Impact of tissue factor expression and administration routes on thrombosis development induced by mesenchymal stem/stromal cell infusions: re-evaluating the dogma

Background: Hyperactive coagulation might cause dangerous complications such as portal vein thrombosis and pulmonary embolism after mesenchymal stem/stromal cell (MSC) therapy. Tissue factor (TF), an initiator of the extrinsic coagulation pathway, has been suggested as a predictor of this process. Methods: The expression of TF and other pro- and anticoagulant genes was analyzed in xeno- and serum-free manufactured MSCs. Furthermore, culture factors affecting its expression in MSCs were investigated. Finally, coagulation tests of fibrinogen, D-dimer, aPPTs, PTs, and TTs were measured in patient serum after umbilical cord (UC)-MSC infusions to challenge a potential connection between TF expression and MSC-induced coagulant activity. Results: Xeno- and serum-free cultured adipose tissue and UC-derived MSCs expressed the highest level of TF, followed by those from dental pulp, and the lowest expression was observed in MSCs of bone marrow origin. Environmental factors such as cell density, hypoxia, and inflammation impact TF expression, so in vitro analysis might fail to reflect their in vivo behaviors. MSCs also expressed heterogeneous levels of the coagulant factor COL1A1 and surface phosphatidylserine and anticoagulant factors TFPI and PTGIR. MSCs of diverse origins induced fibrin clots in healthy plasma that were partially suppressed by an anti-TF inhibitory monoclonal antibody. Furthermore, human umbilical vein endothelial cells exhibited coagulant activity in vitro despite their negative expression of TF and COL1A1. Patients receiving intravenous UC-MSC infusion exhibited a transient increase in D-dimer serum concentration, while this remained stable in the group with intrathecal infusion. There was no correlation between TF expression and D-dimer or other coagulation indicators. Conclusions: The study suggests that TF cannot be used as a solid biomarker to predict MSC-induced hypercoagulation. Local administration, prophylactic intervention with anticoagulation drugs, and monitoring of coagulation indicators are useful to prevent thrombogenic events in patients receiving MSCs. Trial registration NCT05292625. Registered March 23, 2022, retrospectively registered, https://www.clinicaltrials.gov/ct2/show/NCT05292625?term=NCT05292625&draw=2&rank=1. NCT04919135. Registered June 9, 2021, https://www.clinicaltrials.gov/ct2/show/NCT04919135?term=NCT04919135&draw=2&rank=1

PRESENT DAY DEFORMATION IN THE EAST VIETNAM SEA AND SURROUNDING REGIONS

This paper presents velocities of present-day tectonic movement and strain rate in the East Vietnam Sea (South China Sea) and surroundings determined from GPS campaigns between 2007 and 2010. We determine absolute velocities of GPS stations in the ITRF05 frame. The result indicates that GPS stations in the North of East Vietnam Sea move eastwards with the slip rate of 30 - 39 mm/yr, southwards at the velocities of 8 - 11 mm/yr. Song Tu Tay offshore moves eastwards at the rate of ~24 mm/yr and southwards at ~9 mm/yr. GPS stations in the South of East Vietnam Sea move to the east at the rate of ~22 mm/yr and to the south at the velocities of 7 - 11 mm/yr. The effect of relative movement shows that the Western Margin Fault Zone activates as left lateral fault zone at the slip rate less than 4 mm/year.In Western plateau, the first result from 2012 - 2013 GPS measurement shows that the velocities to the east vary from 21.5 mm/yr to 24.7 mm/year. The velocities to the south vary from 10.5 mm/yr to 14.6 mm/year. GPS solutions determined from our campaigns are combined with data from various authors and international projects to determine the strain rate in the East Vietnam Sea. Principal strain rate changes from 15 nanostrain/yr to 9 nanostrain/yr in the East Vietnam Sea. Principal strain rate and maximum shear strain rate along the Red River Fault Zone are in order of 10 nanostrain/year. East Vietnam Sea is considered to belong to the Sunda block

GRADIENT KIẾN TẠO HIỆN ĐẠI KHU VỰC NINH THUẬN VÀ LÂN CẬN

The estimation of the present day tectonic movement and tectonic gradient (strain rate) has an important practical signification in the assessment of active fault and seismic hazards for the selection of Ninh Thuan nuclear power plant. Based on the three campaigns of GPS measurement between 2012 - 2013, we used BERNESE 5.0 software to determine present day slip rates of 13 stations in ITRF08 frame. The GPS stations move eastwards at the slip rates of 22 - 25 mm/yr, southwards at the velocities of 5 - 10 mm/yr. The standard errors in latitudinal and longitudinal directions are 1.2 mm/yr and 0.9 mm/yr, respectively. Combined with GPS data from the project of the study on actual geodynamics in Tay Nguyen TN3/06, we determined the strain rate ranging from 50 to 100 nanostrains with the standard error of 50 nanostrains. The direction of  maximum compressive strain rate is from northwest - southeast to east - west.Đánh giá vận tốc chuyển động kiến tạo hiện đại và gradient kiến tạo hiện đại có ý nghĩa thực tiễn quan trọng trong việc đánh giá đứt gãy hoạt động nguy hiểm động đất phục vụ xây dụng nhà máy điện hạt nhân Ninh Thuận. Trên cơ sở đo 3 chu kỳ GPS vào các năm 2012 - 2013, sử dụng phần mềm BERNESE 5.0, chúng tôi đã xác lập được vận tốc chuyển động kiến tạo hiện đại tại 13 điểm đo GPS trong khu vực lân cận bao gồm kéo dài từ Nha Trang tới đảo Phú Quý. Vận tốc chuyển dịch kiến tạo hiện đại về phía đông thay đổi từ 22 - 25 mm/năm và chuyển dịch về phía nam với vận tốc giao động từ 5 - 10 mm/năm trên hệ tọa độ toàn cầu ITRF08. Sai số vận tốc chuyển dịch kiến tạo về phía đông giao động trong khoảng 1,2 - 1,5 mm/năm và về phía nam giao động trong khoảng 0,9 - 1,2 mm/năm. Liên kết với giá trị đo GPS từ đề tài nghiên cứu địa động lực hiện đại khu vực Tây Nguyên mã số TN3/T06, chúng tôi đã xác định được giá trị vận tốc biến dạng giao động từ 50 nano tới 100 nano biến dạng với sai số giao động trong khoảng 50 nano biến dạng. Trục biến dạng nén cực đại giao động theo phương thay đổi từ bắc nam sang đông bắc - tây nam. Trục biến dạng căng cực đại có phương thay đổi từ tây bắc - đông nam sang phương đông - tây

In search of innovation and customer-related performance superiority : the role of market orientation, marketing capability, and innovation capability interactions

Understanding the mechanisms through which firms realize the value of their market-based knowledge resources such as market orientation is a central interest of innovation scholars and practitioners. The current study contends that realizing the performance impact of market orientation depends on know-how deployment processes and their complementarities in functional areas such as marketing and innovation that co-align with market orientation. More specifically, this study addresses two research questions: (1) to what extent can market orientation be transformed into customer- and innovation-related performance outcomes via marketing and innovation capabilities; and (2) does the complementarity between marketing capability and innovation capability enhance customer- and innovation-related performance outcomes? Drawing upon the resource-based view and capability theory of the firm, a model is developed that integrates market orientation, marketing capability, innovation capability, and customer- and innovation-related performance. The validity of the model is tested based on a sample of 163 manufacturing and services firms. In answer to the first research question, the findings show that market orientation significantly contributes to customer- and innovation-related performance outcomes via marketing and innovation capabilities. This finding is important in that market-based knowledge resources should be configured with the deployment of marketing and innovation capabilities to ensure better performance. In answer to the second research question, the findings indicate that market orientation works through the complementarity between marketing and innovation capabilities to influence customer-related performance but not innovation-related performance. Managers are advised to have a balanced approach to managing the deployment of capabilities. If they seek to achieve superiority in customer-related performance, marketing capability, innovation capability, and their complementarity are essential for attracting, satisfying, building relationships with, and retaining customers. On the other hand, this complementarity would be considerably less important if firms placed greater emphasis on achieving superiority in innovation-related performance. In contrast to many existing studies, this study is the first to model the roles of both innovation capability and marketing capability in mediating the relationship between market orientation and specific performance outcomes (i.e., innovation- and customer-related outcomes).17 page(s

Market orientation versus innovative culture: two routes to superior brand performance

Purpose: The paper aims at providing insights into how market orientation and organisational culture together contribute to brand performance, shedding light on the nexus between innovative culture and market orientation, and examining the relative importance of innovative culture over market orientation in affecting brand performance. Design/methodology/approach: In a cross-sectional survey, a variance-based structural equation modelling was used to test hypotheses on a convenience sample of 180 marketing executives in Australia. Findings: Organisations with a strong innovative culture appear to recognise that building a successful brand depends not always on the interpretation of feedback received from current customers and competitors, but instead on organisations’ ability to innovatively develop unique ways of delivering superior value to customers. The findings were consistent with this advice to both market orientation and innovative culture. In addition, the findings indicate that market orientation is a response partially derived from the organisation’s innovative culture. Finally, it was also found that organisational culture was relatively more important than market orientation in affecting organisational performance. Originality/value: The paper advances the understanding of performance-based market orientation research by investigating structural relationships among market orientation, organisational culture, and organisational performance at the micro level (e.g. brand performance)

Examining the firm's value creation process : a managerial perspective of the firm's value offering strategy and performance

The primary pursuit of any business is to understand what customers value and to create that value for them. While customers are the final arbiter of value, it is the firm's role to explore, interpret and deliver value based on what they believe customers are seeking. Based on this premise we adopt the firm's perspective on value creation to extend both Bowman and Ambrosini's theoretical framework and the work of DeSarbo, Jedidi and Sinha and focus on two issues. The first is the strategic emphasis firms place on the design and delivery of their value offering. The second is the extent the firm's value offering explains performance differentials at the customer-centric performance level. We present a conceptual model of how firms gain positional advantage via their value offering and the realized outcomes they achieve. We present two approaches to modelling the firm's value offering (type II and type IV models) and articulate the theoretical underpinnings and results for these models. Our results validate the conceptualization of the firm's value offering and suggest that creating superior value offerings enables firms to achieve superiority in customer-centric performance.26 page(s

Achieving customer satisfaction in services firms via branding capability and customer empowerment

Purpose – The goal of this paper is to investigate how market sensing (market orientation) and customer linking capabilities (service branding and customer empowerment capabilities) enable firms to achieve superiority in customer satisfaction. Design/methodology/approach - To achieve this goal, a conceptual model was developed, specifying the mediating role of branding and customer empowerment capabilities in the relationship between market orientation and customer satisfaction. The model was tested using partial least squares, on 266 responses obtained via an online survey conducted amongst executives of services firms in Australia. Findings – The findings show that possessing a strong service branding capability and co‐opting customer involvement through customer empowerment in the marketing effort is essential for services firms to realize the potential value of market orientation. This is important if the firm wants to translate the understanding gained from market intelligence (via market orientation as the “know‐what” capability) into superior customer satisfaction. Practical implications – Through interaction activities that centre on utilizing market intelligence and shared sense of brand meaning, customer empowerment practices help institutionalize market orientation and service firms branding capability. Originality/value – This study offers a greater understanding of the underlying processes (i.e. service branding and customer empowerment capabilities) which market orientation works through to contribute to customer satisfaction.8 page(s

The Relationship between business orientations and brand performance

Purpose: The purpose of this paper is to adopt a customer‐centric value creation perspective to provide insights into the contribution of business orientations, especially marketing orientation and innovation orientation to the creation of customer‐centric value (customer equity and brand performance). Design/methodology/approach: To undertake this examination, a model was developed and then tested to validate its applicability in the context of both developed and developing economies. The paper includes partial least squares. Findings: The findings demonstrate that being marketing‐oriented and innovation‐oriented appears to be important in creating customers, keeping them, and increasing add‐on selling to them and rewards the firm with greater brand performance in the marketplace. Importantly, these relationships are universally held across developed and developing business environments. Interestingly, marketing orientation was found to contribute more to the creation of customer‐centric value than innovation orientation in developing business environment, whereas the opposite was found in the context of developed business environment. Research limitations/implications: The data incorporate only the subjective measures of customer‐centric value. Future studies can use financial measures to complement the self‐reporting approach used in this paper. This dual‐approach to measuring the value of customers to the firm (customer equity) and brand performance would provide additional insights into the customer‐centric marketing literature. Practical implications: The findings suggest that managers should strive to develop a high level of marketing orientation and innovation orientation as two efficient ways to achieve higher levels of customer equity. They are also advised that if their firms are more effective in acquiring potential customers, retaining current customers, and enhancing add‐on selling, they see their brands perform better. Importantly, the findings also provide guidance for managers on how to allocate their resources to key business activities (e.g. marketing and innovation) in the context of international business (developing versus developed business environments). Originality/value: This study contributes to customer‐centric marketing theory by enhancing understanding of the contribution of marketing and innovation to the creation of customer‐centric value in different business environments. This study also contributes to the business orientation literature by demonstrating the utility of a cultural‐behavioral approach in measuring marketing orientation and innovation orientation.30 page(s

Performance implications of market orientation, marketing resources, and marketing capabilities

Drawing on the competitive capability theory, this paper examines how market orientation, marketing resources, and marketing capabilities contribute to firm performance. The empirical results show that being market oriented influences the level of marketing resources firms possess and the capability to deploy such resources. The findings show marketing resources and marketing capabilities are significant drivers of firm performance, and their impact is greater when they are complementary to each other.15 page(s