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Gupta, Shruti, and Julie Pirsch. "The company‐cause‐customer fit decision in cause‐related marketing." Journal of Consumer Marketing 23, no. 6 (October 2006): 314–26. http://dx.doi.org/10.1108/07363760610701850.
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Pangan, Ronnie, and Jaehak Shim. "CAUSE-RELATED MARKETING AND CAUSE SPONSORSHIP’S COMPANY-CAUSE FIT AND eWOM: SPREADING CSR ON FACEBOOK." Advanced International Journal of Business, Entrepreneurship and SMEs 3, no. 8 (June 15, 2021): 22–40. http://dx.doi.org/10.35631/aijbes.38002.
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Businesses should utilize Corporate Social Responsibility (CSR) marketing communications to show genuine support for stakeholders affected by the Covid19 pandemic. This study focuses on two forms of CSR marketing communications: cause-related marketing (CRM) and cause sponsorship (CS). This research would look into how CRM and CS’s company cause fit will affect eWOM (electronic word-of-mouth), a type of consumer response. A survey-based within-subjects trial of CRM and CS x 2 company-cause fit will be conducted on active Facebook users aged 18 to 64 years old. Ten (10) pre-selected firms from the Philippines' Top 30 Businesses were selected. These companies posted both CRM and CS Facebook messages. The CRM posts will be shown to half of the sample size (N=272), while the CS posts will be shown to the other half (N=272) and graded via a questionnaire. The research concluded that there were positive relationships between CRM and CS’s company-cause fit and eWOM. Between the two, CRM had a greater effect on eWOM as compared to CS. This was also evident in the models. The higher the company-cause fit, the higher the eWOM response. The suggestion to companies was to concentrate on CRM FB posts with the high company-cause fit so that the occurrence of eWOM would be higher especially during periods of crisis like the Covid19 pandemic. For future researchers, other forms of CSR marketing communications and consumer responses may be studied to further increase the effectiveness of Facebook CSR posts.
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Zhang, Anran, Alex Scodellaro, Bo Pang, Hui-Yi Lo, and Zhengliang Xu. "Attribution and Effectiveness of Cause-Related Marketing: The Interplay between Cause–Brand Fit and Corporate Reputation." Sustainability 12, no. 20 (October 10, 2020): 8338. http://dx.doi.org/10.3390/su12208338.
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In cause-related marketing (CRM) programs, the fit between the cause and brand is an important factor influencing consumer perceptions and behavior. However, the literature demonstrates that there is disagreement regarding the effect of cause–brand fit on consumer responses with varying corporate reputation. This study aims to examine the influence of cause–brand fit on consumer attitudes, attributed company motives, and the moderating role of corporate reputation. With a two (fit: high/low) by three (reputation: low/medium/high) experimental study, we reveal that consumers hold positive attitudes toward companies that engage in CRM campaigns. The effect of cause–brand fit on consumer-attributed company motives is moderated by corporate reputation. For low-reputation companies, a high cause–brand fit CRM campaign resulted in consumers attributing more negative motives to companies than low-fit campaigns. The opposite was true for medium-reputation companies. Meanwhile, high-reputation companies with a high cause–brand fit elicit greater value-driven attributed motives from consumers than other motives. Recommendations for implementing CRM programs and for future research are discussed.
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Lu, Tim, Xia Wei, and Kungchi Li. "Consumer responses to corporate social responsibility programs." Nankai Business Review International 6, no. 4 (November 2, 2015): 364–80. http://dx.doi.org/10.1108/nbri-03-2014-0021.
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Purpose – The paper aims to establish a causal relationship model that helps to realize how consumer involvement with the cause moderates the effect of company-cause fit on consumers’ corporate associations, and how their corporate associations regarding a company’s social responsibility programs influence their satisfaction with the company and the company’s corporate image, in the backdrop that the use of corporate social responsibility initiatives to affect consumers’ preference has become a common strategy. Design/methodology/approach – In the main study, the authors conducted a between-subjects factorial design to test the research model. A total of 400 questionnaires were distributed, and a valid sample of 389 participants was obtained. Findings – The results show that high-fit programs have a positive influence on the perceived corporate ability (CA) and corporate social responsibility (CSR) associations. CA associations directly influence corporate image and consumer satisfaction, while CSR associations indirectly impact consumer satisfaction through corporate image. Furthermore, consumers’ involvement with the cause increases the relationship between company-cause fit and CA associations. Originality/value – These conclusions have important implications for a better understanding of consumer evaluation of CSR initiatives. Theoretically, this research increases understanding of the interaction effects of perceived company-cause fit and consumer involvement with the cause on consumer evaluation of a company engaged in CSR, and a richer insight into the role of CA and CSR associations in consumer evaluations of companies engaged in CSR campaigns. Managerially, this research shows how managers can choose CSR programs causes that are most likely to promote favorable customer CA and CSR associations, thereby improving the company’s corporate image and customer satisfaction.
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Schmeltz, Line. "Getting CSR communication fit: A study of strategically fitting cause, consumers and company in corporate CSR communication." Public Relations Inquiry 6, no. 1 (January 2017): 47–72. http://dx.doi.org/10.1177/2046147x16666731.
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Companies experience increasing legal and societal pressure to communicate about their corporate social responsibility (CSR) engagements from a number of different publics. One very important group is that of young consumers who are predicted to be the most important and influential consumer group in the near future. From a value-theoretical base, this article empirically explores the role and applicability of ‘fit’ in strategic CSR communication targeted at young consumers. Point of departure is taken in the well-known strategic fit (a logical link between a company’s CSR commitment and its core values) and is further developed by introducing two additional fits, the CSR-Consumer fit and the CSR-Consumer-Company fit (Triple Fit). Through a sequential design, the three fits are empirically tested and their potential for meeting young consumers’ expectations for corporate CSR messaging is discussed.
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Doo, Jeong－Wan. "The Effects of Cause－Related Marketing: Moderating Roles of Product Types, Price Discount and Company－Cause Fit." Korea Association of Business Education 32, no. 5 (October 30, 2017): 99–123. http://dx.doi.org/10.23839/kabe.2017.32.5.99.
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Lee, Sun Young, and Sungwon Chung. "Effects of emotional visuals and company–cause fit on memory of CSR information." Public Relations Review 44, no. 3 (September 2018): 353–62. http://dx.doi.org/10.1016/j.pubrev.2018.02.001.
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Cordes, Regina V. Frey, Meike Eilert, Denise Demisch, and Tomás Bayón. "Cause-Company Fit in Cause-Related Marketing Campaigns and Consumer Outcomes: A Replication and Extension Using Field Data." Journal of Marketing Behavior 4, no. 2-4 (2020): 239–48. http://dx.doi.org/10.1561/107.00000068.
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Zasuwa, Grzegorz. "The Role of Company-Cause Fit and Company Involvement in Consumer Responses to CSR Initiatives: A Meta-Analytic Review." Sustainability 9, no. 6 (June 13, 2017): 1016. http://dx.doi.org/10.3390/su9061016.
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Pangan, Ronnie, and Jaehak Shim. "PROPOSED MODELS FOR CSR MARKETING COMMUNICATIONS ON FACEBOOK BASED ON COMPANY-CAUSE FIT AND CONSUMER RESPONSES." Advanced International Journal of Business, Entrepreneurship and SMEs 3, no. 8 (June 15, 2021): 98–118. http://dx.doi.org/10.35631/aijbes.38007.
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Businesses should use Corporate Social Responsibility (CSR) marketing communications to show genuine support for stakeholders affected by the Covid19 pandemic. Two forms of CSR marketing communications were focused on: cause-related marketing (CRM) and cause sponsorship (CS). This research looked into how CRM and CS impact customer responses to: a) like/join the company's Facebook page, b) exchange CSR activities through eWOM (electronic word-of-mouth), and c) intention to buy the company's products and services (purchase intention). The company-cause fit was the dependent variable that was tested against the three responses. A survey-based within-subjects experiment of CRM and CS x 2 (good fit / bad fit) was conducted on active Facebook users aged 18 to 64 years old. Ten (10) pre-selected firms from the Philippines' Top 30 Businesses were listed, These companies released both CRM and CS Facebook posts. The CRM posts were shown to half of the sample size (n=136), while the CS posts were shown to the other half (n=136) and rated by a questionnaire. This research suggested models based on regression analysis and modeling that would advise companies how to better conduct CRM and CS online operations in order to maximize investments, especially during periods of crisis like the Covid19 pandemic.
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Molinillo, Sebastian, Pere Mercadé-Melé, and Teresa De Noronha. "Cause-Related Marketing Influence on Consumer Loyalty in a Medium-Sized City." Sustainability 12, no. 9 (May 1, 2020): 3632. http://dx.doi.org/10.3390/su12093632.
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The purpose of this study is to analyze the effect of the performance of a cause-related marketing action on consumer loyalty by a company. In addition, the study explores the moderating effect of the publicizing medium. The proposed theoretical model was tested based on data gathered from a face-to-face questionnaire completed by 421 respondents living in a medium-sized city. The results validated the proposed model and showed that the functional and image fit between social actions and companies are key antecedents of perceived corporate ability (CA) and company credibility. It was shown that CA directly influences customer satisfaction, that credibility indirectly influences customer satisfaction through perceived corporate social responsibility, and that satisfaction directly and positively impacts customer loyalty. Moreover, the influence of functional and image fit in the model were shown to be moderated by the type of publicizing medium. Specifically, the effect of functional fit on corporate ability is greater for traditional media (TM) than for social media (SM). On the other hand, the effect of image fit on corporate ability is greater for SM than for TM. The theoretical and practical implications of these results are discussed.
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Kim, Kihan, Yunjae Cheong, and Joon Soo Lim. "Choosing the right message for the right cause in social cause advertising: type of social cause message, perceived company–cause fit and the persuasiveness of communication." International Journal of Advertising 34, no. 3 (February 9, 2015): 473–94. http://dx.doi.org/10.1080/02650487.2015.1006081.
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Coleman, Joshua T., and Michael C. Peasley. "Demonstrating a lack of brand/cause effects on point of sale donations." Management & Marketing 10, no. 3 (October 1, 2015): 226–43. http://dx.doi.org/10.1515/mmcks-2015-0016.
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Abstract Point of sale cause-related marketing has raised over $2 billion for charities over the past 30 years, yet the subject remains largely unexplored in academic literature. The subject of brand/cause fit, however, is prolific throughout extant research, with many studies showing that high congruence between a company and a charity is necessary to achieve philanthropic success. This paper challenges current marketing thinking both conceptually and empirically. Employing tests of no-effect hypotheses following the guidelines set out by Cortina and Folger (1998), it is established that, in the point of sale cause-related marketing context, the traditional effects of brand/cause fits do not apply. Across three studies involving experimental designs and over 500 respondents, the results of one-way ANOVA analyses consistently demonstrate that a low brand/cause fit can be just as effective as a high/brand cause fit. These findings contribute to a profound understanding of social efforts such as cause-related marketing may not be as simple or easily understood as was once thought.
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Kim, Yeonsoo, and Mary Ann Ferguson. "Are high-fit CSR programs always better? The effects of corporate reputation and CSR fit on stakeholder responses." Corporate Communications: An International Journal 24, no. 3 (August 5, 2019): 471–98. http://dx.doi.org/10.1108/ccij-05-2018-0061.
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Purpose The purpose of this paper is to examine how corporate reputation interacts with corporate social responsibility (CSR) fit and affects stakeholders’ skeptical attribution (SA) of CSR motives, as well as their attitudes, supportive communication intent and purchase intent. This study proposes that a high-fit CSR program does not necessarily engender more favorable outcomes, nor does it stimulate SA. The study proposes the effects of CSR fit differ by corporate reputation. For bad-reputation companies, low-fit is anticipated to generate more desirable CSR outcomes than high-fit initiatives. Design/methodology/approach Two experiments were conducted. The first experiment employed a randomized 2 (CSR fit: high fit vs low fit) × 2 (good reputation vs bad reputation) × 2 (Industry: food retailing and insurance) full factorial design to examine the suggested hypotheses. The second study employed a randomized 2 (CSR fit: high fit vs low fit) × 2 (good reputation vs bad reputation) full factorial design with consumer samples to replicate the conceptual relationships among variables in the first study. Findings While reputation plays a dominant role in influencing stakeholders’ CSR-related responses across both CSR fit situations, a SA partially mediates the relationship between reputation and stakeholder reactions. CSR fit interacts with reputation, and influences the partial mediation process through SA; under a bad reputation condition, low-fit CSR engenders less SA and results in better stakeholder reactions. A similar tendency was found with supportive communication intent and purchase intent. High-fit CSR initiatives by a negative reputation company engendered the weakest supportive intent and purchase intent. For a reputable company, across both CSR fits, respondents displayed generally very positive attitudes toward, greater intent to support, and intent to purchase from the company. Originality/value The study findings provide useful and empirically supported logical explanations of why high-fit CSR programs sometimes cause backlash effects, despite the general consensus that such initiatives generate positive outcomes. This study offers an alternative and more relevant perspective to conceptualize the complexity of anticipating CSR outcomes.
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Nejati, Mehran. "Successful cause-related marketing." Strategic Direction 30, no. 8 (July 8, 2014): 35–37. http://dx.doi.org/10.1108/sd-11-2013-0091.
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Purpose – The purpose of this study is to highlight the importance of cause-related marketing (CRM) and explain the factors which influence the success of a CRM campaign. Design/methodology/approach – Provides a viewpoint article based on the author's experience and expertise. Findings – Through explaining the key factors which impact the success of CRM, this article provided insights to company directors and management consultants. It has been indicated that the three most important attributes of a case for the success of CRM campaigns include importance, proximity and fit of the cause with firm’s core business. Originality/value – Provides a viewpoint article based on the author's experience and expertise.
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Kay-Tze Hong, Siew-Imm Ng, Raja Nerina Raja Yusof, and Shivee Ranjanee Kaliappan. "What Do Consumers Like to See in a Cause-Related Marketing Campaign Board?" International Journal of Business and Society 22, no. 1 (March 24, 2021): 346–64. http://dx.doi.org/10.33736/ijbs.3182.2021.
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The purpose of this study is to discover elements or contents of a Cause-Related Marketing (CRM) campaign’s communication board that may attract consumers to participate in the CRM program. This study focuses on the design of a CRM campaign communication board exclusively based on the perceptions of Malaysian consumers in the hypermarket context. Besides that, this study also identifies social causes applicable for hypermarkets in Malaysia. Employing a qualitative approach, the data in this study were obtained through focus group interviews and were analysed using a content analysis method. The study has identified seven themes that Malaysian consumers would like to see in a communication board, which were hypermarket initiative, communication, tagline and logos, timeframe, types of support (funds handled by NGOs), company-cause fit, and CRM products that are not limited to local products. These elements, if incorporated into a CRM communication board, will appeal to Malaysian consumers. The findings provide insights into the study of CRM communication board content that appeals to hypermarket consumers in Malaysia. This study also contributed to the CRM literature by exploring the applicability of a fairly new social cause (e.g. supporting underprivileged individuals) that can be championed and supported by the hypermarket. This research also offers practical implications for hypermarket managers. Hypermarkets can incorporate the seven elements (hypermarket initiative, communication, tagline and logos, timeframe, types of support, company-cause fit, and CRM products that are not limited to local products) while designing a CRM communication board.
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Choi, Jihee, and Soobin Seo. "When a stigmatized brand is doing good." International Journal of Contemporary Hospitality Management 31, no. 9 (September 9, 2019): 3447–64. http://dx.doi.org/10.1108/ijchm-10-2018-0806.
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Purpose This study aims to investigate consumer responses to cause-related marketing (CRM) implemented by socially stigmatized industries, especially in fast food restaurants. Design/methodology/approach This experimental study uses a 2 (degree of perceived fit) × 2 (complementary fit) × 2 (brand equity) between-subjects design. Findings Results show significant interaction effects between the degree of fit and brand equity and complementary fit and brand equity on consumers’ brand evaluation. When a company with high brand equity chooses a high fit (vs low fit) or complementary fit (vs non-complimentary fit) for CRM promotion, this leads to consumers’ more positive attitude and higher intent to participate in CRM promotion. Practical implications This study provides practical implications for designing effective CRM promotion in the stigmatized industry such as fast food restaurants and casino. Originality/value Given the increased demand on CRM in the hospitality industry, the paper contributes to extend the realm of CRM literatures by investigating antecedents affecting consumers’ responses toward the CRM in the stigmatized companies or brands.
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Rognsoy, Tone M. "Using ERP Mashups to Improve Business Processes." Global Journal of Enterprise Information System 9, no. 3 (September 27, 2017): 1. http://dx.doi.org/10.18311/gjeis/2017/15646.
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Customizing an Enterprise Resource Planning (ERP) system to fit organizational needs is a complex task. Cost, difficulties with maintenance and upgrade, and loss of vendor support are just some of the factors that cause customizations to fail. Enterprise mashups represent a new way of tailoring an ERP environment in close collaboration with users. We have developed two enterprise mashups for a multinational company in the fish feed industry. The paper describes and discusses how organizations may use mashup technology to improve their processes by customizing their ERP systems. Our study suggests that the case organization indeed has a potential for such improvement.
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Shazly, Rana Essam, and Abeer A. Mahrous. "A Qualitative Study of Cause-Related Marketing Campaigns and Consumers’ Purchase Intention of On-Demand Ride Services in Egypt." World Journal of Business and Management 5, no. 1 (May 27, 2019): 26. http://dx.doi.org/10.5296/wjbm.v5i1.14842.
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Corporate Social Responsibility (CSR) has become a matter of interest for academics and practitioners especially in the form of Cause-Related Marketing (CRM). The paper aims to revisit CRM campaign dimensions shaping consumer responses in terms of attitude toward firms and purchase intention in a less research market such as Egypt. Exploratory qualitative interviews were employed of thirteen in-depth interviews and one focus group (seven participants) with Egyptians using on-demand ride services. The current study shed the lights on the main CRM campaign factors affecting purchase intention and firm attitude. Those factors are cause involvement, consumers’ participation effort, company-cause fit, corporate credibility, altruistic attribution, campaign feedback, socio-demographic dimensions, and skepticism. Results revealed that campaign feedback has a master effect on consumers’ attitudes and purchasing behavior and wasn’t studied heavily in the literature. Also, the importance of the cause itself and how consumers are personally involved in the social issue is of great concern. Consumers’ skepticism and degree of participation effort required from consumers result in negative effects on their attitude toward firms which in turn affect their purchase intention. Yet, managers should inform consumers by how the company is using their donations, additionally; they should hamper consumers’ skepticism and enhance their trust in the socially conscious brands. People have to be updated with the campaign’s achievement and progress on a regular base. Eventually, determining the antecedents of CRM campaigns would help managers in selecting the best partners for an effective social venture.
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An, Dae-Chun, Chen Wang, and Pyo-Hoon Jeon. "A Comparative Analysis of CSR Authenticity between Proactive and Reactive CSR under Corporate Crisis: Moderating Roles of Company-cause Fit and the Firm’s Prior Reputation." Korea International Trade Research Institute 14, no. 1 (February 21, 2018): 585–602. http://dx.doi.org/10.16980/jitc.14.1.201802.585.
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Brown, Alan S. "Neat Little Packages." Mechanical Engineering 138, no. 02 (February 1, 2016): 30–35. http://dx.doi.org/10.1115/1.2016-feb-1.
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This study presents different researches on developing genetic medicines and efficient engineered delivery systems. Researchers have developed a range of approaches to deliver cancer drugs. Many of these techniques would adapt easily for genetic medicine. In fact, many researchers are already putting them to work. Arcturus Therapeutics in San Diego, a ribonucleic acid (RNA) medicines company, is working on development of an advancement over previous lipid-based delivery systems. Arcturus’s solution is a biodegradable lipid with a temporary charge, just enough to wrap medicines and RNA in a loose, yarn-like bundle. When the bundle reaches the targeted cell, the cell engulfs it, trapping it in a small sac that travels into the cell. As engineers test the design of delivery systems, they will find themselves working with scientists to understand how all the pieces fit together. Experts foresee that clinics in 30 years from the present will sequence patients’ genomes and biopsy their conditions, and prescribe treatments that target the precise cause of disease.
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Mercadé-Melé, Pere, Sebastian Molinillo, Antonio Fernández-Morales, and Lucia Porcu. "CSR ACTIVITIES AND CONSUMER LOYALTY: THE EFFECT OF THE TYPE OF PUBLICIZING MEDIUM." Journal of Business Economics and Management 19, no. 3 (November 13, 2018): 431–55. http://dx.doi.org/10.3846/jbem.2018.5203.
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This research develops a model to predict the effect of advertising a socially responsible activity on perceived corporate social responsibility (CSR) and its influence on consumer loyalty. It examines the relationships between company-cause congruence, corporate credibility, altruism attribution and perceived CSR, and CSR with consumer loyalty, and analyzes the moderating effect of the type of communication medium (i.e. traditional medium vs. social medium). This study is original because it fills the gap in the CSR communication literature in the evaluation of how the use of one or another type of medium to advertise a cause related marketing activity influences the effect of perceived CSR on consumer loyalty. An empirical study was conducted with two samples of consumers, each of which was exposed to the same advertisement, inserted in either a newspaper or posted on a social network. Data were analyzed using structural equation modeling. The results carry implications for CSR activities and communications management as they validate the proposed model that integrates the antecedents of perceived CSR and its influence on loyalty, and show that the traditional medium model has a better fit and its overall effect is greater than the social medium model. From a practical perspective, this study has several implications regarding the importance of communicating CSR activities.
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Syam, Mahmud Iqbal, Cecep Hadiyan, and Tusmin Hardi. "Analisa Perbaikan Manajemen Perawatan Dengan Metode Reliability Centered Maintenance Bagian Cnc Wirecut di PT X." Jurnal Penelitian Teknik industri 1, no. 1 (May 20, 2021): 22–30. http://dx.doi.org/10.51999/jpti.v1i1.3.
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PT X is one of the manufacturing companies in Indonesia, which specializes in manufacturing molds and dies which offers products to the internal group and the domestic market. This study discusses the policy analysis of machine repair maintenance management using the RCM (Reliability Centered Maintenance) method approach at the PT X manufacturing company. Some of the problems that occur are sudden engine failure, which will cause over production. One machine that is considered critical is the CNC Wirecut K90 machine. With the application of using RCM it is expected to improve machine reliability through several systematic RCM implementations: system selection and information collection, defining system boundaries, system descriptions and function block diagrams, describing system functions and functional failures, compiling Failure Mode and Effect Analysis (FMEA), composing Logic Tree Analysis (LTA), selection of actions. The new policy set by the Realibility Centered Maintenance (RCM) method consists of 14 failure modes that are resolved by time-directed (CD) and 6 failure modes that are overcome by run to failure (RTF). In the FMEA analysis, there are 4 components that most often fail to function, namely the electrode pin, wire guide, filter and contact fit. The determination of this component is based on the RPN value and data in the field. In the RCM analysis, the electrode pin, wie guide and contact fit components are included in the run to failure (RTF) treatment policy category. Meanwhile, the filter component is in the category of condition direction (CD) maintenance policy with an average failure rate of 29,951 days.
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Hyung-Wook Joo and 백영민. "How and under what condition does the company-cause fit improve customers’ attitudes? Focusing on the mediation effect of customers’ attributional style and the moderation effect of a company’s CSR reputation." Journal of Public Relations 20, no. 3 (August 2016): 1–32. http://dx.doi.org/10.15814/jpr.2016.20.3.1.
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Niranjan, T. T., and Samir K. Srivastava. "Managing Capacity at Sparsh Call Centre." Asian Case Research Journal 12, no. 01 (June 2008): 73–103. http://dx.doi.org/10.1142/s0218927508001084.
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Bangalore based Sparsh Call Centre was set up as a subsidiary of the major telecom software company IP-Trinity, with ambitious plans of becoming a significant player in the booming BPO (business process outsourcing) space. Its strategy, in line with that of its parent group, was to focus on telecom related services. Sparsh began its operations in 2002 with its first client Alfa, a US based VOIP telephone service provider and had three other accounts and employed over 400 people. Financial performance had been lacklustre and top management including Kumar, Director (Operations) was carrying out a review. Operationally, everything appeared to be fine. People management was, to a great extent, managed by sophisticated workforce management software, supplemented by supervisory actions by managers. This case is useful in highlighting the complexities of managing call centres and the unique people issues involved. This case illustrates that besides operational efficiencies, there is a need for a fit between strategy and scale of operations. In particular, high employee attrition can cause reduction in service quality as well as reduced capacity. Fast scale up of operations may be needed to make call centres economically viable. Cost effective innovative retention schemes may be needed to retain call centre staff to achieve this scale up.
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Lukman, Moh. "Perencanaan Peningkatan Kualitas Produk Raket dengan Metode Quality Function Deployment." Jurnal Teknik Industri 10, no. 1 (February 22, 2010): 44. http://dx.doi.org/10.22219/jtiumm.vol10.no1.44-51.
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Small Industry Abadi location in central small industry raket Sukun-Malang, so many kinds racket product are many variables as, racket quality, raket colors, rakets price, will give the customer many choice product rackets. Demand racket products are fluctuative from periods to another periods because there are factors: school holiday, and badminton championship in scale national cup and world cup as All England so demand will be increase. In central small industry raket thre are many small industry racket, so competition raket product increase,so there are the price will be cheap and quality may be too lower. This competition cause qoitition in raket "X" is low. Antisipacition to win competition we will design good quality raket product fit with attribute racket customers, with methode Quality Function Deployment (QFD). From result of analysis can know that attribute obtaining especial priority to customer is among others chicken eye of strong plastic type and handle of racket is not breakable, besides technical respon which made account of by company is among others wrap handle of sponge cloth and of racket don't use extension T. Besides got by price for new desain equal to Rp19.300,- at the price of selling Rp22.500,- got by cheaper price of Rp1.300,- compared to old desain racket that is equal to Rp20.600,- at the price of selling Rp25.000.
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Hamzelo, M., A. Gharagozlou, S. Sadeghian, S. H. Baikpour, and A. Rajabi. "MODELLING OF CARBON MONOXIDE AIR POLLUTION IN LARG CITIES BY EVALUETION OF SPECTRAL LANDSAT8 IMAGES." ISPRS - International Archives of the Photogrammetry, Remote Sensing and Spatial Information Sciences XL-1-W5 (December 11, 2015): 281–85. http://dx.doi.org/10.5194/isprsarchives-xl-1-w5-281-2015.
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Air pollution in large cities is one of the major problems that resolve and reduce it need multiple applications and environmental management. Of The main sources of this pollution is industrial activities, urban and transport that enter large amounts of contaminants into the air and reduces its quality. With Variety of pollutants and high volume manufacturing, local distribution of manufacturing centers, Testing and measuring emissions is difficult. Substances such as carbon monoxide, sulfur dioxide, and unburned hydrocarbons and lead compounds are substances that cause air pollution and carbon monoxide is most important. Today, data exchange systems, processing, analysis and modeling is of important pillars of management system and air quality control. In this study, using the spectral signature of carbon monoxide gas as the most efficient gas pollution LANDSAT8 images in order that have better spatial resolution than appropriate spectral bands and weather meters،SAM classification algorithm and Geographic Information System (GIS ), spatial distribution of carbon monoxide gas in Tehran over a period of one year from the beginning of 2014 until the beginning of 2015 at 11 map have modeled and then to the model valuation ،created maps were compared with the map provided by the Tehran quality comparison air company. Compare involved plans did with the error matrix and results in 4 types of care; overall, producer, user and kappa coefficient was investigated. Results of average accuracy were about than 80%, which indicates the fit method and data used for modeling.
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Berry, P., K. Burrows, R. Hall, A. Gater, H. Bradley, A. Ward, C. Tolley, P. Delong, and E. C. Hsia. "AB1332-HPR ASSESSING THE PATIENT EXPERIENCE OF LUPUS NEPHRITIS: DEVELOPMENT OF A CONCEPTUAL MODEL AND REVIEW OF EXISTING PATIENT-REPORTED OUTCOME (PRO) MEASURES." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1954.1–1955. http://dx.doi.org/10.1136/annrheumdis-2020-eular.5634.
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Background:Lupus nephritis (LN) is an autoimmune disease characterized by inflammation of the kidneys as a result of systemic lupus erythematosus (SLE). Approximately 50% of SLE patients will develop LN, which is considered to be one of the most severe manifestations of SLE and the leading cause of morbidity and mortality in SLE. While there is ample existing evidence on disease experience and PROs used in extra-renal SLE, little research has been done in LN. Qualitative interviews with patients can help identify concepts that are both important and relevant to the patient. In order to effectively evaluate treatment benefit, it is critical that PRO measures used to assess such concepts and define clinical trial endpoints are fit for purpose and have strong evidence of content validity in the specific context of use.Objectives:The objective of this study was to understand the patient experience of LN and to identify and characterize the signs and symptoms of LN and their impact on health-related quality of life (HRQoL) through the development of a disease-specific conceptual model. This model was then used to evaluate the content validity of existing PRO measures available for use in LN.Methods:A structured literature search was conducted in Medline, Embase and PsycINFO to identify qualitative research articles documenting the patient experience of LN. PRO measures developed or commonly used to assess patient experiences of LN were also identified. Semi-structured concept elicitation interviews were conducted with 15 adult patients in the US with a clinician-confirmed diagnosis of LN (defined in accordance with established clinical guidelines). Supplementary qualitative data were also collected from a review of publicly available online blogs/forums. Findings were used to inform the development of a conceptual model detailing the impact of LN signs, symptoms and HRQoL and evaluate the validity of existing measures used within LN.Results:Searches revealed a paucity of qualitative research conducted with LN patients, supporting the need for prospective research in LN. Consistent with existing literature in SLE, the core signs and symptoms identified from the qualitative literature review, interviews and blog/forum review included joint pain, fatigue, joint stiffness, swelling (particularly in the extremities) and skin rashes. LN patients also reported urinary frequency, urgency, foamy urine and blood in their urine. Disease impact on physical functioning, activities of daily living, emotions, social life, work/finances and sleep were reported. PRO measures commonly used to evaluate patient experiences in LN included the SF-36, LupusQOL, LupusPRO, SLE Symptom Checklist, KDQoL and KSQ. Conceptual mapping of instruments against the newly developed conceptual model (Figure 1) highlighted that no single measure provides a comprehensive assessment of all symptoms/impact important to LN patients. Furthermore, items are largely focused on impact of symptoms with few items on symptom severity.Figure 1.Conceptual model of lupus nephritis symptoms and associated impactsConclusion:The presentation of signs and symptoms in LN patients appears similar to those reported in extra-renal SLE populations, with the addition of swelling and urinary symptoms. Qualitative research with LN patients guided the development of a comprehensive LN conceptual model outlining the disease experience from the patients’ perspective. These insights can be useful to inform PRO measurement strategies for clinical trials in LN.Acknowledgments:With thanks to Dr. Betty Diamond and Dr. David Wofsy for their collaboration and helpful insightsDisclosure of Interests:Pamela Berry Employee of: Janssen, Kate Burrows Consultant of: Adelphi Values a health outcomes research company commissioned by Janssen to conduct the research reported in this abstract, Rebecca Hall Consultant of: Adelphi Values a health outcomes research company commissioned by Janssen to conduct the research reported in this abstract., Adam Gater Consultant of: Adelphi Values a health outcomes research company commissioned by Janssen to conduct the research reported in this abstract, Helena Bradley Consultant of: Adelphi Values a health outcomes research company commissioned by Janssen to conduct the research reported in this abstract, Amy Ward Consultant of: Adelphi Values a health outcomes research company commissioned by Janssen to conduct the research reported in this abstract, Chloe Tolley Consultant of: Adelphi Values a health outcomes research company commissioned by Janssen to conduct the research reported in this abstract, Patricia Delong Employee of: Janssen, Elizabeth C Hsia Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC
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WU, SIMON, SAMUEL WANG, MAURICIO F. BLOS, and H. M. WEE. "CAN THE BIG 3 OVERTAKE TOYOTA? — A STUDY BASED ON THE THEORY OF CONSTRAINTS." Journal of Advanced Manufacturing Systems 06, no. 02 (December 2007): 145–57. http://dx.doi.org/10.1142/s0219686707000966.
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Purpose — The aim of this paper is to provide answers to two significant questions. The first question is "what is the comprehensive action for the Big 3 to overtake Toyota Company?" The second question is "Can TOC (Theory of Constraints) really deal with this kind of complicated problem effectively?" Design/methodology/approach — In order to address this question and come out with a reasonable answer, this study uses the Theory of Constraints to discover the root causes and countermeasures for the Big 3 to break through their paradigms. Findings — It is worthwhile to highlight that we have demonstrated that a sophisticated case in global competition of the motor market can provide solutions with only four TOC logic trees. Furthermore, it is interesting to note that the four TOC logic trees fit perfectly well with each of the four problem solving steps in two aspects: (1) It provides a shortcut through mirror imaging process and (2) It enhances the clarity of the thinking process. Research limitations/implications — However, there remains some issues open for further exploration: (1) How can we make sure that the appropriate core problem(s) or root cause(s) has been identified in CRT (Current Reality Tree) and it is indeed the most meaningful one? (2) How can we proceed from CRT to FRT (Future Reality Tree) & further from FRT to PT (Prerequisites Tree) more effectively? (3) How can we discover key obstacles from PT and how to develop action plans from TT (Transition Tree) smoothly? (4) How to refine and integrate these feasible solution sets coming out from TT into the optimal solution scheme to be adapted in the real world? Originality/value — This study demonstrates how TOC problem solving can help to solve the core problems and root causes of "can the Big 3 overtake Toyota?" It not only gives managerial insights for the Big 3 to break through their paradigms to fight back Toyota; but also identify how a complex problem beyond production field can be analyzed and dealt with effectively. Paper type–Case study paper.
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Kim Tran, Sang, and Le Ngoc Hoang Yen. "Viettire’s Dilemma: the expansion strategy in Myanmar." Emerald Emerging Markets Case Studies 8, no. 3 (September 20, 2018): 1–29. http://dx.doi.org/10.1108/eemcs-05-2017-0092.
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Subject area Decision-making seems simple, but, in reality, it is not an easy task to decide the cause for its profound result or consequence, leading to inevitable failures. Therefore, a leader must recognize whether there is something incorrect so as to avoid bad results. A good leader is a person who carefully reviews and analyzes aspects of a problem, knows the strengths and weaknesses of his organization and evaluates what the advantages or risks are. It cannot be denied that the appropriate options will reap many benefits to the business. For such important things, this paper will discuss the dilemma of Viettire, a tire distributor company in Vietnam. Accordingly, its CEO was worried about what strategic option he should adopt to approach the Myanmar market while ensuring a strategic fit to its company’s resources and capabilities and also to the overall market demands of the tire industry environment in both countries. However, with different ideas, the expansion strategies in this new market become controversial. The General Director and Founder of Viettire were wondering how Viettire could expand its existing business into Myanmar. To expand the company to new emerging market in Myanmar, Hoang Nguyen – CEO of Viettire – had conducted a strategic analysis of external environment factors to define the opportunities and threats when doing business in Myanmar by using Porter’s five forces model, S.W.O.T and competitive advantages analysis. The results indicated that Myanmar’s business environment is highly risky for foreign investors because of uncertain political, economic, social reforms in the process. Among three options, namely, exporting, licensing and wholly owned, however, Option 2 is illustrated as the best strategy for its dilemma. Study level/applicability Postgraduate/Graduate Business level. Case overview As for a market mechanism, what produces, how and for whom, is not the business’s demand but the consumer’s demand. The business sells only what the market needs, not what it has. In the period of increasingly competitive conditions, stabilizing and expanding markets are a prerequisite for survival. If stability is seen as a “defensive” way, expansion is a “defensive attack” like trying to hold on the “pie” that the market gives to itself. This strategic action is to strengthen regular, close relationships with existing customers and establish new customers. As a result, the potential market is transformed into a target market. Hence, decision-making of which market, which method is the issue that a leader has to think the choice to avoid risks. Mr Hung, Viettire’s co-owner, suggests that Myanmar should be taken into account as a company’s new entry, thus exploring this potential market to increase the company’s growth and profitability. In the progress, Viettire’s marketing team had been doing a thorough tire market investigation in Myanmar. It was concluded that this emerging country, especially Yangon City, was the most suitable for those who were willing to embark on an overseas investment expansion. They believe this was a good opportunity to gain market share compared with other entrants and competitive rivals; if Viettire hesitated to invest, others definitely had jumped in with a first-mover advantage. However, the CEO, Mr Hoang, was worried about what strategic option he should adopt to approach this new market while ensuring a strategic fit to its company’s resources and capabilities and also to the overall market demands of the tire industry environment in both countries. Expected learning outcomes Understand the basic decisions that firms contemplating foreign expansion must make: which markets to enter, when to enter those markets and at what scale. Recognize the current strategic decisions an organization is facing: positioning, portfolio and market expansion approach. Learn how to develop an effective strategic plan. Be familiar with different strategies for competing globally and their pros and cons. Evaluate various strategic options and decisions in accordance with a company’s resources and capabilities. Supplementary materials Teaching notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes. Subject Code CSS 11: Strategy.
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Natsvaladze, Marine. "THEORETICAL BASICS AND PRACTICAL ASPECTS OF BEHAVIORAL ECONOMICS." Globalization and Business 4, no. 8 (December 27, 2019): 68–73. http://dx.doi.org/10.35945/gb.2019.08.007.
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Traditional Economics looks at the persons as at some kind of rational machine which takes into consideration all available information and then makes optimal decision. Re- ality is rather different. The behavioral economics claims that there is no rational «economic human” and probably will nev- er exist. Person’s behavior is irrational and this irrationality is not random and clueless. Vice-versa - this irrationality is systemic and predictable. Behavioral economics explores what affects people›s economic decisions and the consequences of those decisions for market prices, returns, and resource allocation. Tradition- al economic research assumes that people›s economic deci- sions are based on the rule of maximizing utility. Behavioral economics uses experiments that observe human behavior in order to uncover how we think. Behavior- al economics has been called the science of decision-making. It is a growing academic discipline which uses experiments that observe human behavior in order to uncover how we think. Behavioral economics is about understanding com- mon decision mistakes that people make and why they make them. In particular, a large aspect of behavioral economics is concerned with the gap between intention and action. Classical economic theory assumes that individuals are rational. However, in the real world, we often see irrational behavior – decisions which don›t maximize utility but can cause a loss of economic welfare. It means economists need to take into account the potential for irrationality. Successful marketers must have a profound understand- ing of the consumer’s thought process in order to create a suc- cessful marketing campaign. By understanding the consumer’s decision-making process, marketers are able to develop value propositions that really fit the consumer’s needs. The impor- tance of understanding behavioral economics for marketers is immeasurable as it allows for a better understanding of the human mind. Behavioral economics allows marketing profes- sionals to optimize marketing strategies and get real results. In the article are reviewed applied aspects of behavioral economics, also theoretical and practical results of researches. These results will be useful in company management, for pol- iticians, in private decision making as they give different per- spective to rational-functional models. In case of ignoring the interdisciplinary approaches, integration of economics and psy- chology can result in waste of resources and wrong decisions.
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Mikalef, Patrick, Adamantia Pateli, Ronald S. Batenburg, and Rogier van de Wetering. "Purchasing alignment under multiple contingencies: a configuration theory approach." Industrial Management & Data Systems 115, no. 4 (May 11, 2015): 625–45. http://dx.doi.org/10.1108/imds-10-2014-0298.
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Purpose – Strategic alignment is a theory-based state that is considered as crucial for organizations in order to realize performance gains from information technology (IT) investments and deployments. Within the domain of purchasing and supply chain management there has been a growing interest on how purchasing strategy can be effectively aligned with IT and what conditions facilitate this state. The purpose of this paper is to investigate complex causal relationships of contingency elements that are key in enabling the “fit” between purchasing strategy and IT. Design/methodology/approach – The paper employs a configuration theory approach and propose that purchasing alignment is dependent upon patterns of multiple contingencies. In adherence with contingency theory, the authors group these elements as relating to strategic orientation, organizational factors, and purchasing decisions. On a sample of 172 international companies the authors then apply the novel methodology of fuzzy set qualitative comparative analysis (fsQCA). Findings – The paper empirically demonstrates that depending on the strategic orientation that a company follows, there are alternative combinations of elements that lead to high purchasing alignment. For companies following an operational excellence strategic orientation, a high contract binding scheme, or a small firm size facilitates purchasing alignment. Enabling elements for product leadership companies include a decentralized purchasing structure, a broad supplier base, and a large firm size. Purchasing alignment for customer intimacy companies is supported by a centralized purchasing structure, loose contract binding, and a large supplier base. Practical implications – The findings of this study suggest that practitioners aiming to attain a state of purchasing alignment should consider a number of contingency elements in the process. The paper shows that there is equifinality in the configurations that lead to purchasing alignment. This means that attaining purchasing alignment is dependent upon various clusters of contingency elements which must be taken into account when formulating a purchasing strategy. Originality/value – In contrast with past studies examining purchasing alignment as a result of the isolated impact of several antecedents, we applied a configuration theory approach to demonstrate that it is facilitated by the combined impact of a set of cause-effect relationships. In cases were non-linear and synergistic relationships exist between independent variables, this type of research may be a viable alternative.
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Adineh, Amir Hossein, Zahra Narimani, and Suresh Chandra Satapathy. "Importance of data preprocessing in time series prediction using SARIMA: A case study." International Journal of Knowledge-based and Intelligent Engineering Systems 24, no. 4 (January 18, 2021): 331–42. http://dx.doi.org/10.3233/kes-200065.
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Over last decades, time series data analysis has been in practice of specific importance. Different domains such as financial data analysis, analyzing biological data and speech recognition inherently deal with time dependent signals. Monitoring the past behavior of signals is a key for precise predicting the behavior of a system in near future. In scenarios such as financial data prediction, the predominant signal has a periodic behavior (starting from beginning of the month, week, etc.) and a general trend and seasonal behavior can also be assumed. Autoregressive Integrated Moving Average (ARIMA) model and its seasonal extension, SARIMA, have been widely used in forecasting time-series data, and are also capable of dealing with the seasonal behavior/trend in the data. Although the behavior of data may be autoregressive and trends and seasonality can be detected and handled by SARIMA, the data is not always exactly compatible with SARIMA (or more generally ARIMA) assumptions. In addition, the existence of missing data is not pre-assumed in SARIMA, while in real-world, there can be always missing data for different reasons such as holidays for which no data may be recorded. For different week days, different working hours may be a cause of observing irregular patterns compared to what is expected by SARIMA assumptions. In this paper, we investigate the effectiveness of applying SARIMA on such real-world data, and demonstrate preprocessing methods that can be applied in order to make the data more suitable to be modeled by SARIMA model. The data in the existing research is derived from transactions of a mutual fund investment company, which contains missing values (single point and intervals) and also irregularities as a result of the number of working hours per week days being different from each other which makes the data inconsistent leading to poor result without preprocessing. In addition, the number of data points was not adequate at the time of analysis in order to fit a SARIM model. Preprocessing steps such as filling missing values and tricks to make data consistent has been proposed to deal with existing problems. Results show that prediction performance of SARIMA on this set of real-world data is significantly improved by applying several preprocessing steps introduced in order to deal with mentioned circumstances. The proposed preprocessing steps can be used in other real-world time-series data analysis.
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Rifkin, Robert M., Faith E. Davies, Antonio Palumbo, Jeffrey Zonder, Saulius K. Girnius, Caitlin L. Costello, Saad Z. Usmani, et al. "Global, Prospective, Non-Interventional, Observational Study of Presentation, Treatment Patterns, and Outcomes in Multiple Myeloma Patients: The Insight-MM Study." Blood 128, no. 22 (December 2, 2016): 5681. http://dx.doi.org/10.1182/blood.v128.22.5681.5681.
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Abstract Advances in novel agents and treatment combinations have improved prognosis and increased disease-free and overall survival for patients (pts) with multiple myeloma (MM). However, currently available data on disease presentation, treatment patterns, and outcomes for real-world MM pts at the global level are limited. This is due to several factors, including the overrepresentation of medically fit pts in clinical trials making generalization of outcomes challenging, the large number of treatment combinations, and varying global access/practice patterns. INSIGHT-MM (NCT02761187) is a global, prospective, non-interventional, observational study which aims to further understand disease and pt characteristics at presentation, treatment and clinical outcomes of real-world MM pts, as well as the association of treatment with tolerability, effectiveness, health-related quality of life (HRQoL), and healthcare resource utilization (HRU), on both a country-specific and global basis. As this is an observational study, no formal hypothesis will be tested. The INSIGHT-MM objectives are summarized in the Table. At least 5000 pts aged ≥18 yrs with newly diagnosed or relapsed/refractory MM will be enrolled over a 3-yr period and followed prospectively for ≥5 yrs, until death or end of study, whichever comes first. Pts not available for data collection for >9 mos will have follow-up for survival. No study drug or medications will be provided; no modification of standard of care pt management will be assigned per protocol. Choice of therapy for all pts will be decided by the treating healthcare provider independent of study participation. Baseline pt and MM-specific characteristics, diagnosis, comorbidities, and prior therapies will be recorded based on review of hospital/clinic records. MM management, disease status and safety data will be obtained as part of routine office visits and recorded quarterly by each site in electronic case report forms. Quarterly assessment of MM management will be done based on prior and current treatment and recorded reason for treatment changes. Effectiveness of therapy will be assessed based on response, progression status, time to next therapy, vital status, and date and cause of death. Treatment tolerability will be assessed based on serious and non-serious adverse events leading to treatment discontinuation or dose modification. Incidence of second primary malignancies will be recorded. HRQoL, a specific type of patient reported outcome (PRO), will be collected at study entry and at predefined intervals following initiation of therapy using a secure electronic data collection system. HRQoL will be collected using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the MM module (EORTC QLQ-MY20). To capture pt satisfaction with MM-directed therapy, including the dimension of convenience, the 9-item Treatment Satisfaction Questionnaire for Medication will be used. The 5-dimension, 5-level EuroQol (EQ-5D-5L) PRO instrument will capture self-reported preference-based measures of health status suitable for calculating quality-adjusted life year (QALY) data to inform health economic evaluations. Frailty will be assessed using the Charlson Comorbidity Index, the Katz Index of Independence in Activities of Daily Living, and the Lawton Instrumental Activities of Daily Living. HRU will be evaluated using inpatient and intensive care unit admissions, length of stay, outpatient clinic visits, and emergency room visits. Data for all participating pts will be extracted by healthcare professionals at the site level and entered into a central database; descriptive statistical analyses will be done to address the study objectives. Interim analyses are planned after 1000 and 5000 pts have been enrolled and a final analysis will be conducted within 1 year after the last pt entered has completed ≥5 yrs follow-up. Data will be analyzed biannually to address emerging clinical questions identified by investigators to increase understanding of real-world treatment patterns. INSIGHT-MM aims to promote better understanding of contemporary demographics, patterns of care, and outcomes for real-world MM pts to inform treatment practice, supportive care, and pt outcomes. The study is currently ongoing and recruiting pts; further details regarding study rationale and protocol will be provided. Table 1 Table 1. Disclosures Davies: Takeda: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Palumbo:Janssen Cilag: Honoraria; Takeda: Employment, Honoraria. Zonder:Bristol Myers Squibb: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Prothena: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Pharmacyclics: Other: DSMC membership. Girnius:Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Speakers Bureau. Costello:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Usmani:Array: Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Consultancy, Research Funding, Speakers Bureau; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millenium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Onyx: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; BioPharma: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pharmacyclics: Research Funding; Britsol-Myers Squibb: Consultancy, Research Funding; Skyline: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Speakers Bureau. Berdeja:Abbvie, Acetylon, Amgen, Bluebird, BMS, Calithera, Celgene, Constellation, Curis, Epizyme, Janssen, Karyopharm, Kesios, Novartis, Onyx, Takeda, Tragara: Research Funding. Omel:Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Member of Takeda's "Patient Leadership Council". Token payment. Thompson:Celgene: Membership on an entity's Board of Directors or advisory committees, Other: MDS/AML Registry; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; AIM Specialty Health: Membership on an entity's Board of Directors or advisory committees; VIA Oncology: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Multiple Myeloma International Registry; Doximity: Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Shah:Array: Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Honoraria, Research Funding; Bristol-Myers Squibb: Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Schwartz:Bayer: Consultancy; Blue Cross and Blue Shield Associations: Consultancy; Pfizer: Consultancy; Takeda: Consultancy. Hajek:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Terpos:Amgen: Consultancy, Honoraria, Research Funding; Celgene: Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Genesis: Consultancy, Honoraria, Research Funding; Novartis: Honoraria. Hungria:Takeda: Consultancy; Roche: Consultancy; International Myeloma Foundation Latin America: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Speakers Bureau; Bristol: Consultancy; Amgen: Consultancy. Mateos:Takeda: Honoraria; Amgen: Honoraria; Janssen: Honoraria; Celgene: Honoraria. Cook:Bristol-Myers Squibb: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; Glycomimetics: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau. Leleu:Novartis: Honoraria; LeoPharma: Honoraria; Pierre Fabre: Honoraria; Amgen: Honoraria; Bristol-Myers Squibb: Honoraria; Takeda: Honoraria; Celgene: Honoraria; Janssen: Honoraria; TEVA: Membership on an entity's Board of Directors or advisory committees. Goldschmidt:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Chugai: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium: Membership on an entity's Board of Directors or advisory committees, Research Funding; Onyx: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees. Seal:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment, Equity Ownership. Pashos:Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Stull:Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Romanus:Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Cacioppo:Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Bell:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment, Equity Ownership. Yu:Takeda Restricted Stock Unit (RSU), a publicly traded company: Equity Ownership; Takeda Development Center Americas, Inc., Deerfield, IL, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Luptakova:Takeda Oncology: Employment. Niculescu:Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Noga:Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment, Equity Ownership. Skacel:Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Chari:Array Biopharma: Consultancy, Research Funding; Amgen Inc.: Honoraria, Research Funding; Celgene: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Pharmacyclics: Research Funding; Novartis: Consultancy, Research Funding; Janssen: Consultancy, Research Funding.
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Hakimi, Saeid, Seyed Mojib Zahraee, and Jafri Mohd Rohani. "Application of Six Sigma DMAIC methodology in plain yogurt production process." International Journal of Lean Six Sigma 9, no. 4 (October 8, 2018): 562–78. http://dx.doi.org/10.1108/ijlss-11-2016-0069.
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Purpose This study aims to concentrate on quality improvement in plain yogurt production process at company A through adjusting the factors affecting the acidity of the yogurt and determining the optimal level of these factors. Design/methodology/approach Six Sigma-based framework using define-measure-analyze-improve-control (DMAIC) methodology is adopted through the application of design of experiments tool to focus on customer’s requirements to improve the quality characteristic of plain yogurt production process in dairy products manufacturing company (company A) in Iran. Findings The results showed that incubation time and fat percentage were significant factors on pH values of yogurt and the optimum settings for these factors were defined as 12 h for the incubation time and 1.5 per cent for the fat percentage. Research limitations/implications This study focused solely on the plain yogurt production process in dairy products manufacturing company. Practical implications Simplicity of Six Sigma plays a leading role for enabling any dairy manufacturer to determine the problem and minimize its cause through a systematic approach. Social implications Six Sigma has been considered to be a systematic, powerful technique to continuously improve the processes and develop the new products by using effective analytical and statistical tools and methods. This paper presents a Six Sigma-based framework using DMAIC methodology to improve the quality characteristic of plain yogurt production process in dairy products manufacturing company. Originality/value This study contributes to show a potential area in which Six Sigma DMAIC approach can promote to improve the quality of yogurt production process. This case can prompt managers of the company to apply Six Sigma method to address complicated problems in other processes, where causes particularly are not clear.
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Toninelli, Pier Angelo. "Between Agnelli and Mussolini: Ford's Unsuccessful Attempt to Penetrate the Italian Automobile Market in the Interwar Period." Enterprise & Society 10, no. 2 (June 2009): 335–75. http://dx.doi.org/10.1017/s146722270000803x.
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This article discusses a chapter of the interwar history of the Ford Motor Company in Europe rather neglected by historians, namely its unsuccessful attempt to erect a solid base of operations in Italy. Expansion onto the Italian market had been part of the post-WWI Ford's strategy of internationalization. It seemed to go well beyond the exploitation of an additional demand as its most interesting and promising aspect was the utilization of the Italian branch as a bridgehead into the Balkans, the East Mediterranean region, the Middle East, and North-East Africa. At the beginning this strategy turned out successful. But when in the late 1920s the Company tried to strenghten its position in the country—either setting up its own assembly plant or establishing a joint venture with an Italian firm—its attempt was blocked. To date scholars have focused exclusively on the political and economic barriers to entry erected by the fascist regime, urged by the powerful Fiat lobby. This was certainly the main cause. Yet, this study shows that on several occasions Ford hesitated and even hung back from acting. Therefor a few chances were missed: the most glamorous being an agreement with Fiat itself, so far ignored by historiography.
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Atallah, Ehab L., Rodrigo Maegawa, Dominick Latremouille-Viau, Carmine Rossi, Annie Guerin, and Pallavi Patwardhan. "Real-World Treatment Patterns, Healthcare Resource Utilization and Associated Costs Among Patients with Chronic Myeloid Leukemia in Later Lines of Therapy." Blood 136, Supplement 1 (November 5, 2020): 8–9. http://dx.doi.org/10.1182/blood-2020-136074.
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Introduction: Despite advances in tyrosine kinase inhibitor (TKI) therapy for chronic myeloid leukemia (CML), there remains a sizeable proportion of patients (pts) with CML in chronic phase who are refractory or intolerant to these agents. A good understanding of the most recent real-world patterns of care in these pts is necessary in order to provide context for assessing the potential benefits of new treatments undergoing clinical development. The aim of this study was to evaluate treatment patterns in CML pts cycling through TKI therapies achieving later lines of therapy, and to estimate their healthcare resource utilization (HRU) and costs. Methods: Adult pts with CML in the United States who received at least 3 lines of TKI therapy were identified in the IBM MarketScan Commercial and Medicare Supplement databases (Q1/2001-Q2/2019). Treatment patterns were observed from CML diagnosis. Pt characteristics were measured during the 6 months prior to third line (3L) initiation (baseline period). All-cause HRU (inpatient [IP] admissions and days, days with outpatient [OP] services, and emergency department [ED] visits) and costs (medical and pharmacy) were measured 1) during the course of 3L therapy (from 3L initiation to termination) and 2) between 3L initiation and end of follow-up (stem cell transplant [SCT], or end of data availability/health plan coverage). HRU was reported using monthly incidence rates per 100 pts (IR/100pts); costs (2019 USD) were evaluated per-pt-per-month (PPPM) from a payer's perspective. Results: Of the 48,168 pts identified with CML, a total of 296 CML pts initiated 3L therapy; median age was 58.5 years (30% were aged ≥65 years) and 50% were female. The mean follow-up period from CML diagnosis was 57.8 months and from 3L initiation was 24.5 months. Most pts had their first CML diagnosis in or after 2010 (71%) and achieved 3L in or after 2014 (50%). At baseline, the mean modified Charlson Comorbidity Index score (excluding CML) was 1.6 with 24% of pts with a score ≥3, 64% of pts had a moderate or severe Darkow Disease Complexity Index, and the most prevalent comorbidities were hypertension (45%) and diabetes (25%); 21% of pts (i.e., ≥1 indicator of congestive heart failure, cirrhosis, or end-stage renal disease, or ≥75 years old). The most common sequences of TKIs from first line (1L) to 3L were imatinib → dasatinib → nilotinib (28%), imatinib → nilotinib → dasatinib (16%), imatinib → dasatinib → imatinib (9%), and dasatinib → imatinib → nilotinib (5%). The mean duration of 1L, second line (2L), and 3L therapy was 14.9, 10.4, and 15.6 months, respectively; 62% of pts were still in 3L at the end of follow-up. Only one patient received SCT after 3L. The most common TKIs received at each line were imatinib in 1L (65%), dasatinib in 2L (49%), and nilotinib in 3L (36%). The mean treatment-free period (time between line of therapy termination and next line initiation) between 1L and 2L was 1.3 months, 2.6 months between 2L and 3L, and 1.5 months between 3L and 4L. During 3L therapy, pts had a monthly IR/100pts of 3.4 IP admissions, 21.2 IP days, 248.8 OP days, and 10.2 ED visits (Figure 1A). Pharmacy costs accounted for 69% of the mean total costs of $15,192 PPPM, with medical costs accounting for the remainder (Figure 1B). In 3L therapy and later, pts had a monthly IR/100pts of 3.5 IP admissions, 28.7 IP days, 252.2 OP days, and 10.0 ED visits (Figure 1A). Pharmacy costs accounted for 49% of the mean total costs of $18,767 PPPM, with medical costs mainly driven by IP costs (Figure 1B). Conclusions: This study characterized CML pts receiving later lines of therapy, a clinical population which has not been previously well studied with important unmet treatment needs as they repetitively fail TKI therapy. Although the majority of pts were likely fit for SCT, SCT was rare. In addition, pts quickly switched to the subsequent line of therapy, both facts suggesting that an important proportion of pts were intolerant to previous TKIs. While pharmacy costs accounted for nearly half of the total cost burden during 3L, the proportion of medical costs PPPM took more importance following 3L therapy, with IP costs being the primary cost drivers for this increase. These findings support the need for better treatment options in pts with CML undergoing later lines of therapy. Disclosures Atallah: Novartis Pharmaceutical Corporation: Consultancy; Jazz: Consultancy; Pfizer: Consultancy; Takeda: Consultancy, Research Funding; Abbvie: Consultancy; Genentech: Consultancy. Maegawa:Novartis Pharmaceutical Corporation: Current Employment, Current equity holder in publicly-traded company. Latremouille-Viau:Novartis Pharmaceutical Corporation: Consultancy, Other: Dominique Latremouille-Viau is an employee of Analysis Group, Inc. which received consultancy fees from Novartis.; Sanofi Genzyme: Consultancy, Other: Dominique Latremouille-Viau is an employee of Analysis Group, Inc. which received consultancy fees from Sanofi Genzyme.. Rossi:Novartis Pharmaceutical Corporation: Consultancy, Other: Carmine Rossi is an employee of Analysis Group, Inc. which received consultancy fees from Novartis.. Guerin:Abbvie: Consultancy, Other; Sanofi Genzyme: Consultancy, Other: Annie Guerin is an employee of Analysis Group, Inc. which received consultancy fees from Sanofi Genzyme.; Novartis Pharmaceuticals Corporation: Consultancy, Other: Annie Guerin is an employee of Analysis Group, Inc. which received consultancy fees from Novartis.. Patwardhan:Novartis Pharmaceutical Corporation: Current Employment, Current equity holder in publicly-traded company.
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Sitlinger, Andrea, Dana P. Thompson, Michael A. Deal, Erwin Garcia, Tiffany Stewart, Eross Guadalupe, J. Brice Weinberg, David A. Bartlett, and Danielle M. Brander. "Exercise and Chronic Lymphocytic Leukemia (CLL) - Relationships Among Physical Activity, Fitness, & Inflammation, and Their Impacts on CLL Patients." Blood 132, Supplement 1 (November 29, 2018): 5540. http://dx.doi.org/10.1182/blood-2018-99-117736.
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Abstract Introduction Exercise has potent immune enhancing and anti-inflammatory effects in healthy adults, and is increasingly recognized as a beneficial adjunct to cancer care. Increased maximal aerobic fitness (VO2peak) is a gold standard measure that predicts better outcomes in patients with breast, prostate, and brain cancer. However, in patients with chronic lymphocytic leukemia (CLL), little is known regarding the physiologic and immune/inflammatory impact of physical fitness. GlycA is a recently identified robust inflammatory biomarker that is associated with increased risk for cardiovascular disease, all-cause mortality, diabetes, and is an independent predictor of colorectal cancer outcomes. Further, GlycA levels can be reduced by exercise training. We postulated that GlycA can serve as a marker of disease-associated inflammation and physical fitness in CLL. Our objectives were 1) to determine the feasibility of measuring physical activity and fitness in CLL patients during a standard clinical visit, and 2) to evaluate the associations between physical fitness, chronic inflammation assessed by GlycA levels, and hematologic parameters in untreated CLL patients. Methods During a routine clinical visit, CLL patients completed the validated activity surveys "Incidental and Planned Activity Questionnaire" (IPAQ) and the age-defined "Stanford Brief Activity Survey" (SBAS). Physical function was assessed in a subset of patients by determining grip strength, 6 minute walk test (6MWT), and the short physical performance battery (SPPB). Predicted aerobic fitness (VO2peak) was calculated from a validated algorithm using the 6MWT, age, body weight, resting heart rate, and gender. Complete blood counts with leukocyte differentials, plasma GlycA, and VO2peak function were assessed in all untreated patients who had physical function testing. Given the heterogeneity of CLL, reporting of relationships with VO2peak, function, and GlycA will focus on treatment naïve patients. We used linear regression and Spearman's correlations to determine relationships among outcomes. Results The IPAQ and SBAS surveys both had 90% validity and full completion (n = 141, see table 1 for details). Activity results from all patients were 60% to 70% of age-predicted normative values. Specifically, 48% of patients were inactive or engaged in light activities and 28% moderate intensity activities (by SBAS), with 0 to 129 hours/week of total incidental and planned activity (by IPAQ). The surveys were positively associated with each other (r=0.303, p<0.001). In a 5-month period, 108 patients completed physical fitness testing. The distance covered in the 6MWT was 464±99 meters, grip strength was 35±14 kg, SPPB was 10.8±1.8 (range 4 - 12), and predicted VO2peak was 29±6 mL/kg/min. VO2peak was 64±13% of normative values, and this was positively associated with the SPPB (r=0.336, p<0.001) and SBAS (r=0. 416, p<0.001). After controlling for age and body mass index in untreated patients who completed physical fitness testing (n=40), higher VO2peak was significantly associated with lower levels of GlycA (r=-0.474, p=0.002), and a lower neutrophil: lymphocyte ratio (r=-0.397, p=0.012). Higher GlycA was associated with higher neutrophil counts (r=0.592, p<0.001). Higher VO2peak was significantly associated with lower platelet counts (r=-0.471, p=0.002), but not with lymphocyte counts (r=0.294, p=0.066), neutrophil counts (r=-0.216, p=0.186), or hemoglobin (r=0.133, p=0.402). Conclusion We found that assessing the physical activity and fitness of CLL patients in a clinical setting is feasible. The majority of CLL patients were less active than age-matched normal individuals, and that higher aerobic fitness was associated with lower GlycA, supporting recent findings that GlycA is associated with physical activity levels. Since GlycA is a marker for inflammation, this supports that physical activity may lower clinically relevant inflammation in CLL patients. Regardless of the absolute lymphocyte count, if patients were more physically fit, there was no evidence of inflammation as defined by elevated GlycA and neutrophil count. In summary, we demonstrated that many untreated patients with CLL are physically inactive and have relatively high levels of inflammation by GlycA. Further work will determine if exercise intervention in CLL patients will improve their CLL disease severity and long-term health. Disclosures Garcia: LabCorp: Employment. Brander:Genentech: Consultancy, Honoraria, Other: Institutional research funding for non investigator initiated clinical trial, Research Funding; Novartis: Consultancy, Other: DSMB; Acerta: Other: Institutional research funding for non investigator initiated clinical trial, Research Funding; TG Therapeutics: Consultancy, Honoraria, Other: Institutional research funding for non investigator initiated clinical trial, Research Funding; Pharmacyclics, an AbbVie Company: Consultancy, Honoraria, Research Funding; DTRM: Other: Institutional research funding for non investigator initiated clinical trial, Research Funding; AbbVie: Consultancy, Honoraria, Other: Institutional research funding for non investigator initiated clinical trial, Research Funding; BeiGene: Other: Institutional research funding for non investigator initiated clinical trial, Research Funding; Teva: Consultancy, Honoraria.
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Griffiths, Philip, Laura Grant, Nicola Bonner, Denise D'Alessio, Quentin A. Hill, Drew Provan, Waleed Ghanima, Nichola Cooper, and Ricardo Viana. "The Psychometric Properties of the ITP Life Quality Index Assessed in a Large Multinational "Real-World" Cohort of Immune Thrombocytopaenia Patients." Blood 134, Supplement_1 (November 13, 2019): 386. http://dx.doi.org/10.1182/blood-2019-125766.
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Background Immune Thrombocytopenia (ITP) is an autoimmune disorder caused by immunologic destruction of otherwise normal platelets, most commonly occurring in response to an unknown stimulus. ITP is diagnosed after excluding other possible causes of disease, and symptoms can present across varying severities and treatments. The poor understanding of the symptoms and cause can result in both misdiagnosis and complex treatment patterns, which may significantly affect health related quality of life (HRQoL) in this patient population. There is currently no disease specific prospective tool in routine clinical practice to capture HRQoL in the adult ITP population. To help assess the impact of this condition on HRQOL, the ITP Life Quality Index (ILQI), a 10-item patient-reported outcome (PRO) measure was developed as a tool for clinical practice to aid discussions between patients and physicians about disease experience so to inform patient-centric treatment decisions. The ILQI was originally developed by clinical experts in the field of ITP and content validity was confirmed by conducting qualitative interviews with 15 adult patients with ITP. The ILQI was then cognitively debriefed patients with ITP and items refined following qualitative analysis and additional clinical input. The ILQI was included in the ITP World Impact Survey (I-WISh), a global observational study which collected data on the impact of ITP on patients' HRQoL. This large study provided an opportunity to assess the psychometric properties of the ILQI and confirm the scoring cut-offs. Methods The I-WISh survey resulted in data from 1,507 patients with ITP across 12 countries worldwide and was used to assess the structure, reliability and validity of the ILQI. The structure of the ILQI, how the items fit into total scores and subscales, was assessed by splitting the data into two datasets. One dataset was used for identifying the structure using exploratory factor analysis and one was used for checking the structure using confirmatory factor analysis. Validity, the ability of the ILQI to measure the correct construct, was assessed through known groups and convergent validity methods. Reliability, the consistency of the ILQI items and their ability to create reproducible scores, was assessed via internal consistency methods. To understand whether each ILQI item measured ITP in a similar way across countries, differential item functioning (DIF) was assessed using Cochran-Mantel-Haenszel test and Logistic regression. Finally, existing score cut-offs (20-"significantly impaired QoL"; 30 - "severely impaired QoL") were assessed using receiver operating characteristic (ROC) curves and a simulation study was conducted to develop rules for missing data. Results Results indicated that the ILQI has an essentially unidimensional structure, supporting the creation of a total score including all 10 items. The ILQI items work together to create a reproducible total score, usable for making judgements on an individual patient basis (Omega total and Cronbach's alpha coefficients ≥ 0.90). Known groups methods showed that ILQI monotonically increased with ITP severity (linear trends p's <0.001). Convergent validity methods confirmed hypothesized relationships between ILQI total/item scores and items which measure aspects of HRQOL, suggesting that the ILQI total score and its items measure the same concept of interest (i.e. HRQOL). DIF analyses showed that ILQI item responses were similar between the USA and Western countries. Some uniform DIF was discovered between the USA and other countries, and some non-uniform DIF was found between the USA and China for culturally relevant items as expected. The previous clinical cut-off of 20 for "significantly impaired QoL" was supported, but a cut-off 30 may be too conservative for assessing "severely impaired QoL". Missing data simulation suggests that a total score can be created even when some items are missing. Conclusion The ILQI is a valid and reliable, unidimensional measure to assess HRQoL of patients with ITP. Despite some variations in ILQI item responses between USA and China, adoption of the ILQI in routine care will improve consistency of patient-centric decision making and may lead to better outcomes for those patients whose HRQoL has been affected. The revised cut-off scores for the ILQI developed will also aid patient-centric decision making between patients and physician. Disclosures Griffiths: Adelphi Values Ltd: Employment; Novartis: Consultancy. Grant:Novartis: Consultancy; Adelphi Values Ltd: Employment. Bonner:Adelphi Values Ltd: Employment; Novartis: Consultancy. D'Alessio:Novartis: Employment, Equity Ownership. Hill:Apellis: Honoraria; Bioverativ, a Sanofi company: Honoraria; Novartis: Speakers Bureau; Alexion: Research Funding. Provan:Rigel ONO: Consultancy, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; UCB: Consultancy; MedImunne: Consultancy; ONO Pharmaceutical: Consultancy. Ghanima:Bayer: Honoraria, Research Funding; Amgen: Consultancy, Honoraria; Pfizer/BMS: Research Funding; Novartis: Consultancy, Honoraria, Research Funding. Cooper:Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Rigel: Consultancy, Membership on an entity's Board of Directors or advisory committees; Principia: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Viana:Novartis: Employment, Equity Ownership.
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Fisher, Allison, Veena Sangkhae, Nicolaos J. Palaskas, Tomas Ganz, and Elizabeta Nemeth. "Iron-Dependent Apoptosis Causes Embryotoxicity in Inflamed and Obese Pregnancy." Blood 136, Supplement 1 (November 5, 2020): 12. http://dx.doi.org/10.1182/blood-2020-141128.
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Since iron is essential for pregnancy, iron supplements are routinely prescribed to pregnant women without screening for iron deficiency. Most women in developed countries have sufficient iron stores, prompting concerns of the potential risks of iron supplementation in iron-replete women. A signal of potential harm of this practice is the association of maternal iron marker ferritin and pregnancy complications. Since ferritin is also induced by inflammation, it is unclear whether iron excess, inflammation, or their interaction cause fetal injury. We used mouse models to address this question. Two mouse models of maternal iron excess were used and compared to mice with normal iron status. To model dietary iron supplementation, C57BL/6 females were fed high-iron diet (2500-5000ppm iron) for 1 week prior to and during pregnancy. To model genetic iron loading, hepcidin knockout females were used and fed standard chow (185ppm iron). Two models of maternal inflammation were used. Acute systemic maternal inflammation was induced by a single subcutaneous injection of LPS on E8.5 or 15.5. Obesity was used as a model of mild chronic systemic maternal inflammation and was induced by feeding female mice Western diet. We evaluated the maternal, placental, and embryo response to iron excess in LPS- and obesity-induced inflammation at various time points. In the model of acute inflammation, we observed an adverse synergistic effect on embryo development when dams were both iron-loaded and LPS-injected, but not with either condition alone. On E8.5, LPS injection in iron-loaded dams caused embryo loss and encephalic malformations (Fig 1a) and on E15.5, LPS injection in iron-loaded dams caused embryo demise and resorption (Fig 1b). Western blotting and immunostaining showed increased apoptotic marker cleaved caspase-3 protein localized to endothelia in placentas and embryos, only when the dam was both iron-loaded and LPS-injected. Cytokine screen in vitro identified TNFα as the signal that synergized with iron to potentiate apoptosis of endothelial cells. Treatment of iron-loaded dams with TNFα-neutralizing antibody protected embryos from LPS-induced death, demonstrating the embryotoxic role of maternal TNFα in iron-loaded dams. Furthermore, RNA-Seq analysis of placental endothelial cells showed enrichment in oxidative stress pathways with maternal iron loading. Treatment of iron-loaded dams with antioxidant α-tocopherol protected against LPS-induced embryo death, attenuated placental inflammation and cleaved caspase-3 expression, and prevented endothelial apoptosis in the placenta and embryo. These data show that iron loading causes endothelial oxidative stress, which sensitizes endothelial cells to inflammation-induced apoptosis. In the obesity model, iron loading worsened embryotoxicity, causing subcutaneous hemorrhaging and eye malformations (Fig 1c), and potentiated placental cleaved caspase-3 expression. Iron loading increased TNFα levels in maternal serum. Importantly, treatment of obese iron-loaded dams with neutralizing TNFα antibody throughout pregnancy reduced the incidence of embryo eye malformations, confirming the role of TNFα in causing embryo injury in iron-loaded obese pregnancy. In summary, maternal iron excess worsened inflammation-induced embryo injury. Iron-dependent embryotoxicity was mediated by TNFα causing lethal apoptotic damage to embryo and placental endothelium which was prevented by antioxidant therapy. Our models raise the possibility that women exposed to both excessive iron and inflammation could be at risk for preventable pregnancy complications. Figure 1. Embryo outcomes in mouse pregnancies with maternal iron loading and inflammation. Figure 1 Disclosures Ganz: Akebia: Consultancy; Vifor: Consultancy; Ionis Pharmaceuticals: Consultancy; Silarus Therapeutics: Current equity holder in private company; Intrinsic LifeSciences: Current equity holder in private company; Global Blood Therapeutics: Consultancy; Ambys: Consultancy; Gossamer Bio: Consultancy; Astellas: Consultancy; Rockwell: Consultancy; Sierra Oncology: Consultancy; Disc Medicine: Consultancy; American Regent: Consultancy. Nemeth:Intrinsic LifeSciences: Current equity holder in private company; Vifor: Consultancy; Protagonist: Consultancy; Silarus Therapeutics: Current equity holder in private company; Ionis Pharmaceuticals: Consultancy.
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Ghaswalla, Parinaz, Philippe Thompson-Leduc, Wendy Y. Cheng, Colin Kunzweiler, Min-Jung Wang, Michael Bogart, Brandon J. Patterson, et al. "24. Economic Burden of Herpes Zoster Among Individuals with Chronic Obstructive Pulmonary Disease: A Retrospective Cohort Study." Open Forum Infectious Diseases 7, Supplement_1 (October 1, 2020): S35—S36. http://dx.doi.org/10.1093/ofid/ofaa439.069.
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Abstract Background Previous studies have evaluated the risk of developing herpes zoster (HZ) in patients with chronic obstructive pulmonary disease (COPD), but little is known about the impact of an acute HZ episode on healthcare resource utilization (HCRU) and costs among patients with COPD in the US. Methods A retrospective cohort study of individuals ≥50 years of age was conducted using administrative claims data from Optum Clinformatics for commercially insured and Medicare Advantage members (01/01/2013 – 12/31/2018). Two cohorts of patients with COPD, with (Cohort A) and without (Cohort B) HZ episodes, were identified (Fig.1). COPD and HZ were identified using ICD-9 and ICD-10 diagnosis codes. All-cause HCRU rates were compared between cohorts using adjusted incidence rate ratios (IRRs), calculated using generalized linear models assuming a negative binomial distribution. Differences in all-cause costs were estimated by fitting a two-part model with a logit model in the first part and a gamma distribution for the second part. Potential differences between cohorts were accounted for by propensity scores, calculated using patients’ demographics and clinical characteristics at baseline and included as a covariate in multivariable regression analyses. Results Among patients with COPD, 3,415 patients with HZ (mean age [standard deviation]=73.2 [9.0] years) and 35,360 without HZ (72.4 [9.4] years) were identified. Compared to patients with COPD but without HZ, patients with COPD and HZ had an increased rate of all-cause outpatient visits (adjusted IRR=1.18; 95% confidence interval [CI]=1.15–1.22; p< 0.001) and Emergency Department visits (1.28; 1.20–1.35; p< 0.001) as well as higher all-cause total costs (adjusted cost difference, per patient per month [PPPM]=$313; 95% CI=$110–536; p< 0.004), in the first year of the observation period. All-cause mean costs PPPM and differences between cohorts were higher closer to the date of HZ diagnosis (or an imputed date for Cohort B, Fig.2). Figure 2: All-cause monthly costs Conclusion HCRU and cost burden is higher in patients ≥50 years old with COPD and HZ vs. without HZ. HZ vaccination may potentially reduce this burden among patients with COPD. Funding GlaxoSmithKline Biologicals SA (GSK study identifier: HO-19-19749) Disclosures Parinaz Ghaswalla, PhD, ORCID: 0000-0002-2883-5590, GlaxoSmithKline (Employee, Shareholder) Philippe Thompson-Leduc, MSc, ORCID: 0000-0001-9047-3941, Analysis Group, Inc. (Employee) Wendy Y. Cheng, MPH, PhD, ORCID: 0000-0002-8281-2496, GlaxoSmithKline (Other Financial or Material Support, I am an employee of Analysis Group, a consulting company that received research fund to conduct this study.) Min-Jung Wang, ScD, ORCID: 0000-0003-4432-3330, Analysis Group, Inc. (Employee, Other Financial or Material Support, Analysis Group received grant/research support from GSK) Michael Bogart, PharmD, ORCID: 0000-0002-1681-9710, GlaxoSmithKline (Employee, Shareholder) Brandon J. Patterson, PharmD, PhD, GSK (Employee, Shareholder) Mei-Sheng Duh, MPH, ScD, ORCID: 0000-0001-5035-6687, GlaxoSmithKline (Grant/Research Support) Suna Park, MS, GSK (Other Financial or Material Support, Analysis Group, Inc., where I am an employee, received funding for this study) Barbara P. Yawn, MD, Msc, ORCID: 0000-0001-7278-5810, GSK (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member)
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Gantt, Soren, Caroline Quach, David E. Anderson, Francisco Diaz-Mitoma, and Joanne Langley. "LB18. An Enveloped Virus-like Particle (eVLP) Cytomegalovirus (CMV) Vaccine Is Immunogenic and Safe: Results of a First-in-Humans Study." Open Forum Infectious Diseases 5, suppl_1 (November 2018): S765. http://dx.doi.org/10.1093/ofid/ofy229.2192.
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Abstract Background CMV is the most common cause of congenital infection and may result in permanent neurodevelopmental injury including vision and hearing loss. A vaccine to prevent transmission of CMV during pregnancy or to immunocompromised persons is a public health priority. Neutralizing antibodies (nAb) to the CMV envelope glycoprotein B (gB) in natural infection are thought to confer protection, but some vaccine candidates based on this protein alone have been insufficiently immunogenic. In this FiH dose-ranging, controlled, observer-blinded study the safety and immunogenicity of an eVLP expressing the ectodomain of gB fused to transmembrane and cytoplasmic domains of the vesicular stomatitis virus G protein (gB-G) was evaluated. Method Healthy CMV-seronegative 18–40 year olds at three sites in Canada (Vancouver, Montreal, Halifax) were randomized to one of four dose formulations (0.5 µg, 1 µg, or 2 µg gB content with Alum) or 1 µg gB without Alum, or placebo given on days 0, 56, and 168. Outcome measures were solicited and unsolicited adverse events (AE), severe AE, gB binding antibody titers and avidity assessment, and nAb to CMV infection of fibroblast and epithelial cells. A Data Safety Monitoring Board was in place. Result Among 128 participants, the most common solicited local and general AEs were pain and headache, respectively. No SAEs or withdrawals occurred. A dose-dependent boosting of nAb titers was observed after doses 2 and 3, with the highest titers in the Alum-adjuvanted 2.0 µg dose recipients. Fibroblast cell nAb were seen in 100% of 2.0 µg dose recipients, and epithelial cell nAb in 31%. Epithelial cell nAb was correlated with higher geometric mean gB binding titers, and there was a correlation between fibroblast and epithelial cell nAb titers. Conclusion An eVLP CMV vaccine was immunogenic at very low doses in healthy seronegative adults and no safety signals were seen. Alum adjuvantation increased immunogenicity as did higher antigen content and multiple doses. This phase 1 trial supports further development of this eVLP CMV vaccine candidate. ClinicalTrials.gov NCT02826798 Disclosures S. Gantt, VBI Vaccines: Investigator, No direct financial benefit—company provided institutional support for clinical trial. C. Quach, VBI Vaccines: Investigator, No direct financial benefit—company provided institutional support for clinical trial. D. E. Anderson, VBI Vaccines: Employee and Shareholder, Salary. F. Diaz-Mitoma, VBI Vaccines: Consultant and Shareholder, Salary. J. Langley, VBI Vaccines: Investigator, No direct financial benefit—company provided institutional support for clinical trial.
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Хуршкайнен (Hurshkainen), Татьяна (Tat'yana) Владимировна (Vladimirovna), Владимир (Vladimir) Иванович (Ivanovich) Терентьев (Terentyev), Наталья (Natal'ya) Николаевна (Nikolaevna) Скрипова (Skripova), Наталья (Natal'ya) Николаевна (Nikolaevna) Никонова (Nikonova), and Алла (Alla) Альбертовна (Al'bertovna) Королева (Korolyova). "CHEMICAL COMPOSITION OF BY-PRODUCTS OF CONIFEROUS RAW MATERIALS PROCESSING." chemistry of plant raw material, no. 1 (March 6, 2019): 233–39. http://dx.doi.org/10.14258/jcprm.2019014264.
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Development of natural biological products – an actual problem of rational and economical use of wood bioresources with which Russia is rich. The coniferous raw material is a source of biologically active extractive compounds possessing immunostimulating, fungicidal, bactericidal activity.
Company «Ecovit» makes food and cosmetic production from Pinus Silvestris L., Abies sibirica and Pinus sibirica R. Maur wood greenery. This paper presents results of research of a chemical composition of the by-products formed in coniferous essential oils processing: residue after distillation and florentine water. The extraction of these products is carried out by petroleum ether, diethyl ether, ethyl-acetate consistently and quantitative maintenance of extractive compounds is certain. The qualitative and quantitative analysis of macro- and micro-elements in investigated samples is lead.
Chemical structure of extractive compounds is characterized with use of physicochemical meth-ods. In residue after distillation of Abies and Pinus wood greenery carotenoids, natural phenolic com-pounds, carboxylic acids are identified. Ethanol extracts of the fulfilled pine and cedar raw material contain sesqui- and diterpenes, polyprenols, carotenoids, fat acids and phenolic compounds. In Abies ethanol extracts maltol and triterpenoids are identified. The basic components of pine florentine water are monoterpenoids.
The received results cause practical application of by-products of coniferous raw material processing for obtaining of biologically active additives, preparations for agriculture, pharmacology, perfumer-cosmetic production.
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Gudmundsdottir, Brynja R., Petur I. Jonsson, and Pall T. Onundarson. "INR and Vitamin K Dependent Coagulation Factor Fluctuation during Warfarin Initiation and Stable Therapy in Patients Dosed with the Fiix-Prothrombin Time or the Quick Prothrombin Time. the Fiix Trial." Blood 124, no. 21 (December 6, 2014): 4278. http://dx.doi.org/10.1182/blood.v124.21.4278.4278.
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Abstract Introduction: The Quick prothrombin time (PT) is equally sensitive to the influence of factors (F) II, VII and X but experiments suggest that it is mainly the influence of warfarin on factors (F) II and X that cause its anticoagulant effect. The new Fiix prothrombin time (Fiix-PT) differs from the PT in it being sensitive only to factors (F) II and X and not being sensitive at all to FVII activity in the test plasma. The Fiix-trial has demonstrated increased stability of warfarin anticoagulation and possibly improved efficacy when monitored with Fiix-PT compared to PT monitoring (unpublished data). However, as very low levels of vitamin K dependent (VKD) factors not measured with the Fiix-PT could possibly have deleterious effect on anticoagulation (AC) outcome, we measured the VKD coagulation factors in plasma obtained from patients on stable warfarin anticoagulation and during the first 30 days of warfarin treatment monitored either with the Fiix-PT or the PT. Methods: In order to define stable anticoagulation in terms of coagulation factor activity, samples from patients enrolled in the Fiix trial and monitored either with Fiix-PT or PT were used. Frozen samples from 20 patients were obtained from each monitoring group. All the samples had been drawn from patients during very stable warfarin treatment (INR within range 2-3 for over 10 months by serial monitoring). Serial samples were also obtained from 10 patients in each group during days 1-30 of warfarin initiation. PT, Fiix-PT and VKD coagulation factors were measured. An INR was calculated for both PT and Fiix-PT. Results: During stable AC, the median INR (range) was 2.5 (2.1-3.0) in the Fiix-group vs 2.4 (2.0-3.0) in the PT group (p=ns). The median (95% range) VKD factor percent coagulant activity was as follows in the stable Fiix-group vs the stable PT-group: FII 28 (19-40) vs 25 (18-40), FVII 48 (30-88) vs 42 (23-85), FIX 66 (41-85) vs 61 (36-79), and FX 15 (11-17) vs 15 (10-22). Although the medians tended to be higher in the Fiix group except for FX, p was n.s. for all. In patients starting on warfarin a stable Fiix-INR (defined as two INRs within target range) was reached on day 14 (median) in the Fiix group vs a stable PT-INR on day 11 in the PT controls. Following this, however, the PT-INR fluctuates more out of the INR target range than the Fiix-INR does. As shown in the figures, the earlier rise in INR in the PT group is mainly a reflection of a rapid fall in FVII activity. The FVII level decreases to a nadir of 20% in the Fiix group compared to a nadir of 30% in the PT monitoring group. Subsequently FII, FVII and FX fluctuate less in the Fiix-PT group than in the PT group. During the first 30 days 46% of Fiix-INRs in the Fiix-group were within target range vs 29% of INRs in the controls (p=0.06). Also during the initiation period FII was 47% vs. 30% within the 95% stable range established for the PT method (p=0.06), FVII 60% vs. 73% (p=0.13), FIX 41% vs 36% (p=0.69), and FX 51% vs 38% (p=0.20), respectively. The more fluctuating INR in the PT group is also reflected by a rollercoaster like pattern of warfarin dosing as opposed to the more cascade like pattern that is observed in the Fiix group. Figure 1 Figure 1. Figure 2 Figure 2. Conclusion: During stable warfarin AC VKD factors are similarly reduced with Fiix-PT or PT monitoring.During initiation of warfarin monitored with the Fiix-PT, FVII decreases initially more than with PT monitoring but subsequently stabilizes and fluctuates less. Fiix-PT leads to smoother reduction in FII and X which stabilize faster than during PT monitoring. The smoother anticoagulant effect is also reflected by the warfarin dose pattern during initiation. The results may suggest that the Quick-PT confounds warfarin management during initiation and dose changes. Disclosures Gudmundsdottir: Fiix Diagnostics Ltd: Equity Ownership, I am a co-inventor of the Fiix prothrombin time and have stocks in Fiix Diagnostics, a startup company with the two inventors of the test as majority shareholders. The company is responsible for patent applications in process. Patents & Royalties. Onundarson:Fiix Diagnostics Ltd: Equity Ownership, I am a co-inventor of the Fiix prothrombin time and have stocks in Fiix Diagnostics, a startup company with the two inventors of the test as majority shareholders. The company is responsible for patent applications in process. Patents & Royalties.
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Stein, Brady L., Kamal Patel, Robyn M. Scherber, Jingbo Yu, Dilan Paranagama, and Carole B. Miller. "Mortality and Causes of Death of Patients with Polycythemia Vera: Analysis of the Reveal Prospective, Observational Study." Blood 136, Supplement 1 (November 5, 2020): 36–37. http://dx.doi.org/10.1182/blood-2020-137144.
Full textAbstract:
Background: Previous survival estimates in patients (pts) with polycythemia vera (PV) approach or exceed 20 y from diagnosis. However, survival in pts with PV has most often been evaluated retrospectively; as a result, granularity with respect to causes of death is often lacking. The multicenter, noninterventional, Prospective Observational Study of Patients with Polycythemia Vera in US Clinical Practices (REVEAL; NCT02252159) followed pts with PV treated in 227 community and academic practices in the US. This analysis of final data from REVEAL evaluates the characteristics of deceased pts, survival by risk, and causes of death over the course of the study. Methods: All enrolled pts were included in this analysis. Pts were enrolled between 7/2014 and 8/2016 and were followed during usual care visits for 36 months from the date of last pt enrollment. Clinical characteristics and symptoms data were collected until death, consent withdrawal, or study end. Pts aged ≥ 60 y and/or with thrombotic event (TE) history at enrollment were classified as high-risk per modified ELN criteria. Causes of death were provided by site physicians. Descriptive statistics were used to summarize demographics, characteristics before death, and causes of death. Continuous and categorical variables were compared using t-tests and chi-square tests, respectively. Kaplan-Meier methods were used to summarize survival data. Time specific survival probabilities were compared using tests of proportions. For pts who were categorized as "alive," data were censored at the date of the last known study visit (for those lost to follow-up) or study completion. Results: Of 2510 pts enrolled (mean [SD] age, 66.3 [12.3] y); male, 54.2%), 9.7% (n=244) had died during the study and 2266 (90.3%) were alive at last known visit (mean [SD] duration of follow-up, 110.3 [58] and 179.4 [56.1] wks, respectively). Pts who had died were older at diagnosis (mean [SD] age, 68.5 [11.35] vs 60.2 [13.14] y; P < 0.001) and had numerically longer disease duration than pts who were alive (mean [SD] duration from diagnosis to enrollment, 6.5 [5.7] vs 5.7 [6.2], P = 0.06). Mean (SD) age at death was 77.1 (10.3) y with a mean (SD) disease duration at death of 8.6 (5.8) y. More pts who had died were categorized as high-risk at diagnosis compared with pts who were alive (82.0% vs 59.1%; P < 0.001), primarily due to age ≥ 60 y only (65.2% vs 45.9%; Fig. 1A). More pts who had died (vs pts who were alive) had comorbid cardiac disorders (41.0% [100/244] vs 12.1% [275/2266]), blood and lymphatic system disorders (other than PV: 31.1% [76/244] vs 18.5% [419/2266]), vascular disorders (72.1% [176/244] vs 62.3% [1412/2266]), neoplasms (47.5% [116/244] vs 22.2% [503/2266]); respiratory disorders (55.7% [136/244] vs 33.4% [757/2266]), and infections (41.0% [100/244] vs 26.3% [597/2266]; all P < 0.05). By the time of death, 34.8% (85/244) of pts had experienced a TE. In the 6 months before death, 31.1% (59/190) of pts had ≥1 elevated hematocrit (HCT) value, 57.9% (110/190) had ≥1 elevated white blood cell (WBC) count, 36.8% (70/190) had ≥1 elevated platelet count, and 27.5% (52/189) had both ≥1 elevated WBC and ≥1 elevated platelet count (ie, uncontrolled myeloproliferation). The survival probability (95% CI) in all pts was 98% (0.98-0.99) at 1-y and 89% (0.87-0.90) at 4-y post-enrollment. The survival probability at 4 y was lower for high- vs low-risk pts (86% [0.85-0.88] vs 97% [0.95-0.98]; P < 0.001; Fig. 1A). Among high-risk pts, 4-y survival was 82% for pts aged >60 y and with TE history, 87% for pts aged >60 y alone, and 94% for pts with TE history alone. Of pts with known cause of death (n=175), the most common cause was thrombotic complications (33.1%; Fig. 1B). Conclusions: In this analysis from REVEAL, the largest prospective and contemporary cohort of pts with PV in the US, the estimated 4-y mortality was >10%, a finding that is surprising given the mean age at enrollment was only ~66 y. Approximately one-third of the deaths were due to thrombotic complications; in the 6 months prior to death, more than a quarter of pts had elevated HCT or uncontrolled myeloproliferation. Compared with pts alive at study completion, pts who had died had higher-risk disease, and higher rates of comorbid conditions. The high rate of respiratory disorders observed in the deceased population, both as comorbidities and causes of death, has not been well characterized in other PV mortality studies and warrants further investigation. Disclosures Stein: Kartos: Other: educational content presented; Constellation Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Pharmaessentia: Membership on an entity's Board of Directors or advisory committees; Incyte: Research Funding. Scherber:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Yu:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Paranagama:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Miller:Incyte: Honoraria, Speakers Bureau.
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Lemieux, Christopher, Lori S. Muffly, Sally Arai, Andrew R. Rezvani, Surbhi Sidana, Laura J. Johnston, Wen-Kai Weng, et al. "Outcomes after Second Allogeneic Transplantation and Donor Lymphocyte Infusion for Relapse after a First Allogeneic Transplant." Blood 136, Supplement 1 (November 5, 2020): 22–23. http://dx.doi.org/10.1182/blood-2020-134250.
Full textAbstract:
Introduction: Disease relapse after allogeneic hematopoietic cell transplantation (HCT) is the main cause for an unsuccessful transplant outcome. The prognosis is generally poor and there is no consensus regarding optimal therapy to restore disease control. We retrospectively analyzed 121 patients with hemato-lymphoid malignancies who had disease relapse after a first HCT (HCT1) and received a subsequent allograft (HCT2) or a donor lymphocyte infusion (DLI). The goal of the analyses was to better understand which clinical features was associated with improved outcomes, and to help define the risk-benefit of these two interventions. Methods: Between September 1, 2009 and December 31, 2019, 550 consecutive patients had disease relapse after HCT1 of which 28 (5%) received HCT2 and 93 (17%) received DLI. Results: The HCT1 baseline characteristics were comparable for both groups (Table1). The median time interval from HCT1 to disease relapse was 8 months (range 1-87). Patients who had disease relapse within 6 months of HCT1 had withdrawal of immune suppression (IS) medication whereas most patients with disease relapse beyond 6 months already had had IS drugs discontinued. DLI was the treatment choice for CML, CLL and plasma cell neoplasms, or for a low level of disease relapse/progression. In the HCT2 cohort, the median age was 56 (range 31-70) and 17 (61%) patients were returned to CR with chemotherapy prior to HCT2. Three patients (11%) received a myeloablative regimen and 23 (82%) received a reduced intensity regimen (RIC). The graft source was mobilized peripheral blood in 26 patients (92%) and 20 (71%) had a different donor at HCT2. Karnofsky performance status was >90% in 11 (39%) patients at HCT2. In the DLI cohort, the median age was 60 (range 22-77) and 48 (52%) were returned to CR prior to the first DLI. Patients received a median of one DLI (range 1-4). The median CD3+ T cell dose was 1.0 X107CD3+/kg (range 0.5-30). Karnofsky performance status was >90% in 56 (67%) patients at time of DLI. Both interventions were well tolerated and the 1-year non-relapse mortality (NRM) was 21% (n=6) for HCT2 and 12% (n=11) for DLI. Acute graft-versus-host disease (aGVHD), grades 2-4, occurred in 39% and 24% of the patients who received HCT2 and DLI. The 3-year cumulative incidence of extensive chronic GVHD was 25% for HCT2 and 23% for DLI. The median follow-up for living patients was 37 months. The median event-free survival (EFS) was 18 months for HCT2 and 5 months for DLI (Fig.1A). The estimated 3-year overall survival (OS) was 60% [95% confidence interval (CI): 39-78] for HCT2 and 30% [95% CI: 21-42] for DLI (Fig.1B). The main causes of death were disease progression (n = 4) and GVHD (n = 4) for the HCT2 cohort. The same was true for the DLI cohort, although death from progressive disease was more common (n = 43 patients) compared to death from GVHD (n = 16 patients). Within the limitations of the small number of patients only one factor in univariate analysis was associated with an improved OS for both HCT2 and DLI and this was attainment of complete donor CD3+ T cell chimerism (>95% donor type) after either intervention. The 3-year OS for patients who attained full donor chimerism was 68% and 66% for HCT2 and DLI, respectively, compared to 33% and 24% for these groups if full donor chimerism was not achieved. The KPS at the time of DLI was significantly associated with improved OS: the median OS was 2, 8 and 19 months when KPS was <70%, 70-80% and 90-100% respectively (p=0.0026). The impact of remission duration after HCT1 associated with OS for DLI but not HCT2. Relapse within 6 months after HCT1 portended a poor prognosis for the DLI group with a median OS of 6-months compared to 19-months if relapse occurred beyond 6-months of HCT1. Conclusion: HCT2 and DLI can both offer long-term disease control for disease relapse after HCT1 albeit only a minority of patients receive these interventions. In our analysis, HCT2 and DLI were well tolerated and the risks of NRM and GVHD appear similar to HCT1. Long-term OS for HCT2 is achieved for about half of the patients when using a RIC and when the patient is returned to CR prior to the intervention. For DLI, a higher performance status and a longer remission after HCT1 were both associated with improved long-term survival. Conditions that enable attainment of full donor chimerism are important to maximize graft-versus-tumor effect for both HCT2 and DLI. Disclosures Muffly: Servier: Research Funding; Amgen: Consultancy; Adaptive: Research Funding. Rezvani:Pharmacyclics: Research Funding. Sidana:Janssen: Consultancy. Shiraz:Kite, a Gilead Company: Research Funding; ORCA BioSystems: Research Funding. Meyer:Orca Bio: Research Funding. Shizuru:Jasper Therapeutics, Inc: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees. Miklos:Juno-Celgene-Bristol-Myers Squibb: Consultancy, Other: Travel support, Research Funding; Pharmacyclics: Consultancy, Other: Travel support, Patents & Royalties, Research Funding; Novartis: Consultancy, Other: Travel support, Research Funding; Kite-Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Janssen: Consultancy, Other: Travel support; Miltenyi Biotec: Research Funding; Adaptive Biotech: Consultancy, Other: Travel support, Research Funding; Allogene Therapeutics Inc.: Research Funding. Negrin:Biosource: Current equity holder in private company; UpToDate: Honoraria; KUUR Therapeutics: Consultancy; BioEclipse Therapeutics: Current equity holder in private company; Magenta Therapeutics: Consultancy, Current equity holder in publicly-traded company; Amgen: Consultancy.
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An, Ran, Yuncheng Man, Shamreen Iram, Erdem Kucukal, Muhammad Noman Hasan, Ambar Solis-Fuentes, Allison Bode, et al. "Computer Vision and Deep Learning Assisted Microchip Electrophoresis for Integrated Anemia and Sickle Cell Disease Screening." Blood 136, Supplement 1 (November 5, 2020): 46–47. http://dx.doi.org/10.1182/blood-2020-142548.
Full textAbstract:
Introduction: Anemia affects a third of the world's population with the heaviest burden borne by women and children. Anemia leads to preventable impaired development in children, as well as high morbidity and early mortality among sufferers. Inherited hemoglobin (Hb) disorders, such as sickle cell disease (SCD), are associated with chronic hemolytic anemia causing high morbidity and mortality. Anemia and SCD are inherently associated and are both prevalent in the same regions of the world including sub-Saharan Africa, India, and south-east Asia. Anemia and SCD-related complications can be mitigated by screening, early diagnosis followed by timely intervention. Anemia treatment depends on the accurate characterization of the cause, such as inherited Hb disorders. Meanwhile, Hb disorders or SCD treatments, such as hydroxyurea therapy, requires close monitoring of blood Hb level and the patient's anemia status over time. As a result, it is crucially important to perform integrated detection and monitoring of blood Hb level, anemia status, and Hb variants, especially in areas where anemia and inherited Hb disorders are the most prevalent. Blood Hb level (in g/dL) is used as the main indicator of anemia, while the presence of Hb variants (e.g., sickle Hb or HbS) in blood is the primary indicator of an inherited disorder. The current clinical standards for anemia testing and Hb variant identification are complete blood count (CBC) and High-Performance Liquid Chromatography (HPLC), respectively. State-of-the-art laboratory infrastructure and trained personnel are required for these laboratory tests. However, these resources are typically scarce in low- and middle-income countries, where anemia and Hb disorders are the most prevalent. As a result, there is a dire need for high accuracy portable point-of-care (POC) devices to perform integrated anemia and Hb variant tests with affordable cost and high throughput. Methods: In 2019, the World Health Organization (WHO) listed Hb electrophoresis as an essential in vitro diagnostic (IVD) technology for diagnosing SCD and sickle cell trait. We have leveraged the common Hb electrophoresis method and developed a POC microchip electrophoresis test, Hemoglobin Variant/Anemia (HbVA). This technology is being commercialized under the product name "Gazelle" by Hemex Health Inc. for Hb variant identification with integrated anemia detection (Fig. 1A&B). We hypothesized that computer vision and deep learning will enhance the accuracy and reproducibility of blood Hb level prediction and anemia detection in cellulose acetate based Hb electrophoresis, which is a clinical standard test for Hb variant screening and diagnosis worldwide (Fig. 1C). To test this hypothesis, we integrated, for the first time, a new, computer vision and artificial neural network (ANN) based deep learning imaging and data analysis algorithm, to Hb electrophoresis. Here, we show the feasibility of this new, computer vision and deep learning enabled diagnostic approach via testing of 46 subjects, including individuals with anemia and homozygous (HbSS) or heterozygous (HbSC or Sβ-thalassemia) SCD. Results and Discussion: HbVA computer vision tracked the electrophoresis process real-time and the deep learning neural network algorithm determined Hb levels which demonstrated significant correlation with a Pearson Correlation Coefficient of 0.95 compared to the results of reference standard CBC (Fig.1D). Furthermore, HbVA demonstrated high reproducibly with a mean absolute error of 0.55 g/dL and a bias of -0.10 g/dL (95% limits of agreement: 1.5 g/dL) according to Bland-Altman analysis (Fig. 1E). Anemia determination was achieved with 100% sensitivity and 92.3% specificity with a receiver operating characteristic area under the curve (AUC) of 0.99 (Fig. 1F). Within the same test, subjects with SCD were identified with 100% sensitivity and specificity (Fig. 1G). Overall, the results suggested that computer vision and deep learning methods can be used to extract new information from Hb electrophoresis, enabling, for the first time, reproducible, accurate, and integrated blood Hb level prediction, anemia detection, and Hb variant identification in a single affordable test at the POC. Disclosures An: Hemex Health, Inc.: Patents & Royalties. Hasan:Hemex Health, Inc.: Patents & Royalties. Ahuja:Genentech: Consultancy; Sanofi-Genzyme: Consultancy; XaTec Inc.: Consultancy; XaTec Inc.: Research Funding; XaTec Inc.: Divested equity in a private or publicly-traded company in the past 24 months; Genentech: Honoraria; Sanofi-Genzyme: Honoraria. Little:GBT: Research Funding; Bluebird Bio: Research Funding; BioChip Labs: Patents & Royalties: SCD Biochip (patent, no royalties); Hemex Health, Inc.: Patents & Royalties: Microfluidic electropheresis (patent, no royalties); NHLBI: Research Funding; GBT: Membership on an entity's Board of Directors or advisory committees. Gurkan:Hemex Health, Inc.: Consultancy, Current Employment, Patents & Royalties, Research Funding; BioChip Labs: Patents & Royalties; Xatek Inc.: Patents & Royalties; Dx Now Inc.: Patents & Royalties.
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Hazan, Sabine, Andreas Papoutsis, and Jordan Daniels. "Clostridioides difficile Strains in the Gut by Next-Generation Shotgun Sequencing: Innocent Bystander or Villain?" Infection Control & Hospital Epidemiology 41, S1 (October 2020): s467—s468. http://dx.doi.org/10.1017/ice.2020.1142.
Full textAbstract:
Background: Pathogenic Clostridioides difficile is the most common cause of nosocomial infections in the United States. However, the prevalence of C. difficile colonization in the general population is poorly understood. Objective: In this study, we sought to determine the presence and nature of various strains of Clostridioides difficile colonizing a representative sample of 121 asymptomatic adult volunteers from around the globe, consisting of 110 healthy and 11 stable Crohn’s patients. Methods: Next-generation sequencing was performed on fecal samples from 121 study participants. Stool samples were collected by patients utilizing a Zymo collection kit, which preserves bacterial DNA and RNA. Following collection, DNA was extracted, quantitated, and then normalized for downstream library fabrication utilizing shotgun methodology. Prepared and indexed libraries were subsequently pooled and sequenced on the Illumina NextSeq 550 System. Results: All 121 of 121 subjects (100%) were found to possess the bacterium Clostridioides difficile as identified by the NGS bioinformatics metagenomic pipeline. To visualize comparative abundances of Clostridioides difficile present in study participants, normalized read counts were highlighted (Fig. 1). Conclusions: NGS provides a unique opportunity to increase the resolution and identification of Clostridioides difficile compared to traditional categorizations, such as PCR ribotypes (ie, RT027), restriction endonuclease groups (BI), and North American pulsotypes (ie, NAP1). This is accomplished by its ability to differentiate species based on a nucleotides, while targeting entire bacterial genomes. Our approach for this study was to utilize a bioinformatics pipeline that would provide Clostridioides difficile strain-specific resolution when aligning to genomes in the NCBI (National Center for Biotechnology Information) database. In our representative sample of 121 volunteers, all (100%) possessed at least 1 Clostridioides difficile strain in their gut. Although it is recognized that some Clostridioides difficile strains are pathogenic, our findings suggest that nonpathogenic Clostridioides difficile strains make up an important component of the commensal gut microbiome and may perhaps play a protective role. Although symptomatic toxigenic CDI is a clear indication for therapy, Clostridioides difficile colonization with nontoxigenic strains is not believed to be a direct precursor for CDI. These findings demonstrate the need to be aware of the existence of numerous strains of Clostridioides difficile, and the relevance of sequencing prior to hospitalization or antibiotic treatment to help predict those at risk of CDI, and after treatment to be aware of any loss of what appear to be protective components of our microbiome.Funding: NoneDisclosures: Dr. Sabine Hazan reports that she is the founder and CEO of Ventura Clinical Trials and that she and her spouse receive salaries from the company. She also receives a salary from ProgenaBiome.
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Boddu, Prajwal Chaitanya, Hagop M. Kantarjian, Abdul Rashid Shah, Gautam Borthakur, Srdan Verstovsek, Guillermo Garcia-Manero, Naval Daver, et al. "Life after Ponatinib Failure: Outcomes of Chronic and Accelerated Phase CML Patients Who Discontinued Ponatinib in the Salvage Setting." Blood 128, no. 22 (December 2, 2016): 3073. http://dx.doi.org/10.1182/blood.v128.22.3073.3073.
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Abstract INTRODUCTION: Ponatinib is a pan-tyrosine kinase inhibitor (TKI) with proven efficacy in multi-refractory CML patients (pts) who have failed other TKIs and approved in all CML stages after failure to other TKIs and for pts with T315I mutation. Despite excellent response rates, resistance or intolerance may develop in some cases. Treatment options in these pts are limited and the outcomes have not been described. METHODS: We conducted a retrospective review of the outcomes of pts with refractory chronic (CP) and accelerated (AP) phase CML who discontinued ponatinib in the salvage setting. Pts were assessed for the cause of ponatinib discontinuation, therapies (Rxs) received after discontinuation, response to such Rx, and survival post-ponatinib discontinuation. RESULTS: Among 55 pts treated (32 treated in CP, 23 in AP), 36 (65 %) have discontinued ponatinib at the time of this analysis. Nineteen pts were either lost to follow up (F/U) or died on Rx and excluded from this analysis. Of the 36 pts analyzed, 19 were in CP and 17 in AP at initiation of ponatinib. Pts had received a median of 4 Rxs (2-6) prior to ponatinib. Median age at discontinuation was 67 yrs (22-94). Median duration on ponatinib Rx was 17 mo (1-61). Of 19 CP pts, 5 discontinued due to toxicity (pancreatitis = 2, stroke = 1, headache = 1, thrombocytopenia = 1), 13 for lack of response, 1 per pt choice. At discontinuation, 14 were still in CP [complete cytogenetic response (CCyR) = 3, no/minor CyR (NR/mCyR) = 10, major molecular response (MMR) = 1]; 3 had progressed to AP, and 2 to blast phase (BP). Subsequent therapy for those still in CP included stem cell transplant (SCT) = 4, supportive care only (NT) = 3, dasatinib = 2, omacetaxine = 2, and bosutinib + decitabine (DAC), nilotinib, and imatinib (1 each); the 3 pts that progressed to AP received dasatinib + DAC, low-dose Ara-C (LDAC), and NT = 1 each, respectively; and BP pts received Hyper - CVAD + dasatinib followed by SCT = 1, ponatinib + LDAC = 1. Of the 3 CP pts in CCyR, 1 died from sepsis 1 mo after discontinuing ponatinib due to thrombocytopenia; 1 pt received SCT and died in MMR 11 mo post SCT; 1 developed 7q- /Ph- on ponatinib and received SCT (MMR at 47 mo F/U). The CP pt in MMR discontinued ponatinib after a stroke and lost MMR 38 mo later (still in CCyR off Rx). Two CP pts improved to CCyR after SCT (1 died in 8 mos; 1 in MMR at 25 mo). Thirteen pts (CP 9, AP 3, BP 2; all non-SCT Rx) did not improve their responses post ponatinib (remained in NR/mCyR). The Median survival (OS) post ponatinib discontinuation of the 19 CP pts was 26 mo [Fig 1]. Twelve pts have died: 5 disease related (CP 2, BP 2, AP 1), 4 cause unknown (CP 3, AP 1), 3 from sepsis (CP 2, AP 1). Of 17 AP pts who discontinued, 15 stopped due to poor response and 2 for toxicity (stroke = 1, nausea = 1). At discontinuation, 14 were still in AP [NR/mCyR = 13, partial CyR (PCyR) = 1], 3 had progressed to BP. Subsequent therapy included NT = 5, dasatinib = 4, dasatinib + DAC = 2, SCT = 2, hydroxyurea = 1 for those still in AP, and SCT = 1, BIDFA = 1, mitoxantrone + etoposide + ponatinib = 1 for those in BP. The pt with PCyR at discontinuation died 3 mos after discontinuation of heart failure. Three pts (AP = 2, BP = 1) received SCT: 1 BP pt achieved MMR but died 12 mos post SCT of unknown cause; 1 AP pt maintains MMR 63 mos after SCT; the other AP pt did not respond and relapsed in AP, then received Rx with dasatinib + DAC and died of progressive disease 5 mos later. The remaining 14 pts (AP 12, BP 2; all non-SCT Rx) did not improve their responses post ponatinib (remained in NR/mCyR). The OS post ponatinib discontinuation (17 AP) was 9 mo [Fig 1]. Twelve pts have died: sepsis 3 (AP 3); progression 4 (AP 3, BP1), unidentified 5 (BP 1, AP 4); other 1 (BP 1). The OS for all 36 pts was 16 mos [Fig 2]; OS by stage at discontinuation was 31mo in CP, 9 mo in AP, 13 mo in BP [Fig 3]. The 12-mo survival probabilities for individual post-discontinuation Rx cohorts were: TKI 74%, SCT 56%, supportive 30%, other 50%. The OS for pts who stopped ponatinib because of toxicity vs resistance was 60 mo and 11 mo respectively. CONCLUSIONS: Long term outcomes of pts with ponatinib failure are poor with estimated 1-year OS and EFS rates of 54% and 40% respectively. Lack of response to ponatinib, after failing other TKIs, predicts a considerable risk for subsequent Rx failure. New Rx options are required for this small subset of patients. Figure 1 OS post ponatinib by stage at start of ponatinib Figure 1. OS post ponatinib by stage at start of ponatinib Figure 2 OS after failure for pts treated in CP or AP Figure 2. OS after failure for pts treated in CP or AP Figure 3 OS post ponatinib by stage at the time of ponatinib dc Figure 3. OS post ponatinib by stage at the time of ponatinib dc Disclosures Kantarjian: Amgen: Research Funding; ARIAD: Research Funding; Bristol-Myers Squibb: Research Funding; Pfizer Inc: Research Funding; Delta-Fly Pharma: Research Funding; Novartis: Research Funding. Daver:Otsuka: Consultancy, Honoraria; Sunesis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Karyopharm: Honoraria, Research Funding; Kiromic: Research Funding; BMS: Research Funding; Ariad: Research Funding. Kadia:BMS: Research Funding; Novartis: Honoraria. Ravandi:BMS: Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding. Jain:Pfizer: Consultancy, Honoraria, Research Funding; Incyte: Research Funding; Infinity: Research Funding; BMS: Research Funding; Servier: Consultancy, Honoraria; ADC Therapeutics: Consultancy, Honoraria, Research Funding; Genentech: Research Funding; Abbvie: Research Funding; Novartis: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria, Research Funding; Novimmune: Consultancy, Honoraria; Seattle Genetics: Research Funding; Celgene: Research Funding. Burger:Gilead: Research Funding; Portola: Consultancy; Roche: Other: Travel, Accommodations, Expenses; Janssen: Consultancy, Other: Travel, Accommodations, Expenses; Pharmacyclics, LLC, an AbbVie Company: Research Funding. Jabbour:ARIAD: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Novartis: Research Funding; BMS: Consultancy. Cortes:ARIAD: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Teva: Research Funding.
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Yellala, Amulya, Elizabeth R. Lyden, Heather Nutsch, Avyakta Kallam, Kai Fu, Timothy C. Greiner, Philip Bierman, et al. "Thirty-Five Year Follow-up Analysis of Follicular Lymphoma Patients Treated through the Nebraska Lymphoma Study Group: Prognostic Factor Analysis and Outcomes." Blood 136, Supplement 1 (November 5, 2020): 7–8. http://dx.doi.org/10.1182/blood-2020-142743.
Full textAbstract:
Background Follicular lymphoma (FL) is the second most common type of non-Hodgkin lymphoma (NHL) and most common of the clinically indolent NHLs. Although often considered an incurable disease, overall survival has increased significantly with refinement in diagnostic techniques and the addition of rituximab. The course of FL is quite variable and presence of symptoms, organ dysfunction, cytopenias, aggressiveness of tumor are all taken into consideration when deciding individual treatment. In this study, we evaluated a large patient cohort with FL treated over a 35 year period for progression free survival (PFS), overall survival (OS) based on FLIPI score, tumor grade, and treatment regimen and also looked at causes of late failures. Methods We evaluated 1037 patients (pts) from the Nebraska Lymphoma Study Group that were diagnosed with FL between the years of 1983-2020. Descriptive statistics were stratified according to age, histological subtype, treatment regimen, FLIPI category, presence and type of secondary malignancy. PFS was calculated from the time of diagnosis to progression or death and OS was the time from diagnosis to death from any cause. PFS and OS were plotted as Kaplan-Meier curves with statistically significant p<0.05. Results The median age at diagnosis and treatment was 61 years (yrs, range 17-91). A total of 9.1% were characterized as FLIPI high risk, 37.8% intermediate risk, and 33.6% low risk, 19.5% unavailable. Among the histological grade, 23.1% had FL- grade 1, 30.2% FL-2, 27.3% FL-3A, 2.5 % FL-3B and 16.9 % Composite Lymphoma. Anthracycline + rituximab was given in 24.5% of pts, whereas 43.8% of pts received an anthracycline based regimen without rituximab, 9.8% received rituximab without an anthracycline and 10.6% received neither of these agents. 6.75% (70 pts) were later found to have secondary malignancies of which 11 pts had myelodysplastic syndrome, 10 pts had acute leukemia and 9 pts had lung cancer. With a median follow up of 9.2 yrs and a maximum of 36 yrs, 29.7% (308 pts) had not relapsed. The median PFS across all groups was 4.6 yrs (Fig 1) and OS was 12.1 yrs. Median OS was significantly longer in patients that received rituximab at 16.1 yrs as compared to patients that did not receive rituximab at 9.89 yrs (Fig 2). PFS was 8.6 yrs, 3.6 yrs and 2.1 yrs and OS was 15.1 yrs, 11.7 yrs and 4.9 yrs in FLIPI low, intermediate and high risk groups respectively (p=<0.001) (Fig 3), suggesting that survival was influenced by FLIPI score. Median PFS in FL-3B and FL-3A was 9.2 yrs and 5.2 yrs respectively which is longer than 4.7 yrs and 4.2 yrs for FL-1 and FL-2 (p=0.24). OS in FL-3A and FL-3B subgroups was 10.8 yrs while it was 11.6 yrs and 14.3 yrs in FL-2 and FL-1 (P=0.081). PFS is significantly longer at 10.6 yrs in pts treated with both anthracycline and rituximab containing regimen as compared to 5.3 yrs in pts treated with rituximab alone and 3.05 yrs in pts that had only anthracycline based regimen (p=<0.001) (Fig 4). The median OS also was significantly higher in the combination regimen group at 18.8 yrs as compared to 11.3 yrs in rituximab only group and 9 yrs in anthracycline based regimen group (p=<0.001). When pts with FL-3A and FL-3B were grouped together and stratified according to treatment regimen, the group that received anthracycline and rituximab combination has highest PFS and OS at 13.3 yrs and 18.8 yrs (p<0.001). when pts with FL-3A were analyzed separately and stratified by treatment regimen, the results of PFS and OS were similar and statistically significant. However, of the 24 pts in FL-3B group, analysis revealed that PFS and OS was longer in anthracycline based regimen only group, however results were not statistically significant. Among the pts that relapsed/died after 10 years (n=190), the cause of death was relapsed lymphoma in 13.7%, unknown in 55.8%, secondary malignancies in 4.2%, treatment related in 2.6% and not related to disease in 23.7%. A total of 278 pts survived > 10 yrs, and of these pts, 119 (30%) had not relapsed at the last follow up. Conclusion The addition of rituximab to standard anthracycline based chemotherapy has resulted in significant improvements in the PFS and OS rates of FL. These results also support the prognostic value of the FLIPI in patients treated in the rituximab era. Late relapses after 10 yrs from disease can occur, but 11.5% of patients had not relapsed with long term follow up. Secondary malignancies are also an important consideration in the long term survivors. Disclosures Lunning: Acrotech: Consultancy; TG Therapeutics: Research Funding; Novartis: Consultancy, Honoraria; Kite: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Curis: Research Funding; Beigene: Consultancy, Honoraria; Aeratech: Consultancy, Honoraria; Bristol Meyers Squibb: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria; Legend: Consultancy; Verastem: Consultancy, Honoraria; ADC Therapeutics: Consultancy. Armitage:Trovagene/Cardiff Oncology: Membership on an entity's Board of Directors or advisory committees; Samus Therapeutics: Consultancy; Ascentage: Consultancy. Vose:Bristol-Myers Squibb: Research Funding; Karyopharm Therapeutics: Consultancy, Honoraria; Seattle Genetics: Research Funding; Allogene: Honoraria; AstraZeneca: Consultancy, Honoraria, Research Funding; Kite, a Gilead Company: Honoraria, Research Funding; Wugen: Honoraria; Novartis: Research Funding; Celgene: Honoraria; Incyte: Research Funding; Roche/Genetech: Consultancy, Honoraria, Other; Verastem: Consultancy, Honoraria; Miltenyi Biotec: Honoraria; Loxo: Consultancy, Honoraria, Research Funding; Janssen: Honoraria; Epizyme: Honoraria, Research Funding; AbbVie: Consultancy, Honoraria.