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A Commentary on “The Criminalization of Womenwith Postpartum Psychosis: A Call for Action forJudicial Change”

DOI: 10.31038/AWHC.2024742

   

Postpartum psychosis is a unique and serious mental health challenge. Women are more vulnerable to mental illness surrounding childbirth due to genetic, hormonal and psychosocial factors. The most severe form of postpartum mental illness, postpartum psychosis affects 1 to 2 of 1,000 women or 4,000 or more women in the U.S. each year (Friedman et al.2023; Griffen 2023; Perry et al. 2021; Postpartum Support International: PSI statement on psychosis related tragedies 2004; VanderKruik et al. 2017). These mothers are at an increased risk of suicide (4 to 5 percent), and infanticide, neonaticide and filicide (1 to 4 percent). For 40 to 50 percent of those with postpartum psychosis, this is a first occurrence with no prior history of mental illness (Friedman et al. 2023; Griffen 2023; MGH Center for Women’s Mental Health: Reproductive Psychiatry Resource & Information Center 2018; Perry et al. 2021; Postpartum Support International: PSI statement on psychosis related tragedies 2004). To prevent tragic outcomes, mothers with postpartum psychosis or severe depression with psychotic features require crisis intervention, immediate hospitalization and psychiatric treatment.

The article, “The criminalization of women with postpartum psychosis: a call for action for judicial change,” published in the Archives of Women’s Mental Health, promotes postpartum criminal laws in the U.S. and abroad when criminal culpability is linked to maternal mental illness. Similarly, it is essential to include postpartum psychosis as a diagnostic criteria and classification in the Diagnostic and Statistical Manual of Mental Disorders (DSM) (American Psychiatric Association 2013; Spinelli 2021).

These changes would have enormous influence in trial and sentencing when homicide cases are a consequence of maternal mental illness.

In the U.S., the judicial system has not utilized the advancements and growing body of scientific developments regarding reproductive mental health in the last decades in psychiatry and medicine. This is evident when women with postpartum mental illness are prosecuted. In more than thirty countries worldwide, there is treatment, rehabilitation and mitigation when women commit infanticide as a consequence of psychosis and severe postpartum mental illness in the year following childbirth.

In 1938, the U.K. emphasized treatment and prevention over punishment (Infanticide Act 1938) by adopting laws safeguarding mothers suffering from postpartum depression or psychosis. Currently in the U.K and many other countries, a woman who causes the death of her child within 12 months of delivery is presumed to be mentally ill.

In the U.S., Illinois is the only state that considers maternal mental health as a factor in cases of infanticide. Public Act 100–0574 signed into law in January 2018 and amended in 2019 by PA 101– 411, recognizes postpartum depression and postpartum psychosis as mitigating factors to be considered in trial and sentencing. This law allows women who are currently incarcerated to file for resentencing and allows consideration of postpartum mental illness in past, present and future cases.

It is essential to prioritize awareness and prevention of postpartum mental illness to save the lives of mothers and babies. We must enact comprehensive postpartum laws in every state to address screening and treatment as well as to consider mental health as a mitigating factor when unrecognized and untreated mental illness leads to tragedy and involvement with the criminal justice system. The time is NOW to enact postpartum criminal laws and judicial change throughout the U.S. and abroad.

Building Research Collaboration Across University Departments: A Swot Analysis

DOI: 10.31038/IJNM.2024544

Abstract

Purpose: To challenge the collaborative process in a young research team with evidence on building research collaboration in university departments.

Methods: A structured literature review was combined with a hermeneutic analysis of data from a double survey conducted during a one-week seminar. Eight Norwegian participants provided data through a Strengths, Weaknesses, Opportunities, and Threats (SWOT) template.

Results: The literature review revealed two themes 1) Building a research network, and 2) Networking across university units. A naïve reading of the double survey data showed that participants enjoyed collaborating in research networks. A structured interpretation provided a contextual report on collaborative research processes across university units working to build research collaboration.

Conclusion: Excellent research collaboration emerges through focus, flexibility, trust, persistence, and leadership. A successful research group is dependent on positive engagement between members, the acknowledgment of individual contributions and ideas; and supportive team leadership which is especially facilitated through dialogical leadership.

Keywords

Hermeneutic analysis, Literature review, Leadership, Competence development, Qualitative, SWOT

Introduction

Research collaboration refers to “the working together of researchers to achieve the common goal of producing new scientific knowledge” [1]. In this context, occupational professionals who work in research and development are strategically managed [2] to improve knowledge transfers through transformational leadership [3]. This process is critical, as research collaboration is fundamental to scholarly research success. However, it is often difficult to build a collaborative research team [4]. To clarify the characteristics of such an endeavor, this study reviewed the literature on building collaborative research teams, then compared the results using a collaborative process experienced by a young, publicly funded healthcare research team that spanned multiple university units.

Background

Our initial literature review yielded 443 articles, of which we retained 394 after removing duplicates (Figure 1). Two of the authors then conducted independent screenings, resulting in 23 for potential inclusion. After reviewing the full texts of each, the authors excluded 15 for focusing on collaboration between international teams or separate universities rather than intradepartmental collaboration. Thus, the final sample contained eight articles, with various settings in the United States, Canada, Greece, the United Kingdom, and Ireland. One article introduced a new method for developing strategic research plans [5], while another investigated several issues at a specific research center, including collaboration, multidisciplinary approaches, support, and dissemination [6]. The remaining six articles primarily discussed the experiences of their respective authors and offered relevant reflections [7-12]. No article in our final sample provided a substantial literature review on the process of building a collaborative research team across different units within the same university department. Based on the evidence from these articles, we identified two main themes, including 1) Building a research network and 2) Networking across university units. An additional literature review conducted by two of the authors, in July 2023, did not result in new publications being included, so this topic does not appear to have had recent international research focus.

Figure 1: Flowchart of the literature review process

Building a Research Network

Organizational factors are essential for building research collaboration. To achieve success, three such factors are particularly important: leadership [5-7,9,12], mentorship [5-7,9,12] and cultural background [12]. In this regard, team leaders should promote team learning, serve as role models, support a favorable climate for cooperation, explain rational decisions, and help team members attain self-efficacy [9]. Thus, skilled team leadership and support are critical provisions for a thriving collaborative research team [6]. In a specific example, Best et al. [5] found that the research community was more likely to remain engaged and informed when the team leader frequently sent informative and humorous emails. A collaborative research team provides a platform of interaction for junior and senior researchers, thus facilitating training and mentorship. In the university context, team membership also helps individual researchers avoid isolation, while providing them with more opportunities to complete their own research [6]. According to Davis et al. [12], various challenges may arise when attempting to build a university-based collaborative research team, especially given the existence of different cultural backgrounds, heterogenous responsibilities, various academic practices, cultural factors, and politics. To establish an excellent, research-intensive environment, teams should help all members discuss their methods and struggles in ways that can unite them toward common goals [6].

Networking Across University Units

A researcher’s ability to network across university units depends on their individual values [7-8,10,12], the time available for research [5-7,12] and computer technology [7]. Meanwhile, an excellent collaborative research team requires focus, flexibility, trust, persistence, and leadership, which are developed through combined personal interests and common purposes. Thus, team success requires mutual respect for individual ideas and contributions as well as transparency during each step of the process [7]. Regarding issues faced by individual researchers, four articles mentioned the challenge of finding time to contribute to research teams [5-7,12], while another noted the constraints associated with simultaneous involvement in several international projects [7]. Under such conditions, it is crucial for both the whole group and individual team members to accept varying degrees of participation at different stages [9]. Based on their experiences in the healthcare field, Best et al. [5] explained how successful research collaboration could increase individual involvement in team aims while facilitating knowledge transfers to students and patients. Three articles emphasized that computer technology is essential for maintaining cooperation across university departments [6-7,9]. In one study, Steinke et al. [7] pointed out that personal computer skills are likely to vary among team members, which may create difficulty. Moreover, the strength and quality of the internet connection may pose challenges in cases where team members need to travel or communicate from different time zones during meetings [7]. Overall, these reports suggest that managers must remain aware of how research collaboration is influenced by personal values, contextual management, mentorship, and the time needed to conduct research. At the same time, the interpersonal elements of the research process depend on mutual trust, focus, and flexibility. In addition to the literature review, we conducted a qualitative study [13] based on a double Strengths, Weaknesses, Opportunities, and Threats (SWOT) analysis. Specifically, the SWOT analysis employed a modified standard tool among Norwegian members of a university research team to identify key factors that influenced group performance; these factors were further examined to enhance strengths, optimize opportunities, improve weaknesses, and attenuate threats [14].

Method

Literature Search

We initially gathered evidence on collaborative research team building by searching databases with the assistance of a university librarian, including CINAHL, Medline in PubMed, and PsycInfo. We created search terms using different combinations of the following words: scholarly activities, research, nursing/nursing research, national relation/national cooperation, teamwork, cooperative behavior, and collaboration. For returned articles, we set the following inclusion criteria: peer-reviewed studies with abstracts/full-text articles from 2010 to 2020. These were searched using the Boolean/ phrase technique. We repeated the initial literature search in July 2023 for the time period 2020-2023 and added no new articles to our analysis and findings.

Participants in SWOT Analysis

The SWOT participants included eight members of a university research team established in 2017. Specifically, the team was comprised of four scholars, two lecturers, and two Ph.D. students, with an age range of 35 to 65 years.

Data Collection

We distributed the SWOT template on the first day of a weekly winter summit in 2019, with responses collected shortly after (100% response rate). As the survey took approximately 40 minutes to complete, it is assumed that participants gave their answers spontaneously. We repeated the data collection process on the last day; that is, after the program had ended, but before the evaluation session. Before the distribution of the SWOT template, the participants were informed about the study’s aim, the anonymity of their contribution, and their right to withdraw their written consent anytime. Each participant signed an informed consent form before data collection started. No participant withdrew their participation. In this paper, we have ensured their anonymity by using numerical designations when quoting any statements.

Data Analysis

We analyzed and interpreted the responses from participants with reference to Ricœur’s [13] theory of interpretation. This consisted of a three-level process: a naïve reading, followed by a structural analysis, and concluding with a comprehensive discussion. All authors read and reread the data from the SWOT templates [13], thus identifying a naïve understanding. In the structural analysis, we gathered sections of text (consisting of text portions across the SWOT templates) into larger units of meaning [15]. Finally, we comprehensively discussed the meaning of the text in reference to the selected theory and outcome of the initial literature search.

Results

Naïve Reading

The naïve reading indicated that the participants were responsible, cheerful, and helpful. In general, they enjoyed research collaboration. However, some participants found teamwork burdensome when certain members did not fulfill their obligations. They described new technology as exciting, noting that it streamlined their work. At the same time, good leadership was mentioned as inspiring, while the lack of leadership negatively influenced their ability to work effectively with colleagues. Participants also reported that the process of applying for research funding required too much time when compared to the research outcome, and also affected their ability to attend conferences and meet with the research team.

Structural Analysis

Our structural analysis focused on 311 statements taken from the two surveys (161 and 159 from the first and second rounds, respectively). In both surveys, dominant strengths emerged from statements the participants made about their individual characteristics (35 of 58 and 36 of 50 from the first and second rounds, respectively). On the other hand, weaknesses also emerged. For example, some participants emphasized the challenges of navigating additional tasks (19 of 42 statements from the first round), while others mentioned insufficient knowledge about methodology and scientific factors (14 of 34 statements from the second round). In both rounds, participants highlighted a major opportunity derived from the benefits of being part of a research group (15 of 28 and 19 of 32 from the first and second rounds, respectively). They also identified some threats, including those pertaining to the relationship between their aims and obligations (20 of 33 statements from the first round) and challenges between individuals and their participation in the research team (18 of 34 statements from the second round). Ultimately, we summarized the structural analysis into two themes, including 1) strengths, weaknesses, and threats to building research collaboration and 2) collaborative processes across university units. To keep track of individual statements, we assigned a unique number to each participant (i.e., numbers 1 through 8). Thus, all statements and quotations in the two following subsections are connected to the numbers of relevant participants; to further distinguish between the two rounds of SWOT template completion, we also attached the letter “b” in cases where those statements and quotations were from the second round.

Strengths, Weaknesses, and Threats to Building Research Collaboration

Frequently noted strengths included the ability to work effectively under time pressure (3, 5, 8, 4b, 5b, 6b, 8b) and adopt personal responsibility (2, 4, 7, 8, 2b, 3b, 6b, 8b). One participant stated: “Accountability is an integral part of me as a person” (2). Meanwhile, relevant qualities included courage (2), determination (6, 8, 5b, 8b), curiosity (3, 7, 6b), and commitment (2, 4, 7, 8, 2b, 3b, 4b, 6b). Another strength was the ability to both cope with deadlines and respect the deadlines of others (1, 6, 7). In both surveys, half of the participants said that too many tight deadlines could lead to issues such as pressure (1, 2, 7, 8, 8b) and sleep deprivation (1). Consequently, time pressure was considered a threat to their research activities (1, 1b, 2b, 4, 5, 8, 8b). Some participants wanted their work to be more systematic (2, 7b). For example, one said: “I’m not delivering well under strong pressure; then, I’ll be a little paralyzed” (6b). Only one participant said that she had become better at prioritizing over time (5b). Possessing competence in a specific research method was also considered a strength. In this regard, two participants said that they had extensive research competence (3b, 7b). At the beginning of the seminar, only two participants said that they lacked broad research experience (3, 8); however, four participants mentioned relevant personal weaknesses at the end of the seminar, in terms of either general research competence (3b, 6b, 8b) or a specific lack of expertise linked to quantitative methods (8b) or scientific theories (5b, 8b). Of note, half of the participants identified weaknesses in their own contributions to the research team (4, 5, 6, 8). Some also identified insufficient knowledge about methodology and a lack of fluency in speaking (1) or writing academic English (4, 5, 6, 8). One participant said: “I don’t feel that academic writing comes easy for me” (4). Three participants perceived opportunities regarding new technology, explaining that such provisions could facilitate research collaboration (2, 3, 6, 6b). While one participant said that new technology could enable more efficient work (6b), only one said that technology was an integral part of their field (2).

Collaborative Process Across University Units

As a theme, the collaborative process was focused on interpersonal relationships between participants. For example, they said that they enjoyed collaborating with others (3, 4, 2b, 4b, 8b), and had become more open-minded about each other’s perspectives through teamwork (5). They also perceived themselves as honest (7), loyal (2), and good at listening (5). One participant said that her personal weaknesses were speaking more than listening and losing patience with pessimists (7). Moreover, specific collaboration skills (4, 8, 2b, 6b, 7b, 8b) were considered essential for the development of positive collaborative processes and research networks, particularly including openness to ideas presented by other team members (1, 2, 4, 5b). When describing elements they believed were central to team collaboration, the participants used words and phrases such as encouragement (8), support for progress (8), and the ability to motivate others (6b). Openness to ideas proposed by other people was also a factor that contributed to new perspectives (7b). The participants identified multiple benefits of building research collaboration (1b, 3) and sharing experiences (1b). By jointly collecting data and writing articles, team members developed relationships that helped them enhance their research and produce high-quality publications (8, 8b). They considered research collaboration with both internal and external research partners to be desirable (2b, 8, 7b), noting its contribution to professional development (2, 7b). Other participants said that they received more advice from experienced researchers by building relationships in the research group (3b, 4, 5b), which became an arena for inspiration and support (4b).

Through these relationships, the participants gained access to a “room” where they could be open about their shortcomings and needs (7). There were also threats to building effective collaborative processes, including instances in which others dominated the group (2, 7, 1b, 2b, 4b, 6b, 8b), late (or no) responses from research group members (4, 6, 4b, 7b), the lack of ambition among participants (7, 8), and the absence of mutual trust or respect (5, 4b). Six of the eight participants said that the lack of participation from others was a possible weakness in the collaborative group process (1b, 2b, 3, 3b, 6, 6b, 7, 7b, 8b). For example, one said: “The worst thing when working in a team is when someone says they are going to do something, but they do not do it, or does it badly” (3). Five of the eight participants said that effective team management played a major role in building good collaborative relationships (2, 3, 5, 6, 7, 2b, 8b). As a point of emphasis, leadership was said to motivate and inspire relationships between group members (3, 7). By contrast, individual participants felt discounted when they believed that their leaders did not listen to them (2b, 8b). The ability to establish and maintain local, national, and international networks (7) was considered necessary for group collaboration. Other essential aspects were efforts to include (4) and connect people (2), guide and teach students (7), and teach others how to perform. For example, a phenomenological analysis was mentioned (1). One participant said that it was essential to become involved in research conducted by other members (7b).

Discussion

This study critically reviewed the recent literature on building research collaboration, then compared this evidence with the collaborative process experienced by a publicly funded healthcare research team that spanned multiple university units, as collected via a SWOT analysis. The literature review revealed two main themes:

  1. building a research network and 2) networking across university units. The structured SWOT analysis also identified two themes:
  2. strengths and threats in building research collaboration and
  3. collaborative processes across university units (Table 1). In the following subsections, we incorporate a theoretical perspective to provide a comprehensive discussion that is relevant to our study aim.

Table 1: Themes identified from the literature review and local SWOT analysis

ThemeFrom: Literature reviewFrom: Local SWOT analysis
1Building research networkStrengths and threats to building research teamwork
2Networking across university unitsCollaborative processes across university units
 

Building Research Networks

Evidence from the eight reviewed articles indicated that organizational factors could form barriers to research collaboration in the context of publicly funded specialized healthcare research teams. The SWOT participants mentioned similar issues. For example, their faculty leadership did not understand that tight time schedules influenced their ability to conduct research. As a specific hindrance, time pressure threatened their research activities because it reduced opportunities for sleep. In a previous study, Maslach and Leiter [16] found that burnout was more likely to occur when organizational demands exceeded individual capacities. Although work management abilities vary between researchers, they are still affected by relationships between the researcher, group leader, and faculty leadership [17]. Here, leadership styles matter. Autocratic leaders simply dictate group activities and work tasks [18], thus deciding how much group members should contribute without asking for their input [18]. This diminishes agency within the team, which can be solved through a more democratic leadership style that allows collaborative decision-making [18]. Our data analysis also showed that autocratic management styles could threaten research collaboration, especially when leaders demanded rapid solutions, as this further tightened the time schedule. In the literature review, four articles reported that insufficient financial support was a potential barrier [5,7,9,10]. The same problem was mentioned by three of the SWOT participants. Without funding, it can be much more difficult for researchers to test their ideas [19]. This also creates publication hardship. For example, Malhotra [20] found that most academicians in India faced considerable expenses when attempting to gain journal publication, especially in periodicals with high impact factors. However, our SWOT participants did not mention this barrier, perhaps because public universities in Norway offer publication funding.

Networking Across University Units

The SWOT analysis revealed that personal values, transformational leadership, mentorship, and access to financial resources could influence research network collaboration across university units. Interpersonal elements of the research process were also important, including mutual trust, consistent focus, flexibility, and the ability to find time for group collaboration. Previous research has also shown that collaboration groups can more easily work toward common goals when they are situated in excellent research-intensive environments (6). However, the ability to work effectively under time pressure varied considerably among our SWOT participants. Some expressed feelings of stress when navigating multiple tight deadlines, while others reported improved prioritization ability with increased experience. Mentorship can prevent burnout by helping inexperienced researchers learn how to balance different work tasks [6] and develop new skills [21]. This makes provision of mentorship especially important for young academicians. For nursing scholars, mentorship can encourage positive relational, attitudinal, behavioral, career, and motivational changes [22]. Our SWOT participants mentioned some additional barriers to research collaboration, including limited research experience and difficulties with academic English.

Of note was that four participants emphasized that their weaknesses in both research experience and academic English skills hampered their contributions to the research group, neither of which factors clearly emerged through our literature review. Nevertheless, Dorsey et al. [9] and Cohen et al. [6] said that collaborative group leaders and experienced researchers should jointly serve as role models. Functioning in such a capacity entails facilitating interactions with junior researchers, who can therefore benefit from better training and mentorship for life in academia. Differences in computer skills and internet access can affect availability, thus impacting the degree to which team members can collaborate [7]. As such, researchers should develop and employ technology to improve communication between team members who are geographically distant (Dorsey et al.[9]; Cohen et al. [6]. Moreover, collaborative groups can contact their university’s information/computer technology departments to ensure that necessary computer and web technologies are available [9]. Finally, Steinke et al. [7] recommended a backup plan if videoconferencing fails, including email correspondence or other free internet software applications. In the modern technological environment, numerous tools support collaboration and the development of professional skills in the university setting [23]. In fact, none of our SWOT participants mentioned computer technology as a barrier to the research process or group collaboration, suggesting that they worked in a technology- rich environment. At the same time, personal computers have become increasingly common in research environments.

Motivation is also essential for international collaboration [24]. In this regard, Bass et al. [25] argued that inspirational leadership with a motivational focus on personal behavior could provide meaning while challenging team members to efficiently achieve future goals. According to Anselmann and Mulder [26], transformational leadership can further help leaders identify potential areas of change and encourage necessary adjustments. However, an open-minded view of other perspectives can be interpreted as a wish to view collaborating partners as equals, which may be challenging when team members possess different skills and experiences [27]. According to our findings, mentorship can reduce problems related to time pressure and the lack of academic skills. This is greatly beneficial for inexperienced researchers, who can realize personal development, increased research productivity, and better career opportunities [28]. As a practical example, our SWOT participants expressed the desire to develop skills in writing applications under the guidance of senior members. Based on our experiences in this study, we envision opportunities for research group leaders to employ SWOT templates. Such an approach will clarify team strengths and weaknesses, which can help them customize their mentorship accordingly.

Study Strengths and Limitations

As regards strengths, this study conducted a preliminary comprehensive literature review, which became a benchmark when discussing our analysis and findings. However, there were also some limitations. First, the participants were exclusively invited to participate in the research seminar, and may have therefore been more positive and open toward both their own development and SWOT factors in general. However, the group was also comprised of novice and expert researchers, who addressed a situation that similar research teams may experience, which constitutes a strength. Second, the participants were required to complete the SWOT template within a limited time, which may have elicited superficial answers to the four explored areas. However, they were also able to build on their initial answers during the second survey round, which thus constitutes a strength in data collection, as evident in the enhanced development of their responses.

Conclusion

This study found that supportive leadership and active mentorship between experienced and inexperienced team members could facilitate the research process and increase collaboration in the context of a publicly funded specialized healthcare research team. Of note, supportive leadership is highly essential. Our SWOT participants said that their ability to motivate and support other team members depended on whether the team leader offered the same provisions. Our perception is that supportive and motivated team leaders can serve as positive role models for the entire team, thus creating a group culture that prevents non-participation or late responses from members. In most scientific endeavors, the establishment and maintenance of a collaborative research team are fundamental to success.

Implications for Nursing

  • Supportive leadership is highly essential for nurse researchers to flourish.
  • Nurse managers may not have research experience or necessary insight into the working conditions that support research collaboration
  • It is important to adopt a transformational leadership style in which a dialogical practice can support specialized healthcare research teams in their positions.

Conflicting Interest

None.

Disclosure

The authors report no conflicts of interest in this work.

Funding

We thank Nord University for funding a Winter Summit in 2019 and providing a grant for Mrs. Hansen to act as a research assistant for professor Uhrenfeldt in 2019-20.

Ethical Approval

No ethical approval was required for this research. The study is registered at Nord University (FSH by j.no 24.04.20).

Author Contributions

Study design: LU. Data collection (Literature search); quality appraisal and data analysis: MCH, LU, KI. Data collection (SWOT analysis): MCH supervised by LU. Manuscript preparation MCH, supervision, and critical review by LU, KI. All authors critically reviewed and approved the final manuscript.

Language Editing

This paper is edited by The Golden Pen.

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Effect of Tonisity Px™ Administration on Pre-weaning Mortality Under Field Conditions: A Meta-Analysis

DOI: 10.31038/IJVB.2024822

Abstract

Modern sows are characterized by a high prolificacy as indicated by the increased number of total born piglets, which results in a higher pre-weaning mortality. Tonisity Px (TPx) is an isotonic protein drink administered to piglets from d2 to d8 of life during the suckling period to support intestinal health and development. The aim of the present study was to analyze the effects of TPx administration on the pre-weaning mortality under field conditions in 10 sow farms in Belgium and the Netherlands. Therefore, 10 sow farms with a pre-weaning mortality between 3.3 and 13.8% were enrolled in the study. Supplementation of Tonisity Px was compared with standard Control treatment in the same batch. Number of piglets on d2 and the day before weaning was counted and pre-weaning mortality was calculated. Subsequently, reduction in pre-weaning mortality between Control and Tonisity Px group was calculated at farm level. Based on these results, a scatterplot was designed and a trendline formula for the effect of Tonisity Px was calculated. Applying the trendline formula, an economic calculation was run to find the weaned piglets and end-nursery piglet market price for a positive return-on-investment (ROI = or > 1). Supplementation of Tonisity Px resulted in a significant reduction (P = 0.003) of pre-weaning mortality from 7.38 to 5.41%, which is a 23.40% reduction in pre-weaning mortality. Economic analysis revealed that Tonisity Px supplementation has a positive economic return-on-investment from 6.0% pre-weaning mortality onwards under the current end-nursery 25 kg piglet market prices. In conclusion, supplementation of Tonisity Px from d2-8 in the suckling period results in a 23.4% reduction in pre-weaning mortality with a positive return-on-investment from 6.0% pre-weaning mortality onwards.

Keywords

Tonisity Px, Pre-weaning mortality, Field results, Meta-analysis

Introduction

Modern sows are characterized by a high prolificacy as indicated by the increased number of total born piglets (TBP). Under Danish conditions, the number of TBP has increased from 12.9 in 2000 to 19.6 piglets per litter in 2020 [1-4]. Modern sows may commonly wean 33-35 piglets per sow per year, but herds with the highest productivity now wean more than 40 piglets per sow per year. The increased litter size is, however, accompanied by a clear decrease in the average piglet birth weight [5-9]. Moreover, due to the limited amount of available colostrum, a decrease in colostrum volume consumed per piglets could be observed [5,12]. This may increase the vulnerability of piglets born from modern high prolific sows [8], which in turn decreases livability from farrowing to weaning. In addition, the small intestine of newborn piglets undergoes major developmental changes during the first 10 days of life. Therefore, this critical period has been identified as a ‘window of opportunity’ for potential nutritional interventions to support the development of intestinal structure, including digestion, absorption and growth, and the maturation of the immune system resulting in potential lifelong effects [3,6,10,11]. These factors create an opportunity to provide supplemental nutrition in the first days of the piglets’ lives to increase livability. Tonisity Px™ (TPx) is a highly palatable isotonic protein solution that provides microenteral nutrition to the intestinal cells. Tonisity Px™ is administered as a 3% solution to neonatal piglets for a 7-day period from day 2 after birth (d2) until day 8 after birth (d8). Tonisity Px™ has been demonstrated to improve intestinal morphology with taller villi (+ 8.3%) and a thicker mucosal layer (+ 9.0%) by d9 in suckling piglets [7]. Furthermore, administration of TPx increased the abundance of beneficial bacterial populations, such as Lactobacillus and Bacteriodes species, and reduced potentially pathogenic bacterial populations, such as Escherichia coli and Prevotellaceae, in the pre-weaning period [1,2]. The aim of the present study was to analyze the effects of TPx administration during the suckling period from d2 to d8 on the pre-weaning mortality under field conditions in 10 sow farms in Belgium and the Netherlands.

Materials and Methods

Test Ingredient

The test ingredient consisted of an isotonic protein solution (Tonisity Px™; Tonisity Ltd, Dublin, Ireland), which provides easily-absorbable nutrients (glucose, amino acids, and peptides) and electrolytes that can be used directly by the enterocytes.

Study Population

Ten farrow-to-wean sow farms in Belgium and the Netherlands with an average number of 733 ± 182 productive sows (min. 200, max. 2000) were enrolled in the field study (Table 1).

The sow herds were run according to different batch-management systems (BMS), such as 1-week BMS (n = 2), 3-week BMS (n = 1), 4-week BMS (n = 6), and 5-week BMS (n = 1). The piglets were weaned at an average age of 23 ± 0.82 days of age (min. 21, max. 26). The average pre-weaning mortality was 7.4 ± 1.1% (min. 3.3, max. 13.8). All sow herds were high prolific with 15.5 live born piglets (LBP) and 32.1 piglets weaned per sow per year.

Table 1: Description of the relevant farm characteristics (obtained prior to the study enrollment) of all 10 sow farms included in the trial comparing standard piglet treatment to supplementation of Tonisity Px (Tonisity Ltd, Dublin, Ireland).

Farm ID

# Sows Breed BMS1 Weaning age % PWM2 LBP3 PSY4

Standard program

A

800

DanBred

4

21

7.4

15.67

32.60

Electrolyte solution

B

250

Topigs-Norsvin

1

26 3.9 14.83

31.23

No supplementation

C

400

Topigs-Norsvin

4

21 10.0 14.53

29.22

No supplementation

D

200

DanBred

4

21 4.9 16.41

35.17

No supplementation

E

1,150

DanBred

1

26 13.8 16.00

30.38

Water

F

2,000

Topigs-Norsvin

4

21 3.3 15.52

33.72

No supplementation

G

1,000

DanBred

4

21 5.3 16.61

35.47

No supplementation

H

1,000

DanBred

4

21 5.3 14.82

33.17

No supplementation

I

280

Hypor

3

26 8.6 15.01

29.45

No supplementation

J

250

Topigs-Norsvin

5

28 11.3 15.45

30.12

No supplementation

1BMS: Batch Management System
2PWM: Pre-Weaning Mortality
3LBP: Live Born Piglets
4PSY: Piglets Weaned per Sow per Year

Experimental Design

Litters within the same farrowing batch were allocated to one of 2 groups, Control or supplementation with TPx. The allocation was balanced according to sow parity (gilts vs. older sows) and number of LBP. In 8 out of 10 sow herds, the piglets in the Control group did not receive any supplementation. However, in farm A, the Control group received a supplementation with a standard electrolyte solution, and in farm E, the Control group was supplemented with water during the study period from d2 to d8. Litters in the TPx group were given 250 mL of 3% TPx solution on d2 of age, and from d3-8 of age TPx litters received 500-600 mL of 3% TPx once daily in a clean waterbowl.

Measurements

The number of piglets per litter was counted at d2, the start of TPx administration, and at the day prior to weaning. Pre-weaning mortality was calculated per litter and per batch as the number of dead pigs pre-weaning divided by the number of piglets at d2.

Meta-Analysis

The PWM results obtained in the Control and TPx group were plotted and a trendline was calculated for both the Control and TPx group. Based on the trendline formula of the TPx group, a simulation was performed on potential PWM reduction within the range of 4 to 15% PWM under field conditions. These data were subsequently applied to run an economic calculation for return-on-investment (ROI) of the test product.

Economic Calculations

Return-on-investment calculations were performed based on the number of extra piglets per 1000 piglets enrolled by TPx administration. The cut-off value of weaned and end-nursery piglet market price was calculated for a ROI value of 1.

Therefore, the following formula was used based on the cost of treatment for 1000 piglets enrolled: y = 390 / x, with x = number of extra piglets per 1000 piglets enrolled and y = cut-off value of weaned piglet market price. The cut-off value of end-nursery piglet market price was calculated by adding € 25.00 to the cut-off value of weaned piglet market price.

Statistical Analysis

Data were analyzed using JMP 17.0 and results were significant at P < 0.05.

Results

Pre-weaning Mortality

The results on pre-weaning mortality in both Control and TPx groups, including the overall percentage of reduction in pre-weaning mortality in the 10 farms enrolled in the study are given in Table 2.

Supplementation of TPx resulted in a significant (P = 0.003) reduction in PWM as compared to the Control group. In the Control group, PWM was between 3.3 and 13.8%, whereas in the TPx group PWM was between 2.7 and 8.6%. The overall percentage of reduction varied between 5.1% at minimum and 37.7% at maximum.

Table 2: Pre-weaning mortality and overall reduction in pre-weaning mortality in the farms enrolled in the study evaluating Tonisity Px supplementation from day 2 to 8 versus a standard on-farm program for the neonatal piglets.

Farm ID

PWM control (%) PWM Tonisity Px (%)

% PWM reduction

A

7.4 5.7 23.0
B 3.9 3.7

5.1

C

10.0 5.6 44.5
D 4.9 3.3

32.7

E

13.8 8.6 37.7
F 3.3 2.7

17.2

G

5.3 4.7 10.8
H 5.3 4.0

23,8

I

8.6 8.6 10.9
J 11.3 8.1

28.3

Pre-weaning Mortality According to Breed, Weaning Age and Number of Live Born Piglets

Further detailed analysis of PWM according to breed, weaning age and number of live born piglets in both Control and TPx group are given in Table 3.

For sow breeds, DanBred sows in the Control group had an average PWM of 7.99% in contrast to other breeds (Topigs-Norsvin, Hypor) had a PWM of 6.47%. In the TPx group, both sow breeds had a lower PWM of 5.73% and 4.92% for DanBred and other breeds, respectively.

For weaning age, litters weaned at 21 days of age had a lower PWM (6.03%) as compared to litters weaned at a later age of 26-28 days (9.41%) in the Control group. In the TPx group, PWN decreased to 4.33% and 7.02% for litters weaned at 21 and 26-28 days of age, respectively.

For number of live born piglets, litters with an LBP < 16 piglets had a lower PWM (6.92%) as compared to litters with an LBP ≥ 16 (7.84%) in the Control group. In the TPx group, PWM decreased to 5.00% and 5.82% for litters with an LBP < 16 and an LBP ≥ 16, respectively.

Table 3: Detailed analysis of overall percentage of PWM in control and Tonisity Px supplemented group, considering sow breed (DanBred vs. other breeds), weaning age (early 21 d vs. late 26-28 d), and number of live born piglets (low LBP < 15.5 vs. high LBP ≥ 15.5). Significant differences at P < 0.05 are indicated with a different letter in supercript.

Parameter

PWM control (%) PWM Tonisity Px (%)

% PWM reduction

All farms

7.38 ± 1.11

5.41 ± 0.67

23.40 ± 4.01

Sow breed      
DanBred

7.99 ± 1.52

5.73 ± 0.89

26.04 ± 3.79

Other breeds

6.47 ± 1.71

4.92 ± 1.10

19.44 ± 8.71

Weaning age      
21 d

6.03 ± 1.98

4.33 ± 0.50a

25.33 ± 4.85

26-28 d

9.41 ± 2.12

7.02 ± 1.12b

20.51 ± 7.55

Live born piglets
LBP < 16

6.92 ± 1.84

5.00 ± 1.04

24.27 ± 4.91

LBP ≥ 16

7.84 ± 1.41

5.82 ± 0.91

22.52 ± 6.92

Meta-analysis of Pre-weaning Mortality Data

The scatterplot of percentage PWM in Control and TPx group of the 10 farms enrolled in the study demonstrates the reduction in PWM percentage following supplementation of TPx from d2 to d8 (blue trendline) as compared to the PWM in the Control group (orange line) (Figure 1). The trendline formula obtained based on the results was: y = 0.5581 x + 0.0129 with an R² of 0.8561. This trendline formula will be used in the simulations for the economic calculation of ROI following supplementation of TPx in different scenarios of PWM percentages.

Figure 1: Scatterplot of percentage PWM in Control and Tonisity group of the10 farms enrolled in the study. Orange squares, datapoints of the Control group; blue squares, datapoints of the Tonisity Px supplemented group in relation to their initial percentage of PWM. Trendline shows the correlation between initial percentage of PWM (Control) and the percentage of PWM obtained following supplementation with Tonisity Px.

Economic Calculations

The simulation of PWM reduction following supplementation of TPx based on the trendline formula obtained in relation to the initial on-farm PWM with calculation of the number of extra pigs per litter and per 1000 born piglets based on the PWM reduction is given in Table 4. Simulation with the obtained trendline formula using an initial PWM ranging from 4.0% to 15% resulted in calculated PWM with TPx application from 3.52% to 9.66%, which was equal to a PWM reduction percentage of 11.9 to 35.6%. Based on these numbers, the number of extra piglets per litter and per 1000 piglets born were calculated. At 4.0% initial PWM, a reduction of 11.9% resulted in 0.08 extra piglets per litter and 5 extra piglets per 1000 piglets born.

Applying the formula y = 390/x, we obtained a weaned piglet price at ROI = 1 breakpoint of € 81.66 and of € 106.66 for end-nursery piglet price. Based on current market prices for weaned piglets and end-nursery piglets (20 September 2024; Flemish piglet price), TPx supplementation has an ROI of 1 or more starting from a PWM percentage of at least 6.0% (indicated by the dotted red line on the figure) (Figure 2).

Table 4: Simulation of PWM reduction following supplementation of Tonisity Px based on the trendline in relation to the initial on-farm PWM with calculation of the number of extra pigs per litter and per 1000 born piglets based on the PWM reduction. Calculation of weaned piglet price and piglet price end-nursery (25 kg) in relation to the return-on-investment breakpoint (ROI = 1.0) based on the average cost of Tonisity Px for 1000 supplemented piglets.

Initial PWM

PWM Tonisity Px Simulated PWM reduction Extra piglets/litter Extra piglets per 1000 piglets born Weaned piglet price at ROI = 1 breakpoint (€)

Piglet price end-nursery at ROI = 1 breakpoint (€)

4.0%

3.52% -11.9% 0.08 5  € 81.66  € 106.66
5.0% 4.08% -18.4% 0.15 9  € 42.41

 € 67.41

6.0%

4.64% -22.7% 0.22 14  € 28.65  € 53.65
7.0% 5.20% -25.8% 0.29 18  € 21.63

 € 46.63

8.0%

5.75% -28.1% 0.36 22  € 17.37  € 42.37
9.0% 6.31% -29.9% 0.43 27  € 14.51

 € 39.51

10.0%

6.87% -31.3% 0.50 31  € 12.46  € 37.46
11.0% 7.43% -32.5% 0.57 36  € 10.92

 € 35.92

12.0%

7.99% -33.4% 0.64 40  € 9.72  € 34.72
13.0% 8.55% -34.3% 0.71 45  € 8.75

 € 33.75

14.0%

9.10% -35.0% 0.78 49  € 7.96  € 32.96
15.0% 9.66% -35.6% 0.85 53  € 7.31

 € 32.31

fig 2

Figure 2: Analysis of return-on-investment breakpoint (ROI = 1) related to market price of weaned piglets (6 kg; orange bars) and piglets at end of nursery (25 kg; green bars). The dashed red line is set at the piglet price (25 kg, end of nursery) of € 56.50 which is the current market price for end-nursery 25 kg piglets (20.09.2024; Flemish piglet price).

Discussion

Supplementation of Tonisity Px from d2 to d8 of life resulted in a significant (P = 0.003) reduction of PWM as compared to a simultaneous Control group in 10 farms with difference in management approach under field conditions. This observation is in line with previous studies on the effect of TPx (Carlson et al., 2019). In 8 out of 10 farms, PWM reduction due to TPx was compared to a non-supplemented Control group, whereas in 2 farms a standard supplementation of plain water or electrolyte solution was applied in the Control group. Moreover, the effect of TPx supplementation was evaluated in different sow breeds, such as DanBred (n = 5), Topigs-Norsvin (n =4) and Hypor (n = 1). These breeds are known to be highly prolific which can be confirmed by the high number of LBP (15.01 to 16.41 LBP per litter) and the number of piglets weaned per sow per year (29.22 to 35.47 PSY). As expected, farms with an already low PWM could only observe a mild to moderate further reduction in PWM (5-10%), whereas farms with a rather high PWM had a major reduction in PWM (37-44%).

Detailed analysis on TPx effect related to sow breed, weaning age and number of LBP revealed that in all scenarios, TPx supplementation resulted in a decrease of PWM percentage as compared to the Control. As observed in practice, DanBred sows have a higher PWM as compared to other breeds such as Topigs-Norsvin and Hypor. As expected, TPx supplementation resulted in a higher PWM reduction (26.04%) in DanBred sows as compared to other sow breeds (19.44%). Litters weaned at 26/28 days of age had a more than 50% higher PWM both in the Control and TPx group as compared to litters already weaned at 21 days of age. There is no clear explanation for this observation. Since most of the PWM occurs in the first 3-5 days of life, length of the lactation period should not further impact PWM. The difference in PWM for litters with more or less than 16 LBP was very limited, as was the reduction in PWM following TPx supplementation. Indeed, all 10 selected farms were highly prolific and therefore the range of LBP was quite limited (15.01 to 16.41 LBP per litter).

Analysis of the scatterplot of PWM percentage in the Control and TPx group resulted in a trendline formule of y = 0.5581 x + 0.0129 with 85.61% of the changes in y (PWM supplementing TPx) that could be explained by changes in x (PWM under standard control situation). Application of this trendline formula in a simulation with control PWM ranging from 4.0 to 15.0% resulted in a presumed PWM supplementing TPx ranging from 3.52 to 9.66%. It could be observed that a gradual increase in PWM reduction was present with higher initial PWM. Based on these data both the number of extra piglets per litter and per 1000 piglets born could be calculated (Table 4). These data were used to calculate the minimal piglet market value for a ROI of 1, both in weaned piglets, which are not regularly sold onto the market under our local Belgian and Dutch conditions, and end-nursery piglets sold at 25 kg standard weight. Further comparison of these end-nursery piglet prices to the current piglet market prices (Flemish pig price, 20.09.2024) demonstrated that TPx supplementation can result in a positive ROI (ROI equal to or higher than 1) from 6.0% PWM onwards.

Conclusions

The administration of TPx from d2 to d8 during lactation resulted in a significant reduction of PWM in 10 farms under field conditions in Belgium and the Netherlands. Supplementation of TPx resulted in a positive ROI (= or > 1) when PWM at farm level was equal to or higher than 6.0% under current end-nursery piglet market prices.

Abbreviations

PWM: Pre-Weaning Mortality; TPx: Tonisity Px™; d2: Day 2 After Birth; d8: Day 8 After Birth; TBP: Total Born Piglets; LBP: Live Born Piglets; ROI: Return-On-Investment

References

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  3. Carlson A, Eisenhart M, Bretey K, Buzoianu S, Firth AM (2019) Early-life administration of Tonisity Px™ isotonic protein drink to pigs improves farrowing livability and growth to end-nursery. Proceedings 50th Annual Meeting of American Association of Swine Veterinarians. Orlando, Florida, US. p. 119-123.
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A Modified Palatoplasty for Palate Cleft: A Case Report and Literature Review

DOI: 10.31038/JDMR.2024722

Abstract

Introduction: Cleft palate is a common congenital defect with several described surgical repairs. It is generally an isolated congenital abnormality but can be associated with multiple syndromes. Although there are a multitude of surgical options, many are variations of a previously described repair, and the most successful treatment modality remains a controversy.

Case Summary: The patient, a man, age 25 years old, had a Class III cleft lip and palate Veau classification, underwent a modified palatoplasty and acquired a favourable palatopharyngeal closure function, decreased hemorrhage and swelling.

Conclusion: In this study, we provide a modified palatoplasty for all palate cleft variations, it may benefit for uvula intact, reduce bleeding and swelling.

Keywords

Congenital cleft palate, Modified palatoplasty, Cleft palate repair

Introduction

Cleft of the palate, CP, is one of the most prevalent orofacial birth defects around the world occurring in about 0.33 in every 1000 live births regardless of race, and there was no significant difference between men and women [1,2]. The cleft palate is generally an isolated congenital abnormality but can be associated with other anomalies or multiple syndromes, with or without the presence of lip or alveolar clefting [3]. According to the Veau classification, the cleft palate is divided into four groups depending on the extent of involvement: Group I is limited to the soft palate only; Group II involves the soft and hard palates; Group III includes the soft and hard palate as well as the lip; and Group IV is bilateral complete clefts Figure 1 [4].

fig 1

Figure 1: Veau classification. A class I. defects of the soft palate only; B class II. Defects involving the hard palate and soft palate; C class III. Defects involving the soft palate to the alveolus, usually involving the lip; D class IV. Complete bilateral clefts.

Congenital palate defect is caused by disturbed embryonic development when the palatal shelves fail to fuse during the 6th~12th week of pregnancy [5]. It is multifactorial, influenced by genetic factors recessive or incompletely dominant polygenic inheritance and exogenous factors drugs, folic acid deficiency, viral infections, etc [6]. It has been difficult to point to a single etiologic mechanism responsible for this complex trait, resulting in severe speech, nutrition, and mental and social developmental disorders that significantly reduce patients’ quality of life [7].The diagnosis of cleft palate is not difficult because of its obvious features. Treatment of cleft palate ordinarily requires multiple interventions spanning time from birth to adulthood [8]. However, current treatment for this disease generally demands early surgery and face reconstruction procedures that may be revised during childhood and infancy, causing a great number of patient complaints and economic burdens on health systems that need to be minimized [9]. In this study, we report a modified operation of palatoplasty that provides a choice for these patients to shorten operation time, and reduce intraoperative bleeding, trauma, and postoperative swelling.

Case Report

A 25-year-old Chinese man came with a congenital cleft of lip and palate, he received lip repair in the local hospital when he was 4 years old. However, palatal repair was suspended because of a lack of money. Nowadays, the patient was referred to our hospital for palatal cleft repair which significantly affects pronunciation. The patient denied other abnormal parts of the body and his parents are both normal. After comprehensive examination and imaging evaluation by a professional maxillofacial surgeon, he was diagnosed with CP group III, Class III skeletal pattern malocclusion, microdontia, defect of dentition, and dental cavity Figure 2. At this time, the patient only wanted to receive palatal cleft repair.

fig 2

Figure 2: Clinical information of the patient. A-C the profile photo of the patient; D-F the itro-oral film of the patient; G the computerized tomography imaging of the patient.

A cleft of the soft and hard palate with cleft lip postoperative was seen in our patient. Our modified palatoplasty involves: 1. relaxing incisions along the lateral edge of the hard palate, starting anteriorly near the palatomaxillary suture line, going posteriorly just medial to the alveolar ridge, and ending lateral to the hamulus, approximately to the tuberosity of the alveoli. 2. The incision posterior to the maxillary tuberosities was widened by blunt dissection, the hamulus was identified and the hamulus pterygoideus was broken. 3. The mucosa along the edges of the cleft starting at the palatal alveolar to anteriorly 5 mm of uvula was also incised Figure 3A and 3B. 4. The entire mucoperiosteum was then raised from the oral surface of the hard palate; care was taken to preserve the two neurovascular pedicles, the greater palatine pedicle posteriorly and the incisive pedicle anteriorly. Thus, bi-pedicled mucoperiosteal flaps were created on both sides of the cleft Figure 3C. 5. Three layers, including an oral mucosal layer, muscle layer, and nasal layer were dissected which tends to relieve tension on the repair and reduce the postoperative fistula rate. 6. Firstly, the nasal side of the cleft was closed, using redundant mucoperiosteum from the incision along the cleft edge Figure 3D. 7. Secondly, residual mucosa along the edges of the cleft uvula fissa was incised, and seamed the nasal layer. 8. Next, the muscle layer was closed approximately using an intravelar veloplasty. 9. Lastly, the bi-pedicled oral mucosal flaps were approximated to cover the oral surface of the cleft Figure 3E. A month later, the patient returned to our clinic, the palatine mucosa was integrity and the uvula recovered Figure 3F. The speech quality of this man was also improved and had a good velopharyngeal function (Figure 4).

fig 3

Figure 3: Surgical procedures of the patient and postoperative manifestation. A-E the operative procedues of the patient; F one month postoperative follow-up of the patient.

fig 4

Figure 4: Traditional surgery and modified operation. (A) a-c the traditional surgery of the palatoplasty; (B) d-g the modified surgery of the palatoplasty.

Discussion

The goals of palatoplasty are to acquire complete and intact closure of the palate and restoration of the velopharyngeal sphincter. Besides, reducing hemorrhage, avoiding palatal fistula, and decreasing postoperative swelling also should include care. After decades, there are many techniques for cleft palate repair and each has its advantages. To repair the soft palate, Intravelar Veloplasty, and Furlow Double-Opposing Z-Plasty are widely applied [10,11]. To repair the hard palate, the Von Langenbeck Palate palatoplasty, Veau-Wardill-Kilner palatoplasty, Two-Flap palatoplasty, and Vomer Flap techniques are employed around the world [11-14]. Nonetheless, the most successful treatment modality remains controversial. According to Veau classifications, surgeons are recommended to choose appropriate surgical techniques for the patients after evaluating the results as they see fit to provide the best functional outcomes for their patients [15]. However, all the techniques above mentioned may cause uvula injury due to incision without suture immediately and improve the occurrence of velopharyngeal incompetence. The rate of oronasal fistula following primary cleft palate surgery was about 3.8~6.1% [16]. In this study, we raise a modified palatoplasty: delayed incision of the uvula and earlier suture of the nasal layer. It is beneficial for uvula integrity, reducing uvula tears, and decreasing hemorrhage and swelling.

Fusion of particular orofacial structures during early gestation is required for proper development of the upper lip and jaw. Failure of this process leads to an orofacial cleft, which manifests as a gap in the tissue of the upper lip, the palate, or both [17]. Treatment of cleft lip and palate ordinarily requires multiple interventions spanning the time of birth to adulthood [18]. This process includes a multidisciplinary evaluation, involving pediatric dentists, oral and maxillofacial surgeons, orthodontists, prosthodontists, speech therapists, and psychological consultation teachers. In this study, our patient only underwent the necessary surgery because of financial difficulty, we sincerely advise he achieve serial therapy shortly.

Conclusion

We preferred the modified palatoplasty for all cleft variations. The use of modified palatoplasty in the cleft palate seems to contribute to a reduction of hemorrhage, uvula varies, and postoperative swelling.

Acknowledgement

Cailing Jiang contributed to the conception, design, analysis and interpretation of data, and drafting of this article. Chong Jiang, Zijun Guo and Haiyou Wang contributed to data collection and analysis. Sui Jiang contributed to the conception and design, critical review of the article, and final approval.

Declaration

The authors declare no conflict of interest.

Funding

The preparation of this manuscript was not supported by any funding or grants.

Ethics Approval

Ethics approval was received from the ethics committee of Guangdong Provincial People’s Hospital (KY2023-827-03).

References

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Prognostic Modeling of Gynecological Complications in Tamoxifen Therapy

DOI: 10.31038/CST.2024934

Abstract

The risk of endometrial hyperplasia (EH) increases during adjuvant therapy of breast cancer (BC) with tamoxifen. Currently, the problem of endometrial hyperplasia and endometrial cancer due to long-term use of tamoxifen is relevant, since the incidence of endometrial pathology has a direct correlation with the duration of use of tamoxifen. In order to improve early detection of endometrial cancer and avoid unnecessary invasive procedures, surveillance by a gynecologist should be tailored to the risk of endometrial cancer in women who have had breast cancer.

We developed a prognostic model to determine the likelihood of developing a composite endpoint (polyp, endometrial hyperplasia, abnormal uterine bleeding) depending on anamnestic and genetic risk factors. A comprehensive association analysis using mathematical modeling allowed us to build a predictive model of the risk of developing such adverse events as endometrial hyperplasia, endometrial polyp and abnormal uterine bleeding. This prognostic model has demonstrated high diagnostic efficiency, which allows its implementation in the clinical practice of gynecologists.

Keywords

Tamoxifen, Endometrial hyperplasia, Endometrial polyp, Abnormal uterine bleeding, Predictive modeling

Introduction

Breast cancer (breast cancer) is hormone-dependent in 60-70% of cases. Due to the fact that estrogens enhance cell proliferation of hormone-dependent breast tumors, endocrine therapy with tamoxifen (TAM) or aromatase inhibitors (IA) is an important stage in the treatment of such patients [1,2]. According to the literature, taking tamoxifen for 5 years reduces the risk of breast cancer recurrence by 39% [3]. The use of tamoxifen may be limited due to the adverse drug reactions (ADR). It is known that the adjuvant breast cancer therapy with tamoxifen increases the risk of endometrial hyperplasia (EH) because tamoxifen acts as an antagonist of estrogen receptors on breast tissue and as an agonist on the endometrium [4]. According to Neven P. and Vernaeve H. 50% of women who received long-term TAM treatment experienced any adverse effects on the endometrium [5]. Currently, the problem of hyperplastic processes and endometrial cancer is especially relevant during long-term tamoxifen administration, since the frequency of endometrial pathology has a direct correlation with the duration of TAM administration [6]. The supervision of a gynecologist should be adapted to the risk of endometrial cancer in women who have undergone breast cancer in order to improve the early detection of endometrial cancer and avoid unnecessary invasive procedures.

The Purpose of the Study

To determine the prognosis of tamoxifen ADR including endometrial hyperplastic processes, endometrial polyps and abnormal uterine bleeding, based on mathematical modeling in conjunction with the carrier of polymorphic variants of genes of cytochrome P450 enzyme and drug transporter proteins.

Hypothesis

Women with breast cancer taking endocrinotherapy have predictors of the development of local gynecological symptoms that require additional attention from an obstetrician-gynecologist. These predictors are not only clinical factors, but also genetic determinants responsible for the metabolism and transport of tamoxifen.

Materials and Methods

A prospective clinical and epidemiological and simultaneous pharmacogenetic study involved 120 patients with luminal breast cancer of stage I-III who were on adjuvant TAM therapy. Anamnestic, clinical, laboratory and instrumental data obtained from a survey of patients and extracts from medical records (results of the last hospitalization) were analyzed. The collection of biological material for genetic research (double buccal scraping) was carried out simultaneously in the Clinic named after Professor Y.N. Kasatkin in 2018-2019 years in Moscow. Informed voluntary consent was signed by all participants of the study before taking the genetic material. Polymorphic variants of the CYP2D6, CYP2C, and CYP3A genes were studied: CYP2D6*4, CYP3A5*3, CYP2C9*2, CYP2C9*3, CYP2C19*2, CYP2C19*3, as well as the polymorphic marker of the ABCB1 gene (C3435T) encoding the P-glycoprotein. Polymorphic gene variants were determined by the polymerase chain reaction method in real time at the Russian Medical Academy of Continuing Professional Education (RMACPE) of the Ministry of Health of the Russian Federation. The study was approved by the Ethics Committee of the RMACPE of the Ministry of Health of the Russian Federation (Protocol No. 1 dated 17.01.2017) and was conducted in accordance with the legislation of the Russian Federation and international regulatory documents. The program SPSS Statistics 26.0 (USA) was used for statistical processing of the results. The normality of the distribution was checked by the Kolmogorov–Smirnov method with the Lilliefors correction. The intergroup differences were assessed using the Student’s t-test and the Mann-Whitney U–test. Comparative analysis was used using either Pearson’s χ2 or Fisher’s exact test. To form mathematical predictive models, the method of constructing a logistic function using binary logistic regression with step-by-step selection of factors and, if necessary, additional construction of ROC curves followed by ROC analysis was used.

Results and Discussion

Tamoxifen’s ADR structure contains both systemic and local ADR, and systemic ones dominate over local ones with the highest representation of tides as vasa-active symptoms from the autonomic nervous system (67.3%). Local gynecological symptoms are represented by endometrial hyperplasia (GE), abnormal uterine bleeding (AMC) and endometrial polyp (PE) are much less common (20.2%; 12.5% and 12.5%, respectively), but in total they amount to 45.2%, which, taking into account a low subjective assessment (frequent asymptomatic course, absence of complaints), requires close attention from obstetricians and gynecologists. The high percentage of local gynecological symptoms we obtained turned out to be close to the data of Neven P and Vernaeve H., indicating 50% of any adverse effects on the endometrium in women taking TAM [5]. Taking into account the high total frequency of occurrence of local gynecological symptoms (%EH+%AUB+%PE=45.2%) and the presence of reliable associative links between local and systemic ADR, as well as genetic and non-genetic parameters obtained earlier [7-9], we developed a prognostic model to determine the development of a combined endpoint (polyp, endometrial hyperplasia, abnormal uterine bleeding). The resulting model included 9 predictors, taking into account the determination coefficient of the Neidlekerk, included 40% of the factors determining the development of the combined endpoint, and was reliable (p<0.001). The observed dependence is described by the equation:

for

where p is the probability of developing a combined endpoint (polyp, endometrial hyperplasia, AUB) (in fractions of one); XWeight loss – Weight loss during TAM therapy, kg; XMenopause – menopause (0 – no, 1 – yes) ; XAge– age, years ; XAsthenia – asthenia (0 – no, 1- yes); Xnumber of births – number of births; Xnumber of pregnancies – number of pregnancies; XABCB1 3435_TT – TT genotype of polymorphic variant ABCB1 3435 (0 – no, 1 – yes); XCYP2D6_4_GG– GG genotype of polymorphic variant CYP2D6*4 (0 – no, 1 – yes); XCYP3A5_GG– GG genotype of polymorphic variant CYP3A5 (0 – no, 1 – yes).

Based on the values of the regression coefficients, factors such as weight loss, the presence of asthenia, an increase in the number of births, the presence of the TT genotype of the polymorphic variant ABCB1 3435, the presence of the genotype GG of the polymorphic variant CYP2D6*4, GG of the polymorphic variant CYP3A5 have a direct relationship with the probability of developing a combined endpoint. While the presence of menopause, an increase in the number of pregnancies in the anamnesis and an increase in age reduce the likelihood of developing a combined endpoint. Table 1 shows the parameters of the relationship of each of the predictors of the model, including both clinical and anamnestic data and genetic factors responsible for metabolism and transport of TAM, with the chances of developing a combined endpoint of local gynecological symptoms.

Table 1: Evaluation of the relationship between the predictors of the model and the chances of developing a combined endpoint of local gynecological symptoms.

Predictor

COR (95% Cl) p AOR (95% Cl)

p

Weight loss

2.4 (0.93-6.13)

0.07 2.94 (0.98-8.8)

0.054

Menopause

0.55 (0.23-1.3)

0.160 0.5 (0.14-1.8)

0.302

Age

0.96 (0.9-1.01)

0.113 0.97 (0.89-1.05)

0.393

Asthenia

3.2 (1.3-7.3)

0.009* 3.78 (1.3-11)

0.014*

Number of births

1.8 (1.02-3.1)

0.041* 2.94 (1.13-7.66)

0.027*

Number of pregnancies

0.97 (0.76-1.2)

0.804 0.689 (0.42-1.12)

0.132

ТТ ABCB1 3435

2.77 (1.16-6.6)

0.021* 1.85 (0.64-5.3)

0.255

GG CYP2D6*4

2.6 (1.07-6.4)

0.035* 5 (1.6-15.6)

0.006*

GG CYP3A5

1.15 (0.49-2.7)

0.746 1.9 (0.66-5.59)

0.227

*The association with the predictor is statistically significant.

To confirm the results obtained, the most optimal value of the predictive function P was additionally determined using ROC analysis and a ROC curve was constructed (Figure 1).

Figure 1 is a ROC curve characterizing the dependence of the forecast of the combined endpoint on the value of the logistic function P. The area under the ROC curve was 0.827±0.043 (95% CI: 0.743-0.911). The value of the logistic function P at the cut-off point was 0.273. Patients with P values equal to 0.273 or higher were predicted to have a high risk of developing EH, endometrial polyp and AUB, and with P <0.273, a low risk. The sensitivity of the model at the selected cut-off point value was 82.4% (28 correct predictions out of 34 cases of combined endpoint), specificity was 72.9% (51 correct predictions out of 70 cases of absence of combined endpoint development). The overall diagnostic efficiency is 76%. According to the results, independent predictors of the development of the combined endpoint are the presence of asthenia, the number of births, the presence of the genotype GG polymorphic variant CYP2D6*4, the genotype TT polymorphic variant ABCB1 3435 and GG polymorphic variant CYP3A5.

fig 1

Figure 1: A ROC curve characterizing the dependence of the forecast of the combined endpoint on the value of the logistic function P.

Conclusion

The conducted complex associative analysis allowed us, using mathematical modeling, to construct a prognostic model of the risk of developing combined local gynecological symptoms, such as endometrial hyperplasia, endometrial polyp and AUB. These local gynecological symptoms are a natural manifestation of the pharmacodynamic effects of tamoxifen, as an agonist of estrogen receptors on the endometrium in women with breast cancer. The result obtained determines the need for increased alertness of obstetricians and gynecologists regarding endometrial hyperplastic processes in women with breast cancer undergoing tamoxifen endocrinotherapy and, accordingly, the development of measures for their prevention. In addition, this predictive model has demonstrated high diagnostic effectiveness, which allows it to be implemented in the clinical practice of an obstetrician-gynecologist, including through medical decision support programs.

References

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  9. Golubenko EO, Savel’yeva MI, Sozayeva ZHA, et al. (2022) Klinicheskoe znacheniie geneticheskogo polimorfizma fermentov metabolizma i transporterov tamoksifena pri rake molochnoi zhelezy: rezul’taty populiatsionnogo kogortnogo issledovaniia. Farmateka.

Endotoxin Challenge: Optimizing Experimental Models for Antipyretic Drug Development

DOI: 10.31038/IDT.2024521

Abstract

The endotoxin challenge serves as a valuable experimental model for antipyretic drug development, providing insights into systemic inflammatory responses and the efficacy of novel treatments. By inducing predictable physiological reactions, it mirrors the inflammatory profile of sepsis, allowing for investigations into the pathophysiology of fever and inflammation, as well as the evaluation of antipyretic therapies. This review examines the varied applications of endotoxin administration, particularly intravenous bolus dosing, and highlights the potential of combined bolus-infusion paradigms to sustain systemic responses and better align with therapeutic pharmacokinetics and pharmacodynamics. Furthermore, mathematical modeling and simulation techniques offer innovative approaches to optimizing experimental designs and data analysis. Despite its broad application, there remains a need for models that elicit a safe, sustained, and measurable systemic response, allowing for the thorough evaluation of antipyretics. Developing such models is crucial to enhancing the efficiency of drug development and improving clinical management of pyrexia across various settings.

Keywords

Endotoxin challenge, Antipyretic drug development, Systemic inflammation, Experimental medicine models, Pharmacokinetic – pharmacodynamic optimization

Introduction

The endotoxin challenge is an experimental medicine tool that has been used for over a century across a number of investigational efforts and in some settings even as a therapeutic. Kamisoglu et al. have shown that the plasma metabolomic profile following an endotoxin challenge is concordant with that from sepsis survivors, affirming the validity of the endotoxin challenge as a viable model to recapitulate homeostatic responses to inflammatory and pyrogenic challenges [1]. Uses of the endotoxin challenge in clinical investigation include attempts to characterize pathophysiology of pyrexia and inflammatory and anti-inflammatory pathways, describe time-course of clinical and molecular events as well as assessment of the degree of benefit of novel anti-pyretic and anti-inflammatory therapies. The doses and routes of endotoxin administration vary depending on the scientific question at hand. In turn, there are some challenges to design of an endotoxin challenge tailored to address specific questions, particularly in the context of definition of quantitative estimates of therapeutic benefit.

The innate risk of administering endotoxin especially to healthy volunteers is partly balanced by the somewhat predictable nature and time-course of the systemic response it elicits [2]. To further deliver on the twin need to ensure safe use of endotoxin for investigational purposes as well as to guide drug development, the NIH and FDA jointly oversaw an effort to develop a “national biological reference standard to be made available to pharmaceutical manufacturers and qualified biomedical investigators as an aid to standardization of bioassays and research with endotoxin”. This standard developed using endotoxin from Escherichia coli O: 113: H10: K negative has also been adopted by the WHO as its reference for endotoxin assays [2].

Pyrexia or fever is defined as a state in which the central thermoregulatory set point is increased, primarily via disinhibition of thermogenesis, and pyrogens are agents that induce pyrexia [3,4]. In general, exogenous pyrogens such as bacterial and viral antigens or exotoxins activate the Toll-like receptor (TLR) pathway, that triggers a signal transduction cascade leading to increased generation of endogenous pyrogens such as prostaglandins, culminating in the pathophysiologic events that constitute the pyrexia response [3,5]. The purported teleologic role of pyrexia in the setting of disease, particularly infectious disease, is an adaptive response to inhibit microorganism proliferation and amplify endogenous immunological response [6]. However, this is accompanied by increases in metabolic demand as well as undue stress on the cardiovascular, respiratory and other systems that are less than welcome [6]. Timely and prudent use of antipyretics tailored to rein in the unwarranted systemic effects of pyrexia without impacting its benefits as an adaptive response relies heavily on clinical judgment [6]. However, there is limited standardization to guide the use of antipyretics, particularly so from a contextual perspective [6]. It is also important to note that antipyretics themselves may carry side-effects and there is a paucity of data and limited interest in developing newer antipyretics [6]. Given that fever is one of the commonest clinical symptoms and signs, there is an urgent need to develop newer antipyretics with optimized time-action and benefit-risk profiles to enable fit-for-purpose use based on the setting in which fever occurs.

The sterile inflammatory state induced by an endotoxin challenge makes it especially valuable to characterize pyrexia and evaluate antipyretics. Although endotoxin may be administered by various routes, in the context of pyrexia, given the need to elicit a measurable systemic response, intravenous (IV) administration remains the preferred route. Systemic responses have been reported in settings of high and low dose administration. Following an IV endotoxin (E. coli O: 113) bolus in the range of 2 to 4 ng/kg body weight in healthy volunteers, Suffredini et al. and others reported a monophasic febrile response with onset 1 to 2 hours after administration, peaking at 3 to 4 hours to reach a maximal rise in body temperature over baseline with spontaneous resolution of the febrile response between 8 and 12 hours after the bolus administration [2,7]. In a placebo-controlled study, Pernerstorfer et al. were able to successfully demonstrate superiority of the antipyretic effects of acetaminophen over aspirin using a 4ng/ kg IV endotoxin bolus challenge [8]. Dose-limiting toxicities at doses greater than 4ng/kg have generally precluded their routine use. The brisk and robust febrile response following IV endotoxin at the 2-4ng/ kg dose is preceded by flu-like symptoms (chills, rigors, malaise, nausea and headache) starting one hour after administration and resolving spontaneously within 3 to 5 hours [2]. Other systemic changes accompanying the febrile response include a drop in blood pressure and increases in heart and respiratory rates with alterations in various blood- based measures including leukocytosis, cytokines and hormones [7]. It is important to note that while the rapid-onset responses are a direct effect of endotoxin, some of the other observed responses are a result of triggering of the inflammatory and cytokine cascade rather than a direct effect of the endotoxin itself, whose half-life when administered as an IV bolus is short lived. The IV bolus endotoxin challenge therefore allows for insights into the inflammatory event cascade and its mediators and at the same time also sheds light on whether a novel therapeutic has antipyretic or anti-inflammatory benefits. However, its ability to inform on the magnitude and duration of such benefit is particularly dependent on the synchrony between the temporal profile of action of the investigational agent and that of the responses to the endotoxin challenge. This is especially true for a novel antipyretic.

An alternate option would be administration of endotoxin as a continuous IV infusion to attempt to synchronize temporal profiles across the endotoxin challenge and investigational agent. However, the pharmacokinetics of a continuous infusion may limit the ability to achieve a peak challenge that is sufficiently robust to trigger a measurable systemic response. And indeed, Andreason et al. [9] have reported that lower doses of endotoxin in the range of 0.06-0.08 ng/kg, achieved via IV bolus or continuous IV infusion elicit what appears to be a submaximal inflammatory response with no detectable changes in vital signs including body temperature.

There is a need for development of a reliable yet feasible endotoxin challenge model that enables elicitation of a peak systemic response that is sustained over several hours, while not exceeding the total amount of endotoxin that can be safely administered and in a paradigm that is flexible enough to investigate a range of PK-PD profiles across agents and escalating doses. This need is particularly urgent in the context of novel antipyretics where onset and offset of effects and synchrony with the febrile response are critical parameters of success. One potential option would be a combined bolus-infusion approach, where a bolus administration of endotoxin is followed by a continuous infusion such that the total dose of endotoxin does not lead to dose-limiting toxicities. Van Lier et al. have proposed that a continuous infusion of endotoxin may better reflect the prolonged systemic responses including fever observed in the setting of infection and inflammation in man [10]. In a model of endotoxin challenge with a bolus dose of 1mg/kg followed by an infusion at 0.5ng/kg/hour for 3 hours, Jansen et al. were able to successfully demonstrate the beneficial anti-inflammatory effects of Cytosorb hemoperfusion in a group of healthy volunteers [11]. In a study with endotoxin challenges on two separate occasions, using a paradigm that combined a bolus administration of endotoxin at 1ng/kg followed by an infusion at 1ng/ kg/hour for 3 hours in a group of healthy volunteers, Leijte et al. were able to show endotoxin tolerance and reversal, confirming that the total dose administered in such a paradigm is safe and that the model is able to successfully detect treatment differences [12]. In a head-to- head comparison of a bolus only paradigm (2ng/kg) versus a combined bolus-infusion paradigm (1ng/kg bolus followed by a 3-hour infusion at 1ng/kg/hr) in the context of experimental endotoxemia, Kiers et al. found that subjects attained comparable peak levels and exhibited more prolonged and sustained duration of symptoms including fever during the endotoxin challenge model of a bolus followed by a continuous infusion vs bolus only method [13]. Kiers et al. also found that subjects attained higher peak cytokine levels that were sustained for longer durations following the combined bolus-infusion paradigm vs the bolus only paradigm [13]. Hence it is possible that a carefully developed combined bolus-infusion paradigm may permit administration of higher total amounts of endotoxin that could lead to a temperature response with slower onset but more sustained duration. Yet another novel approach would be to use modeling and simulation tools either as standalone approaches or in combination with in vivo efforts to optimize experimental paradigms and data analyses strategies. Using mathematical modeling of data collated across multiple endotoxin challenge experiments and investigator groups, Windoloski et al. showed that a continuous infusion elicits a stronger response that lasts longer than a bolus only paradigm, while potentially allowing for delivery of maximal total doses of endotoxin that can be safely administered [14]. Liu et al. have used mathematical modeling to describe and predict the dynamics of responses to endotoxin challenges with intent to inform on novel clinical trial design, particularly in the context of drug development [15].

Taken together, a combined bolus-infusion paradigm coupled with a mathematical modeling and simulation strategy may be the optimal solution to provide an experimental model of endotoxin challenge that is safe but provides a measurable response while allowing for synchronization with the PK-PD properties of a novel therapeutic. Although there is evidence that speaks to each component of the above approach, data to confirm validity of the approach and develop an integrated strategy are currently lacking. Therefore, there is an urgent need for targeted experimentation to address the above gaps and provide a consolidated strategy that integrates human in vivo experimentation and modeling and simulation tools that delivers on a fit-fit-for-purpose endotoxin challenge design.

References

  1. Kamisoglu K, Haimovich B, Calvano SE, Coyle SM, Corbett SA, et (2015) Human metabolic response to systemic inflammation: Assessment of the concordance between experimental endotoxemia and clinical cases of sepsis/SIRS. Critical Care 19. [crossref]
  2. Suffredini AF, Noveck RJ (2014) Human endotoxin administration as an experimental model in drug Clinical Pharmacology & Therapeutics 96: 418-422. [crossref]
  3. Bartfai T, Conti B (2010) The Scientific World JOURNAL 10: 490-503.
  4. Ogoina D (2011) Fever, fever patterns and diseases called ‘fever’ – A Journal of Infection and Public Health 4: 108-124. [crossref]
  5. Blatteis CM, Sehic E, Li S (2000) Pyrogen sensing and signaling: Old Views and new Clinical Infectious Diseases 31. [crossref]
  6. Mehmood KT, Al-Baldawi S, Zúñiga Salazar G, Zúñiga D, Balasubramanian S (2024) Antipyretic use in noncritically ill patients with fever: A Cureus.
  7. Godin PJ, Fleisher LA, Eidsath A, Vandivier RW, Preas HL, et (1996) Experimental human endotoxemia increases cardiac regularity. Critical Care Medicine 24: 1117- 1124. [crossref]
  8. Pernerstorfer T, Schmid R, Bieglmayer C, Eichler H, Kapiotis S, et al. (1999) Acetaminophen has greater antipyretic efficacy than aspirin in endotoxemia: A randomized, double-blind, placebo-controlled trial. Clinical Pharmacology & Therapeutics 66: 51-57. [crossref]
  9. Andreasen A, Krabbe K, Krogh-Madsen R, Taudorf S, Pedersen B, et al. (2008) Human Endotoxemia as a model of systemic inflammation. Current Medicinal Chemistry 15: 1697-1705. [crossref]
  10. van Lier D, Geven C, Leijte GP, Pickkers P (2019) Experimental human Endotoxemia as a model of systemic inflammation. Biochimie 159: 99-106. [crossref]
  11. Jansen A, Waalders NJ, van Lier DP, Kox M, Pickkers P (2023) CytoSorb hemoperfusion markedly attenuates circulating cytokine concentrations during systemic inflammation in humans in vivo. Critical Care 27.
  12. Leijte GP, Kiers D, van der Heijden W, Jansen A, Gerretsen J, et (2019) Treatment with acetylsalicylic acid reverses endotoxin tolerance in humans in vivo: A randomized placebo-controlled study. Crit Care Med 47: 508-516. [crossref]
  13. Kiers D, Leijte GP, Gerretsen J, Zwaag J, Kox M, et (2019) Comparison of different lots of endotoxin and evaluation of in vivo potency over time in the experimental human ENDOTOXEMIA model. Innate Immunity 25: 34-45. [crossref]
  14. Windoloski KA, Janum S, Berg RM, Olufsen MS (2024) Characterization of differences in immune responses during bolus and continuous infusion endotoxin challenges using mathematical modelling. Experimental Physiology 109: 689-710. [crossref]
  15. Liu F, Aulin LB, Guo T, Krekels EH, Moerland M, et al. (2022) Modelling inflammatory biomarker dynamics in a human lipopolysaccharide (LPS) challenge study using delay differential equations. British Journal of Clinical Pharmacology 88: 5420-5427. [crossref]

Growth Rates, Feed Efficiency, and Condition Indices of Clarias gariepinus in Biofloc System Using Treated and Untreated Rice Bran as Carbon Sources

DOI: 10.31038/AFS.2024612

Abstract

The biofloc system uses the presence of microorganisms in the culture system to generate flocs from nitrogen waste, thus permitting continued water use. Factors like carbon source, carbon-to-nitrogen ratio, and stocking density affect the quality and density of microorganisms and the productivity of the system. This study aims to determine the growth, feed conversion ratio (FCR), and condition indices of catfish reared in a biofloc system using rice bran (RBB), fermented rice bran (FRB), and hydrolyzed fermented rice bran (HFRB) as carbon sources. Fingerling catfish with an initial mean weight of 11.15 ± 1.60 g were stocked in outdoor 200-liter plastic tanks in a randomized design with the three treatments in two replications. A biomass (g) to volume (l) ratio of 1:2 was maintained throughout the experiment. The carbon-nitrogen content was adjusted to 5:1 C-N in the system. The results showed that the water quality parameters of all the treatments were within the range recommended for aquaculture. The HFRB treatment showed significantly higher floc (P<0.05) compared with RBB and FRB. The weight of the catfish at the end of the 8-week rearing trials showed the catfish culture using RBB (80.26 ± 3.20 g), FRB (81.70 ± 2.5 g), and HFRB (85.50 ± 2.55 g) were significantly different (P<0.05). A similar trend was observed in the feed conversion ratio. The condition indices of catfish were also higher in FRB treatment. The FCR value and protein efficiency ratio were not significantly different (P>0.05) between RBB and HFRB treatments. However, the percentage survival was significantly lower in the HFRB treatment (P < 0.05) compared with the FRB and RBB treatments. While fermentation of rice bran has gained much consideration, this study demonstrated that acid-hydrolyzed fermentation of rice bran could boost its performance as a biofloc carbon source.

Keywords

Fermented rice bran, Acid-hydrolyzed rice bran, Biofloc, Carbon sources

Introduction

The African catfish, Clarias gariepinus, is valued as the most economically important fish cultured in Africa. This species is reputed for its desired aquaculture traits, including high fecundity, fast growth, hardiness, and market attractiveness. It is one of the most researched culturable fish in Nigeria. Modern culture techniques such as aquaponics and biofloc systems have also adopted catfish as one of the experimental species for the viability of the systems. Biofloc aquculture systems transform fish waste into microorganism biomass through the addition of carbon sources. The type of carbon source significantly influenced the water quality of the system. The floc serves as additional food for the fish, leading to faster growth and higher production of fish compared to traditional methods. Microorganism- enriched floc confers immunological enhancement to fish, thereby improving fish health. Many ingredients, such as grains, sucrose, sugarcane byproducts, tapioca, rice, wheat bran, etc., have been used as carbon supplements in biofloc systems. Ligno-cellulose materials like bran showed limited success in biofloc systems due to the to the slow release of carbon, but tends to have higher microbial diversity and immune-boosting potential for cultured organisms. Researcher efforts to improve carbon release and utilization of lignified and cellulose materials in biofloc systems remain pertinent. This work compared the growth performance and condition indices of catfish in biofloc systems where untreated, fermented, and hydrolyzed fermented rice bran were used as carbon sources. In ethanol production, acid hydrolysis of rice bran resulted in the conversion of its starch and cellulose component into reducing sugar, and fermentation has been used to increase the nutrient value of rice bran. While fermented rice bran has been well experimented with in biofloc, we hypothesize that acid hydrolyzed once could also serve in the system [1-12].

Materials and Methods

Experimental Setup

The experiment was conducted at the biological garden, Umaru Musa Yar’adua University. Fingerlings of African catfish, Clarias gariepinus, of 11.15 ± 1.50 g initial weight were obtained from hatchery-reared stock and kept in a 200-liter plastic tank for a 7-day acclimation period. The fish were fed a diet containing 40% crude protein at 5% body weight during 8:00–18.00 hours daily. Experimental tanks were seeded with 1 liter of water from a pre-fertilized earthen fish pond containing abundant phytoplankton. The fish were randomly distributed to the three experimental treatments of untreated, fermented, and hydrolyzed fermented rice bran biofloc in a triplicate of 20 fish per tank at a 2:1 biomass (g) to volume (l) ratio. Each experimental setup was seeded with 2 liters of water from a pre-fertilized earthen fish pond containing abundant phytoplankton.

Fermentation and Acid Hydrolysis of Rice Bran

Milled rice bran was sieved through a 0.50 mm sieve and sterilized in an autoclave. The solid-phase fermentation procedure described by [13] was followed with slight modifications. 50 g of rice bran was added to 45 ml of distilled water, while 5 g of baker’s yeast dissolved in 5 ml of water was added to make up a 1:1 weight-to-volume ratio of rice bran to water. The mixture was incubated in a beaker at a temperature of 27°C for 24 hours. Acid hydrolysis of rice bran was carried out using 50 ml of 2% sulfuric acid mixed with 50 g of rice bran, and the mixture was incubated at 90°C for 3.5 h. This was modified from. The hydrolyzed product was subjected to fermentation as described before. The fermented and hydrolyzed fermented products were oven dried at 45°C for 6 h, powdered, and sieved through 100 µm mesh. The fermented rice bran (FRB) and hydrolyzed fermented rice bran (HFRB) were used as carbon sources in biofloc production catfish [11].

Water Quality and Floc Monitoring

Water parameters were measured every two weeks. The temperature (°C) was determined using a mercury in glass thermometer, while the pH was measured using a Metrohm Herisau E520 pH meter. Dissolved oxygen concentration was determined through the Winkler-Azide method [14]. Chemical oxygen demand (COD) was determined titrimetrically, while biological oxygen demand (BOD) was determined using the incubation method at 20°C for five days [15]. The total ammonia nitrogen concentration was determined using the phenate method [16], while nitrate was determined using spectrophotometry [14]. By assuming 16% of protein is nitrogen and 46% carbon in rice bran, the amount of carbon to be added was calculated following. The total feed consumed per day was estimated, and the C:N was adjusted daily to 15:1 by adding treatments C of untreated, fermented, or hydrolyzed rice bran. The treatment carbon was mixed with 1 liter of water from the treatment before being added to the experimental setup. Biofloc volume (ml/L) was measured every 14 days for each experimental treatment using an Imhoff cone. The floc solution was allowed to settle down for one hour before the reading was taken [17-19].

Data Collection

The total length (TL) of fish in centimeters from each replicate was measured from the tip of the snout to the end of the caudal fin using a meter rule. Body weight was measured using an electronic digital balance. At the end of the experiment, all fish in the tank were counted, and the survival rate was determined. Growth performance in each treatment was estimated by weighing 10 randomly selected fish from each treatment and replicates on a biweekly basis, and the following growth and condition indices parameters were estimated:

Absolute growth (ΔG, g) = (W2 – W1), g.

Absolute growth rate (AGR, g/day)= (W2−W1)/t Relative growth (RG %) = (W2 – W1/ W1) × 100

Specific growth rate weight (%∕day) = (ln mean final weight − ln mean initial weight)/ no. of culture days ×100,

Where W1 is the initial mean weight (g), W2 is the final mean weight ( g), and t is the experimental duration.

Survival (%) = (Number of harvested fish/ number of stocked fish) × 100,

FCR = Total Feed fed (g)/Total wet weight gain (g).

Protein efficiency ratio PER = (Body weight gain g)/protein intake g)

Condition factor (CF) = [Body weight, g)/ Body length, cm3)] ×100 [20]

Hepatosomatic index (HIS) = (Liver weight, g)/(Whole body weight, g) ×100

Viscerosomatic index (VSI) = (Viscera weight, g)/ (Whole body weight, g) ×100

Statistical Analysis

Results were presented as mean ± SD. A one-way ANOVA was used to analyze the data, and the means werecompared using Duncan’s multiple range test. All the analyses were performed using SPSS 21.

Results

Water Quality Parameters

The average temperature recorded in this experiment did not differ significantly among all treatments (Table 1). A significant lower (p < 0.05) dissolved oxygen (DO) level was observed in FRB (5.95 ± 0.40 mg/L) compared to RBB (6.55 ± 0.50 mg/L) and HFRB (6.15 ± 0.10 mg/L). The highest DO and COD levels were recorded in the RBB treatment (Table 1). The average values for biological oxygen demand (BOD), total dissolved solids (TDS), and pH were highest in RBB treatment, while TDS and BOD had the highest average values in FRB treatment. HFRB treatment recorded the highest average value for nitrite. A significantly lower value of pH (6.75) was recorded in HFRB treatment (p < 0.05).

Table 1: Physicochemical parameters of water in a catfish biofloc system where rice bran, fermented rice bran, and hydrolyzed fermented rice bran (HFRB) were used as carbon sources.

Carbon sources
 

Parameters

Rice bran (RBB) Fermented rice bran (FRB) Hydrolyzed fermented rice bran (HFRB)

Significant level

Temp °C

27.80 ± 0.30a

27.50 ± 0.50a 27.60 ± 0.40a

P > 0.05

pH

7.70 ± 0.10a

7.20 ± 0.35b 6.75 ± 0.50c

P < 0.05

TDS (mg/l)

195.00 ± 10.00a

243.00 ± 15.50b 205.00 ± 18.50c

P < 0.05

COD (mg/l)

102.50 ± 5.50a

115.20 ± 8.70b 98.00 ± 5.50b

P < 0.05

BOD (mg/l)

55.50 ± 6.50a

60.45 ± 10.50a 41.50 ± 8.00b

P < 0.05

DO (mg/l)

6.55 ± 0.5a

5.95 ± 0.4ab 6.15 ± 0.10b

P < 0.05

TAN (mg/l)

3.85 ± 0.55a

2.52 ± .0.45b 2.60 ± 0.50b

P < 0.05

Nitrite (mg/l)

0.35± 0.10a

0.30± 0.10b 0.33 ± 0.10c

P < 0.05

Means with a different superscript in the same row are significantly different (P < 0.05).

Floc Production

The biofloc volume was significantly higher in HFRB starting from week 2 of the experiment compared to all other treatments (Figure 1). The floc volume reached maximum in week 7 with values of 135.1 ml/l, 166.6 ml/l, and 111.0 ml/l for HFRB, FRB, and RBB treatments, respectively.

fig 1

Figure 1: Floc production in the catfish biofloc system where rice bran, fermented rice bran, and hydrolyzed fermented rice bran were used as carbon sources.

Growth Parameters and Feed Efficiency

The growth rates, survival, and feed utilization of catfish in the biofloc system for the 8 weeks of rearing (Table 2) showed that treatment of rice bran through solid phase fermentation and acid hydrolysis enhanced its utilization as carbon sources in biofloc as the final weight and specific growth rates were higher compared with untreated rice bran. The highest final weight (85.5 g) was recorded in HFRB treatment, while the lowest value of weight gain (80.26) was in RBB. The feed conversion ratio was also highest in HFRB treatment. The survival was however lowest in HFRB, and this was significant (P < 0.05). The growth of catfish in biofloc utilizing hydrolyzed fermented rice bran as a carbon source in this experiment was better than that in untreated bran, as the growth rates were higher. The best FCR obtained for catfish (1.52 ± 0.05) was recorded in HFRB treatment, and this was significantly higher (P < 0.05). The percentage survival was significantly lower in HFRB treatment (P < 0.05).

Table 2: Growth parameters of catfish reared in a biofloc system where rice bran, fermented rice bran, and hydrolyzed fermented rice bran were used as carbon sources.

Parameters

Rice bran (RBB) Fermented rice bran (FRB)

Hydrolyzed rice bran (HFRB)

Initial weight (g)

11.15 ± 1.60a

11.15 ± 1.60a

11.55 ± 1.60a

Final weight (g)

80.26 ± 3.20a

81.70 ± 2.50b

85.50 ± 2.55b

Absolute growth (g)

70.15 ± 2.80a

70.65 ± 1.80c

74.53 ± 1.50b

Absolute growth rates(g/day)

0.992 ± 0.03a

1.000 ± 0.03c

1.031 ± 0.02b

Relative growth (%)

8.643 ± 0.21a

8.695 ± 0.11a

8.964 ± 0.10b

Specific growth rate(%/day)

1.211 ± 0.16a

1.23 ± 0.14a

1.28 ± 0.13b

Survival%

92 ± 1.55a

95 ± 1.50a

86 ± 1.52b

Feed conversion ratio

1.65 ± 0.04a

1.68 ± 0.03a

1.52 ± 0.05b

Protein efficiency ratio

0.403 ± 0.03a

0.405 ± 0.04a

0.421 ± 0.05b

Means (n=10) followed by different letters in each rows are significantly different (P < 0.05).

Condition Indices

Condition factor (Fulton factor) calculated showed that catfish in the FRB treatment had higher values (0.54) followed by those in RBB (0.47) and HFRB (0.44) treatment fishes (Figure 2). Similar trends were observed with hepatosomatic index and viscerosomatic index in this experiment. The HIS showed a significantly higher value of 5.9% in the FRB treatment (P < 0.05).

fig 2

Figure 2: HIS (hepatosomatic index), CF (condition factor), VSI (viscerosomatic index) African catfish, C. gariepinus fingerlings reared in a biofloc system where rice bran, fermented rice bran, and hydrolyzed fermented rice bran were used as carbon sources.

Discussion

This experiment demonstrated that differential treatment of rice bran influenced its performance as a carbon source in biofloc production of catfish. Even though fermented bran has been well researched in this system, our findings suggest that acid-hydrolyzed fermented rice bran also has potential for consideration as well. Acid hydrolysis of rice bran resulted in the conversion of its starch and cellulose components into reducing sugar [11]. This may improve its performance in carbon release in the biofloc system. Slow carbon release by rice bran has been attributed to its low performance as a biofloc carbon source [5,21]. Rice bran is a cheap carbon source; efforts towards boosting its carbon release have been the focus of research. All the water quality parameters recorded in the system were within the range recommended for aquaculture and catfish production. Temperature is an important ecological factor with a profound effect on fitness, growth, and metabolism performance in aquatic organisms [22-24]. Variations in the temperature in our research were not significant, indicating no external influence on the treatment used. DO is an important abiotic factor influencing the growth and survival of fish. A significant reduction in the level of dissolved oxygen (DO) observed in FRB compared to the rest of the treatment could be due to higher microorganisms in this system, as reported in previous findings [25-27]. The pH range of 7-8.5 was said to be suitable for biofloc system performance, while recommends an average pH of 6.7, as biofloc systems tend to lose their buffering capacity at lower pH. The stability of the bioflocs was found to be dictated by the pH. All the treatments used in the current research maintained the pH of catfish biofloc within the recommended range [28-31], even though the pH level in the HFRB treatment was significantly lower (P < 0.05). Recovery of the acid after the hydrolysis process is a major bottleneck, and this informed our modified method for reducing acid utilization in the hydrolysis process. Future research towards optimizing acid hydrolysis of bran for biofloc carbon usage may be important. The survival rates of RBB and FRB treatments were significantly higher (P < 0.05) than HFRB treatments. This may be connected to lower pH in HFRB treatment. In this study, a higher concentration of total ammonium nitrate was recorded in HFRB treatment even though not significant (P > 0.05). This is in line with the findings of [27,32], who reported the use of complex carbon such as bran to decrease ammonia concentration in biofloc when compared to other carbon sources with simple sugar. The growth parameters of the catfish in the biofloc system after 8 weeks of rearing in this experiment showed that treatment of rice bran through solid phase fermentation and fermentation after acid hydrolysis enhanced its utilization as carbon sources in biofloc as the final weight and specific growth rates were higher compared with untreated rice bran. Organosomatic indices of catfish in this research showed a direct link between the effects of change in carbon source and environment on the fish; the response in such indices in response to nutrition has been well reported [33,34]. The use of acid-hydrolyzed fermented bran in this research proved efficacious in the system, as the growth parameters of this fish therefrom were well above the untreated rice bran treatment. The floc level was also higher in the hydrolyzed fermented bran treatment in this research. The observed drawback in this use of hydrolyzed bran is the low pH produced in the biofloc system. This might account for the reduced survival rates of the fish in this system. In conclusion, the results of this study suggest that hydrolyzed fermented rice bran can be used in catfish biofloc systems as a carbon source without negative consequences on water quality, growth, and feed utilization. However, adjusting the pH may be required for better performance and is recommended. Further research is needed to investigate the optimal hydrolization condition of bran for their usage as carbon sources in biofloc systems.

Acknowledgements

We would like to thank, Umaru Musa Yar’Adua University for their technical assistance. This work was supported by the Tertiary Education Trust Fund, Nigeria.

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Participation of the Leukemia Inhibitory Factor on Ovarian Function

DOI: 10.31038/EDMJ.2024833

Abstract

Leukaemia inhibitory factor (LIF), a cytokine in the interleukin 6 family, is considered a pleiotropic molecule with diverse functions and is expressed in different tissues and cell types. The role of LIF in the reproductive system during the implantation process has been described; however, to date, there is little available information about the effect of LIF on the function and development of the female gonad. The focus of this review is to analyse the structure of LIF, the signalling pathway involved, and the expression of LIF and its receptor in different ovarian cell types. In addition, the participation of LIF and its receptor in ovarian function, follicular development, steroidogenesis and ovulation is discussed.

Introduction

Leukaemia inhibitory factor (LIF) is a cytokine that belongs to the interleukin 6 (IL-6) family and is considered a pleiotropic molecule since it is expressed in different tissues and cell types and has diverse functions. The first observed effect of LIF was its ability to function as a differentiation inducer and proliferation inhibitor of the myeloid leukemic cell line (M1) to macrophages in an in vitro model [18]. Other specific functions of LIF have been reported, such as its participation in bone resorption [36,37] neonatal neuronal transdifferentiation [40,41] and its involvement in cardiac remodelling [19-21], folliculogenesis and spermatogenesis [14]

Currently, the study of this cytokine in the female reproductive system has attracted interest since it is found in different tissues of the female reproductive system [22]. LIF was initially discovered to be necessary for the uterine implantation process [10], and in recent decades, it has been found to be present in the oviduct [23] and ovary, but its functions at these levels have not been fully understood. In the ovaries of different species and from different study models, both in vitro and in vivo, LIF has been shown to fulfil important functions depending on folliculogenesis stage, mainly during the neonatal and fertile periods of female reproductive life; however, the role of LIF during the female subfertile period is unclear. Therefore, in the present review, we discuss the available data on the role of LIF in ovarian folliculogenesis during female reproductive life.

Lif and Its Receptor

LIF is a protein with an approximate molecular weight of 20 kDa, but its molecular weight can range from 38-67 kDa due to differences in posttranslational modifications [38,39]. Among the modifications that mature proteins present are glycosylations, which are mainly associated with asparagine residues. Although glycosylations explain, to some extent, the variations in the molecular weight of LIF (38-67 kDa) [3], we still cannot determine how the glycosylation pattern affects the function and stability of the protein. LIF is described as long-chain cytokine with four α-helices in an up-down-up configuration, as has also been shown for other IL-6 family members such as ciliary neurotrophic factor (CNTF), growth hormone (GH), granulocyte colony-stimulating factor [42,45] Although a low degree of homology is observed between the primary structures of these cytokines, they show a high degree of homology in their tertiary structures and in the functional epitopes of their receptors, as demonstrated by X-ray crystallography resonance imaging [43].

Lif Receptors as a Heterodimer and Associated Signalling Pathways

For LIF to carry out its action, it must interact with a heterodimeric plasmatic membrane receptor formed by two proteins, gp130 and LIFRβ. The LIFRβ subunit which can also interact with other cytokines of the IL-6 family, such as CNTF and oncostatin M and the gp130 is a subunit common for all IL-6 family cytokines [46]. LIF interacts specifically and directly with the LIFRβ subunit but with a relatively low affinity (Kd=1∗10−9). When the gp130 subunit interacts with the LIF-LIFRβ complex, a high-affinity trimeric LIF-LIFRβ-gp130 complex is formed (Kd=1∗10^−10), which is necessary for receptor activation and therefore intracellular signalling [24]. The interaction between LIF and LIFRβ is 80-fold greater than that between LIF and gp130, which is not surprising given that gp130 also interacts with other cytokines [25].

IL-6 family cytokine-associated receptors do not exhibit kinase activity. The binding of LIF to its heteroreceptor causes conformational changes in the subunits that allow cytoplasmic activation of Janus kinase (JAK), tyrosine phosphorylation of the heteroreceptor and phosphorylation of signal transducer and activator of transcription (STAT). It has been observed that LIF can activate the JAK1/STAT3 pathway, which is considered to be the canonical signalling pathway involved (Figure 1), but importantly, the JAK/STAT signalling cascade is a signalling pathway shared by several cytokine receptors [47]. In addition to activating the JAK/STAT pathway, the interaction between LIF and LIFR can activate other signalling pathways, such as the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) pathways; however, the effects vary and may even be opposite depending on the cell type involved, having been observed to either induce or inhibit cell differentiation in a variety of cases [48].

fig 1

Figure 1: Canonical LIF signaling pathway in the ovarian follicle. LIF is expressed in the ovaries of various animal models, such as mice, rats, nonhuman primates, and humans. Specifically, it has been observed that LIF is expressed in different ovarian cells such as theca cells, granulosa cells and oocyte. In the scheme, granulosa cells of antral follicles are used as an example of localization of the signaling cascade associated with LIF. The LIF molecule is shown in green. The LIF receptor as a heterodimer consists of the LIFRβ subunit in blue and the gp130 subunit in red. Upon interaction of LIF with the LIFRβ subunit of the LIF receptor, the gp130 subunit is recruited to form the heterotrimer. When this occurs the signaling cascade is triggered where JAK1 phosphorylation is induced to be activated. JAK1 upon activation subsequently phosphorylates STAT3 so that it can homodimerize and translocate to the nucleus to act as a transcription factor in the regulation of gene expression.

Role of Lif in the Female Reproductive System

Function of Lif In Utero

It has been widely reported that LIF participates in the implantation process in the uterus of several mammals [50,51]. An increase in LIF levels in utero has been observed at 2 crucial moments of pregnancy: the first is in the oestrus stage, coinciding with the ovulation process [57], and the second is on the 4th and 5th days of pregnancy. In situ hybridization has shown that LIF expression in pregnant mice is confined to the endometrial glands [39]. After the 5th day of pregnancy, once implantation and decidualization occur, the glands begin to degenerate, and LIF secretion ceases. This observation suggests that the peak LIF signal produced during pregnancy could be decisive at the time of implantation; this was corroborated in female LIF-deficient (LIF-/-) homozygous mice whose ova fertilized by either LIF-/- or wild-type (WT) males reached the blastocyst stage without problems. However, these mice could not reach the implantation stage [49] when these embryos were transferred to a pseudopregnant WT female, the pregnancy reached full term, suggesting that the implantation failure was due to a maternal defect, which was essentially attributed to the lack of LIF. Based on these studies, LIF was found to be a fundamental factor in the implantation process. However, the action of LIF in this process is subject to regulation by other factors, including kisspeptin (KP).

KP is a key neuropeptide involved in the regulation of reproductive function through the hypothalamic-pituitary-gonadal (HPG) axis [52]. Despite the important role of the KP at the central level, it also regulates gonadotrophins secretion [26,27]. Calder et al. confirmed that KP (Kiss1-/-) deficient female mice mated with WT males are unable to achieve pregnancy due to implantation defects [11]. This finding led us to consider whether Kiss1-/- females lacked some determinant signals for the implantation process. In this regard, as mentioned above, studies have shown that LIF is an essential factor for the implantation process in mice. Indeed, a therapy based on the exogenous administration of recombinant LIF was able to partially rescue the implantation process in Kiss1-/- females. Based on these findings, it was hypothesized that LIF expression was reduced in female Kiss1-/- mice, which was subsequently confirmed by the marked reduction in LIF expression at the level of the uterine glandular lumen in Kiss1-/- females compared to WT female mice. This is the first study to demonstrate that uterine KP signalling regulates glandular levels of LIF.

Function of Lif in Ovary

LIF is expressed not only in endometrial tissue in the female reproductive system but also in the ovary (Senturk & Arici 1998). LIF is expressed in the ovaries of various animal models, such as mice, rats, nonhuman primates, and humans [5,6,31,32]. During the fertile stage in human and nonhuman primates, LIF has been shown to be present in the follicular fluid of preovulatory follicles [30]. In rats, ovarian LIF levels change during the oestrous cycle, with the highest levels being observed at the night of proestrus, corresponding to oestrus and metaestrus/diestrous [28,29]. We have seen in a rat model that the ovarian expression of LIF, in addition to being different during the oestrous cycle, is different during the reproductive life of the rat, as indicated by a greater expression of this cytokine in the fertile stage and a markedly lower expression during lactation. In neonatal rats, LIF is localized to granulosa cells in primordial and primary follicles and in oocytes [53]. In mouse ovaries, LIF is localized to cumulus cells and oocytes from antral follicles. In these cells, the intensity of the LIF marker increases in growing and mature follicles [54]. According to the IHC technique, LIF is localized in theca cells, granulosa cells and oocytes from healthy antral follicles and mainly in luteal cells of the corpus luteum in fertile rats in the oestrous stage [58]. These data suggest a possible autocrine/paracrine role of LIF during the neonatal and fertile periods in females, as well as a role in the stages of cyclical recruitment, ovulation, corpora lutea development and steroid hormone production.

This paracrine or autocrine action of LIF is suggested by the fact that ovarian cells express LIF receptors. The LIF receptor has been found to localize to different ovarian follicular cells in different species [44]. In the ovaries of fertile female monkeys, LIFRβ and gp130 (also known as IL6ST) are localized by IHQ in theca cells and granulosa cells of antral follicles [33]. In humans, LIFRβ and gp130 have been identified by RT‒qPCR and IHQ in granulosa cells and oocytes from primordial follicles of foetal ovaries and in granulosa cells from primary and secondary follicles in adult ovaries [1]. The activation of the LIF receptor in ovarian follicular cells of monkeys in the fertile stage and in the human granulosa cell line COV434 is related to the signalling pathway corresponding to JAK1/STAT3 (Figure 1) and phosphorylated STAT3 after an ovulatory stimulus [35]. On the other hand, in vitro studies in pig ovaries revealed an increase in the phosphorylated form of STAT3 associated with the cumulus–oocyte complex [34]. We recently reported that, in rat ovaries incubated with LIF for 30 minutes, STAT3 phosphorylation increases [37]. LIF and its receptors can activate other signalling pathways [23] in a paracrine or autocrine manner. It must be determined whether these signalling pathways can also be activated in the ovary, for which further studies are needed.

Participation of LIF in Follicular Recruitment

LIF has been shown to promote the transition from primordial to preantral follicle in a neonatal rat and goat in vitro study [58,59] and it has been proposed that this effect in rats is indirect and mediated by an increase in the expression of kit ligand (KL), a known factor that promotes the passage from primordial to primary follicles. We recently published results that support the idea that chronic treatment with LIF for 28 days in vivo decreases the total number of small primary and secondary follicles in the ovaries of fertile rats. In contrast, the number of primordial follicles does not change with LIF treatment and therefore does not explain the decrease found in primary and secondary follicles. LIF has been shown to decrease the growth of developing follicles both in vitro in prepubertal mice [55] and in vivo in fertile rats [56] Specifically, it has been observed in vitro that both secondary and antral follicles are small in size when ovaries are incubated with LIF [60]. This decrease in the development of preantral follicles disagrees with the results of Nilsson et al. and may be due to the chronic in vivo treatment of LIF. However, the effects of LIF on apoptosis are still controversial [16]. To determine whether LIF induces apoptosis in vivo, it is necessary to carry out studies with shorter treatment durations because at 28 days, no pyknotic nuclei were observed during the morphology analysis. LIF regulates the recruitment of primordial follicles, which is relevant for maintaining the cohort of reserve follicles in the ovary. Its effect could be associated with the maintenance and avoidance of a massive loss of the ovarian follicular reserve during reproductive life. Studies focused on the subfertility stage are also necessary.

Follicular atresia corresponds to the degeneration or death of the ovarian follicle so that healthy follicles can develop normally, while defective follicles degenerate and die by apoptosis or autophagy, depending on the stage of follicular development [12,51]. Autophagic atresia has been documented to occur mainly in preantral follicles, whereas apoptosis-induced atresia occurs mainly at the antral follicle stage during cyclical recruitment. It has been observed that atresia in antral follicles is due to the lack of FSH signalling [53] and that this process is associated with the activation of the LIF-STAT3 pathway in the granulosa cells of bovine ovarian follicles [24]. FSH is important for the selection and development of antral follicles, mainly through cyclical recruitment [66]. However, treatment with LIF in rat ovaries for 28 days does not induce follicular atresia, and serum FSH levels do not change with respect to those of the control at the end of treatment. These results suggest that LIF alone does not have an effect on follicular atresia, and it is probable that atresia due to lack of FSH is due to another mechanism and not through LIF.

Participation of LIF in Ovulation and Corpus Lutea

The effect of LIF on ovulation has been evaluated by Murphy et al., 2016. In this work, LIF concentrations were determined in the follicular fluid of preovulatory follicles of fertile female rhesus macaques, and an increase in LIF was observed after hCG administration as an ovulatory stimulus and prior to ovulation. A similar phenomenon has been observed in follicular fluid from preovulatory follicles in humans after hCG has been administered [13]. These results support the premise that LIF is produced in granulosa cells, cumulus cells, and oocytes, as has been observed in rodents [65]. LIF is produced during all stages of follicular development, apparently regulating the growth and maturation of follicles and oocytes and ultimately contributing to ovulation. In summary, the data suggest that LH can stimulate the production and secretion of LIF in granulosa cells, specifically in preovulatory follicles, which express the LH receptor (LHR), to promote ovulation. For example, the administration of hCG (500 IU/ml) provoked a significant increase in intrauterine LIF, VEGF and MMP-9 (Licht et al., 2007).

There are no data in humans that evaluate the effect of LIF on ovulation itself, but when determining the concentration of LIF in the follicular fluid and in the serum of women suffering from polycystic ovarian syndrome (PCOS), a condition characterized by oligo- or anovulation, women with PCOS have decreased levels of LIF compared to what is observed in control women [64]. A study carried out in a rat model revealed that local LIF administration to the ovary for 28 days can increase the number of large corpora lutea and the serum progesterone concentration at the end of 28 days of treatment with LIF. Large corpora lutea are associated with recent ovulation of preovulatory follicles and increased progesterone production [15]. This is because the luteal cells of newly formed corpora lutea express higher levels of 3β-hydroxysteroid dehydrogenase (3β-HSD) than do those of involuting corpora lutea (from previous ovulations), suggesting that LIF could be important for the ovulatory process. In addition, luteal cells present positive immunoreactivity for LIF in the ovaries of fertile rats, and the highest levels of the messenger RNA that codes for LIF are detected in oestrous and metaestrus/diestrus [63], stages of the oestrous cycle, where the greatest amount of progesterone is produced and newly formed corpora lutea are observed. It is possible that LIF may also influence the survival of the corpora lutea, but this possibility requires further study. LIF not only locally regulates the ovulatory process but also participates at the central nervous system level. LIF induces an increase in GnRH at the hypothalamic level, regulating reproductive function locally in the gonad and in the central nervous system [17].

LIF Involvement in Ovarian Steroidogenesis

However, studies regarding the effect of LIF on steroidogenesis are rare. The first observations of the possible effect of LIF on this process were obtained from experiments carried out in the adrenal cortex and in the human adrenocortical cell line NCI-H295R, where the results indicated that LIF could increase the secretion of cortisol and aldosterone through a mechanism mediated by ACTH [4,8]. On the basis of these findings, LIF can increase the expression of the regulatory protein of acute steroidogenesis (StAR) [62], and in vitro studies of Leydig cells from immature rats incubated with different concentrations of LIF revealed that at low concentrations, this cytokine could increase androgen production, apparently increasing the expression of StAR and 17-hydroxysteroid dehydrogenase 3 (Hsd17b3) [61]. In both cases, LIF can increase the expression of the StAR protein in vitro, which suggests, on the one hand, that the increase in steroid hormone levels in vitro is due to this effect and, on the other hand, that this phenomenon could be replicated in cells of other steroidogenic tissues, such as the ovary. However, until now, there has been no published evidence supporting the involvement of LIF in enzymes or transporters involved in ovarian steroidogenesis.

Conclusions and Perspectives

LIF is a pleiotropic cytokine that has various functions and activates various intracellular signalling pathways, depending on the cell type and tissue in which it participates. The LIF-LIFR system has been studied in the immune system and cancer, and its therapeutic role has been studied in various pathologies; its participation in the implantation process and therapeutic use in the reproductive system have been described. Recently, publications on the role of the male gonad in development and spermatogenesis have emerged. In this review, we analysed the participation of LIF in the ovary and discussed its possible signalling pathways and localization in different cell types in the female gonad. LIF is expressed at different levels during the oestrous cycle stage, and during ovary development, it participates in follicular development, ovulation (Figure 2) and steroidogenesis. We cannot exclude our analysis because, in the context of infertility pathology caused by ovarian dysfunction, LIF could also play a key role in considering future therapy or therapeutic use, but further studies are needed.

fig 2

Figure 2: Summary scheme of the effects of LIF on ovarian folliculogenesis. As discussed in the review, LIF can modulate the different stages of ovarian folliculogenesis in vitro and in vivo. During initial recruitment (passage from primordial follicle to preantal follicle), LIF promotes recruitment by increasing the number of developing follicles (primary and secondary follicles) in an in vitro neonatal ovary model [43]. In the fertile stage, LIF produces a decrease in the number of preantral follicles, in an in vivo model [48]. In studies carried out in the prepubertal stage [27] and in the fertile stage, it is observed that LIF decreases the size and number of antral follicles. It has also been observed that LIF is necessary for ovulation to occur [41], which could be closely related to the increase in the number of large corpora lutea following chronic treatment with this cytokine.

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Self-removal of Urinary Catheter Following Pelvic Floor Surgeries: A Cost-effective Way to Reduce Hospital Stay and Improve Patient Satisfaction

DOI: 10.31038/IGOJ.2024712

Abstract

Objectives: To assess the effectiveness of patients to remove urinary catheters by themselves after pelvic floor surgery done as day cases.

Design: This was a non-randomized, single centre, prospective pilot study which included patients who have had pelvic floor surgeries (anterior and/ or posterior colporrhaphies and colpocleisis) done as day cases between February 2021 and November 2023.

Sefling: UK DGH hospital urogynecology department.

Population: All patients who had anterior, posterior colporrhaphy, and colpocleisis and fulfilled our inclusion criteria for an elective day-case surgery

Methods: Non-randomized, single centre, prospective pilot study which assess the effectiveness of day-case pelvic floor surgeries, with patients being discharged home with urinary catheters. They were instructed on how to remove these catheters on the first day following the operation. Subsequently, participants were monitored postoperatively and attended a clinic appointment six weeks later. Additionally, they were provided with a questionnaire to fill out, which was to be returned one week after the procedure.

Results: The data obtained was over a 33-month period between February 2021 and November 2023. A total of 123 patients were included in the study. 65 patients (52%) had anterior repairs; 42 rectoceles (34%); 6 Enterocele (4%) and 10 colpoclesis (8%). Ages of the participants ranged from 42 years to 89 years.

Overall, 77% of feedback questionnaires were returned. Amongst the enrolled patients, 98% would prefer not to wait for another admission date where a bed will be available, 97% of our patients removed the urinary catheter by themselves and found it to be easy, 88% of our patients would prefer not to come to the hospital or have a nurse sent to their homes to remove the catheter, and finally, 89% of our patients would recommend this service to a friend.

Conclusion: Our study demonstrated that removal of patient’s own catheter following pelvic floor surgery is cost-saving and highly acceptable to this cohort of patients.

Introduction

The COVID-19 pandemic has led to a significantly increase in pressure on the already stretched National Health Service (NHS) with high demands of hospital bed space and prolonged waiting times for outpatient appointments and elective surgeries across the country [1].

A lot of healthcare services across the NHS had to be adjusted to cope with increased pressures. To help reduce waiting times for urogynaecological operations and effectively manage hospital bed space, we have introduced a new service by performing pelvic floor surgery as day cases and allowing patients to go home with an urinary catheter to be removed by themselves day 1 (D1) postoperatively. This begun as a quality improvement project and has evolved into a change of practice [2].

Before the onset of the pandemic, patients who are having elective anterior and posterior colporrhaphy would be admitted for an overnight stay in the hospital and discharged the following day provided that their trial-without-catheter (TWOC) was successful.

Due to the growing demand for hospital beds, we have initially adapted the service by performing the pelvic floor surgeries as day cases and allowing women to be discharged with urinary catheters, which would be taken out by a nurse at their homes on the first day after surgery. Nevertheless, considering the increasing COVID-19 cases and the emergence of new strains, we initiated an innovative quality improvement project to evaluate the capability of patients to self-remove their urinary catheters after undergoing day-case anterior or posterior colporrhaphy without compromising the quality of their care. The service was extended to encompass colpocleisis procedures as the study progressed.

Anterior colporrhaphy can be described as surgically correcting a vaginal wall defect resulting from the protrusion of the bladder into the vagina, while a posterior repair addresses a defect in the vaginal wall that causes the rectum to protrude into the vagina. These defects tend to affect the quality of life of these patients and can be associated with a range of bowel , urinary and sexual symptoms [3].

Colpocleisis is a surgical intervention employed to address pelvic organ prolapse in women. This procedure entails excising a portion of the vaginal wall and then joining the remaining tissue together to provide support for the pelvic organs [4].

In a previous study by Weemhoff et al. 2011, the importance of inserting urinary catheters following vaginal wall surgeries to address postoperative urinary retention was highlighted. This finding is particularly significant as it was observed that 40% of patients experienced urinary retention when the catheter was removed on the same day [5].

The primary objective of this study is to evaluate the effectiveness and safety of patients self-removal of urinary catheters after undergoing pelvic floor surgery.

Methodology

We have conducted a prospective pilot study in a single DGH hospital. Patients who were having pelvic floor surgeries were recruited between February 2021 to November 2023. A total of 123 patients were enrolled in the study.

Given that this project is focused on quality improvement and service development, ethical approval was not indicated.

The process commenced at the urogynaceology outpatient clinic, where patients received information and provided consent for the surgical procedure. A member of the urogynaecology team facilitated the consent to participate in the study.

Patients who met the inclusion criteria were subsequently counseled about the study, which entailed them independently removing their urinary catheter at home on D1 postoperatively.

A practical demonstration is done in clinic and the patients are given a hands-on experience to ensure that they were confident in deflating the catheter balloon and removing the catheter. All questions and concerns are addressed during this session.

Our inclusion and exclusion criteria are listed below:

Inclusion Criteria

  1. Fit and well women with no significant co-morbidities and suitable for day-case procedures.
  2. Must be consented to partake in the study.
  3. Women must have someone to care for them at home for the first 24 hours.

Exclusion Criteria

  1. Visually impaired.
  2. Women with cognitive disorders or learning disabilities.
  3. Patients with no support at home or living on their own.
  4. Patients who do not want a day surgery.
  5. Patients with significant medical.

On the day of the surgery, a repeated practical demonstration of deflating the catheter balloon is performed in the morning, and the patients’ willingness to participate is confirmed.

The surgical procedure begins with infiltration with 40 mls 1: 200,000 Adrenaline in 0.25% Marcaine to the vaginal wall. A vertical elliptical incision was made at the lowest point of 1 cm above POP: Q(Aa) in an anterior repair and POP: Q(Ap) in a posterior repair. Dissection was performed to the paravaginal tissue and opposed in midline by plication of fascia using 3/0 PDS. The vagina was closed with interrupted 3/0 PDS and completed by a continuous locking haemostatic 3/0 PDS. None of our patients required a vaginal pack. All patients were catheterized after the procedure and was sent home when they met the discharge criteria. Upon discharge, patients were given Voltarol suppository, either 50 mg or 100 mg to be used at night. For those sensitive to non-steroidal anti-inflammatory drugs, an alternative of Co-dydramol 10/500 mg tablets (2 tablets taken four times a day) were provided, or simply paracetamol 1g four times a day if codeine could not be tolerated. To prevent constipation, patients were prescribed Lactulose, to be taken in 10 ml doses twice daily. The postoperative medications are given for a duration of 5 days Additionally, they were sent home with a 10ml syringe, which is to be used for deflating their urinary catheters at 7am the next morning.

Some adjustments had to be made during the study as we noticed that the catheter was removed with ease when filled with 8 ml of saline rather than the standard 10mls. We then modified our practice by using silicone catheters, rather than the latex made ones which were previously used after a patient reported with a faulty latex catheter. Participants were provided with safety net advice along with an emergency contact number for seeking advice or expressing concerns in the postoperative period. Patients were provided with feedback questionnaires prior to discharge, and they were encouraged to complete them one week following the procedure. A follow-up appointment with the consultant was also scheduled for 4-6 weeks postoperatively.

Initially, for the first 17 patients, follow-up calls were scheduled on the first day postoperatively. This involved two calls in the morning and one in the afternoon. However, the team later determined that these multiple calls were unnecessary. As a result, the protocol was adjusted to only one call made by a team member from the urogynecology department in the evening. All patients were provided with an emergency contact number in case they experienced any issues. Patients who experienced difficulties with catheter removal or were suspected of being in urinary retention were encouraged to visit our gynecology ward for a comprehensive assessment. Patients who experienced urinary retention underwent re-catheterization. Following this, a subsequent follow-up appointment with our nurse specialist was arranged for a repeat TWOC in a week’s time.

Results

The data obtained from the prospective study was obtained over a 33-month period. A total of 123 patients were included in our study. This included 65 patients (53%) who had anterior repairs; 42 rectoceles (34%); 6 Enterocele (4%) and 10 colpoclesis (8%) (Figure 1).

fig 1

Figure 1: Distribution of cases in percentages.

The ages of the participants ranged from 42 years to 89 years, with a mean age of 67 years. Majority of the patients enrolled were between 70-79 years and the least number of patients were aged between 40-49 as illustrated in Figure 2.

fig 2

Figure 2: Age distribution of patients in the study (the x-axis shows the age groups of the patients and the Y-axis shows the number of patients in each group).

Ninety-five questionnaires were returned, yielding a response rate of 77% and the outcomes were highly favorable.

One participant out of the 123 (0.8%) experienced urinary retention and required re-catheterization for one week, subsequently passing her TWOC without further issues.

Additionally, another patient (0.8%) had to be admitted for overnight observation due to significant nausea and vomiting following general anesthesia. Lastly, one patient (0.8%) faced complications with a defective catheter, necessitating them reporting to the hospital for removal. Finally, 99% of patients did not require a bladder scan, suggesting routine bladder scan post pelvic floor surgery may not be indicated.

Some common theme of feedback received is seen in Table 1.

Table 1: Patient feedback.

Easy to remove catheter by myself Quick and no time wasted in the hospital
Recovered better at home than in hospital Easier than I expected
Felt better that hospital contacted me the next day, because if I had a problem, it could be solved Nervous about taking my own catheter
Less risk of COVID Did not know how to correctly remove catheter
Consultant and his team were efficient Long wait from pharmacy to get discharge medications
Very good care and well looked after… Need to wear loose clothing during a day case to hide the urinary catheter.

In terms of patient feedback, ninety eight percent of enrolled patients expressed a preference not to wait for another admission date with an available bed. Additionally, ninety seven percent successfully removed the urinary catheter themselves, finding the process easy. Eighty eight percent of patients preferred not to come to the hospital or have a nurse sent to their homes for catheter removal. Furthermore, eighty nine percent would recommend this service to a friend. A significant portion (90%) would rather avoid hospital visits or nurse home visits for catheter removal due to concerns about COVID-19.

We have received largely positive feedback from our patients stating that they were pleased with the arrangements as they felt more comfortable to be at home. Although a few patients were nervous about removing their own catheters, the vast majority of patients expressed that it was straightforward, and they were reassured by a single phone calls from the team.

Discussion

The initial motivation for this study was to find an innovative, practical and efficient way to continue urogynecological surgeries during the COVID-19 pandemic.

The Covid -19 pandemic placed an enormous amount of stress and strain on the heath service resources. It has led to changes to routine practices alternative options for the patients by reducing unnecessary contact with the health service thus reducing the risk of transmitting of Covid-19. This was particularly important in our group of patients as the average age was 65, thus placing them in the vulnerable category. On the other hand, there were delays in performing surgeries during the pandemic due to increased pressure on bed space and staffing which further complicated the issue. Recent studies have proven delays in healthcare provision to be associated with adverse outcomes and poor patient satisfaction [6-8].

Seeking to achieve a balance between patient satisfaction and safety, we launched this quality improvement project to address the extended waiting times for elective pelvic floor surgeries. Our goal was to mitigate the risk of COVID exposure without compromising patient well-being.

The outcomes of this pilot prospective study were notably positive, with over 98% of participants expressing ease in self-removing their urinary catheters postoperatively. Although majority of our patients fall into an older age group, this did not pose a hindrance to the study. Reassuringly, as we have demonstrated that this is widely acceptable to the older population, this suggests that there is a strong possibility for replicating this study outcome in different age groups. The practice could also be extrapolated to other clinical and surgical disciplines faced with similar challenges [9].

The findings of this study underscore several benefits, aligning with NICE recommendations that advocate for greater patient involvement in their care. This study, in turn, places the patient at the forefront of their care, contributing to the overall improvement of healthcare practices. It is important to point out the potential cost-saving benefits observed in our study. Considering an estimated cost of £400 for a hospital bed during an overnight stay at Southend Hospital, we have saved a total of £ 49,200 ( 123 cases x£400) over the duration of our study [10-12].

Further cost savings were made by reassigning the specialist nurse who would have otherwise gone to the homes of the patients to remove the urinary catheters. Instead, they can be deployed to cover over- stretched clinical areas in the hospital as there is currently a national shortage of nurses coupled with increased staff pressures [13].

Patients filled out the feedback forms one week after the procedure, providing them with ample time to reflect on any encountered issues and to weigh the pros and cons of participating in the study. The study received positive response from the ‘family and friends’ test as 89% would recommend it to their friends. One of the common themes in the feedback was the reassurance they had knowing that there was a point of contact they could reach out to if they had any concerns.

As the study progressed, we noted that patients when given additional time, managed to pass urine without any further intervention. This prompted the team to adjust the calling times only once daily in the evening, rather than the initial three times. Also, the patients were given the number of the gynaecology ward so that they can contact the team rather than being called multiple times by the doctor.

We expanded the service to patients undergoing colpocleisis, again with positive results. In the near future, our aim is to further extend this to other gynecology procedures as it has proven to not only be cost-effective but also associated with high patient satisfaction.

Conclusion

The majority of our patients who underwent elective vaginal wall surgeries expressed high satisfaction with the procedure being conducted as day cases and with the subsequent self-removal of their catheters.

This project allowed improvement in capacity to provide elective surgeries with better efficiency and high patient satisfaction without compromising patient safety.

With over 1250 NHS hospitals, this could lead to a potential saving of 20 million pounds, if 40 repairs are done per year which equates to over 50,000 repairs being performed multiplied by only the estimated cost of an inpatient bed (1250×40 repairs /year x £400). Furthermore, additional cost savings will be made by re-deploying nursing staff who were initially assigned to care for these patients.

We conclude that this is a sustainable service that can be continued, and we hope to extend this to other elective gynecological procedures. The inpatient beds can be redistributed for other elective surgeries.

Finally, our study demonstrated that removal of patient’s own catheter following pelvic floor surgeries is not only cost-saving, but also safe and highly acceptable to this cohort of patients.

Future Considerations

With the effective vaccination program, COVID-19 is no longer causing as much strain to our hospitals compared to three years ago, when our project was launched. However, the demand for hospital beds and waiting list for elective surgery are constant struggles within the NHS, our study outcomes should reassure other hospitals that self-TWOC post operatively with uncomplicated pelvic floor surgeries is a safe and cost-effective way of reducing the pressure on the ever- increasing demand of the NHS system.

Patient’s consent: Only anonymous data are included in the study and therefore no individual patient’s consent was required.

Disclosure of Interests

There no conflict of interests declared for this study.

Ethical Approval

Also, no ethical permission was required as it was registered as a Quality improvement project at Southend University Hospital.

Funding

This study was a quality improvement project no external funding was obtained.

Roles of Authors

Dr Papa Yaw Opoku-Ansah (trainee doctor in Obstetrics and Gynaecology ) – Lead author, I used to see the patients pre and post operatively, assist in the surgery, call the patients post operatively, did the write up of the paper.

Dr Candice Cheung – Senior Registrar – saw the patients pre and post operatively, assisted and performed the surgery, called the patients post operatively, made input to the write up of the paper.

Mr Lee – Consultant Urogynecologist, the patients were under his care, he consented the patients, operated on the patients, followed them up, made numerous changes and edits to the paper

References

  1. Uimonen M, et (2021) The impact of the COVID-19 pandemic on waiting times for elective surgery patients: A multicenter study. PLoS One 16(7).
  2. Surgeons, RCo (2020) RCS Managing elective surgery guidance 16 Dec pdf.
  3. Belayneh T, et (2021) Pelvic organ prolapse surgery and health-related quality of life: a follow-up study. BMC Womens Health 21(1). [crossref]
  4. Felder L, et (2022) How does colpocleisis for pelvic organ prolapse in older women affect quality of life, body image, and sexuality? A critical review of the literature. Womens Health (Lond) 18: [crossref]
  5. Weemhoff, et (2011) Postoperative catheterization after anterior colporrhaphy: 2 versus 5 days. A multicentre randomized controlled trial.BMC Women Health.22(4). [crossref]
  6. Moynihan R, et al. (2021) Impact of COVID-19 pandemic on utilisation of healthcare services: a systematic review. BMJ open 11(3). [crossref]
  7. Romero Starke K, et al. (2021) The isolated effect of age on the risk of COVID-19 severe outcomes: a systematic review with meta-analysis. BMJ Global Health 6(12). [crossref]
  8. Sud A, et (2020) Effect of delays in the 2-week-wait cancer referral pathway during the COVID-19 pandemic on cancer survival in the UK: a modelling study. The Lancet Oncology 21(8).
  9. Apramian T, et al. (2016) They Have to Adapt to Learn: Surgeons’ Perspectives on the Role of Procedural Variation in Surgical J Surg Educ 73(2). [crossref]
  10. NICE (2016) Patients should be more involved in decisions about their care, says NICE.
  11. Krist AH, et (2017) Engaging Patients in Decision-Making and Behavior Change to Promote Prevention. Stud Health Technol Inform 240: 284-302. [crossref]
  12. Fund, K. (2022) Key factsnabd figures. Retrieved 03-10-22, 2022, Available from: https://www.kingsfund.org.uk/audio-video/key-facts-figures-nhs.
  13. Melissa Macdonald, CB (2020) Nursing workforce shortage in England. Available From: https://researchbriefings.files.parliament.uk/documents/CDP-2020-0037/ CDP-2020-0037.pdf

New Building in an Established Residential Neighborhood: Understanding Local Issues Using a Template-driven, AI-Empowered System

DOI: 10.31038/GEMS.2024654

Abstract

The paper presents the use of AI-generated ideas in a study on evaluating offers by a builder to local neighborhood regarding use of land for building new development. The novelty of the approach comes from the use of AI-generated material evaluated by human respondents, and the use of such approach to help create an efficient system to deal with local issues. The paper moves the emerging science of Mind Genomics towards dealing with the everyday problem of negotiations about civic and property issues, showing the power of AI (Idea Coach) to make the process affordable and doable in real time.

Introduction

In the ‘project of science’ research studies are assumed to emerge as efforts to contribute to a picture of ‘how the world works.’ Those who publish their investigations are often described as ‘filling gaps in our knowledge.’ Indeed, much of the edifice of science rests on the practice of what is called the ‘hypothetico-deductive’ system, the system which requires that the researcher propose a hypothesis and do the experiment to either support the hypothesis or falsify it. It is by the accretion of such studies that the edifice of science is created, the picture of the world [1]. The assumption in science is that the researcher somehow ‘knows’ a great deal about the topic and can identify what might be the next experiment to perform. The experiments often end up as simple reports, supported by statistics, and introduced by detailed literature reviews. The research ends up being done and incorporated into the edifice. At the other side of the project of science is grounded theory [2]. Here the researcher does a study or reports a set of observations. It is from those observations that hypotheses emerge. Once again, however, the effort assumes at the start that the researcher does the experiment, and thus implicitly assumes that the researcher is beginning with a knowledgeable conjecture.

What then happens in those increasingly frequent cases where the issues are new, or at least new combinations of old issues, and where there has not been sufficient time to create a literature, or even to develop grounded theory and hypotheses? Can a method be developed which allows the exploration of issues in a manner which is quick, simple, yet profound in the depths of information and insight that it can promote, and even create? This paper presents such an approach with a worked example, and a timetable of events. The topic concerns repurposing and redeveloping land in a way suitable to the existing community while allowing the developer to maximize profits.

The approach presented here, Mind Genomics, comes from a combination of three disciplines, and has evolved since the late 1990’s. The disciplines are:

  1. Consumer research. This area of applied science studies the way people make decisions about the topics of daily life.
  2. Mathematical psychology and psychophysics; The study of how we subjectively ‘measure’ external stimuli and situations in our ‘mind’, to create an algebra of the mind. For the current topic of environment and health, mathematical psychology and psychophysics will help us create the structure of how we think about topics.
  3. Statistics, specifically experimental design. This is the study of how we can combine different variables to represent alternative ‘realities’, these realities equivalent to different descriptions of how the world works. The normal, everyday experience of the world comes in packets of stimuli, not in single ideas. Rather than surveying the person, giving that person single questions, we create combinations of those questions, and give the person these combinations. The person then rates the combinations on a defined scale.

The issue dealt with in this paper comes from a real situation lasting several years. The issue was the sale of a large plot of land on which previously was a now bankrupt golf club. As is the case with many similar pieces of land, the golf club extended over a large area, encompassing different types of land, presenting different types of issues such as a small lake in the premises, and of course the houses that had been built in proximity to the golf course over the period of a century.

The case itself, with the different points of view espoused by local homeowners, by the local city government, and by the builder brought up the possibility that cases of this type might be amenable to study using Mind Genomics. The ingoing notion was that one could define the situation, use AI (artificial intelligence) to suggest reasonable questions and answer, and then test responses to those answer among real people. The objective was to see what would emerge from this exercise, and whether there might be an opportunity to bring Mind Genomics into an entirely new world.

Applying Mind Genomics to Legal Issues and the Law

The origin of Mind Genomics can be traced to experimental psychology, and specifically to the study of perception. After years of experiments relating physical stimuli to sensed quality and magnitude, respectively, the notion of measuring ideas began to take shape [3,4]. Researchers have long measured the strength of ideas using a rating scale, with the respondent presented with a variety of different single ideas and asked to rate each idea, one at a time, in terms of importance. This approach, the typical questionnaire, although simple to do and quite popular, does not really get at the notion of measuring the power of meaningful ideas. Rather, the questions ask for the magnitude of general classes, such as the importance of general features, e.g., the importance of affordability, the importance of ecological stability, and so forth.

At least two key issues emerge when researchers work with questionnaires.

  1. The misleading simplicity inherent in general questions. People live in a granular world, not in the world of the general. To talk about general aspects of an issue, e.g., service, price, and so forth, requires that the survey respondent abstract a single answer from a variety of experiences. The abstraction may be simple and straightforward, but the reality is that the survey respondent has to understand the aspect being questioned, pull up the specific experiences (unknown to the researcher), and then assign a rating to the memory of the issue or topic. In other words, no one really knows the basis on which the survey respondent is assigning the rating,
  2. The desire to give the right answer to the interviewer, or now to the interviewing machine. Again, and again researchers are faced with the conscious or often subconscious desire by survey takers to give the ‘right’ or the ‘politically correct’ answers. Indeed, when respondents are academics, they are often the most vocal about questionnaires, insisting that the answers be simple, so that the survey taker is not at all confused. This ends up allowing the survey taker to ‘game the system’, producing the occasionally misleading result, such as what happened in political polls with surveys about voting for a new term for then President Trump [5].

The Mind Genomics approach emerged from studies about decision making [6], not so much with the desire to avoid biases as with the desire to present to survey takers or research respondents with more meaningful test stimuli. Rather than asking the respondent to rate the single ideas, the early research efforts presented the respondents with combinations of ideas, vignettes, which presented a situation. The respondent was to either choose between two vignettes in terms of some criterion (e.g., preference) in what was called a ‘choice experiment’ (ref) or was to rate the vignette, this combination, on a scale. In either case the ratings of the choices were analyzed to show the ‘driving’ power of each individual component of the vignette. Respondents were not required to intellectualize, but simply to choose. In the Mind Genomics system, the vignettes, combinations of ideas or messages about a topic, are created according to a systematic plan called an experimental design. Rather than presenting respondents with single ideas, Mind Genomics presents the respondents with sets of ideas or elements. These messages are combined into vignettes by the experimental design in a way which allows each vignette to contain a small number of different elements, a minimum of two, and a maximum of four. In this way the vignettes are short, easy to read or more realistically to ‘scan’ as the researcher grazes across the vignette taking in the relevant information.

The Mind Genomics system creates 24 unique vignettes for each respondent or survey taker. That is, the 24 vignettes created for the first respondent are different from the 24 vignettes created for the second respondent, etc. Furthermore, the vignettes are set up so that a valid, powerful statistical analysis, OLS (ordinary least squares) regression can be performed on the results from one respondent, independent of all of the other respondents. The uniqueness of the 24 vignettes is guaranteed by a permutation algorithm [7]. The variables themselves, the elements or messages, are coded in a simple fashion, namely present or absent, called ‘dummy variable coding’ [8]. The happy result is that the researcher can identify a topic, and simply explore the topic by creating different elements or messages bout topics relevant to the topic. There does not have to be much up-front thinking. That is, the structure of the Mind Genomics design promotes exploring of different ideas, promoting experimentation and data rather than extensive army chair hypothesizing. In some quarters this up-front thinking is called ‘analysis paralysis’ … over analyzing the problem up-front before doing the experiment. In this paper we explore the use of Mind Genomics as a rapid, inexpensive tool to deal with a local problem, a problem which has proved to be fractious. The problem involves the activities of a builder in a local residential area, the building having purchased the lands belonging to a defunct golf club, the builder desirous of building single family houses on the land to maximize sales revenue after the construction. We explore how this problem can be approached by a combination of AI, artificial intelligence, to suggest ideas, and people, to evaluate these ideas.

Setting Up the Mind Genomics Study

The Mind Genomics platform uses a templated approach, the template having evolved over a 30-year span since the introduction of its predecessor, IdeaMap®, during the 1993 conference of ESOMAR in Copenhagen [9]. By templating the approach, it became possible to fulfill the objective of ‘democratizing research’ world-wide, making it possible for anyone to understand the mind of people as they make decisions about the topics of the everyday

Step 1 – Name the study (Figure 1, Panel A)

‘Naming’ seems to be a simple task, but the sheer effort to reduce the research to a word or two focuses the researcher’s mind. Often the naming step turns into an exercise to hone the ‘big idea’ into something tractable, a realization which emerges after the effort is success. All too often those researchers who are new to Mind Genomics end up trying to name their study using a long phrases which ends up constraining the thinking. Forcing the researcher to use a short name opens up the researcher to thinking about the topic in a more creative fashion.

Step 2 – Develop Four Questions or ‘Categories’ Pertaining to the Topic (Figure 1, Panel B)

It is at this step that many researcher become unusually nervous as they begin to stumble about. This inability to craft questions seems endemic, across ages and cultures. It seems almost that we are taught to answer questions, but not taught to pose questions. Even seasoned researchers react with consternation and frustration at being asked to come up with four questions which ‘tell a story’, or at least four questions which end up painting a coherent picture of a topic (Figure 1).

The requirement to create four questions became simpler to fulfill with the advent of available AI, specifically ChatGPT 3.5 [10]. AI was incorporated into the BimiLeap program through Idea Coach, a program specifically developed to create questions. When invoked, Idea Coach required that the research specify the topic, background, and the nature of the level of the answer. Idea Coach would then return with 15 proposed questions from which the research could select 0-4 questions and drop those questions into the study. Idea Coach allowed the researcher to modify the specification if desired, or maintain the specification, and afterwards re-run a second time. By running the Idea Coach many times, the researcher would end up creating separate sets of 15 questions, few repeating questions, but many new questions. The ability to request Idea Coach to produce sets of 15 questions was augmented by a summarizer, with each set of 15 questions separately summarized through AI. Thus, in a matter of five minutes or so, the researcher could create up to 10 different sets of 15 questions. These sets of 15 questions would be stored in an Excel workbook. At the end of selecting the questions and answers (see below), the BimiLeap program would then take each of the pages of questions or answers, 15 per page, and summarize that page with a fixed set of AI based queries. Table 1 shows an example of one page of questions, ad the Idea Coach summarization available almost immediately after program set-up. When considering the depth of information in Table 1, one can appreciate the ‘education’ virtually immediately available to the researcher who knows little about the topic, an education which otherwise might have required a year of intensive research.

FIG 1

Figure 1: Panel A – name the study. Panel B – create four questions Panel C – create four answers to question #1.

Table 1: Summarization by AI of Idea Coach’s first iteration of 15 suggested questions, generated in the effort to create four test questions for the Mind Genomics experiment.

TAB 1(1)

TAB 1(2)

TAB 1(3)

Step 3 – Create Four Answers to Each of the Four Questions (Figure 1, Panel C)

Table 2 shows an example of 15 answers returned by Idea Coach as an attempt to answer Question #1. It is worth noting that the actual question posed to the Idea Coach moves beyond the simple question. The prompt requests that the answer ‘explain in depth’, as well as being both short (fewer than 15 words), and understandable to a 12-year-old. It is in this way that the researcher works with the AI in Idea Coach to craft a reasonable set of answers that the respondent can understand when participating in the Mind Genomics experiment. Table 2 shows both the ‘edited question’ and the first set of answers. Once again the summarizer works on each set of answers. Thus, once again the Idea Book, viz., the summarized sets of different sets of 15 questions or answers provides in 20 minutes of effort what night have taken a year or two.

Table 2: First set of answers to Question #1, followed by AI summarization of these 15 answers.

TAB 2(1)

TAB 2(2)

TAB 2(3)

TAB 2(4)

Step 4: Raw Materials Test Stimuli – Elements (Phrases Painting Word Pictures) Combined by Experimental Design

The actual raw material ends up being 16 different phrases, four selected as answers to each of the four questions. Table 3 shows these four questions and their answers. The questions and answers were generated by the combination of the researcher and the AI embedded in Idea Coach. It is important to keep in mind that the researcher is able to edit the elements at any time before the actual experiment wherein human respondents will evaluate the test stimuli.

Table 3: The final questions and their associated answers (elements).

TAB 3

Step 5: Create the Test Stimuli, Vignettes, Using Experimental Design

The actual stimuli rated by respondents comprise vignettes, combinations of the 16 elements. The combinations are specified by an underlying experimental design, which prescribes 24 different vignettes. Each vignette comprises a minimum of two elements and a maximum of four elements, at most one element from a question. There is no effect made to connect the elements to each other. Rather, the elements are presented in a simple, stark fashion, with one element atop the other. This starkness makes it easier for the respondent to scan the vignette and assign a rating, instead of forcing the respondent to dig through a mass of text to identify the salient messages. In author HRM’s experience, presenting respondents with complete paragraphs, connectives and all, with grammatically correct sentences ends up fatiguing the respondent by forcing the respondent to engage with the material in an effortful manner through the effort reading rather than simple inspection.

The 24 vignettes for each respondent differ from each other, as noted above [7]. This set of differences ensures that the vignettes cover a great number of possible combinations in the so-called design space, allowing the researcher to quickly explore the topic without having to know much about the topic at the beginning. Furthermore, the 24 vignettes are set up for individual-level analysis of OLS (ordinary least squares) regression, necessary when the research goal is to discover how each element drives the rating. Finally, the vignettes more naturally approach what might be experienced, because the respondent has to deal with combinations of elements and cannot game the system. There is no apparent pattern, forcing the respondent to stop looking for a pattern, and simply to respond naturally. In other words, the system frustrates the search for patterns, making the respondent guess in a fashion which seems unmotivated, but which ends up working effectively.

Step 6: Create a Set of Self-profiling Questions Which Allows the Researcher to Better Understand the Mind of the Respondent

The Mind Genomics platform automatically requests the respondent to provide information about gender and age, and then gives the researcher an additional eight questions to use, each question allowing 2-8 possible answers, from which the respondent is instructed to choose one answer. In the data analyses these groups Table 4 presents these self-profiling questions and answers, along with the rating scale (see Step 7). Figure 2, Panel A shows the respondent experience when presented with these self-profiling questions, at the start of the experiment.

FIG 2

Figure 2: The respondent experience. Panel A – The pull-down menu for the self-profiling questions. Panel B – example of a screen showing the vignette along with the introduction and rating scale.

Table 4: The self-profiling questions (Section A), and the introduction to study topic, and the rating scale (Section B).

TAB 4

Step 7: Create the Introduction to the Vignettes, and the Rating Question for Each Vignette

The respondent first reads an informative introduction to the situation, and then is presented with 24 ‘screens’, each ‘screen’ comprising a shortened version of the introduction, the rating scale, and then the vignette. The rating question focuses on the mind of the respondent. It is through the rating question that the researcher will end up understanding the way the respondent thinks about the topic. The introduction and rating question appear below. Note that the rating question asks the respondent to select the answer, with the answer have ‘two sides.’ The two aspects are the nature of the concessions by the builder (good versus poor), and acceptance by the community of the concession (accepts versus rejects Figure 2, Panel B shows an example.

Figure 2: The respondent experience. Panel A shows the pull-down menu for the self-profiling question. Panel B shows an example of the short introduction to the vignette, the rating scale, and then one of the vignettes. The respondent will see 24 screens similar to Panel B, as well as a first ‘training’ screen (Figure 2).

Step 8: Collect the Data by Internet-executed Experiment and Prepare the Data for Statistical Analysis

Respondents in the New York state area were invited to participate. The respondents were to have incomes above $40,000, and 30 years or older. The respondents were members of various on-line research panels, available to Luc.id Inc., a panel aggregator. The respondents were invited by email. Those who participated pressed a link embedded in the email invitation, were led to the study, read the introduction and proceeded, first with the self-profiling questions, and then with the test vignettes.

The BimiLeap program collected the ratings and created a database. The database comprised 24 rows. Each row corresponded to one of the vignettes evaluated by the respondent. The first set of columns were devoted to identifying the study, the respondent, and the self-profiling information for the respondent, respectively. The second set of columns show the order of the vignette (1 to 24), and the composition of the vignette, expressed as 16 columns, one column for each of the 16 elements, respectively. When the element was present in the particular vignette the cell was given the value ‘1’ When the element was absent from the particular vignette the cell was given the value ‘0’. The final set of columns showed the rating, and the response time (RT) in 100ths of a second.

The data collected must be transformed for subsequent analysis by OLS (ordinary least-squares) regression [11]. OLS will relate the presence/absence of the 16 elements (Table 5) to the dependent variable.. The scale is set up to allow for several dependent variables:

R5x – good concession, neighborhood accepts. The rating of 5 transformed to 100, ratings of 1,2,3 and 4 transformed to 0.

R3x – cannot decide. The rating of 3 transformed to 100, rating of 1,2 4 or 5 transformed to 0.

R54x – good builder concession. Rating of 5 or 4 transformed to 100, rating of 1,2 or 3 transformed to 0

R52x – neighborhood accepts. Rating of 5 or 2 transformed to 100, rating of 4,3 or 1 transformed to 0.

R41x – neighborhood rejects. Rating of 4 or 1 transformed to 100, rating of 5, 3, or 2 transformed to 0

R21x – poor builder concession. Rating of 2 or 1 transformed to 100, rating of 5,4 or 3 transformed to 0.

After the transformation was made, a vanishingly small random number was added to the newly created transformed variable in order to add the needed variability to allow the OLS regression to ‘run’, and not ‘crash’. When the OLS regression encounters a dependent variable with no variability, the analysis crashes. The very small number (<10-4) is a prophylactic measure which ensures against crashes.

Table 5: Parameters for linear models for the total panel relating the presence/absence of the 16 elements to the binary dependent variables and to response time (RT). The elements are sorted by the coefficient for R54.

TAB 5

Step 9: Use OLS Regression to Relate the Presence/Absence of the 16 Elements to the Newly Created Binary Dependent Variables

The OLS regression is run on the full set of 2424 cases, 24 cases or observation for each of the 101 respondents. The equation is simple, showing the degree to which each of the 16 elements ‘drives’ the newly created binary scale, as well as how the elements drive response time.

Dependent variable = k1A1 + k2A2 +… k16D4

The equation does not have an additive constant. Previous analyses incorporated the additive constant as the 17th term of the equation. Although somewhat more statistically ‘rigorous’, estimating the additive constant created problems in the comparison of the coefficients across groups, and across studies. Analysis of the coefficients estimated with versus without the additive constant in the equation showed that the coefficients were of different values, as expected, but strongly and positively correlated with each other. Strong performing elements were strong whether estimated with an additive constant or without an additive constant. Table 5 shows the coefficients for the different binary dependent variables, and the response time. The top of Table 5 shows the meaning of the dependent variable. For this study, the key dependent variable will be R54x, a good concession from the builder, but it is instructive to consider all of the binary dependent variables and the response time. Most concessions offered by the builder were seen to be positive. Coefficients for R54 equal or greater than 21 are shown in shaded cells. Despite the strong performance of most elements, however, there is no sense of a pattern in the mind of the respondents. The coefficients are close together, hovering around 21, some coefficient lower, some coefficients higher.

Table 5 shows a ‘flatness’ of rating value across the elements. Of course, in the absence of anything else the researcher could simply look at the strong performing elements, and stop there, listing out these elements, as well as listing the. Table 5 does not reveal a clear relation between strength of performance and long response time.

Uncovering Different Ways of Thinking about the Topic Through Mind-set Segmentation

A hallmark of Mind Genomics is that people differ from each other in the way that they think about a topic, with these different ways not necessarily being random person to person variation. Rather, many studies suggest that when it comes to the topic of the everyday world, people’s different opinions about aspects of the topic appear to form clearly distinct groupings, mind-sets in the language of Mind Genomics, clusters in the language of statistics [12]. These differences in the way people think about topics is clear when we deal with products, especially food, but also many of the products and services that we purchase and consume [13]. The differences emerge in responses to social issues, and clearly emerge in the law, except perhaps for one topic, murder, where these mind-sets do not seem to loom large [14]. With the prevalence of mind-sets in the population, can we find these mind-sets in the population of our 101 respondents who are dealing with the issue of their response to builder concessions with regard to building of a community of stand-alone houses in a community. The large number of high positive coefficients for the 16 elements in Table 5 (Total Panel; R54x) presents us with an interesting possibility, namely that all of the elements are positive, viz., that all of the builder concessions appear to be good ones. Faced with this somewhat flat distribution of coefficients from a low of +17 to a high of +23 for R54x (good concession), will this case of builder concession become an example of how there are no clear mind-set?. The possibility is certainly real. Nothing dictates that every issue should comprise within it radically different mind-sets. Attitudes about builder concessions may be shared by all people. Table 6 shows the outcome of clustering the 101 respondents, first into two clusters or mind-set, then into three clusters or mind-sets. The method of clustering, k-means, divides the 101 respondents by the pattern of their 16 coefficients. The distance between any two respondents is defined as (1 – Pearson R, or correlation coefficient). The Pearson R ranges between a value of 1 when two sets of objects, e.g., coefficients, align perfectly, viz. are parallel, going in the precise same direction, and a value of -1 when two sets if objects move in opposite direction. The k-means clustering technique is purely mathematical, attempting to satisfy several criteria at the same time [15].

Table 6: Results from the segmentation of respondent on the basis of R54x, builder provides good concessions. The criteria for ‘strong performing’ element has been increased from the conventional value of 21 to a more stringent value of 25+ in order to allow for clearer definition of the nature of the mind-sets.

TAB 6

The clustering was done on the coefficients for R54, viz., perception that the builder concessions are good. One could also do the clustering on the basis of R52, acceptance of the builder concessions, but for this paper we focus only on R54x. Table 6 shows a great number of positive coefficients, magnitude 21+. The coefficient value of 21 may be too lenient a criterion. In Table 6 we highlight the coefficients of 25+, making the criterion more stringent. The two-mind-set solution can be more easily interpreted than the three-mind-set solution. With this more stringent criterion in place the mind-sets may be interpreted as:

Mind-Set 1 of 2 – Focus on a pleasant environment for both people and wildlife

Mind-Set 2 of 2 – Focus on traffic as well as maintaining the local environment.

Coming to an Agreement

The relative flatness of the data in terms of range, along with the strong performance of many of the elements in terms of how good the respondents feel about the builder concessions generates a situation not typical to Mind Genomics. For most topics dealt with in previous studies, the experiment presented above have shown clearly different mind-sets. Perhaps the only case where there has not been clear and strong differences between or among mind-sets has been the case of murder [14]. Yet, here we have the situation of most elements being positive. The issue now evolves to selecting the best element from the total panel, C3. Orient houses away from potential noise sources, such as major roads or industrial areas, to minimize noise impact on residents. The wisdom of selecting C3 is confirmed by listing the strong performing elements for both mind-sets, as is done in Table 7. The table shows the strong performing elements for both mind-sets. C3 is common to both mind-sets and thus should be the key concession accepted by the local community. In addition, the negotiation might consider two other requests from the builder, in order to satisfy the two mind-sets:

Mind-Set 1: D1    Create nesting areas, bird boxes, and other structures to encourage wildlife to thrive within the golf course environment.

Mind-Set 2: C4    Establish a community noise complaint resolution process, where residents can voice their concerns, and ensure that their issues are addressed promptly and effectively.

The benefit of a Mind Genomics experiment in this case emerges as a way to find ‘second best’ ideas that will work for the different mind-sets.

Table 7: Selecting the best single concession (C3) and one additional concession to satisfy each mind-set more deeply.

TAB 7

How Good are the Ideas the Ideas – Index of Divergent Thought (IDT)

A continuing issue in Mind Genomics revolves around the topic of the elements, specifically are the elements ‘good’ or ‘poor’. This question is relevant, indeed increasingly so, as the ability of people to think critically seems to be diminishing. Certainly, the pre-AI days showed that the effort to create four questions ended up being a frustrating experience, and a clear stumbling block to the use of Mind Genomics. It was only after the introduction of AI in the form of the Idea Coach that the task became easier. Let us now merge the use of AI with the specific topic dealt with here, viz., the issues regarding the concessions offered by a builder. The elements were developed in conjunction with AI. The data suggest a large number of strongly positive elements. In order to quantify the true strength of the ideas, a computational method should be developed which accounts for the strength of the elements, as well as the proportion of the population among which the elements perform strongly. Thus, the underlying ‘thinking’ becomes much more impressive when the elements perform strongly, viz., have high coefficients, with large groups in the population. In contrast, when elements perform strongly, but only among a small size group of respondents in the population, we can say that the thinking is not quite as good. Table 8 shows the computations leading up to the IDT, the index of divergent thought. The IDT provides one empirical way to measure the strength of performance. The IDT ends up being the square root of the weighted sum of square of all the elements with positive coefficients, across six groups: total panel, the two mind-sets, and the three mind-sets, respectively. Typical results in the past have ranged from a low near 55 and a high near 75. The 87 generated in this study suggests that the thinking is particularly good, perhaps aided by the fact that the strong performing elements because there are no counter-current patterns generated by mind-set with opposing ideas. That is, the basic ideas are good, that good performance reinforced by the similar patterns of mind-sets which differ only slightly from each other.

Table 8: Computation of the IDT, Index of Divergent Thought.

TAB 8

Deeper Thinking about Mind-sets for R54 (Good Builder Concessions) Using AI Summarization

The final analysis for this rich set of data regarding a local community issue comes from the AI summarization of the strong performing elements for R54 (good builder concessions), done for the two mind-sets. Table 9 shows the summarization, based upon a series of queries submitted to AI (Idea Coach), which looked only at the elements with coefficients of 21 or higher for the mind-set, for dependent variable R54. The AI provides the researcher with what ends up being a ‘second pair of eyes.’

Table 9: AI summarization of the strong performing elements for the two mind-sets, based upon the coefficients for R54 (Good concession from the builder).

TAB 9(1)

TAB 9(2)

TAB 9(3)

Do Open Ended Comments Give Any Deeper Insight into the Mind-sets

After the respondent finished rating all 24 vignettes, the respondent was presented with the instruction to answer the following question by writing one or more sentences: How does being a judge about this negotiation between builder and community make you feel? Table 10 shows the AI summarization of the open ends, with slight editorial changes by the authors to make the summarization more relevant to parties in a negotiation. The summarization was done by QuillBot, an AI editor [16]. The differences between the mind-sets emerge in Table 10, but once again the differences are a matter of ‘shading’ rather than of radically different points of view.

Table 10: AI summarization of the open-ended question.

TAB 10

Discussion and Conclusions

The goal of this paper, dealing with a local property development issue, represents a new direction for Mind Genomics, one perhaps frequently encountered in legal and professional circles, rather than in research papers. The original efforts of Mind Genomics were based in the effort to understand the preferences of people for the ‘stuff’ of everyday life, whether products or services. The almost universal finding from all of the Mind Genomics experiments was the emergence of a limited number of clearly defined mind-sets. When the research moved to political polling [13] or to social research of serious problems [17] clearly different mind-set once again emerged. It is only with problems of the local community that we see the absence of such strong mind-sets. The mind-sets do emerge, as they must with statistical processing forcing them out of the data. However, the mind-sets are similar to each other in the response to most of the messages. It is only the ‘shading’ of the responses where we find differences, and where we struggle to come out with these different groups. The subtlety of point of view of such issues has already been recognized, although not in the language of Mind Genomics [18-22]. As we go through these results, the question now emerges as to how to treat differences of opinion in the situations where the mind-sets reflect modest quantitative differences, shadings of opinion rather than striking differences. It may well be that in many situations dealing with negotiations, the different offerings brought by the parties are almost all equally acceptable. In such cases Mind Genomics may reveal an entirely new opportunity to study the way people make decisions, not so much in the world of preference patterns but rather in the world of graduated ‘give and take’, the world of subtleties in negotiation, rather than dramatic differences in thinking about a topic.

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