Based on a three-stage stackelberg dynamic game analysis, this paper constructs a product quality control strategy model for three types of distribution channels  in a three-echelon supply chain, which is composed of one manufacturer, one retailer and the final customer. This paper studies how to design a distribution channel strategy and provides a product quality control strategy. Furthermore, this paper analyzes three types of distribution channels strategy in the context of how they influence a manufacturer’s product quality decision and quality prevention strategy, a retailer’s product pricing decision and quality inspection strategy, and the final customer’s product demand decision. We compare the manufacturer’s product quality level, quality prevention effort level, wholesale price, direct sale price and the retailer’s quality inspection effort level, retail price in three types of distribution channels and determine the manufacturer’s and retailer’s expected profits function and the final customer’s consumer surplus. In addition, we introduce the distribution channels demand elasticity ratio to analyze the influence of determining the product quality control strategy. Most importantly, we conduct a numerical sample analysis that will prove the model’s effectiveness and indicate a specific application in practice. In recent years, with the rising of network economy and e-commerce, in addition to the traditional retail channel, more and more customers or consumers choose to purchase products from the internet channel(direct channel), which have become an important way of products sale. With the changing in customer or consumer buying behavior, more and more companies are beginning to redesign or rebuild their distribution channel structure; what’s more, the different types of distribution channels structure in supply chain how to influence the manufacturer’s product quality decision and quality prevention strategy, the retailer’s product pricing decision and quality inspection strategy, and the final customer’s product demand decision; above all, how to influence the manufacturer’s and retailer’s expected profits function and the final customer’s consumer surplus, and how to determine a product quality control strategy in order to eliminate “channel conflict” and “free-riding behavior”. All of these problems and difficulties have not been fully resolved, which are also important research directions for current researchers.In this paper, we will construct a distribution channel strategy model in a three echelon supply chain that is composed of one manufacturer, one retailer and a final customer based on a three-stage stackelberg dynamic game. Furthermore, we will introduce the distribution channel demand elasticity ratio and investigate how to craft a product quality control strategy in three types of distribution channels , which will eliminate the influence of “channel conflict” and “free-riding behavior”. Most important, we will determine the manufacturer’s product quality level, quality prevention effort level, wholesale price, direct sale price, and the retailer’s product quality inspection effort level and retail price, the manufacturer’s and retailer’s expected profits function, and the final customer’s consumer surplus. Then, we will conduct a numerical sample analysis that will indicate a specific application in practice.This paper is chiefly related to three streams of literature. The first stream is the research on how to design a distribution channels structure strategy, the different types of distribution channels structure and how to influence the product quality decision in a supply chain. Yunchuan Liu 2011)  establis  establiThe second stream pertains to designing a product quality contract and establishing a quality incentive mechanism in a supply chain. Peng Ma et al. 2013)  created 13  creatThe third stream of related literature concerns research on product quality risk sharing and the quality strategy of distribution channels in a supply chain. Zhu Lilong et al. (2011)  exploredIn this paper, first of all, we will introduce the distribution channel demand elasticity ratio and investigating how to construct a product quality control strategy model and channel coordination in three types of distribution channels ; what’s more, we consider the manufacturer’s product quality decision and quality prevention strategy, the retailer’s product pricing decision and quality inspection strategy, and the final customer’s product demand decision in a three-echelon supply chain; above all, we also establish a product quality control strategy model in three types of distribution channels to eliminate the influence of “channel conflict” and “free-riding behavior”, which will improve the manufacturer’s and retailer’s expected profits and the final customer’s consumer surplus.The remainder of our paper is organized as follows: in section 3, we describe the model and the basic assumption; in section 4, we consider the product quality strategy in the direct channel and determine the first-best contact parameters; in section 5, we investigate the product quality strategy in the retail channel and establish the manufacturer’s and retailer’s stackelberg “leader-follower” quality control model, and we compare the contract parameter differences with the direct channel. In section 6, we investigate the product quality strategy in the mixed channel that includes a retail channel and a direct channel scenario simultaneously, and in section 7 we present a numerical example analysis to verify our model results. Finally, we provide the research conclusions and direction for future research.qi is the manufacturer’s product quality level; furthermore, i ∈ {D,R,MC} denote the direct channel, the retail channel and the mixed channel respectively. The product quality cost function is k is the manufacturer’s production technology elasticity); so, we assume Ci (0) = Ci′(0) = 0, Ci′(+∞) = +∞, i.e. Ci(qi) is the convex function of increasing marginal cost. λm is the manufacturer’s product quality prevention effort level, and λm ∈ uniform distribution, i.e. a is the final customer lower limit of distribution quantity, b is the final customer upper limit of distribution quantity, and the corresponding final customer’s consumer surplus is (θqi– pi).The final customer’s quality utility is βi is the product demand price elasticity.The final customer’s product demand function will be In this paper, the manufacturer will determine the three types of distribution channels including a direct channel, a retail channel and a mixed channel. The three-stage stackelberg game is in the following order: in stage one, the manufacturer determines the product quality level in a different distribution channel and determines the product quality prevention effort level; in stage two, the manufacturer determines the wholesale price in a retail channel or the direct sale price in a direct channel; and in stage three, the retailer determines the product quality inspection effort level and the retail price.And then, the three types of distribution channels decision system is described as qD, the quality prevention effort level λm and the direct sale price pD.In the direct channel, the manufacturer sells its product to the final customer directly through an internet or online ordering system; then, the manufacturer determines the product quality level, the quality prevention effort level and the direct sale price. Therefore, the manufacturer’s expected profits’ function model is as follows.Proposition 1 In the direct channel, with the final customer’s product demand price elasticity decreases, the manufacturer’s product quality level and direct sale price will increase, and the quality prevention effort level will also increase. In this scenario, the manufacturer’s expected profits’ function is concave; i.e. an optimal product quality level exists that will to be maximum. Then, the final customer’s consumer surplus will increase with the decreasing in the demand price elasticity.Proof. Based on the stackelberg game analysis, this paper will use the backward induction method to solve the equation. Thus, using the first-order and second-order optimal condition with respect to pD in formula (1) yields the following:λm, which yields the following:pD and λmD is the manufacturer’s first-best sales price, and the quality effort level occurs with a direct channel.qD in Thereafter, we use the first-order and second-order optimal conditions with respect to Based on proposition 1, we conclude that, in the direct channel, the manufacturer’s product quality level, the direct sale price and the quality prevention effort level will increase with a decrease in the final customer’s product demand price elasticity. In addition, the manufacturer’s expected profits function is concave, and In the retail channel, the manufacturer sells product to the retailer, which will determine a product quality inspection strategy and then sell the product to the final customer. The manufacturer determines the product quality level, the quality prevention effort level and the wholesale price, and the retailer determines the quality inspection level and the retail price. Therefore, the manufacturer’s and retailer’s stackelberg “leader-follower” control model is described as follows:Proposition 2 In the retail channel, with the final customer’s product demand price elasticity decreases, the manufacturer’s product quality level and wholesale price will increase, and the retailer’s product retail price will also increase. In comparison with the direct channel scenario, the product quality level and the retail price will be much higher.Proof. In this paper, we still use the backward induction method to solve the model. Thus, we use the first-order optimal condition with respect to pR and λr in formula (16), which yields the following:w, and we obtain thatλm, which yields the following:βD = εβR, where ε is the demand elasticity ratio in a different distribution channel condition and ε >1. The demand price elasticity for the direct channel will be greater than for the retail channel; i.e., the final customers are more sensitive to price in the direct channel. Samar K.M (2008) earlier had proved that ηm = ηr.We compare Eqs Based on proposition 2, we conclude that the manufacturer’s product quality level in the retail channel will be much higher than that in the direct channel scenario; the retailer’s retail price will be greater than the wholesale price, which will be also much higher than the manufacturer’s sales price in the direct channel scenario.Corollary 2.1ε > 2).Proof. We compare the manufacturer’s quality prevention effort level and the retailer’s quality inspection effort level in the retail channel with that in the direct channel; then, we determine thatBased on corollary 2.1, we can infer that the manufacturer’s quality prevention effort level in the retail channel will be greater than the retailer’s quality inspection effort level, which will also be greater than the manufacturer’s quality prevention effort level in the direct channel.Corollary 2.2Proof. We substitute formula (25), (26) and (27) into Eqs Based on corollary 2.2, we conclude that the manufacturer’s expected profits in the retail channel will be greater than that in the direct channel scenario.Corollary 2.3.R*CS  > D*CS .Proof. The final customer’s consumer surplus in the retail channel will be described as followsBased on corollary 2.3, we conclude that the final customer’s consumer surplus in the retail channel will be greater than that in the direct channel.T is the transfer payment.In the mixed channel, the manufacturer may sell a product to the final customer directly through an online ordering system or sell wholesale to the retailer who will continue to sell the product to the final customer. Thereafter, the manufacturer will determine a transfer payment to the retailer to eliminate the channel conflict. Therefore, the manufacturer determines the product quality level, the quality prevention effort level, the wholesale price and the direct sale price, and the retailer determines the quality inspection level and the retail price. The manufacturer and the retailer’s stackelberg “leader-follower” control model can be described as follows:Proposition 3 In the mixed channel, in comparison with a direct channel and a retail channel scenario, the manufacturer’s product quality level will be greater than which in the direct channel and less than which in the retail channel, i.e. Proof. We still use the backward induction method to solve the model. Thus, we use the first-order optimal condition with respect to Rp and rλ in formula (32), which yields the following:w and Dp in formula (37) and obtain thatBased on proposition 3, we conclude that, in the mixed channel, the manufacturer’s product quality level will be greater than which in the direct channel and less than which in the retail channel. In addition, the wholesale price will decrease, the manufacturer’s direct sale price will increase and the retailer’s retail price will decrease.Corollary 3.1Proof. We compare the manufacturer’s quality prevention effort level and the retailer’s quality inspection effort level in the mixed channel with which in the direct channel and the retail channel scenario and obtain the following:Based on corollary 3.1, we conclude that, in the mixed channel, the manufacturer’s quality prevention effort level will be greater than that in the retail channel and the direct channel, and the retailer’s quality inspection effort level will be greater than that in the retail channel, which will effectively eliminate the “free-riding behavior.Corollary 3.2Proof. We substitute formula (42), (43) and (44) into Eqs Based on corollary 3.2, we infer that, in the mixed channel, the manufacturer’s expected profits will be less than that in the retail channel but will be greater than the profits in the direct channel; additionally, the retailer’s expected profits will be greater than that in the retail channel.Corollary 3.3Proof. The final customer’s consumer surplus in a mixed channel will be described as followsWe find that Based on corollary 3.3, we can infer that, in the mixed channel, the final customer’s consumer surplus will be greater than that in the retail channel and the direct channel.k = 2, ηm = ηr = 1, α = 60, θ ~ U, T = 120, ε = {2.5, 3.0}, βR ~ . We use numerical computing by Matlab 7.0 and obtain the results, as shown in Tables In this paper, we assume a manufacturer that sells computer components through a retailer (retail channel) or internet online system (direct channel) or through a mixed channel to the final customer. The parameters are described as follows: Based on Based on Based on Tables In this paper, we construct a product quality control model of three types of distribution channel  in a three-echelon supply chain, which is comprised by one manufacturer, one retailer and the final customer, and then we discuss how to design a distribution channel strategy and craft a quality control strategy. Furthermore, our paper analyzes three types of distribution channel strategies regarding how to influence the manufacturer’s product quality decision and quality prevention strategy, the retailer’s product pricing decision and quality inspection strategy, and the final customer’s product demand decision. We compare the product quality level in three types of distribution channels and solve the manufacturer’s and retailer’s expected profits functions and the final customer’s consumer surplus. In addition, we introduce the distribution channel demand elasticity ratio to analyze the influence of determining the product quality control strategy.Our paper demonstrates that, in the direct channel, the manufacturer’s product quality level, the quality prevention effort level and the direct sale price will increase, and the customer’s consumer surplus will also increase with the decreasing in the products demand price elasticity. In addition, in the retail channel which is compared with the direct channel scenario, the manufacturer’s product quality level, the wholesale price, the quality prevention effort level and expected profits will increase, and the retailer’s retail price, the quality inspection effort level and the customer’s consumer surplus will be much higher. In the mixed channel, the manufacturer will determine the transfer payment to eliminate channel conflict, the manufacturer’s quality prevention effort level and the retailer’s quality inspection effort level will increase, which will effectively eliminate the “free-riding behavior”. In addition, the manufacturer’s expected profits will be higher than that in the direct channel and less than that in the retail channel. The retailer’s expected profits and the final consumer surplus will also increase, and our conclusions will be a strong complement to the research field. Most importantly, we conduct a numerical sample analysis that demonstrates the model’s effectiveness and the conclusions’ correctness and will also indicate a specific application in practice.In further research, we will assume that the manufacturer’s quality prevention effort level and the retailer’s quality inspection effort level have incomplete information regarding how to craft a product quality control strategy in three types of distribution channels; then, we will also attempt to construct a multi-stage, repeat and asymmetry information dynamic game model and analyze the distribution channel strategy regarding how to influence the manufacturer’s and retailer’s expected profits function, the final customer’s consumer surplus and social welfare. 8 Jan 2020PONE-D-19-20228Supply Chain Product Quality Control Strategy in Three Types of Distribution ChannelsPLOS ONEDear Authors,Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.We would appreciate receiving your revised manuscript by 30.1.2020. When you are ready to submit your revision, log on to If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter.http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocolsTo enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see: Please include the following items when submitting your revised manuscript:A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). This letter should be uploaded as separate file and labeled 'Response to Reviewers'.A marked-up copy of your manuscript that highlights changes made to the original version. This file should be uploaded as separate file and labeled 'Revised Manuscript with Track Changes'.An unmarked version of your revised paper without tracked changes. This file should be uploaded as separate file and labeled 'Manuscript'.Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.We look forward to receiving your revised manuscript.Kind regards,Dejan Dragan, PhDAcademic EditorPLOS ONEAdditional Editor Comments (if provided):Editor's initial comments to the paper:Supply Chain Product Quality Control Strategy in Three Types of Distribution ChannelsThe paper deploys a three-stage Stackelberg dynamic game analysis and constructs a product quality control strategy model for three types of distribution channels  in a three-echelon supply chain, which is composed of one manufacturer, one retailer and the final customer. Furthermore, the paper studies how to design a distribution channel strategy and provides a product quality control strategy. Here, three types of distribution channels strategy in the context of how they influence a manufacturer’s product quality decision and prevention strategy, a retailer’s product pricing decision and quality inspection strategy, and the final customer’s product demand decision, are analyzed. The subject of this research is up-to-date and fundamentally interesting for scholars from the field of SCM and OR.The paper, in general, roughly satisfies all rigor requirements that are demanded from Plos One. The red clue remains more or less consistent all over the paper, while the derivations of equations seem to be adequate.However, the editor has detected some major issues based on his own perception, the review of the additional reviewer, and the Plos One criteria for the papers, which should be corrected prior to the further publishing process.Comments of the AE:1. It is not clear enough emphasized what the main contribution of the paper is, i.e., what has been done new, if compared with the work of the other researchers. Here, the borderline should be clearly highlighted, while the main contributions  should be more explicitly given in the introduction and other places, where necessary.2. Figure 1 should be improved in the sense of informative content meaning that the reader immediately understands the main point without even looking at the corresponding text.Comments regarding the Plos One criteria for the papers:http://journals.plos.org/plosone/s/submission-guidelines#loc-methods-software-databases-and-tools. On this basis, the AE warns the authors to reconsider these facts and give the rationale and/or explanation fortified with the facts, let be in the paper itself or in the answers to reviewers or cover letter.There exists a certain doubt whether the paper meets PLOS ONE criteria for papers that describe new methods or software for applications. Specifically, these reports must meet the criteria of utility, validation, and availability, which are described in detail at Comments of Reviewer #1Summary (see reviewer 1 comments.pdf):Additional comments are available in the file: reviewer 1 comments.pdf.Journal Requirements:When submitting your revision, we need you to address these additional requirements:http://www.plosone.org/attachments/PLOSOne_formatting_sample_main_body.pdf and http://www.plosone.org/attachments/PLOSOne_formatting_sample_title_authors_affiliations.pdf1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at 2. Thank you for stating the following in the Acknowledgments Section of your manuscript: "This work was supported by the Humanities and Social Sciences Foundation of the Ministry of Education in China under grant No.17YJA630147, Nature Science Foundation of Shandong Province under grant No.ZR2019MG017 and National Social Science Foundation of China under grant No.13AGL012."We note that you have provided funding information that is not currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form.Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows:"The author(s) received no specific funding for this work."3. Please include your tables as part of your main manuscript and remove the individual files. Please note that supplementary tables should be uploaded as separate "supporting information" files.http://journals.plos.org/plosone/s/supporting-information.4. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: [Note: HTML markup is below. Please do not edit.]Reviewers' comments:Reviewer's Responses to QuestionsComments to the Author1. Is the manuscript technically sound, and do the data support the conclusions?The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Partly**********2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes**********3. Have the authors made all data underlying the findings in their manuscript fully available?PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.The Reviewer #1: Yes**********4. Is the manuscript presented in an intelligible fashion and written in standard English?PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.Reviewer #1: No**********5. Review Comments to the AuthorPlease use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. Reviewer #1: 1. The language of the article should be more concise and accurate.2. It is better to complement the differences between this study and the existing research literature.3. The conclusions of the study for the the objectives mentioned in the abstract as ‘This paper studies how to design a distribution channel strategy and provides a product quality control strategy’ are not very clear.4. In this article, we can not see how consumer utility and consumer behavior affect product market demand.5. In Mixed Channel, how does the product demand between the two channels affect each other?**********what does this mean?). If published, this will include your full peer review and any attached files.6. PLOS authors have the option to publish the peer review history of their article  digital diagnostic tool, AttachmentEditor - initial review.docxSubmitted filename: Click here for additional data file.AttachmentReviewer 1 Comments.pdfSubmitted filename: Click here for additional data file. 2 Feb 2020Responses to Editors and ReviewersDear Professor Dejan Dragan and Reviewers,Thank you very much for your suggestions and critical comments about our paper submitted to PLOS ONE (Manuscript ID: PONE-D-19-20228). The revised title is “Supply Chain Product Quality Control Strategy in Three Types of Distribution Channels”.We are also thankful to the reviewers for their critical reading and valuable comments on the manuscript. Those comments were very helpful for providing direction for our further studies. We have tried our best to revise our manuscript according to the comments. Attached, please find the revised version, which we would like to resubmit for your kind consideration. The main revised parts are marked in blue in the paper. The following is a detailed explanation how we have complied with the editor’s and reviewers’ suggestions.Responds to the editor’s comments:Comment #1:The paper deploys a three-stage Stackelberg dynamic game analysis and constructs a product quality control strategy model for three types of distribution channels  in a three-echelon supply chain, which is composed of one manufacturer, one retailer and the final customer. Furthermore, the paper studies how to design a distribution channel strategy and provides a product quality control strategy. Here, three types of distribution channels strategy in the context of how they influence a manufacturer’s product quality decision and prevention strategy, a retailer’s product pricing decision and quality inspection strategy, and the final customer’s product demand decision, are analyzed. The subject of this research is up-to-date and fundamentally interesting for scholars from the field of SCM and OR.The paper, in general, roughly satisfies all rigor requirements that are demanded from Plos One. The red clue remains more or less consistent all over the paper, while the derivations of equations seem to be adequate.Response: Thank you very much for the highly praises and the valuable suggestions. Our paper constructs a product quality control strategy model for three types of distribution channels  in a three-echelon supply chain which use a three-stage stackelberg dynamic game analysis, and then, analyzes three types of distribution channels strategy in the context of how they influence a manufacturer’s product quality decision and quality prevention strategy, a retailer’s product pricing decision and quality inspection strategy, and the final customer’s product demand decision. Most importantly, we conduct a numerical sample analysis that will prove the model’s effectiveness and indicate a specific application in practice.Comment #2: It is not clear enough emphasized what the main contribution of the paper is, i.e., what has been done new, if compared with the work of the other researchers. Here, the borderline should be clearly highlighted, while the main contributions  should be more explicitly given in the introduction and other places, where necessary.Response: Thank you very much for the valuable suggestions. We rewrite and emphasize the paper’s main contributions in every paragraph in “2 Related Literature”, just like: (1) Our paper differs from the existing literature by introducing the distribution channel demand elasticity ratio and investigating how to construct a product quality control strategy model and channel coordination in three types of distribution channels  by providing a new perspective. (2) Our model contributes to the product quality control strategy research by constructing a distribution channel model in a three-echelon supply chain which is composed of one manufacturer, one retailer and the final customer based on a three-stage stackelberg dynamic game. Then, the model considers the manufacturer’s product quality decision and quality prevention strategy, the retailer’s product pricing decision and quality inspection strategy, and the final customer’s product demand decision. (3) we also establish a product quality control strategy model in three types of distribution channels to eliminate the influence of “channel conflict” and “free-riding behavior”, which will improve the manufacturer’s and retailer’s expected profits and the final customer’s consumer surplus.Comment #3: Figure 1 should be improved in the sense of informative content meaning that the reader immediately understands the main point without even looking at the corresponding text.Response: Thank you very much for the valuable suggestions. We redraw the Figure 1 Three types of distribution channels decision system which improve in the sense of informative content meaning that the reader immediately understands the main point of our paper.Figure 1 Three types of distribution channels decision systemResponds to the reviewer’s comments:Comment #1:The language of the article should be more concise and accurate.Response: Thank you very much for the valuable suggestions. We made necessary revisions and language editing in the manuscript according to your suggestions, and the English has also been edited by Wiley English Language Editing Services.Comment #2:It is better to complement the differences between this study and the existing research literature.Response: Thank you very much for the valuable suggestions. We rewrite and emphasize the paper’s main contributions in every paragraph in “2 Related Literature”, just like: (1) Our paper differs from the existing literature by introducing the distribution channel demand elasticity ratio and investigating how to construct a product quality control strategy model and channel coordination in three types of distribution channels  by providing a new perspective. (2) Our model contributes to the product quality control strategy research by constructing a distribution channel model in a three-echelon supply chain which is composed of one manufacturer, one retailer and the final customer based on a three-stage stackelberg dynamic game. Then, the model considers the manufacturer’s product quality decision and quality prevention strategy, the retailer’s product pricing decision and quality inspection strategy, and the final customer’s product demand decision. (3) we also establish a product quality control strategy model in three types of distribution channels to eliminate the influence of “channel conflict” and “free-riding behavior”, which will improve the manufacturer’s and retailer’s expected profits and the final customer’s consumer surplus.Comment #3: The conclusions of the study for the objectives mentioned in the abstract as ‘This paper studies how to design a distribution channel strategy and provides a product quality control strategy’ are not very clear.Response: Thank you very much for the valuable suggestions. With the changing in customer or consumer buying behavior, more and more companies are beginning to redesign or rebuild their distribution channel structure, Such as HP, Nike, Lenovo, in addition to focus on the traditional retail channel, have also opened up an internet channel(direct channel); Dell, MI has been focused on internet channel in the past, and now also began selling products in traditional retail channel; and Apple, Haier sell their products in the traditional retail channel and internet channel in the same time, which used a mixed channel structure. In our paper, we will construct a distribution channel strategy model in a three echelon supply chain that is composed of one manufacturer, one retailer and a final customer based on a three-stage stackelberg dynamic game. Furthermore, we will introduce the distribution channel demand elasticity ratio and investigate how to craft a product quality control strategy in three types of distribution channels , Most important, we will determine the manufacturer’s product quality level, quality prevention effort level, wholesale price, direct sale price, and the retailer’s product quality inspection effort level and retail price, the manufacturer’s and retailer’s expected profits function, and the final customer’s consumer surplus.Comment #4: In this article, we can not see how consumer utility and consumer behavior affect product market demand.Response: Thank you very much for the valuable suggestions. In “3 The Model and Assumption”, we describe that the final customer’s quality utility is, and denotes the type of final customer, is the manufacturer’s product quality level; furthermore, denote the direct channel, the retail channel and the mixed channel respectively; then, we assume ～ uniform distribution, and the corresponding final customer’s consumer surplus is. Therefore, in direct channel, we can describe the final customer’s consumer surplus as = = (14)In retail channel, we can describe the final customer’s consumer surplus as = = (30)In mixed channel, we can describe the final customer’s consumer surplus as = + = (52)Comment #5: In Mixed Channel, how does the product demand between the two channels affect each other?Response: Thank you very much for the valuable suggestions. In our paper, we describe the mixed channel that the manufacturer sells their products in the traditional retail channel by the retailer, in the same time, the manufacturer sells their products to the final customer in direct channel (internet channel). The final customer’s product demand function will be ; denotes the market maximum demand, and is the product demand price elasticity. Therefore, In mixed channel, the manufacturer and the retailer’s stackelberg “leader-follower” control model can be described as follows:  = + - - (31) s.t.  = (32)The product demand in retail channel as The product demand in direct channel as  is the manufacturer’s product quality level in mixed channel, is the product demand price elasticity in retail channel, is the product demand price elasticity in direct channel, is the manufacturer’s wholesale price, is the retailer’s retail price, is the direct sale price in a direct channel, the manufacturer’s product quality cost function in direct channel is .We have tried our best to improve the manuscript and made some substantial changes and necessary deletions according to the editors’ and reviewers’ comments. We earnestly appreciate the editors’ and reviewers’ professional work and hope that the corrections will make our manuscript suitable for publication in PLOS ONE. We are looking forward to receiving comments from reviewers in the future.Once again, thank you very much for your valuable comments and suggestions.Best wishes.Yours sincerely,Lilong Zhu (Correspondence)zhulilong2008@126.comE-mail: Tel: + 86 13853193366, Fax: + 86 531 8618 2769School of Management, Shandong University, Ji’nan Shandong, 250100, ChinaCollege of Business, Shandong Normal University, Ji’nan 250014, Shandong, ChinaAttachmentResponse to Reviewers.docSubmitted filename: Click here for additional data file. 16 Mar 2020PONE-D-19-20228R1Supply Chain Product Quality Control Strategy in Three Types of Distribution ChannelsPLOS ONEDear Authors,Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.==============================Please see below==============================https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.We would appreciate receiving your revised manuscript by 29.3.2020. When you are ready to submit your revision, log on to If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter.http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocolsTo enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see: Please include the following items when submitting your revised manuscript:A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). This letter should be uploaded as separate file and labeled 'Response to Reviewers'.A marked-up copy of your manuscript that highlights changes made to the original version. This file should be uploaded as separate file and labeled 'Revised Manuscript with Track Changes'.An unmarked version of your revised paper without tracked changes. This file should be uploaded as separate file and labeled 'Manuscript'.Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.We look forward to receiving your revised manuscript.Kind regards,Dejan Dragan, PhDAcademic EditorPLOS ONE[Note: HTML markup is below. Please do not edit.]Reviewers' comments:Reviewer's Responses to QuestionsComments to the Author1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.Reviewer #2: (No Response)Reviewer #3: All comments have been addressed**********2. Is the manuscript technically sound, and do the data support the conclusions?The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #2: YesReviewer #3: Yes**********3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #2: YesReviewer #3: Yes**********4. Have the authors made all data underlying the findings in their manuscript fully available?PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.The Reviewer #2: YesReviewer #3: Yes**********5. Is the manuscript presented in an intelligible fashion and written in standard English?PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.Reviewer #2: YesReviewer #3: Yes**********6. Review Comments to the AuthorPlease use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. Reviewer #2: Really, the paper has been greatly improved as all comments provided by all other reviewers in the first round.Reviewer #3: 1. It is a very nice thing that the new literature review part is added. But it seems to be to be too detailed. It will be better that the author just mentioned 2~3 related papers and on top of that, provide their own contributions. Moreover, those contributions should be more precise, instead of "..by providing a newperspective.", the author need to be more specific about what exactly the new perspective is.2. The model and assumption need to be more concise and concrete. For example, when the author mentioned the customer type follow a U, it needs more clarify about the value means and the types they are referring to. It will be better if the author check the model and assumption part one more time and provide additional explanation if necessary**********what does this mean?). If published, this will include your full peer review and any attached files.7. PLOS authors have the option to publish the peer review history of their article  digital diagnostic tool,  25 Mar 2020Responses to Editors and ReviewersDear Professor Dejan Dragan and Reviewers,Thank you very much for your suggestions and valuable comments about our paper submitted to PLOS ONE (Manuscript ID: PONE-D-19-20228R1). The manuscript’s title is “Supply Chain Product Quality Control Strategy in Three Types of Distribution Channels”.We are also thankful to the reviewers for their critical reading and valuable comments on the manuscript. Those comments were very helpful for providing direction for our further studies. We have tried our best to revise our manuscript according to the comments. Attached, please find the revised version, which we would like to resubmit for your kind consideration. The main revised parts are marked in red in the paper. The following is a detailed explanation how we have complied with the editor’s and reviewers’ suggestions.Responds to the editor’s comments:Comment:Please include the following items when submitting your revised manuscript:• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). This letter should be uploaded as separate file and labeled 'Response to Reviewers'.• A marked-up copy of your manuscript that highlights changes made to the original version. This file should be uploaded as separate file and labeled 'Revised Manuscript with Track Changes'.• An unmarked version of your revised paper without tracked changes. This file should be uploaded as separate file and labeled 'Manuscript'.Response: Thank you very much for the highly praises and the valuable suggestions for this manuscript. According to the editor’s and reviewers’ suggestions, we have completed all the revision which each point raised by the academic editor and reviewers, the file is labeled 'Response to Reviewers'. We have completed a marked-up copy of our manuscript that highlights changes made to the original version, the file is labeled 'Revised Manuscript with Track Changes'. We also have completed an unmarked version of our revised paper without tracked changes, the file is labeled 'Manuscript'.Comment #2: Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.Response: Yes, I would like to make the peer review history publicly available.Responds to the reviewer’s comments:Comment #1:If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.Reviewer #2: (No Response)Reviewer #3: All comments have been addressedResponse: Thank you very much for the valuable suggestions. We have addressed and completed all the revised comments in the new 'Manuscript'.Comment #2:Is the manuscript technically sound, and do the data support the conclusions?The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.Reviewer #2: YesReviewer #3: YesResponse: Thank you very much for the valuable suggestions. In this manuscript, all the data support the conclusions.Comment #3:Has the statistical analysis been performed appropriately and rigorously?Reviewer #2: YesReviewer #3: YesResponse: Thank you very much for the valuable suggestions.Comment #4:Have the authors made all data underlying the findings in their manuscript fully available?Reviewer #2: YesReviewer #3: YesResponse: Thank you very much for the valuable suggestions.Comment #5:Is the manuscript presented in an intelligible fashion and written in standard English?Reviewer #2: YesReviewer #3: YesResponse: Thank you very much for the valuable suggestions. We made necessary revisions and language editing in the manuscript according to your suggestions, and the English has also been edited by Wiley English Language Editing Services.Comment #6:Review Comments to the Author.Reviewer #2: Really, the paper has been greatly improved as all comments provided by all other reviewers in the first round.Reviewer #3: 1. It is a very nice thing that the new literature review part is added. But it seems to be to be too detailed. It will be better that the author just mentioned 2~3 related papers and on top of that, provide their own contributions. Moreover, those contributions should be more precise, instead of ". by providing a new perspective, the author need to be more specific about what exactly the new perspective is.2. The model and assumption need to be more concise and concrete. For example, when the author mentioned the customer type follow a U, it needs more clarify about the value means and the types they are referring to. It will be better if the author check the model and assumption part one more time and provide additional explanation if necessary.Response to Reviewer #2: Thank you very much for the valuable suggestions. We have revised and completed all comments provided by the editor and reviewers in the first round.Response to Reviewer #3: Thank you very much for the valuable suggestions.1. We have revised the literature review part, which is chiefly related to three streams of literature, it seems not to be too detailed, which is mentioned the related papers and on top of that, provide their own contributions. Moreover, those contributions should be more precise as line 150-160.In this paper, first of all, we will introduce the distribution channel demand elasticity ratio and investigating how to construct a product quality control strategy model and channel coordination in three types of distribution channels ; what’s more, we consider the manufacturer’s product quality decision and quality prevention strategy, the retailer’s product pricing decision and quality inspection strategy, and the final customer’s product demand decision in a three-echelon supply chain; above all, we also establish a product quality control strategy model in three types of distribution channels to eliminate the influence of “channel conflict” and “free-riding behavior”, which will improve the manufacturer’s and retailer’s expected profits and the final customer’s consumer surplus.2. We have revised model and assumption more concise and concrete in line 174-l96. For example, The final customer’s quality utility is , and denotes the type of final customer; then, we assume Ɵ~U uniform distribution, i.e. a is the final customer lower limit of distribution quantity, b is the final customer upper limit of distribution quantity, and the corresponding final customer’s consumer surplus is .We have checked the model and assumption part one more time, and then, provided additional explanation more clearly and accurately.We have tried our best to improve the manuscript and made some substantial changes and necessary deletions according to the editors’ and reviewers’ comments. We earnestly appreciate the editors’ and reviewers’ professional work and hope that the corrections will make our manuscript suitable for publication in PLOS ONE. We are looking forward to receiving comments from reviewers in the future.Once again, thank you very much for your valuable comments and suggestions.Best wishes.Sincerely yours,Lilong ZhuAttachmentResponse to Reviewers.docSubmitted filename: Click here for additional data file. 31 Mar 2020Supply Chain Product Quality Control Strategy in Three Types of Distribution ChannelsPONE-D-19-20228R2Dear authors,We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication.https://www.editorialmanager.com/pone/, click the "Update My Information" link at the top of the page, and update your user information. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.Shortly after the formal acceptance letter is sent, an invoice for payment will follow. To ensure an efficient production and billing process, please log into Editorial Manager at onepress@plos.org.If your institution or institutions have a press office, please notify them about your upcoming paper to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, you must inform our press team as soon as possible and no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact With kind regards,Dejan Dragan, PhDAcademic EditorPLOS ONEAdditional Editor Comments :The improvements have been noticeable so that the paper deserves to be published in the Plos One.Reviewers' comments: 6 Apr 2020PONE-D-19-20228R2 Supply Chain Product Quality Control Strategy in Three Types of Distribution Channels Dear Dr. Zhu:I am pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. onepress@plos.org.If your institution or institutions have a press office, please notify them about your upcoming paper at this point, to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact plosone@plos.org. For any other questions or concerns, please email Thank you for submitting your work to PLOS ONE.With kind regards,PLOS ONE Editorial Office Staffon behalf ofDr. Dejan Dragan Academic EditorPLOS ONE


During mechanical recanalization of large vessel occlusions (LVO), the use of proximal flow arrest with balloon guide catheters (BGC) was shown to be associated with better angiographic and even clinical outcome. The aim of the study was to analyze the impact of BGC use on microstructural alterations in the salvaged penumbra.All patients who underwent mechanical recanalization of LVO of the anterior circulation were reviewed within a prospective stroke registry of a single comprehensive stroke center. Fifty-two patients received an admission CT perfusion together with post-interventional diffusion tensor imaging. Technical details such as BGC usage were correlated with microstructural integrity changes of the salvaged gray matter through the mean diffusivity (MD) index. Moderation analysis was performed to test the interaction of BGC on the correlation between angiographic and clinical outcomes.p = 0.04). The importance of complete reperfusion for good clinical outcome is predominantly based on patients treated with BGC .For all patients with complete reperfusion, microstructural integrity changes with lowered MD index were found within the salvaged penumbra for cases of non-BGC usage (mean − 0.02) compared to cases with BGC usage  contains supplementary material, which is available to authorized users. Endovascular mechanical thrombectomy (MT) is used as the current standard procedure for large intracranial vessel occlusions (LVO) of the anterior circulation, based on the major five randomized trials, in which so-called stent retrievers were an integral part of endovascular therapy (EVT) –5. RecenEspecially the use of balloon guide catheters (BGC) has been established within the standard procedure in many neuro-interventional institutions by now, as it became evident that improved angiographic and clinical results can be achieved by using this technique –13. ThisThe aim of acute stroke treatment is to save the so-called penumbra. “Penumbra” means the potentially salvageable brain tissue that is at risk of definite infarction if no successful reperfusion therapy will be performed immediately.The penumbra presents the range of cerebral perfusion between temporary loss of electrical activity and irreversible neuronal depolarization and plays an essential role as the degree of “tissue at risk” can be assessed , 16. ThiPrevious analyses have suggested that microstructural alterations also occur in the salvaged penumbra, which does not undergo final infarction –21. MicrWe hypothesize that the processes that take place in the penumbra until successful reperfusion are influenced by technical specifications of the MT technique such as usage of BGC.Therefore, the primary aim of the present study was to analyze the impact of applied procedural techniques on penumbral processes. A specific focus was laid on the use of BGC, and the microstructural changes within the salvaged penumbra in the acute stroke phase after mechanical recanalization of an acute intracranial vessel occlusion were assessed. Additionally, the interaction of the techniques on the correlation between angiographic and clinical outcomes should be tested.The study cohort is based on a prospectively collected stroke registry of a single comprehensive stroke center. All patients treated with MT between April 2016 and December 2018 were included. The database query revealed four hundred thirty-nine patients that had undergone EVT due to LVO of the anterior circulation .n = 192). Exclusion criteria were incomplete or insufficient MRI acquisition (n = 20), space-consuming malignant infarction, or intracranial hemorrhage (n = 7). From the residual 165 patients, 52 met the further required inclusion criteria: (a) in-house-acquired admission CT perfusion imaging that was essential to determine the penumbral tissue immediately before EVT; (b) clearly identifiable angiographic technique  after MT, including diffusion tensor imaging (DTI) and structural T1-weighted imaging  score at the time of admission and at the time of MRI acquisition. The modified Rankin Scale (mRS) score was used to measure disability at day 90 after stroke onset, either on a routinely scheduled clinical visit or by a structured telephone interview.This study was approved by the local ethics committee and the need for patient consent was waived.For all study patients, the procedure of MT was classified by two experienced neuro-interventionalists  in consensus regarding the technical approach. The following categories of intervention techniques were differentiated  is composed of all patients that were treated with proximal flow arrest in a setting of BGC usage (PROTECT or PROTECTPLUS):n = 11) [PROTECT: PRoximal balloon Occlusion TogEther with direCt Thrombus aspiration during stent retriever thrombectomy (n = 11) : BGC + aPLUS (n = 18) [PROTECT(n = 18) : BGC + aThe BGC group (n = 23) is composed of all patients treated without BGC usage:SOLUMBRA : GuidingThe non-BGC group ) were excluded for direct comparisons of BGC vs. non-BGC. A possible bias within this group arises from the high conversion rates of this approach (secondary stent retriever application). Consequently, procedural and outcome results of the cases that used only the ADAPT technique are artificially good.Due to the exclusion criteria of mixed techniques , patients treated with only ADAPT  was necessary.The modified thrombolysis in cerebral infarction (mTICI) score  was deteSalvaged penumbral tissue was identified for each patient. Final infarct assessed with an MRI acquisition including DTI in the acute post-stroke phase was subtracted from the tissue at risk (penumbra) of co-aligned admission CT perfusion imaging. Hereby, salvaged penumbra was identified in the acute post-stroke phase and its microstructural integrity was analyzed see Fig. .Fig. 1ExTo identify the tissue at risk (penumbra) in the acute stage immediately before mechanical recanalization, CT perfusion imaging was acquired and post-processed by the fully automated software RAPID (iSchemaView Inc.). Perfusion maps were verified by an at least 3-year experienced neuroradiologist (M.B.)  with suI − MDH) / (MDI + MDH). A negative MD index means lower MD values within the penumbral gray matter compared with the non-affected side. In a previous work, this MD index was effectively used for characterizing microstructural integrity within the salvaged penumbra [By co-registering of admission CT perfusion imaging and MRI acquisition in the acute post-stroke phase, salvaged penumbra was calculated for each patient by a subtraction of tissue at risk and final infarction. After processing of DTI images using FSL’s FDT toolbox, MD maps were created. To find gray matter alterations within the salvaged penumbra, MD values of the penumbra on the infarcted side (I) were assessed and compared with MD values of the corresponding voxels on the contralateral, non-affected side (H). MD index was calculated by using the following formula: MD index =  and good clinical outcome (mRS ≤ 2 after 90 days) under consideration of the covariates age, sex, and reperfusion time. Moderation analysis was performed to check the interaction of the subgroups of BGC/non-BGC on the association between complete reperfusion and good clinical outcome.In total, 52 patients met the inclusion criteria as described above. An overview of demographic, clinical, and interventional data of patients and a comparison between the BGC and non-BGC groups can be found in Table p = 0.016).For completely reperfused patients, there is a significantly lower incidence of peripheral emboli in the BGC group (50%) in comparison with the non-BGC group .For directly comparing penumbral integrity of the different techniques, the precondition of mTICI 3 should be met. MD index of the BGC group shows significantly higher values (mean ± SD: 0.009 ± 0.035) than MD index of the non-BGC group . To exclude an influence of the volume of infarction on the impact of BGC on MD index as mentioned above, volume distributions for the technique groups in dependency of angiographic success can be found in Fig. p = 0.5) groups.Values of MD index are inversely correlated to the volume of infarction (Pearson’s p = 0.017). The covariates age, sex, and reperfusion time showed no significant influence on the analysis.Complete reperfusion success (mTICI 3) is significantly associated with good clinical outcome (mRS ≤ 2 after 90 days) in a logistic regression analysis . For the non-BGC group, the conditional effect was lowered and lost its significance on the 5% level . That implies that the importance of mTICI 3 reperfusion for good clinical outcome is predominantly based on patients treated with BGC.In a second step, the impact of the subgroups BGC/non-BGC on this association was tested in a moderation analysis under consideration of the abovementioned covariates. The conditional effect of complete reperfusion success on good clinical outcome remained significant for the BGC group  by BGC usage. The main new finding is the preserved microstructural integrity (higher MD index) when using BGC that is known to impact the clinical course of patients . To avoiAs expected, there is an interaction of MD index of the salvaged penumbra with the volume of infarction. The more the ischemic demarcation is visible, the higher the integrity loss of salvaged penumbra can be measured. This coherence makes it necessary to check the distribution of ischemic volume for the technical subgroups (BGC/non-BGC) that in the end showed no volume differences. That confirms the supposed hypothesis that BGC usage saves the microstructural integrity of the salvaged penumbral tissue for the case of complete reperfusion, independently from the extent of final infarction. However, this point does not apply to the same extent to incomplete reperfusions. The remaining vessel occlusions impact penumbral tissue integrity so much (broad range of infarction volume for both groups) that no clear microstructural benefit is detectable for the cases of BGC usage, but only a trend to higher MD indices.It can be supposed that clot fragmentation and micro-embolization into the occlusion-dependent brain tissue during MT would affect microstructural, ischemic-like damage within the salvaged penumbra. This damage can be measured by MD index that gives information about the tissue integrity of the salvaged gray matter, compared with the contralateral non-affected hemisphere. By assessing MD values using DTI, changes of the molecular diffusion rate can be detected that give information about subtle integrity alterations . For theA previous study showed that MD index for gray matter is a very accurate parameter for characterizing penumbral integrity . CertainFinally, it cannot be proven that the microstructural damage in the salvaged penumbra, that was shown for the non-BGC group, did not exist before recanalization. However, the mTICI 3/BGC group showed no microstructural damage, which implies that this developed secondarily, possibly induced by clot fragmentation and micro-embolization. A bias in performing the groups of BGC/non-BGC cannot be excluded, but it is rather unlikely in the study’s cohort: since the implementation of BGC in this single comprehensive stroke center, nearly every endovascular treatment was made by the use of BGC, and the non-BGC group consists of patients mostly treated in 2016–2017, before BGC was routinely applied. The exclusion of ADAPT cases reduces the generalizability of the findings as these are only applicable for the case of stent retriever application. A further limitation is the moderate sample size within the groups that makes a fine matched analysis too powerless. Especially in the beginning phase of the study, not all patients who were mechanically recanalized were examined with MRI, arising from internal organization problems . Patients with disability for an MRI examination could also not be included. These patients often present extended ischemia or space-consuming hemorrhage that makes a DTI analysis impossible. This subgroup of patients with distinct worse outcome is missing in the analysis.In summary, the present study highlights the importance of technical aspects during mechanical recanalization of acute LVO. With the use of DTI, it was shown that achieving complete reperfusion in a setting of BGC usage minimizes microstructural tissue damage in the salvaged penumbra and improves long-term outcome. This reinforces the importance of using BGC in endovascular stroke treatment.ESM 1(DOCX 32 kb)


Growth behavior, of both shoots and roots, was recorded and correlated to plant physiological responses. 11CO2 fixation, leaf export of [11C]-photosynthates, and their rate of transport increased systematically with increasing BA concentrations, while the fraction of [11C]-photosynthates delivered to the roots under 0 mM and 0.5 mM BA treatments was lower than under 0.05 mM BA treatment, likely due to changes in root growth. Additionally, solid-phase extraction coupled with gamma counting, radio-fluorescence thin layer chromatography, and radio-fluorescence high-performance liquid chromatography techniques applied to tissue extracts provided insight into the effects of BA treatment on ‘new’ carbon (as 11C) metabolism. Most notable was the strong influence reducing boron levels had on raising 11C partitioning into glutamine, aspartic acid, and asparagine. Altogether, the growth of maize under different regimes of boron affected 11CO2 fixation, its metabolism and allocation belowground, and altered root growth. Finally, inductively coupled plasma mass spectrometry provided insight into the effects of BA treatment on plant uptake of other essential nutrients. Here, levels of boron and zinc systematically increased in foliar tissues with increasing BA concentration. However, levels of magnesium, potassium, calcium, manganese, and iron remained unaffected by treatment. The rise in foliar zinc levels with increased BA concentration may contribute to improved 11CO2 fixation under these conditions.In agriculture, boron is known to play a critical role in healthy plant growth. To dissect the role of boron in maize metabolism, radioactive carbon-11 (t Crop yields are negatively impacted by various biotic and abiotic stresses and by nutrient deficiencies. Boron is a micronutrient essential for plant growth and development , affectiBoron deficiency primarily leads to a cessation of growth in plant meristems (groups of undifferentiated stem cells) ,11,12. BZea mays (maize), have a lower boron requirement compared to dicotyledonous species -photosynthates -Physiology Measurements: After 11CO2 pulsing, plants were incubated for 3 h before separating the load leaf from shoots and roots. During that time, levels of radioactivity were monitored using two radiation detectors  affixed to the plant 8 cm above the base of the stem and below the base of the stem . Measurement of 11C radioactivity was performed using gamma counting and data was decay-corrected to end of bombardment. The individual components were summed together for total plant 11C radioactivity and normalized based on fresh tissue weight. Individual components were used to calculate leaf export and root allocation fractions.Whole-Plant [the stem  which pr11C]-Metabolite Analyses: After 11CO2 pulsing, the load leaf was removed 20 min later and subjected to metabolite analyses following published procedures -sugars were measured by radio thin layer chromatography (TLC) using glass-backed NH2-silica HPTLC plates  purchased from Sorbent Technologies  according to published procedures -sugar content was related to the 11C radioactivity quantified along the sample lane of the TLC plate and then corrected to percent total fixed 11CO2 using gamma count data from the insoluble and soluble fractions.Total soluble [ocedures . A mobil11C]-amino acids were analyzed following published procedures [v/v with 0.5 M sodium acetate:methanol) and Solvent B (70:30 methanol:18 MΩ water) starting at 75:25 and switching to 25:75 within 30 min at a flow rate of 0.7 mL min−1. On-line fluorescence detection  was used for correlating retention times of standards with those of [11C]-amino acids in biological samples. A NaI gamma radiation detector  enabled direct measurement of radiolabeled metabolites. Data was acquired using PeakSimple™ chromatography software  and radioactivity assigned to peaks was corrected for radioactive decay, summed for a total [11C]-amino acid value, and related back to the amount of 11C radioactivity fixed by the plant at the start of the study  using 1 N NaOH, and the total volume was processed through an Accell QMA Plus Light Sep-Pak™  followed by rinsing of the contents with 10 mL of DI water. Cartridges were then counted for 11C radioactivity with a NaI gamma counter.For [11C]-basic metabolite analysis, 200 mL of tissue extract was processed through a strong cation exchange cartridge  followed by rinsing of the cartridge using 10 mL of DI water. The cartridge was subjected to gamma counting for quantification of this metabolite pool.For [Inductively Coupled Plasma-Mass Spectrometry (ICP-MS): For ICP-MS analyses of nutrients, leaf 2 samples were harvested at the V2 developmental stage from plants, and 1 cm of leaf tips and lower sheath regions were removed. Tissues were air dried at 70 °C for 1 week and ground to a powder using a mortar and pestle. Ground tissue was weighed and digested in 3.0 mL of concentrated nitric acid at 190 °C using a Milestone Ethos Plus  microwave digestion system, then diluted to 50 mL with ultrapure water followed by gravimetric dilution by a factor of 10 with 0.45 N nitric acid. Samples were analyzed with a Perkin-Elmer NexION ICP-MS in Kinetic Energy Discrimination mode. Reference materials included NIST SRM 1570 spinach leaves and NIST SRM 1573 tomato leaves prepared in the same way. Internal standards at known concentrations were prepared from stock solutions  and used to calibrate instrument response.p < 0.05.Statistical Analysis: Data was subjected to the Shapiro–Wilk Normality Test to identify outliers, so all data groups reflected normal distributions. Data was then subjected to one-way analysis of variance (ANOVA) in R using the multcompview package . Tukey’s11C-radiotracing allowed us to quantify changes in the plants’ physiological status by examining changes in 11CO2 fixation, leaf export of 11C-photosynthates, their rate of transport, and the amount of photosynthates that were allocated to roots. Furthermore, these biological functions were correlated with the growth performance of plants, both aboveground and belowground, as well as correlated with plant uptake of essential nutrients. Finally, 11C-radiotracing provided a way to examine changes in metabolic regulation by measuring 11C-partitioning across all the plant metabolite pools and by measuring certain individual metabolites within these pools. Our study therefore provides unprecedented insight into the effects of boron on maize physiological and metabolic processes. By examining the flux of ‘new’ carbon (as 11C) into metabolites, one can often gain greater insight into boron’s influence on plant metabolism and its regulation than by simply profiling the endogenous metabolite concentrations. Most notable here were the strong influence that reducing boron levels had on raising 11C partitioning into glutamine, aspartic acid, and asparagine, which may be part of a plant stress response to boron deficiency.Using a combination of radiotracer tools and ICP-MS, we were able to gain new insight into the physiological and metabolic responses of maize plants subjected to different levels of BA treatment during growth spanning low to high boron levels. 11CO2 fixation under these conditions. Altogether, boron appears to have a selective effect on the uptake of only certain plant micronutrients. Further studies will be needed to elucidate the mechanisms for this behavior.Finally, inductively coupled plasma mass spectrometry provided another layer of insight into the effects of boron on plant uptake of essential micronutrients. Here, levels of boron and zinc were seen to systematically increase in foliar tissues with increasing BA concentration, while levels of magnesium, potassium, calcium, manganese, and iron remained unaffected by treatment. This rise in foliar zinc levels with increased BA concentrations may contribute to improved


Staphylococcus spp. isolates recovered from raw goat milk in Brazil.Antimicrobial resistance poses a major threat to global public health. Foodstuff of animal origin can serve as potential vehicles for the dissemination of antimicrobial-resistant bacteria and resistance genes to consumers. In view of the lack of knowledge about antimicrobial resistance in bacteria associated with goat milk, the aim of this study was to report species-level identification and antimicrobial susceptibility profiles of a large collection of Staphylococcus spp. isolates originated from 510 goat milk samples in Northeast Brazil were investigated. The isolates were obtained by conventional microbiological methods. Species identification and antimicrobial susceptibility testing were performed by means of a semi-automated system using a panel for biochemical tests and broth microdilution method for 19 antimicrobial drugs.A total of 434 Staphylococcus aureus (22.6%) accounted for the majority of the isolates, a total of 13 different non-aureus staphylococci spp. were identified. High resistance rates against erythromycin (40.8%), and the beta-lactams ampicillin (45.9%) and penicillin (42.9%) were observed among S. aureus isolates. The most significant findings were related to the resistance against quinupristin-dalfopristin, a drug of last resort used in human medicine to treat infections caused by vancomycin-resistant S. aureus and enterococci.Although Staphylococcus spp. showing phenotypic resistance against different antimicrobial drugs encourages further investigations on the real impact of these bacteria as reservoirs of antimicrobial resistance genes to consumers. Furthermore, the potential impact of technological processes, such as pasteurization, fermentation, and maturation, on the maintenance and dissemination of antimicrobial resistance among the microbial populations in milk and dairy products must also be investigated.The high diversity of  Opuntia ficus) as fodder [Paraiba is the leading goat milk producer state in Brazil, with a total production of 5.63 million litters, representing 23.9% of the revenue attributed to the whole Brazilian goat milk sector . In ParaStaphylococcus spp. are of public health concern. Although the extensive use of antimicrobials in human medicine is a major driver for the emergence and dissemination of antimicrobial resistance [Staphylococcus spp., the most common disease affecting the dairy industry worldwide [Staphylococcus associated with intramammary infections in goats is limited [Staphylococcus associated with milk and dairy products, as the majority of the studies identify isolates as Staphylococcus aureus and non-aureus staphylococci (NAS) spp. The identification of the most frequent Staphylococcus spp. and the determination of their antimicrobial susceptibility rates are important for controlling and prevention purposes at both farm and industry levels [Although dairy goat production plays an important socioeconomic role in low-income Northeast Brazil, very little is known regarding staphylococcal contamination in milk produced by smallholders in semi-arid Brazil. Besides, the fact that staphylococci are leading foodborne pathogens worldwide due to the capacity of some strains to produce toxins ,5, inclusistance , foodstusistance . The emesistance . Subclinorldwide , are assorldwide . However limited . Anothery levels .Staphylococci are highly capable of acquiring resistance to several classes of drugs, including the highest priority critically important antimicrobials (HPCIA), which are drugs of last resort to treat serious bacterial infections in people. EstimatStaphylococcus contaminating goat milk and to assess their susceptibility profiles against antimicrobials, including some drugs commonly used in human medicine to treat staphylococcal infections.The aim of the present study was to investigate the most common spp. of Ethics approval was not required for this study. Verbal consent was obtained from farmers allowing milk samples to be collected during routine milking procedures.The milk samples were collected from Cariri region, Paraíba State, Northeastern Brazil from March 2015 to February 2016. Milk samples were processed at the Laboratory for Animal-derived Foods (LAPOA) of the College for Agricultural Sciences, Federal University of Paraíba (CCA/UFPB).Staphylococcus spp. isolates originated from goat milk (n=434) were investigated in this study. The isolates were recovered from 510 milk samples collected in Cariri, a semi-arid region in Paraiba State, Northeast Brazil. Samples (10 mL) were streaked onto Baird Parker agar  and incubated at 37°C for 24-48 h Colonies showing typical and non-typical Staphylococcus characteristics were tested for catalase, oxidase and examined microscopically after conventional Gram staining procedure. Confirmed Staphylococcus isolates were further identified by means of a biochemical panel , including the following tests: Crystal violet reaction, nitrate reduction, novobiocin resistance, Voges–Proskauer, sensitivity to optochin, alkaline phosphatase, bile esculin, production of pyrrolidone, dehydrolyzation of arginine, breakage of arginine, glycosidase production, hydroxylation of indoxyl phosphatase, urea, phenol red, growth at 6.5% NaCl, bacitracin resistance, use of pyruvate, presence of β-lactamase, and hemolysis. Species identification was based on automatic interpretation of the biochemical test results by AutoScan4 software .S. aureus/Staphylococcus lugdunensis); penicillin (Pen) (≥0.25); rifampin (Rif) (≥4); trimethoprim/sulfamethoxazole (Sxt) (≥4/76); and tetracycline (Tet) (≥16). The interpretation of the results was performed according to the Clinical and Laboratory Standards Institute criteria [S. aureus ATCC 25923 was used as control.Phenotypic antimicrobial susceptibility was assessed by means of a semi-automated microdilution method  for the following drugs and their respective cutoff values (μg/mL): Ampicillin/sulbactam (Sam) (≥32/16); ampicillin (Amp) (≥0.5); amoxicillin/clavulanate de K (≥8/4); ceftriaxone (≥64); clindamycin (Cli) (≥4); ciprofloxacin (Cip) (≥4); daptomycin (Dap) (≥2); erythromycin (Eri) (≥8); gentamicin (Gen) (≥16); nitrofurantoin (≥128); quinupristin/dalfopristin (QD) (≥4); levofloxacin (Lvx) (≥8); linezolid (Lzd) (>4); moxifloxacin (Mxf) (≥8); oxacillin (Oxa)  isolates .S. aureus  and Staphylococcus epidermidis  were the most frequent spp. cultured from raw goat milk  is noteworthy. S. aureus and NAS. Pan-susceptibility was observed in 155 (35.7%) isolates. Interestingly, we detected NAS showing resistance to the highest priority critically important antimicrobials that are used exclusively to treat skin and urinary tract infections in humans [oat milk . A totaln humans ,21.S. aureus and 6.3% of NAS isolates were resistant to amoxicillin/clavulanate. We also detected resistance against QD among the NAS. This group showed higher resistance rates against Cli and Eri (p<0.05) than S. aureus.In our study, 4.1% of Staphylococcus spp. isolated from goat milk. A total of 134 (30.9%) MDR isolates were detected. One S. aureus isolate was resistant to 14 drugs .S. aureus in our study was expected as this species is commonly isolated from dairy animals worldwide. Nonetheless, this finding is of public health significance, as S. aureus is among the main Staphylococcus species causing food poisoning in humans due to the production of heat-stable enterotoxins [S. hyicus among the goat milk samples in the present study is surprising, since S. hyicus has not been commonly detected in milk. Considering that S. hyicus originates from skin sources [Staphylococcus xylosus, Staphylococcus schleiferi, and Staphylococcus simulans, and have been reported as emerging zoonotic pathogens [The high occurrence of rotoxins . The obs sources , the hig sources  that can sources  were detathogens -27.S. aureus, S. epidermidis, and S. hyicus are leading pathogenic staphylococci in veterinary medicine [S. epidermidis, S. simulans, and S. xylosus have been commonly isolated from intramammary infections [S. epidermidis in our study is in accordance with a recent study in Mexico [Staphylococcus spp. cultured from goat milk. S. epidermidis high frequency in goat milk has also been reported in previous studies, possibly associated with subclinical mastitis in dairy goats [medicine . In dairfections ,29,30. Tn Mexico  reportinS. aureus from foodstuffs (1150 samples), the highest resistance rates were observed against Pen (83%), Lzd (67.7%), and Eri (52.1%); however, significant differences were observed according to the type of food [According to a previous investigation on the antimicrobial susceptibility of a large set of  of food .S. aureus and NAS resistance to amoxicillin/clavulanate suggests that some Staphylococcus strains found in raw goat milk can harbor different resistance mechanisms, such as serine-β-lactamase production, including extended-spectrum β-lactamases that could hydrolyze later-generation cephalosporins and carbapenemases. Thus, NAS can be considered reservoirs of antimicrobial resistance, although S. aureus has been considered the key spp. involved in both food poisoning outbreaks and clinical infections in humans. This is also corroborated by the high resistance rates observed in NAS isolated from food animal sources, particularly resistance against macrolides, Tet, and streptogramins [The detection of ogramins .S. aureus and enterococci, and these are among the most rapidly growing multidrug-resistant bacteria affecting humans [Considering that quinupristin is a drug of last resort used to treat infections caused by vancomycin-resistant g humans , furtherTet has been commonly used for therapeutic purposes on farm animals for decades and high rates of resistance against this drug have been observed among different organisms, including pathogenic bacteria .Staphylococcus spp. contaminating goat milk on the putative dissemination of antimicrobial resistance to humans is beyond the scope of this study. However, considering that pasteurization is a mild heat treatment, and the fact that milk is a suitable medium for the maintenance and growth of bacteria, it is plausible to consider that milk can serve as source of antimicrobial resistance genes to the human gut microbiota, supporting previous assumptions [The real impact of antimicrobial-resistant umptions ,37. The Finally, staphylococci can serve as reservoirs of antimicrobial resistance genes to milk microorganisms. A large number of antimicrobial resistance genes have been identified in lactic acid bacteria ,39. IncrS. aureus and NAS in goat milk produced in the investigated region reveal the potential role of milk as a reservoir of antimicrobial resistance genes. The findings encourage further investigation of putative effects of technological processes, such as pasteurization, fermentation, and maturation, on the maintenance and dissemination of antimicrobial resistance genes in the microbiota of goat milk and dairy products. Such knowledge could be important to mitigate the spread of antimicrobial resistance in the dairy industry. Finally, our results highlight the importance of on-herd hygiene measures to reduce microbial contamination in milk produced by smallholders and the continuous awareness of producers toward antimicrobial stewardship.The high antimicrobial resistance rates in CJBO and LSF: Study conception and design. AESJ, MMSS, NMVS, and PCV Acquisition of data, analysis and interpretation of data. PENG, AESJ and LSF: Drafting of the manuscript: PENG, NMVS and CJBO: Supervision. PENG and CJBO: Critical revision. All authors read and approved the final manuscript.


On August 12, 2021, the Food and Drug Administration (FDA) amended Emergency Use Authorizations (EUAs) for the Pfizer-BioNTech and Moderna COVID-19 vaccines to authorize administration of an additional dose after completion of a primary vaccination series to eligible persons with moderate to severe immunocompromising conditions . Persons who reported receiving a primary series from different manufacturers or a manufacturer that was unknown or unavailable in the United States, or 2 doses of vaccine after receipt of a Janssen (Johnson & Johnson) single-dose vaccine (150) were excluded from the analysis of adverse reactions after receipt of the additional dose. Time elapsed from completion of the primary vaccination series to receipt of an additional dose was described by pattern of vaccination. Adverse event profiles after doses 2 and 3 were compared for registrants who received mRNA vaccine from the same manufacturer for all 3 doses.**During August 12–September 19, 2021, a total of 22,191 v-safe registrants reported receipt of an additional dose of COVID-19 vaccine after completing the primary series . Among tAmong the 22,191 v-safe registrants, the median interval from completion of the primary COVID-19 vaccination series to receipt of an additional dose was 182 days (interquartile range [IQR] = 160–202 days) . Among tLocal  and systemic  reactions were frequently reported during the week after an additional dose of COVID-19 vaccine, most commonly on the day after vaccination. Frequently reported reactions were injection site pain , fatigue , and headache .Among 22,191 additional dose recipients, a total of 7,067 (31.8%) reported health impacts, and approximately 28.3%  reported they were unable to perform normal daily activities, most commonly on the day after vaccination. Medical care was sought by 401 (1.8%) registrants, and thirteen (0.1%) were hospitalized. Reasons for receiving medical care or hospitalization were not identified in the v-safe survey; however, registrants who indicate that medical attention was sought after vaccination are contacted by VAERS staff and encouraged to complete a VAERS report.Among 21,658 v-safe registrants who received the same mRNA vaccine for all 3 doses, 12,591 (58.1%) completed at least one health check-in survey on days 0–7 after all 3 doses; 79.4% and 74.1% reported local or systemic reactions, respectively, after dose 3, compared with 77.6% and 76.5% who reported local or systemic reactions, respectively, after dose 2. Among registrants who received 3 doses of Moderna , local reactions were reported more frequently after dose 3 than dose 2  . SystemiAs of September 19, 2021, approximately 2.21 million persons in the United States had received additional doses of COVID-19 vaccinesThe number of registrants who indicated that they received 2 doses of Janssen vaccine or received their additional dose from a manufacturer different from that of their primary series was small, limiting any conclusions. Data on the safety or effectiveness of vaccination with COVID-19 vaccine products from different manufacturers are limited; the Advisory Committee on Immunization Practices (ACIP) recommends that persons with moderately to severely immunocompromising conditions receive a third dose of mRNA COVID-19 vaccine from the same manufacturer as their primary series (During the period covered by this study, ACIP recommendations for an additional dose of COVID-19 vaccine were limited to persons with moderately to severely immunocompromising conditions who had received 2 doses of an mRNA vaccine.The findings in this report are subject to at least four limitations. First, enrollment in v-safe is voluntary and likely not representative of the vaccinated U.S. population; the majority of participants identified themselves as White and non-Hispanic. Second, during this study period, additional dose recommendations were limited to persons with immunocompromising conditions who completed a primary mRNA COVID-19 vaccination series; however, v-safe does not include information about immune status. Additional-dose recipients likely include persons with and without immunocompromising conditions. Third, a causal relationship between a vaccine and clinically serious adverse event reported after vaccination cannot be established using v-safe data. Finally, insufficient data were available to determine patterns of adverse reactions after receipt of an additional dose from a manufacturer different from the primary series or for the Janssen vaccine.An additional dose of mRNA COVID-19 vaccine is recommended for persons with moderately to severely immunocompromising conditions (Among 306 Pfizer-BioNTech clinical trial participants, adverse reactions after dose 3 were similar to those after dose 2.During August 12–September 19, 2021, among 12,591 v-safe registrants who completed a health check-in survey after all 3 doses of an mRNA COVID-19 vaccine, 79.4% and 74.1% reported local or systemic reactions, respectively, after the third dose; 77.6% and 76.5% reported local or systemic reactions after the second dose, respectively.Voluntary reports to v-safe found no unexpected patterns of adverse reactions after an additional dose of COVID-19 vaccine. CDC will continue to monitor vaccine safety, including for additional COVID-19 doses.


Vaccination against SARS-CoV-2 (the virus that causes COVID-19) is highly effective at preventing hospitalization due to SARS-CoV-2 infection and booster and additional primary dose COVID-19 vaccinations increase protection  recommended that moderately or severely immunocompromised recipients of an mRNA COVID-19 vaccine (Pfizer-BioNTech or Moderna) primary series receive a homologous additional primary dose ≥28 days after the second dose in the primary series . Tests for statistical significance were not conducted because these data are reflective of the U.S. population aged ≥65 years and were not based on population samples. This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy.Among 42.5 million eligible persons aged ≥65 years, 18,745,803 (44.1%) received a booster or additional primary dose of COVID-19 vaccine during August 13–November 19, 2021 , includiAmong Pfizer-BioNTech recipients, the daily number of persons who received a booster or additional primary dose peaked 5 days after release of the Pfizer-BioNTech booster recommendations  with 341,395 recipients vaccinated . After rAs of November 19, 2021, 44.1% of 42.5 million eligible adults aged ≥65 years had received a booster or additional primary dose, leaving an estimated 23.8 million eligible adults in this age group in need of a booster or additional primary dose. Coverage with booster or additional primary COVID-19 vaccine doses varied by the primary series vaccine product and race/ethnicity; approximately one third of eligible American Indian or Alaska Native persons, Hispanic or Latino persons, and Native Hawaiian or Other Pacific Islander persons received a booster or additional dose, compared with approximately one half of non-Hispanic White and multiple/other race persons. All adults aged ≥65 years should be vaccinated against COVID-19, including receiving an additional primary dose if they are immunocompromised and/or a booster dose after the minimum recommended interval after primary series completion.Differences in coverage between recipients of different primary series vaccine products can partially be explained by the staggered timing of ACIP recommendations, which also lowered overall coverage because not all persons represented in these results had an equal amount of time to receive a booster or additional primary dose. For example, based on timing of recommendations, Pfizer-BioNTech primary series recipients had 28 days longer to receive a booster dose than did Moderna or Janssen recipients. In addition, Moderna and Pfizer-BioNTech coverage includes recipients of additional primary doses administered since August 13, whereas Janssen coverage does not. However, only 10.7% of booster or additional primary dose recipients received an additional primary dose before booster dose recommendations, so inclusion of these recipients in mRNA primary series coverage cannot account for the differences observed. Certain groups  were recommended to receive a homologous dose, while the first recommendations for Janssen recipients allowed a heterologous booster dose. Although 61.5% of Janssen recipients received a heterologous booster dose, this represents only 227,079 persons, or 1.2% of overall booster or additional primary dose recipients.The findings in this report are subject to at least five limitations. First, the use of a composite measure for coverage and absence of information on the immunocompromise status of vaccine recipients limits the conclusions that can be drawn from the analysis and might also have resulted in underestimation of the eligible population because immunocompromised persons who completed a primary series after May 19, 2021, could not be identified. Second, identification of booster or additional primary dose recipients depends on linkage between vaccination records in jurisdiction-specific immunization information systems or other data systems. Persons who received a booster or additional primary dose in a different jurisdiction from that of their primary series, or who for other reasons were not able to be linked back to their primary series, might not be represented in these results. Third, restricting the source population to persons aged ≥65 years at the time of primary series completion might have excluded some valid recipients, including those who reached age 65 years between completion of the primary series and administration of the booster or additional primary dose, and persons with a missing, incorrect, or incomplete date of birthA booster or additional primary dose of COVID-19 vaccine provides a robust immune response (Although COVID-19 vaccines are highly effective, vaccine effectiveness wanes over time, and adults aged ≥65 years are at increased risk for severe COVID-19–associated illness. Booster and additional primary vaccine doses increase protection.During August 13–November 19, 2021, 18.7 million persons aged ≥65 years received a booster or additional primary dose of COVID-19 vaccine, constituting 44.1% of eligible persons aged ≥65 years. Coverage differed by primary series vaccine product and race/ethnicity.Strategic efforts are needed to encourage eligible persons aged ≥18 years, especially those aged ≥65 years and those who are immunocompromised, to receive a booster and/or additional primary dose to ensure maximal protection against COVID-19.