable in preliminary phases of BSP090 to be validated in a large collaborative study. In this study, the candidate ELISA systems were compared with respect to accuracy, precision and variability. Thirteen participating laboratories tested model samples containing the CRS as well as spiked and unspiked birch pollen extracts. Both in pre-testing and in the collaborative study, the 2 candidate ELISA systems confirmed their suitability to quantify recombinant and native Bet v 1. As no clear-cut decision for one of the ELISA systems could be made based on the results of the collaborative study, a post-study testing was performed. Bet v 1 content of 30 birch pollen allergen products was determined in parallel in both ELISA systems. Consequently, 1 candidate ELISA system was selected to be proposed as the future European Pharmacopoeia standard method for Bet v 1 quantification.</p>","PeriodicalId":39192,"journal":{"name":"Pharmeuropa bio & scientific notes","volume":"2017 ","pages":"69-87"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35558013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Collaborative study for the establishment of the Ph. Eur. Hepatitis E virus RNA for NAT testing biological reference preparation batch 1.","authors":"S A Baylis,&nbsp;E Terao,&nbsp;J Blümel,&nbsp;K-M O Hanschmann","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>A new European Pharmacopoeia (Ph. Eur.) biological reference preparation (BRP) had to be established further to the decision to include nucleic acid testing (NAT) for the detection of hepatitis E virus (HEV) RNA in the monograph Human plasma (pooled and treated for virus inactivation) (1646). To this purpose, an international collaborative study was launched in the framework of the Biological Standardisation Programme (BSP) of the European Directorate for the Quality of Medicines & HealthCare (EDQM) and the Commission of the European Union (EU). The study was run in conjunction with the establishment of the 1^st World Health Organization (WHO) international reference panel (IRP) for hepatitis E virus RNA genotypes (8578/13). Twenty-three laboratories used in-house developed and commercially available assays to calibrate a lyophilised candidate BRP prepared from a HEV 3f strain positive human plasma against the 1^st WHO International Standard (IS) for HEV RNA (6329/10). Results from quantitative and qualitative assays were in good agreement and were combined to calculate an assigned potency. Real-time stability studies indicated that the candidate BRP is very stable at lower temperatures and is thus suitable for long-term use. Based on these results, in February 2016, the Ph. Eur. Commission adopted the candidate material as the hepatitis E virus RNA for NAT testing BRP batch 1, with an assigned unitage of 2.1 × 10⁴ IU/vial (4.32 log₁₀ IU/vial).</p>","PeriodicalId":39192,"journal":{"name":"Pharmeuropa bio & scientific notes","volume":"2017 ","pages":"12-28"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34799773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of UV spectrophotometry for determination of plasmid DNA concentration in vector preparations for human gene therapy products.","authors":"X Chenivesse,&nbsp;B Anliker,&nbsp;A Daas,&nbsp;S Ferro,&nbsp;R Meier,&nbsp;M Renner,&nbsp;A Costanzo","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The European Pharmacopoeia (Ph. Eur.) general chapter 5.14. Gene transfer medicinal products for human use suggests the use of absorbance measurements at 260 nm to determine the DNA concentration of plasmid vectors used for the preparation of gene therapy products for human use. An international collaborative study was organised by the European Directorate for the Quality of Medicines & HealthCare (EDQM) to confirm the suitability of UV spectrophotometry for the quantification of plasmid vectors used in gene therapy (GT). Three Official Medicine Control Laboratories (OMCLs of the European OMCL Network) and members of the OMCL Working Group for GT products took part in the study, in which various types of spectrophotometers were assessed using common test samples. Results of the study demonstrated that UV spectrophotometry can be considered suitable for the quantification of plasmid DNA in GT products regardless of the instrument used.</p>","PeriodicalId":39192,"journal":{"name":"Pharmeuropa bio & scientific notes","volume":"2017 ","pages":"88-112"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35299190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Calibration of the Ph. Eur. human coagulation Factor VIII concentrate BRP batch 5.","authors":"S Raut,&nbsp;A Costanzo,&nbsp;A Daas,&nbsp;K H Buchheit","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The European Pharmacopoeia Biological Reference Preparation (Ph. Eur. BRP) for Factor VIII Concentrate batch 5 was established through a collaborative study involving 14 laboratories organised by the European Directorate for the Quality of Medicines & HealthCare (EDQM, Council of Europe) to be used as working standard for potency determination of human coagulation Factor VIII (FVIII) preparations. The potency of the BRP batch 5 was assigned with reference to the WHO 8^th International Standard (IS) for FVIII Concentrate and the BRP batch 4. Participants were instructed to perform 3 independent Factor VIII potency assays following their own routine validated methods by the chromogenic assay as it is the assay prescribed by the European Pharmacopoeia. This publication reports the results obtained during the study. The consensus potency, 9.9 IU/ampoule (n = 14) when assessed against both standards, with inter-laboratory geometric coefficients of variation (GCV) of 3.2 % and 1.9 % against the WHO 8^th IS and the BRP batch 4 respectively, was consistent with the expected value. The Ph. Eur. BRP batch 5 is a freeze-dried, plasma-derived concentrate. Based on accelerated degradation studies, the stability of the material is suitable as a reference preparation. The Ph. Eur. BRP batch 5 was adopted at the 151^st session of the European Pharmacopoeia Commission in March 2015 and is available from the EDQM.</p>","PeriodicalId":39192,"journal":{"name":"Pharmeuropa bio & scientific notes","volume":"2017 ","pages":"1-11"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34799907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Collaborative study on saccharide quantification of the <i>Haemophilus influenzae</i> type b component in liquid vaccine presentations.","authors":"U Rosskopf, A Daas, E Terao, C von Hunolstein","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Before release onto the market, it must be demonstrated that the total and free polysaccharide (poly ribosyl-ribitol-phosphate, PRP) content of <i>Haemophilus influenzae</i> type b (Hib) vaccine complies with requirements. However, manufacturers use different methods to assay PRP content: a national control laboratory must establish and validate the relevant manufacturer methodology before using it to determine PRP content. An international study was organised by the World Health Organization (WHO), in collaboration with the Biological Standardisation Programme (BSP) of the Council of Europe/European Directorate for the Quality of Medicines & HealthCare (EDQM) and of the European Union Commission, to verify the suitability of a single method for determining PRP content in liquid pentavalent vaccines (DTwP-HepB-Hib) containing a whole-cell pertussis component. It consists of HCl hydrolysis followed by chromatographic separation and quantification of ribitol on a CarboPac MA1 column using high-performance anion exchange chromatography coupled with pulsed amperometric detection (HPAEC-PAD). The unconjugated, free, PRP is separated from the total PRP using C4 solid-phase extraction cartridges (SPE C4). Ten quality control laboratories performed two independent analyses applying the proposed analytical test protocol to five vaccine samples, including a vaccine lot with sub-potent PRP content and very high free PRP content. Both WHO PRP standard and ribitol reference standard were included as calibrating standards. A significant bias between WHO PRP standard and ribitol reference standard was observed. Study results showed that the proposed analytical method is, in principle, suitable for the intended use provided that a validation is performed as usually expected from quality control laboratories.</p>","PeriodicalId":39192,"journal":{"name":"Pharmeuropa bio & scientific notes","volume":"2017 ","pages":"44-68"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35491600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transferability study of CHO cell clustering assays for monitoring of pertussis toxin activity in acellular pertussis vaccines.","authors":"R Isbrucker,&nbsp;A Daas,&nbsp;L Wagner,&nbsp;A Costanzo","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Current regulations for acellular pertussis (aP) vaccines require that they are tested for the presence of residual or reversion-derived pertussis toxin (PTx) activity using the mouse histamine sensitisation test (HIST). Although a CHO cell clustering assay can be used by manufacturers to verify if sufficient inactivation of the substance has occurred in-process, this assay cannot be used at present for the final product due to the presence of aluminium adjuvants which interfere with mammalian cell cultures. Recently, 2 modified CHO cell clustering assays which accommodate for the adjuvant effects have been proposed as alternatives to the HIST. These modified assays eliminate the adjuvant-induced cytotoxicity either through dilution of the vaccine (called the Direct Method) or by introducing a porous barrier between the adjuvant and the cells (the Indirect Method). Transferability and suitability of these methods for testing of products present on the European market were investigated during a collaborative study organised by the European Directorate for the Quality of Medicines & HealthCare (EDQM). Thirteen laboratories participated in this study which included 4 aP-containing vaccines spiked by addition of PTx. This study also assessed the transferability of a standardised CHO cell clustering assay protocol for use with non-adjuvanted PTx preparations. Results showed that the majority of laboratories were able to detect the PTx spike in all 4 vaccines at concentrations of 4 IU/mL or lower using the Indirect Method. This sensitivity is in the range of the theoretical sensitivity of the HIST. The Direct Method however did not show the expected results and would need additional development work.</p>","PeriodicalId":39192,"journal":{"name":"Pharmeuropa bio & scientific notes","volume":"2015 ","pages":"97-114"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34636713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alternative to Ph. Eur. pour-plate method for detection of microbial contamination in non-sterile pharmaceutical preparations.","authors":"A Palicz,&nbsp;A Paul,&nbsp;A Hofmann,&nbsp;K Denzel","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The current European Pharmacopoeia (Ph. Eur.) texts for Interferon (IFN)-alfa-2 include a nonspecific photometric protein assay using albumin as calibrator and a highly variable cell-based assay for the potency determination of the protective effects. A request was expressed by the Official Medicines Control Laboratories (OMCLs) for improved methods for the batch control of recombinant interferon alfa-2 bulk and market surveillance testing of finished products, including those formulated with Human Serum Albumin (HSA). A HPLC method was developed at the Medical Products Agency (MPA, Sweden) for the testing of IFN-alfa-2 products. An initial collaborative study run under the Biological Standardisation Programme (BSP; study code BSP039) revealed the need for minor changes to improve linearity of the calibration curves, assay reproducibility and robustness. The goal of the collaborative study, coded BSP071, was to transfer and further validate this improved HPLC method. Ten laboratories participated in the study. Four marketed IFN-alfa-2 preparations (one containing HSA) together with the Ph. Eur. Chemical Reference Substance (CRS) for IFN-alfa-2a and IFN-alfa-2b, and in-house reference standards from two manufacturers were used for the quantitative assay. The modified method was successfully transferred to all laboratories despite local variation in equipment. The resolution between the main and the oxidised forms of IFN-alfa-2 was improved compared to the results from the BSP039 study. The improved method even allowed partial resolution of an extra peak after the principal peak. Symmetry of the main IFN peak was acceptable for all samples in all laboratories. Calibration curves established with the Ph. Eur. IFN-alfa-2a and IFN-alfa-2b CRSs showed excellent linearity with intercepts close to the origin and coefficients of determination greater than 0.9995. Assay repeatability, intermediate precision and reproducibility varied with the tested sample within acceptable ranges. Test accuracy estimated by comparing the values obtained by the participants to the declared contents determined by the manufacturers was good despite the absence of a common reference preparation. In conclusion, the present study showed that the new method is suitable, reproducible and transferable. Proposals for the revision of Ph. Eur. texts are presented. </p>","PeriodicalId":39192,"journal":{"name":"Pharmeuropa bio & scientific notes","volume":"2015 ","pages":"48-81"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34742088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Collaborative study for the validation of an improved HPLC assay for recombinant IFN-alfa-2.","authors":"K H Jönsson,&nbsp;A Daas,&nbsp;K H Buchheit,&nbsp;E Terao","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The current European Pharmacopoeia (Ph. Eur.) texts for Interferon (IFN)-alfa-2 include a nonspecific photometric protein assay using albumin as calibrator and a highly variable cell-based assay for the potency determination of the protective effects. A request was expressed by the Official Medicines Control Laboratories (OMCLs) for improved methods for the batch control of recombinant interferon alfa-2 bulk and market surveillance testing of finished products, including those formulated with Human Serum Albumin (HSA). A HPLC method was developed at the Medical Products Agency (MPA, Sweden) for the testing of IFN-alfa-2 products. An initial collaborative study run under the Biological Standardisation Programme (BSP; study code BSP039) revealed the need for minor changes to improve linearity of the calibration curves, assay reproducibility and robustness. The goal of the collaborative study, coded BSP071, was to transfer and further validate this improved HPLC method. Ten laboratories participated in the study. Four marketed IFN-alfa-2 preparations (one containing HSA) together with the Ph. Eur. Chemical Reference Substance (CRS) for IFN-alfa-2a and IFN-alfa-2b, and in-house reference standards from two manufacturers were used for the quantitative assay. The modified method was successfully transferred to all laboratories despite local variation in equipment. The resolution between the main and the oxidised forms of IFN-alfa-2 was improved compared to the results from the BSP039 study. The improved method even allowed partial resolution of an extra peak after the principal peak. Symmetry of the main IFN peak was acceptable for all samples in all laboratories. Calibration curves established with the Ph. Eur. IFN-alfa-2a and IFN-alfa-2b CRSs showed excellent linearity with intercepts close to the origin and coefficients of determination greater than 0.9995. Assay repeatability, intermediate precision and reproducibility varied with the tested sample within acceptable ranges. Test accuracy estimated by comparing the values obtained by the participants to the declared contents determined by the manufacturers was good despite the absence of a common reference preparation. In conclusion, the present study showed that the new method is suitable, reproducible and transferable. Proposals for the revision of Ph. Eur. texts are presented. </p>","PeriodicalId":39192,"journal":{"name":"Pharmeuropa bio & scientific notes","volume":"2015 ","pages":"1-34"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34356330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}