Characterization of the hotel sample.
\r\n\tEven though video surveillance systems have been part an integral part of the public and security sectors for decades, there is a significant interest in them outside of those industries. This interest is largely due to increased crime rates and security threats all around the globe, which are driving a continuous growth of the video surveillance market. According to a recent report, the video surveillance market was valued at $29.98 billion in 2016 and is expected to reach a value of $72.19 billion by 2022. This market potential is also propelled by recent advances in Artificial Intelligence and Computer Vision research fields—boosting the intelligence, scalability, and accuracy of intelligent video surveillance solutions.
\r\n\r\n\tThe book's goal is to provide a game-changing and cross-disciplinary forum that brings together experts from academia, industry, and government to advance the frontiers of theories, methods, systems, and applications.
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Every day overwhelming volumes of information are produced and published online, and these seem to exert a critical influence on service choices and purchase decisions. This context is very much facilitated by the dissemination of technologies that encourage the production and sharing of user crated content. Likewise, there is a growing familiarity of customers with Internet technologies that is fueling this trend. Service providers, by their turn are keeping the pace by implementing and adhering to online tools that offer efficient ways for users to make their ideas available to vast audiences in a fast manner [1]. The importance of such form of communication, known as electronic word-of-mouth (eWOM) or word-of-mouse, has been extensively acknowledged in the literature, often being referred as a more effective means to influence customers’ consumption decisions than other tools, such as personal sales or advertising, because it can be perceived by costumers as a rather reliable source of information. Whereas customer reviews are now a common feature in many company websites, and platforms, research is still necessary to gain knowledge about how to effectively use eWOM data as a valued adding tool to inform customer decision making, as well as to guide managerial actions towards service improvement and innovation. This study proposes a contribution in this direction.
The study describes the development of a methodology to support the analysis of eWOM, in order to facilitate the systematic analysis and visualization of insights from online reviews concerning service quality. The proposed methodology is useful to both academics and managers as it proposes a concise display of the data analysis results, allowing for a quick identification and debate about priorities and concerns for quality management, while building on a frame of reference for quality attributes that is derived from service management literature. The study was developed in the particular context of the hotel industry in Portugal, as a representative business sector for the volume and reach of online consumer reviews. The development of the proposed data analysis and display method was built on a selected sample of customer reviews extracted from a prevalent online service for hotel bookings. The hotel industry offers an adequate and rich context for the nature of this study for the fact that the travel and tourism industry is known for being a pioneer for the growing trends of promotion and distribution of services over the Internet [2].
The chapter offers an approach for making sense of customer reviews, by identifying relevant service quality dimensions embedded in the voices of hotel customers, while offering a concise tool for the visualization of the results. To this end, the study employed the principles of importance-performance analysis (IPA), a marketing research technique acknowledged for offering a concise graphical representation of results, to develop a framework for identifying salient hotel service attributes from the available and uncategorized information provided by customer reviews. The study offers a timely approach for assisting managers in the task of sense making from growing volumes of user generated information from a key source of information for the identification of priorities for service improvement and innovation.
Following this introduction, this chapter offers in Section 2 an overview of the conceptual background of the study, namely addressing on the topics of service quality and service quality assessment approaches while discussing some of the key challenges in measuring service results. In Section 3 is devoted to describe the application of the importance-performance analysis (IPA) approach to the context of eWOM in hotel services, and to presented and discuss some representative results of the application of this methodology to extract meaning from user generated context. The chapter closes with a presentation of key contributions and conclusions in the last section.
The understanding of service quality and the deployment of robust and replicable methods to conduct its assessment have been in the core of the agendas of service management scholars and practitioners for many years. Despite an early consensus about the relevance of service quality for customer satisfaction, loyalty and company’s profitability [3, 4], the operationalization of methods and tools to measure service quality and inform managerial practice and consumer decision making has generated extensive debate and challenges. Many of the results of service experiences lack tangibility and for this reason many approaches for service quality assessment rely on information from customers’ “perceived” experiences [5, 6].
Many of the prevalent approaches to capture consumers quality perceptions build on the development of survey methods for data collection, consisting of multi-item scales. Such multidimensionality is aligned with the conceptualization of services as experiences that enact perceptions about multiple attributes and dimensions that affect customer value such as service responsiveness, reliability, and even elements such as the characteristics of the tangible elements such as service facilities, equipment, etc., and the performance and empathy of service professionals. In service experiences customers receive a combination of outcomes including direct process results (e.g., availability of required items in a retail store, on-time arrival to a flight destination in transportation services, etc.) along with other results related to the process experience resulting from customers’ contact and involvement in the service process (e.g., store atmosphere in retail services, comfort in a flight, etc.). Service quality is therefore conceptualized as a construct, featuring distinct dimensions that correspond to the diverse benefits that a customer can derive from a service. These dimensions of service quality are present across the prevalent service quality models and mirrored in the generalized generic scales such as SERVQUAL, SERVPERF, along with other sector specific scales where items are adapted to business particularities, such as in retail, health or hospitality and tourism services. Prevalent models account for the recognized dual nature of service quality determinants, i.e. the quality of service outputs as well as the quality of the experience with the delivery processes [4].
Overall service quality models, and the derived methods for its assessment, analysis and interpretation are built on customers’ perceptions about the performance of service delivery, rather than on objective assessments of quality items [7, 8]. Perceived service quality is defined as the customer’s evaluation of the overall excellence of a service and has been persistently distinguished from objective quality measurements, which were typically associated to the quality assessment of manufacturing products. The use of perceived service quality models is motivated by the specific nature of service outputs, which involves both tangible and intangible components and, as such, are often hard to assess and can result into very heterogeneous evaluations across customers.
Despite of the popularity of the [quantitative] multi-attribute type of measurement that has prevailed in the service quality domain along the years, several debates have highlighted the limits of such instruments. Among these are the difficulties of interpreting and using the standardized results of multi-attribute measurements. Data collected in this form offers only limited information about the richness, and the details, that contextualize customer perceptions about a service. More importantly, survey data fails from capture information about contradictions in service experiences as the respondents are forced to aggregate their quality experiences into ratings for a limited number of items. Any comprehensive listing of all quality aspects would result into lengthy questionnaires that would exceed customer’s willingness to answer and therefore hurt the validity of the information collected. A customer of an accommodation service of asked to evaluate the friendliness contact employees is forced to choose a single point on a scale despite the number of contacts and different staff met whose behavior and friendliness might vary considerably.
Overall the standard attribute-based quality and satisfaction surveys are not perfect when it comes to capturing all relevant managerial information, and for this reason other complementary approaches have been advanced, such as focus groups studies, analysis of critical incidents, among others, in order to capture richer consumer insights. In this context, word-of-mouth, i.e. the expressions about the service experiences as expressed in the words of the consumers have always been acknowledged as an important source of information, and a key determinant for consumer choice. Generally, it is referred to as an informal and personal form of communication [9] that has been acknowledged by its influence for customers ‘decisions [10], being source of trusted information [11].
In recent years, the advent of electronic-word of-mouth (eWOM) has created a rich field of data for deepening the understating about consumer experiences. Differently from traditional WOM, the its electronic version eWOM offers the advantage of being preserved, and accessible, over time in a written format that can be revisited and analyzed in detail, with distinct lenses.
The volume and reach of eWOM content have expended enormously, and are increasingly calling for the development of methods and tools that can assist consumers and managers to filter and make sense, in a timely manner of such large and rich amount of information. Consumers are expressing their opinions using multiple sources that include blogs, online reviews, and social networking websites, while interacting virtually to share information about their experiences with all sorts of goods, services, and brands [12]. eWOM has been defined as “any positive or negative statement made by potential, actual or former customers about a product or company, that is made available to a multitude of people and institutions via the internet” ([1], p. 39).
The tourism sector is a prominent example of a setting where eWOM has grown in volume and popularity, notably by means of online reviews that are the concrete examples of electronic versions of traditional WOM and result in a volume of comments from travelers about their experiences, the products, and the services they find along their journeys [13]. eWOM is available for other tourist to read and revisit, as well as for service managers to learn about their experiences. In fact many of the tourism service providers actively encourage their consumers to post reviews on their sites, social media platforms and other sources of reference [14]. The growth in eWOM is motivating increased research attention in several fronts, such as the investigation of the impacts of eWOM on sales, on consumer behavior. In tourism industry the results support that eWOM is considered credible [15], reducing consumers resistance to booking [16] and affects the sales of hotel rooms [17] and the motivations to visit some specific destinations [18]. Despite the growing number of studies that cover, the field is still far from being fully covered, and is still very much concentrated in exploring the behavioral implications of eWOM on travelers [19]. In this study we take a different approach aimed at developing approaches to make sense of the rich information contained in the reviews’ texts with the purpose of advancing in the creation of tools to support data analysis and visualization that can assist managers and consumers in extracting valuable information from eWOM sources.
Importance-performance analysis is a popular approach for interpreting customer satisfaction and for setting up priorities for upgrading service quality proposed by [20]. IPA builds on customers’ assessments concerning the importance and the performance of quality attributes in order to diagnose areas for improvement—typically using data collected by means of questionnaires employing service scales. IPA offers a plot representation for the measurements for importance-performance, declared by customers, consisting of a four quadrants matrix. The IPA matrix plots these values against two axes: a vertical axis—for the values of performance of service attributes; and an horizontal axis—for the values of attribute importance (see Figure 1).
Quad chart illustrating the breakdown of traditional importance-performance analysis approach. Desirable re-allocation of resources would go from the lower right quadrant to the upper left quadrant. Source: Adapted from Martilla and James [
Such concise display enables the quick visual identification of what elements demand for managerial improvement actions (i.e. attributes ranked in the quadrant for high importance vs. low performance) as well as others where the providers efforts are potentially misplaced (i.e. attributes ranked in the quadrant for low (customer) importance vs. high (provider) performance).
Subsequent studies have proposed modified approaches building on the principles of the IPA framework, extending its scope of application. For example CIPA, that stands for “Competitive Importance Performance Analysis”, is focused on the gaps of the performance of a given service company and that of its competitors, offering a tool to diagnose which competitive attributes demand for improvement. In this adaptation the horizontal axis represents the differences between a company’s performance towards the other market players.
Other formulations of IPA aim to address criticisms about its assumptions, namely the independence between the importance and performance measures and the linear relationship between the attributes and the performance. The so-called IPA with the three factor theory employs also a matrix representation for the measurements but takes into account the fact that not all service attributes are equally important for customer satisfaction [21, 22, 23]. This approach distinguishes three types of factors: (i) basic factors, i.e. minimum requirements that cause dissatisfaction if not fulfilled while not leading to customer satisfaction if fulfilled; (ii) performance factors, i.e. elements that cause satisfaction or dissatisfaction, depending on their performance level and (iii) excitement factors that can increase customer satisfaction if delivered but do not cause dissatisfaction if not delivered [24]. The modified IPA approach employs this three factor theory [25] and uses estimations of the relative importance of the quality attributes, instead of using customer declared information. The importance-performance lens of analysis therefore offers a versatile methodology for approaching the prioritization of service attributes.
This study builds on prevalent approaches of extending the applications of IPA by developing a modified version of IPA for identifying areas for service improvement building on qualitative data in the context of hotel experiences.
The main purpose of this work is to develop a flexible and concise methodology to make sense for the ever growing online customer reviews that are available for a wide diversity of service business, in an abundant and unstructured manner. Despite the volume and richness of data available, the ability of both customers and providers to summarize and interpret customer generated content is still very limited and often done ad hoc by managers, therefore hurting its utility and value for customer decision and company improvements. Yet recent research results confirm that such sources of information are increasingly accessed by customers to support purchase decisions [26]. To this end, the study focuses on customer online reviews in the context of the hotel industry for several reasons. Tourism and hospitality services are experiential in nature which makes pre-purchase quality assessments rather difficult, leading customers to search for various clues and information to support their choices. In this context the opinions of other customers assume a critical role. In addition this service industry has a pioneering record in the utilization of online means for customer service interactions (e.g. travel reservations), and for the abundance of eWOM behavior.
The study addresses a sample of customer reviews for a selected number of hotels in a medium sized tourist destination city in Portugal available in the online reservation website Booking.com. The choice of using Booking.com as a source is justified for being the website offering the largest volume of reviews and diversity of customer profiles, and for offering a significant volume of data for all the units in the selected sample of hotels. Data extraction returned a volume of over 5.600 customer reviews, for a set of 11 hotel units (described in Table 1), for a period of 1 year.
Hotel | Star rating | Rooms | Location* | Available services | Average price** |
---|---|---|---|---|---|
Moliceiro | 4 | 49 | 0 | 16 | € 99 |
Aveiro palace | 4 | 49 | 0 | 13 | € 62 |
Melia Ria | 4 | 128 | 10 min | 22 | € 94 |
Américas | 4 | 70 | 5 | 16 | € 79 |
Imperial | 3 | 107 | 0 | 8 | € 63 |
Jardim | 3 | 48 | 0 | 11 | € 56 |
Afonso V | 3 | 78 | 5 | 6 | € 49 |
Veneza | 3 | 49 | 0 | 7 | € 68 |
Aveiro center | 2 | 24 | 0 | 8 | € 58 |
J. Estevão | 2 | 12 | 1 | 6 | € 57 |
Salinas | 2 | 18 | 0 | 7 | € 58 |
Characterization of the hotel sample.
Walking time to the city center (minutes).
Standard double room, average.
The first column contains the hotel name, the second column the official star rating at the time of the study, the third contains the number of rooms and the fourth the estimated walking time to the city center. The fifth and sixth columns present the number of services available at the hotel and the average price per night, respectively.
The chosen hotel reservation Website exhibits written online customer reviews, organized into groups—positive and negative reviews—as well as a rating obtained from customer scoring. In order to guarantee reliability, i.e. that the reviews resort from individual experiences, the Website only allows for reviews from customer who have effectively made a reservation.
The IPA addresses the data from the sample of extracted customer reviews. The first step in the analysis involves the identification of the most frequent terms and expressions about the hotel experience as stated by customers, for which text mining tools were employed, including a preliminary cleaning of symbols and words with no relevant meaning, and the standardization of terms, whenever synonyms are used to refer to a same hotel service element. The terms and expressions with higher frequency were retained for inclusion in the IPA analysis. A second step involves the identification of dimensions of affinity for the service quality attributes present in customers’ statements. This process leads to the identification of three dominant service quality elements, motivating the expression of (positive or negative) customer opinions: room, location and staff. Whereas a more detailed list if attributes can be retained the choice is for the use of a more aggregated level of analysis given the exploratory nature of the study.
The IPA matrix for the 11 hotels is displayed in Figure 2, where the data points for importance-performance for the three salient attributes, room, location and staff are, respectively ●, ▲ and *. In the traditional IPA the horizontal and vertical axis represent the coordinates for the values of importance, and the performance as perceived by the customers, usually resulting from structured questionnaire answers, using ordinal scales (e.g. 1–7), where customers sate their expectations (i.e. interpreted as importance) and service perceptions (i.e. experienced performance). In the current study, and given the qualitative nature of the available data—the reviews—the values for the matrix coordinates are obtained as follows.
Modified IPA graph for the hotel sample in the study.
For each service attribute (room, location and staff) the total frequency (considering all the terms and expressions associated to a given service attribute) is employed as a proxy for the importance of the attribute, therefore assuming, that customers express more opinions for items that are more relevant for their experience. As for performance, the analysis employs the ratio of the number of positive reviews towards the sum of positive and negative comments, for a given service attribute. According to this logic a hotel for which the proportion of positive comments is higher than the negatives corresponds to a positive performance. This proxy measurement for performance therefore varies between 0 (when all comments are negative) and 1 (when all comments are positive). Also, the traditional IPA usually employs a central tendency measure (e.g. mean, median) to split each axis and identify the four quadrants. In the current study the value of the mean is employed to split the plot area.
The interpretation of the IPA graph offers a number of interesting insights. Overall, for each hotel unit, the three service attributes considered in the analysis are closely positioned next to each other. This suggests that when hotel customers are pleased with a hotel, or with the particular performance of one service attribute and they engage in offering positive comments, they tend to be positive about the remaining attributes. Whereas there’s some natural dispersion in the points exhibited in Figure 2 most service attributes, for the diverse hotels, is positioned in the quadrants II and IV pointing towards urgent action and resource underutilization, respectively.
Overall the service attributes for the various hotel units are positioned very closely in the IPA map. A look at the positioning of the service attributes (room, location and staff) the one with stronger consistency in customers’ opinions is staff, as in 90% of cases appears as the most important attribute. An opposed pattern is shown for the attribute room, for which customers seem to hold more heterogeneous opinions about its importance. Overall the data suggests some inconsistency in customers’ perceptions about the importance of the service attributes. Of particular interest is the observation that there is a great variability in what regards the number of positive or negative comments. Most of the hotels exhibit a value for the performance measure (i.e. positive comments divided by the sum of positive and negative comments) not very distant from 0.5, therefore suggesting the existence of some level of service inconsistency across customers, a characteristic that is rather undesirable in service settings. The proposed analysis is susceptible of being conducted at a more fine grained level, i.e. in this case, for each hotel (see for example Figure 3).
Modified IPA displaying in detail the positioning of the three salient attributes [room, location and staff] for a single hotel unit (Hotel Afonso V).
This study, although exploratory and restricted to a small sample of service providers, from a specific service context—hotels—offers an illustrative insight of how existing managerial analytical tools can be adapted to help making sense of large volume of customer generated content. Whereas the study was applied in the context of hotel services, it is clear that the principles of the tool are applicable to any service industry, given that there is some kind of customer content to work with. Customer reviews are proliferating across service websites, platforms and social media contexts, therefore providing an ample and rich field for the development of new approaches to develop knowledge about service quality. The study illustrates that is possible to apply tools to offer a concise and structured view of the content generated by customers in their service reviews, and therefore to extract value from this abundant source of information. The extracted service attributes (room, location and staff) are particular to this study, its context and the limitations of sample selection, not meaning that they are the overall more important in the hotel industry. In order to do so, the study would have to be extended to a wider sample, and account for any conditioning variables (e.g. seasonality, weather, customer experience, etc.). As such this work suggested that there is a vast array of models and tools for assessing service quality that can be called to help make sense of the overwhelming volume of eWOM.
An aortic aneurysm is defined as a permanent localized dilation of the aorta with at least a 50% increase in diameter compared with a normal aortic diameter [1]. Aortic aneurysms can be classified according to location as thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA). TAA occurs in all-age people without sexual dimorphism and is highly associated with hereditary conditions [2]. By contrast, AAA is typically associated with aging, male sex, smoking, atherosclerosis, and hypertension [3, 4, 5]. AAA is the most common form of aortic aneurysm [6], affecting 4–8% of men and 0.5–1.5% of women over the age of 60 and currently accounting for nearly 2% of all deaths in Western countries [2, 3, 7]. Aortic aneurysm is an asymptomatic condition that tends to progress over time with a high mortality rate (65–85%) if rupture occurs [8]. Unfortunately, repair through open or endovascular surgery is currently the only therapeutic option for aortic aneurysm; no drug has been approved for treatment of this devastating disease [3, 5]. One of the major barriers in the field is a lack of an animal model that fully resembles human aortic aneurysm.
\nOver the last few decades, a number of rodent models of AAA and TAA have been developed and have been increasingly utilized to be used in understanding the etiology of human AAA and TAA [2, 9, 10, 11]. Aortic aneurysm animal models can be classified into three groups [2, 9, 10, 11]: (1) genetically predisposed animal models (i.e., fibrillin-1 (FBN1) mutation (Marfan syndrome) mouse model [2, 12]), (2) chemical-induced animal models (i.e., Ang II infusion hyperlipidemia mouse model [9, 13]), and (3) physical or surgical animal models (i.e., decellularized aortic xenograft rat model [10, 14]). Among them, calcium chloride adventitial application model [15, 16], porcine pancreatic elastase (PPE) model [17, 18], and Ang II infusion hyperlipidemia mouse model [13, 19, 20, 21, 22, 23] are the commonest animal models currently studied in the world.
\nOne of the fundamental pathological characteristics in human TAA and AAA is thoracic aortic dissection (TAD) and abdominal aortic dissection (AAD), both of which can lead to aneurysmal rupture with high mortality [1, 2, 3, 4, 5, 6, 7]. Many genetically predisposed animal models have TAD and AAD (i.e., fibrillin-1 mutation mouse model [2, 12]). Some of the chemical-induced animal models also have TAD and AAD (i.e., fibrillin-1 mutation and Ang II infusion hyperlipidemia mouse models [13, 19, 20, 21, 22, 23]). Recently, a new chemical-induced mouse model for more potently induction of TAD and AAD was developed by administration of β-aminopropionitrile monofumarate (BAPN) to mice to inhibit lysyl oxidase (LOX) and/or Ang II infusion [24, 25]. Kurihara et al. demonstrated that BAPN/Ang II induced TAD in 100% of FVB mice [24]. Ren et al. confirmed this finding and further demonstrated that BAPN/Ang II induced TAD and AAD in 75% of C57BL/6J mice, whereas BAPN alone induced TAD in 87% of C57BL/6J [25].
\nAlthough no single animal model fully reproduces the histological characteristics and natural history of the human aortic aneurysm, each of these animal models more or less recapitulate human aortic aneurysm and have significantly contributed to the current understanding of clinical management and treatment of patients with AAA and TAA [2, 9, 10, 11]. Several clinical trials have begun enrollment to examine whether angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB) are effective in the treatment of human aortic aneurysm. However, the results from these clinical trials are inconsistent and disappointing: either effective [26], no effect [27], or, even worse [28], indicating that the current understanding about the etiologies of aortic aneurysm is limited and additional unknown signaling and mechanism may underlie aortic aneurysm and account for the failure of these clinical trials.
\nIn sharp contrast to the well-established role of Ang II in aortic aneurysm [13, 19, 20, 21, 22, 23], little is known about the role of aldosterone (Aldo) in aortic aneurysm. Aldo is a steroid hormone primarily synthesized and released by the adrenal glands. Aldo is a downstream effect of Ang II and is well recognized for its critical role in renal sodium reabsorption and water retention and consequently extracellular volume and blood pressure [29, 30]. Accumulated data over the last decade, however, demonstrate that Aldo not only acts on the kidney but also targets many other organelles, including those in the cardiovascular system, where it is critically involved in diverse pathophysiological processes [31, 32, 33].
\nSeveral lines of clinical study implicate Aldo signaling in aortic aneurysm. First, individual case reports demonstrated that primary hyperaldosteronism is associated with aortic dissection [34, 35, 36]. Second, a retrospective study demonstrated that aldosteronism is associated with high morbidity and mortality from the early onset of hemorrhagic stroke and ruptured intracranial aneurysms [37]. Third, a few small studies have shown an association between obesity and increased levels of Aldo [38] and increased AAA [39]. Finally, perhaps also the most compellingly, an analysis of drug modulation of AAA development through 25 years of surveillance in 1269 patients demonstrated a strong association between mineralocorticoid receptor (MR; also known as Aldo receptor) blockers and slowed AAA progression [40]. However, whether Aldo causes aortic aneurysm is unknown.
\nBy incidence, we discovered that administration of deoxycorticosterone acetate (DOCA) to 10-month-old C57BL/6 male mice caused substantial animal death in the presence of high salt due to aortic aneurysmal rupture. A subsequent serial of substantial studies demonstrated that activation of MR by either implantation of DOCA pellet or infusion of Aldo in 10-month-old C57BL/6 male mice was sufficient to induce AAA and TAA formation and aneurysmal rupture in the presence of high salt [41, 42, 43]. Recently, we published the detailed methodology on how to implant DOCA pellet or Aldo pumps to induce aortic aneurysm [44]. Here, we will focus on the significant novel finding of this new AAA mouse model, highlight its unique features that mimic human aortic aneurysm, and discuss its significance and potential impact on the current understanding, diagnosis, and treatment of human aortic aneurysm.
\nIn an independent pilot study using 10- to 12-month-old C57BL/6 male mice to investigate DOCA-salt-induced hypertension, we unexpectedly observed that many mice died from AAA rupture. We were intrigued by this observation since it raised the possibility that activation of the MR by DOCA can cause AAA in the presence of high salt. Given that administration of DOCA and salt to mice or rats have been used extensively as an experimental model of low-renin hypertension [45], it was surprising that DOCA-salt-induced AAA has not been reported in previous studies. While the exact reasons for this discrepancy are unclear, our results suggest that the age of mice (i.e., 10-month old
To verify our pilot studies and define whether DOCA, salt, or both is critical for DOCA-salt-induced aortic aneurysm, 10-month-old C57BL/6 male mice received DOCA alone (subcutaneous implantation of DOCA pellets; 50 mg, 21-day release; Innovative Research of America, USA), salt alone (drinking water containing 0.9% NaCl plus 0.2% KCl), DOCA and salt, or no treatment (controls). We used C57BL/6 mice because C57BL/6 mice are more susceptible to chemical (i.e., BAPN/Ang II)-induced TAD, AAD, and aneurysmal rupture than other strains of mice (i.e., FVB mice) [24, 25]. We used 10-month-old rather than 10-week-old mice because we found that DOCA- or Aldo-salt-induced aortic aneurysm were aging dependent [41, 43]. We used male mice rather than female mice because DOCA- or Aldo-salt-induced aortic aneurysm has sex difference (unpublished data). All mice were euthanized 3 weeks after treatment.
\nWe used three different approaches to quantify DOCA-salt-induced aortic aneurysm. First, the maximal intraluminal diameters of abdominal aortas were quantified in vivo by a high-resolution ultrasound imaging system (Vevo 2100, Visualsonics, Toronto, Canada). The results showed that both DOCA and salt but not DOCA or salt alone could potently induce abdominal aortic dilation relative to the control [41]. Second, the maximal external diameters of isolated abdominal and thoracic aortas were quantified ex vivo by Nikon SMZ800 Stereo Microscope with a digital camera and NIS-Elements software. Consistently with the ultrasound data, both DOCA and salt but not DOCA or salt alone significantly increased external diameters of abdominal and thoracic aortas relative to the control [41].
\nThird, we calculated the incidence of DOCA-sat-induced AAA, TAA, and aneurysmal rupture based on the definition that AAA or TAA has at least a 50% increase in diameter compared with the normal diameter of the aorta [1]. Of the 45 mice treated with DOCA-salt, 28 mice developed AAA (62%), 22 mice developed TAA (42%), and 8 mice died of aortic aneurysmal rupture (18%). In contrast, no AAA, TAA, or aortic aneurysmal rupture was observed in control, DOCA, or salt alone. Interestingly, AAA was only found in the suprarenal abdominal aorta, which is similar to that in the Ang II AAA mouse model [13], whereas TAA was mostly associated with AAA and was mostly observed in the descending thoracic aorta, indicating that TAA is likely derived from AAA.
\nSince DOCA is a synthetic MR agonist, we wondered whether Aldo, a physiologic ligand of MR in our body, could induce aortic aneurysm in the presence of high salt. To define the concentration of Aldo that is sufficient to induce aortic aneurysm in the presence of high salt, 10-month-old C57BL/6 male mice were infused with three different doses of Aldo (200, 500, and 700 μg/kg/day) for 4 weeks. Aldo was delivered to mice via subcutaneous implantation of osmotic minipump (Alzet model 2004; DURECT, USA) containing Aldo solubilized in 50% DMSO. All groups of mice were treated for 4 weeks.
\nInfusion of mice with all three doses of Aldo was very similar to implantation of mice with DOCA pellets and markedly increased maximal intraluminal and external diameters of suprarenal abdominal aortas compared to the control mice (without treatment). Similarly, infusion of mice with all three doses of Aldo is also similar to implantation of mice with DOCA pellets and potently induced AAA (over 58%), TAA (over 42%), and aneurysmal rupture (over 25%) compared to the control mice. These data demonstrated that the infusion of mice with 200 μg/kg/day Aldo is sufficient to induce AAA in the presence of high salt.
\nWe measured the plasma Aldo concentrations by a commercial EIA kit (Enzo Life Science, USA) 4 weeks after Aldo and salt administration. We found that plasma Aldo concentrations were elevated in a dose-dependent manner. Of note, infusions of mice with 200 μg/kg/day Aldo resulted in plasma Aldo concentrations to ~10 nM, which could be seen in some human diseases such as congestive heart failure and primary aldosteronism [31, 46, 47]. These results indicate that the Aldo-salt AAA mouse model is a physiopathological model that mimics human diseases rather than a pharmacological model that would cause concerns due to the use of high doses of reagent.
\nAlthough systematic plasma renin and Ang II concentrations are suppressed in animals administered with DOCA and salt [45], local aortic Ang II concentration can be increased due to activation of vascular RAAS, which was thought to be of pathophysiological relevance to the development of atherosclerosis [48]. Moreover, there is a synergistic interaction between Ang II and Aldo in VSMCs [49, 50]. Therefore, it is interesting to investigate whether DOCA-salt-induced aortic aneurysm is dependent upon Ang II. To address this important question, 10-month-old C57BL/6 male mice were treated with either an ACE inhibitor (enalapril) or an ARB (losartan) before (1 week) and after (4 weeks) DOCA-salt administration. As expected, enalapril or losartan effectively decreased blood pressure, but enalapril or losartan had little effect on the DOCA-salt-induced aortic dilation, aortic aneurysm formation, and aneurysmal rupture [41]. These results demonstrate that the DOCA-salt-induced aortic aneurysm is independent of Ang II thus provide an alternative mouse model of aortic aneurysm for investigators in the field who need an Ang II-independent mouse model to verify their key findings.
\nTo define the role of MR in DOCA- or Aldo-salt-induced aortic aneurysm, we treated 10-month-old C57BL/6 male mice with an MR antagonist eplerenone 1 week before and 4 weeks after Aldo-salt administration [41]. Eplerenone (Pfizer, USA) was delivered by feeding mice with custom diets (chow supplemented with eplerenone at 2.5 mg/g, Research Diets, Inc., USA). In contrast to the minimal effect of blocking Ang II with enalapril or losartan, treatment of mice with eplerenone completely abolished Aldo-salt-induced aortic dilation, AAA formation, and aortic aneurysmal rupture [41]. A similar but less potent effect on DOCA-salt-induced AAA was also found in mice treated with spironolactone [41]. These results suggest that activation of MR by DOCA or Aldo is a prerequisite for DOCA- or Aldo-salt to induce aortic aneurysm.
\nAdministration of DOCA and salt to mice or rats has been used in the field to induce hypertension [45]. Hypertension is recognized as a potential risk factor for aortic aneurysm [3, 4, 5]. Thus, it is important to determine whether hypertension contributes to DOCA-salt-induced aortic aneurysm. Blood pressure was measured using a noninvasive tail-cuff system (Coda 6; Kent Scientific Corp., USA). As expected, administration of DOCA or Aldo plus salt to 10-month-old male mice increased both blood pressure and external diameters of the abdominal aorta [41, 43]. However, there was no correlation between blood pressure increase and external diameters of abdominal aorta after DOCA-salt treatment. Similarly, there was also no difference in blood pressure between the mice with aortic aneurysm and the mice without aortic aneurysm. Moreover, treatment of mice with ACE inhibitor enalapril or ARB losartan effectively decreased blood pressure, but both enalapril and losartan had little effect on DOCA-salt-induced aortic aneurysm. Thus, we concluded that DOCA-salt induces aortic aneurysm independent of increased blood pressure. This conclusion is consistent with that in the Ang II infusion AAA mouse model [19].
\nHuman aortic aneurysm is characterized by elastin and collagen degradation, matrix metalloproteinase (MMP), upregulation, inflammatory cell infiltration, vascular smooth muscle cell degeneration, and oxidative stress [51]. To investigate whether DOCA- or Aldo-salt-induced aortic aneurysms have these pathologic features, paraffin-embedded aortic cross-sections were subjected to Elastic-Van Gieson staining of elastin. Interestingly, elastin degradation was only observed in AAA induced by DOCA- or Aldo-salt [41, 43]. Immunocytochemistry studies revealed that MMP2, MMP9, F4/80 (macrophages), Ly6B2 (neutrophils), caldesmon (smooth muscle cells), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL; apoptosis), and dihydroethidium (DHE; oxidative stress) were increased in aortas with AAA compared with that in control aortas [41, 43].
\nIn agreement with these immunocytochemical studies, we determined mRNA expression of several inflammatory genes, including vascular cell adhesion molecule 1 (Vcam-1), chemokine (C-C motif) ligand 2 (Ccl2, also known as MCP-1), tumor necrosis factor (Tnf), and Ncf1 (also known as p47phox) in both abdominal and thoracic aortas from mice-administrated DOCA-salt or control mice. We found that Vcam-1, Ccl2, Ncf1, and Tnf were all markedly upregulated in thoracic aortas from mice-administrated DOCA-salt compared to control mice. Interestingly, Vcam-1, Ccl2, and Ncf1, but not Tnf, were also significantly upregulated by DOCA-salt in abdominal aorta from mice-administrated DOCA-salt compared to control mice [41, 43].
\nThe DOCA- or Aldo-salt mouse model exhibited several unique features that may be relevant to the human aortic aneurysm. First, DOCA- or Aldo-salt-induced aortic aneurysm required to use 10-month-old mice [41, 43] rather than 10-week-old mice (mostly used by the Ang II AAA mouse model [13, 19, 20, 21, 22, 23] and other chemical-induced mouse modes [17, 18, 24, 25]). Given the fact that human AAA occurs in old peoples [2, 3, 7], the DOCA- or Aldo-salt mouse model of aortic aneurysm may more resemble human AAA than other chemical-induced aortic aneurysms in this regard. Second, DOCA- or Aldo-salt-induced aortic aneurysm used wild-type C57BL/6 mice [41, 43] rather than hyperlipidemia mice (i.e., apolipoprotein E-deficient (ApoE−/−) used by Ang II infusion mouse models [13, 19, 20, 21, 22, 23]), thus avoiding the potential confounding effects of hyperlipidemia on aortic aneurysm. Third, using Aldo, a physiological agonist of MR, rather than chemicals (i.e., calcium chloride or pancreatic elastase) to induce aortic aneurysm, highlights its potential role in the etiology of aortic aneurysm. Moreover, the plasma concentration of Aldo in mice infused with Aldo [41] could be seen in human congestive heart failure and primary aldosteronism [31, 46, 47], suggesting that the Aldo-salt AAA mouse model is a pathological model rather than a pharmacological model that would cause concerns due to the use of high doses of reagent. Finally, high salt intake was required for DOCA to induce aortic aneurysm [41], indicating that high salt intake may be a new risk factor for the development of human AAA.
\nWe described a new mouse model of aortic aneurysm induced by administration of MR agonist DOCA or Aldo plus high salt to 10-month-old male mice and provided compelling preclinical evidence that reveals a previously unrecognized, but potentially significant, role of Aldo, MR, and high salt in the pathogenesis of AAA. It is worth pointing out that this new mouse model of aortic aneurysm could be used as a platform to study intervention including medication (i.e., we have tested the effect of ACE inhibitor (enalapril), ARB (losartan), and MR antagonist (eplerenone and spironolactone) [41]). It is also worth pointing out at least three significance and potential impact of the DOCA- or Aldo-salt mouse model of aortic aneurysm on the current basic research and clinical practice on the etiology, clinic diagnosis, evaluation, and treatment of AAA.
\nFirst, in agreement with the pivotal role of Aldo in cardiovascular diseases (i.e., hypertension and heart failure) [31, 32, 46], our studies highlight a potentially important but previously unrecognized role of Aldo in the etiology of human aortic aneurysm. Our studies suggest that increased plasma concentration of Aldo may be a new risk factor for human aortic aneurysm or may serve as a new plasma biomarker for evaluation of aortic aneurysm progression.
\nSecond, it is well recognized that unfavorably excessive dietary sodium intakes remain prevalent around the world and are associated with an increased risk for cardiovascular diseases including hypertension, stroke, coronary heart disease, heart failure, and renal disease [52, 53, 54]. However, it is unknown that excessive dietary sodium intake may also be detrimental to the aorta with respect to aortic aneurysm. Our finding that excessive dietary sodium intake was essential for MR agonist to induce aortic aneurysm in mice suggests that excessive dietary sodium intakes may also be implicated in the etiology of human aortic aneurysm. In agreement with our findings, it was recently reported that high salt intake was associated with an increased prevalence of AAA in older men [55]. Moreover, our findings indicate that lifestyle change such as reduction of dietary sodium intakes may be effective to prevent old people from the development and progression of aortic aneurysm.
\nThird, given the fact that currently there is no approved drug for treatment of AAA, our studies suggest that spironolactone and eplerenone, two clinically approved drugs that have been used for the treatment of human heart failure and essential hypertension [56], may also be effective in the treatment of human aortic aneurysm. Recently, a proof-of-concept randomized controlled clinical trial has been initiated based on our findings and is currently going on in Australia, which aims to test the effect of eplerenone on the progression of AAA (https://clinicaltrials.gov/ct2/show/study/NCT02345590).
\n\n
Subcutaneous implantation of MR agonist DOCA pellets to 10-month-old C57BL/6 male mice can potently induce aortic aneurysm formation and rupture in the presence of high salt. Both DOCA and salt, but not DOCA or salt alone, are required to induce aortic aneurysm formation and rupture in mice.
Infusion of 10-month-old C57BL/6 male mice by subcutaneous implantation of osmotic pumps to release Aldo to a pathological level can also induce aortic aneurysm formation and rupture, suggesting that increased plasma concentration of Aldo may be implicated in the etiology of human aortic aneurysm.
DOCA- or Aldo-salt-induced AAA mimics human AAA with respect to elastin degradation, MMP activation, inflammatory cell infiltration, smooth muscle cell degeneration, and oxidative stress.
Treatment of mice with ACE inhibitor enalapril or an ARB losartan has little effect on DOCA-salt-induced aortic aneurysm, suggesting that DOCA-salt-induced aortic aneurysm is independent of Ang II.
Treatment of mice with MR antagonist spironolactone and eplerenone effectively abolishes or diminishes DOCa- or Aldo-salt-induced aortic aneurysm, suggesting that activation of MR is a prerequisite for DOCA- or Aldo-salt to induce aortic aneurysm, and more importantly, spironolactone and eplerenone, two clinically approved drugs, may also be effective for the treatment of some aortic aneurysm.
There is no correlation between blood pressure and aortic dilation or AAA formation in the DOCA- or Aldo-salt mouse model of aortic aneurysm, suggesting that DOCA-salt induces AAA independent of increased blood pressure.
This work was supported by the US National Institutes of Health (NIH) Grants HL125228 and HL106843 and HL142973 (to M.C.G. and Z.G.), the US Department of Veteran Affairs I01BX002141 (to Z.G.), and the Institutional Development Award (IDeA) from the US National Institute of General Medical Sciences of NIH, under grant number P30 GM127211.
\nThe authors have no potential conflicts of interest with respect to the research, authorship, and publication of this article.
The Internet has irrevocably changed the dynamics of scholarly communication and publishing. Consequently, we find it necessary to indicate, unambiguously, our definition of what we consider to be a published scientific work.
",metaTitle:"Prior Publication Policy",metaDescription:"Prior Publication Policy",metaKeywords:null,canonicalURL:"/page/prior-publication-policy",contentRaw:'[{"type":"htmlEditorComponent","content":"A significant number of working papers, early drafts, and similar work in progress are openly shared online between members of the scientific community. It has become common to announce one’s own research on a personal website or a blog to gather comments and suggestions from other researchers. Such works and online postings are, indeed, published in the sense that they are made publicly available. However, this does not mean that if submitted for publication by IntechOpen they are not original works. We differentiate between reviewed and non-reviewed works when determining whether a work is original and has been published in a scholarly sense or not.
\\n\\nThe significance of Peer Review cannot be overstated when it comes to defining, in our terms, what constitutes a published scientific work. Peer Review is widely considered to be the cornerstone of modern publishing processes and the key value-adding contribution to a scholarly manuscript that a publisher can make.
\\n\\nOther than the issue of originality, research misconduct is another major issue that all publishers have to address. IntechOpen’s Retraction & Correction Policy and various publication ethics guidelines identify both redundant publication and (self)plagiarism to fall within the definition of research misconduct, thus constituting grounds for rejection or the issue of a Retraction if the work has already been published.
\\n\\nIn order to facilitate the tracking of a manuscript’s publishing history and its development from its earliest draft to the manuscript submitted, we encourage Authors to disclose any instances of a manuscript’s prior publication, whether it be through a conference presentation, a newspaper article, a working paper publicly available in a repository or a blog post.
\\n\\nA note to the Academic Editor containing detailed information about a submitted manuscript’s previous public availability is the preferred means of reporting prior publication. This helps us determine if there are any earlier versions of a manuscript that should be disclosed to our readers or if any of those earlier versions should be cited and listed in a manuscript’s references.
\\n\\nSome basic information about the editorial treatment of different varieties of prior publication is laid out below:
\\n\\n1. CONFERENCE PAPERS & PRESENTATIONS
\\n\\nGiven that conference papers and presentations generally pass through some sort of peer or editorial review, we consider them to be published in the accepted scholarly sense, particularly if they are published as a part of conference proceedings.
\\n\\nAll submitted manuscripts originating from a previously published conference paper must contain at least 50% of new original content to be accepted for review and considered for publication.
\\n\\nAuthors are required to report any links their manuscript might have with their earlier conference papers and presentations in a note to the Academic Editor, as well as in the manuscript itself. Additionally, Authors should obtain any necessary permissions from the publisher of their conference paper if copyright transfer occurred during the publishing process. Failure to do so may prevent Us from publishing an otherwise worthy work.
\\n\\n2. NEWSPAPER & MAGAZINE ARTICLES
\\n\\nNewspaper and magazine articles usually do not pass through any extensive peer or editorial review and we do not consider them to be published in the scholarly sense. Articles appearing in newspapers and magazines rarely possess the depth and structure characteristic of scholarly articles.
\\n\\nSubmitted manuscripts stemming from a previous newspaper or magazine article will be accepted for review and considered for publication. However, Authors are strongly advised to report any such publication in an accompanying note to the External Editor.
\\n\\nAs with the conference papers and presentations, Authors should obtain any necessary permissions from the newspaper or magazine that published the work, and indicate that they have done so in a note to the External Editor.
\\n\\n3. GREY LITERATURE
\\n\\nWhite papers, working papers, technical reports and all other forms of papers which fall within the scope of the ‘Luxembourg definition’ of grey literature do not pass through any extensive peer or editorial review and we do not consider them to be published in the scholarly sense.
\\n\\nAlthough such papers are regularly made publicly available via personal websites and institutional repositories, their general purpose is to gather comments and feedback from Authors’ colleagues in order to further improve a manuscript intended for future publication.
\\n\\nWhen submitting their work, Authors are required to disclose the existence of any publicly available earlier drafts in a note to the Academic Editor. In cases where earlier drafts of the submitted version of the manuscript are publicly available, any overlap between the versions will generally not be considered an instance of self-plagiarism.
\\n\\n4. SOCIAL MEDIA, BLOG & MESSAGE BOARD POSTINGS
\\n\\nWe feel that social media, blogs and message boards are generally used with the same intention as grey literature, to formulate ideas for a manuscript and gather early feedback from like-minded researchers in order to improve a particular piece of work before submitting it for publication. Therefore, we do not consider such internet postings to be publication in the scholarly sense.
\\n\\nNevertheless, Authors are encouraged to disclose the existence of any internet postings in which they outline and describe their research or posted passages of their manuscripts in a note to the Academic Editor. Please note that we will not strictly enforce this request in the same way that we would instructions we consider to be part of our conditions of acceptance for publication. We understand that it may be difficult to keep track of all one’s internet postings in which the researcher´s current work might be mentioned.
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\\n"}]'},components:[{type:"htmlEditorComponent",content:'A significant number of working papers, early drafts, and similar work in progress are openly shared online between members of the scientific community. It has become common to announce one’s own research on a personal website or a blog to gather comments and suggestions from other researchers. Such works and online postings are, indeed, published in the sense that they are made publicly available. However, this does not mean that if submitted for publication by IntechOpen they are not original works. We differentiate between reviewed and non-reviewed works when determining whether a work is original and has been published in a scholarly sense or not.
\n\nThe significance of Peer Review cannot be overstated when it comes to defining, in our terms, what constitutes a published scientific work. Peer Review is widely considered to be the cornerstone of modern publishing processes and the key value-adding contribution to a scholarly manuscript that a publisher can make.
\n\nOther than the issue of originality, research misconduct is another major issue that all publishers have to address. IntechOpen’s Retraction & Correction Policy and various publication ethics guidelines identify both redundant publication and (self)plagiarism to fall within the definition of research misconduct, thus constituting grounds for rejection or the issue of a Retraction if the work has already been published.
\n\nIn order to facilitate the tracking of a manuscript’s publishing history and its development from its earliest draft to the manuscript submitted, we encourage Authors to disclose any instances of a manuscript’s prior publication, whether it be through a conference presentation, a newspaper article, a working paper publicly available in a repository or a blog post.
\n\nA note to the Academic Editor containing detailed information about a submitted manuscript’s previous public availability is the preferred means of reporting prior publication. This helps us determine if there are any earlier versions of a manuscript that should be disclosed to our readers or if any of those earlier versions should be cited and listed in a manuscript’s references.
\n\nSome basic information about the editorial treatment of different varieties of prior publication is laid out below:
\n\n1. CONFERENCE PAPERS & PRESENTATIONS
\n\nGiven that conference papers and presentations generally pass through some sort of peer or editorial review, we consider them to be published in the accepted scholarly sense, particularly if they are published as a part of conference proceedings.
\n\nAll submitted manuscripts originating from a previously published conference paper must contain at least 50% of new original content to be accepted for review and considered for publication.
\n\nAuthors are required to report any links their manuscript might have with their earlier conference papers and presentations in a note to the Academic Editor, as well as in the manuscript itself. Additionally, Authors should obtain any necessary permissions from the publisher of their conference paper if copyright transfer occurred during the publishing process. Failure to do so may prevent Us from publishing an otherwise worthy work.
\n\n2. NEWSPAPER & MAGAZINE ARTICLES
\n\nNewspaper and magazine articles usually do not pass through any extensive peer or editorial review and we do not consider them to be published in the scholarly sense. Articles appearing in newspapers and magazines rarely possess the depth and structure characteristic of scholarly articles.
\n\nSubmitted manuscripts stemming from a previous newspaper or magazine article will be accepted for review and considered for publication. However, Authors are strongly advised to report any such publication in an accompanying note to the External Editor.
\n\nAs with the conference papers and presentations, Authors should obtain any necessary permissions from the newspaper or magazine that published the work, and indicate that they have done so in a note to the External Editor.
\n\n3. GREY LITERATURE
\n\nWhite papers, working papers, technical reports and all other forms of papers which fall within the scope of the ‘Luxembourg definition’ of grey literature do not pass through any extensive peer or editorial review and we do not consider them to be published in the scholarly sense.
\n\nAlthough such papers are regularly made publicly available via personal websites and institutional repositories, their general purpose is to gather comments and feedback from Authors’ colleagues in order to further improve a manuscript intended for future publication.
\n\nWhen submitting their work, Authors are required to disclose the existence of any publicly available earlier drafts in a note to the Academic Editor. In cases where earlier drafts of the submitted version of the manuscript are publicly available, any overlap between the versions will generally not be considered an instance of self-plagiarism.
\n\n4. SOCIAL MEDIA, BLOG & MESSAGE BOARD POSTINGS
\n\nWe feel that social media, blogs and message boards are generally used with the same intention as grey literature, to formulate ideas for a manuscript and gather early feedback from like-minded researchers in order to improve a particular piece of work before submitting it for publication. Therefore, we do not consider such internet postings to be publication in the scholarly sense.
\n\nNevertheless, Authors are encouraged to disclose the existence of any internet postings in which they outline and describe their research or posted passages of their manuscripts in a note to the Academic Editor. Please note that we will not strictly enforce this request in the same way that we would instructions we consider to be part of our conditions of acceptance for publication. We understand that it may be difficult to keep track of all one’s internet postings in which the researcher´s current work might be mentioned.
\n\nIn cases where there is any overlap between the Author´s submitted manuscript and related internet postings, we will generally not consider it to be an instance of self-plagiarism. This also holds true for any co-Author as well.
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Usually, SLE symptoms include high fever, hair loss, mouth ulcers, chest pain, swollen lymph nodes, painful and swollen joints, increased fatigue, and appearance of red rash more often on the face. The exact reason of SLE appearance is not really clear. Detection of catalytic Abs (abzymes) was shown to be the earliest indicator of different AI disease development. Some abzymes are cytotoxic and can play a dangerous negative role in the pathogenesis of AI diseases. SLE is characterized by the appearance of abzymes with several different catalytic functions including hydrolysis of peptides and proteins, DNA, RNA, and oligosaccharides. 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