Experiences may be complicated by living at the intersection of systemically oppressed identities, including gender, race, social class, and cancer-related disability. Using the Black Feminist Thought (BFT) framework and the PEN-3 cultural model, this qualitative study sought to: (a) understand African American women breast cancer survivors’ lived experiences; (b) examine how the multiple intersecting factors of race, gender, social class/socioeconomic status, and cancer-related disability impact their quality of life; and (c) inform future health promotion programming that is culturally relevant to AAWBCS to improve their quality of life. (2) Methods: Seven focus groups were conducted with 30 African American breast cancer survivors in a Midwestern metropolitan region. Focus groups were audiotaped and transcribed verbatim. Framework analyses were conducted to identify themes with NVivo qualitative analysis software. (3) Results: Four themes emerged: (a) caregiving roles provide both support and challenges for survivors, (b) the “strong Black woman” is inherent in survivor experiences, (c) intersectionality impacts survivorship, and (d) African American women resist oppression through culturally specific supports and advocacy. (4) Conclusions: The intervention point of entry should be at the peer support group level and centered on family and provide community-based support and services. Future research should move upstream to address social determinants of health, including racism, sexism, and ableism; there is a critical need to discuss how structural racism affects health care and develop interventions to address racial discrimination and racial bias in health care. Breast cancer is the most common cancer diagnosed in women and the second leading cause of cancer-related death among U.S. women. African American women experience disparities in breast cancer survival and are 42% more likely to die from breast cancer than their White counterparts . While aTo better understand the unique experiences and challenges of AAWBCS, this study applied the Black Feminist Thought (BFT) critical social theory as the framework. Established by Patricia Collins as a critical social theory, BFT centers the experiences of Black women while asserting that they experience life at multiple intersections of oppression, including race, class, gender, and sexual oppression ,5. This BFT has been used to explain the adverse health outcomes, including the lower rates of breastfeeding among Black women  and the Garnering “intersected” knowledge is not enough. Our ultimate goal is to reduce breast cancer disparities by translating this knowledge into health promotion programming. To inform the development of culturally relevant intervention programming, this study applied the PEN-3 cultural model ,15. The Previous studies have used the PEN-3 model to inform various breast cancer research among African American women. For example, the PEN-3 model was used to guide qualitative studies to make cultural adaptations to breast cancer education pamphlets to (1) acknowledge African American cultural values related to community, self-reliance, and spirituality ; (2) optGuided by the BFT intersectionality framework and the PEN-3 model, this study will determine the intervention points of entry. These may occur at the level of persons , extended family members , or neighborhoods (communities). The second dimension, relationships and expectations, is used to determine the perceptions, enablers, and nurturers that impact survivors’ health behaviors, such as self-care or healthful lifestyle behaviors. Perceptions include the knowledge, attitude, values, and beliefs that either facilitate or hinder a woman’s behavior, e.g., reliance on God for cancer coping ,22,23. ETo our knowledge, this study will be the first to explore the intersectional experiences of AAWBCS through a qualitative inquiry process. By centering intersecting identities, recommendations attend to AAWBCS in their entirety and avoid segmenting African American women’s identities. Using qualitative methods and applying the BFT framework and the PEN-3 cultural model, the current study’s objectives were three-fold: (1) to understand AAWBCS’ lived experiences, including their challenges and resilience during and following treatment; (2) to examine how the multiple intersecting factors of race, gender, social class/socioeconomic status, and cancer-related disability impact quality of life in AAWBCS; and (3) to inform future health promotion programming that is culturally relevant to AAWBCS to improve their quality of life.Participants were recruited from health-care provider referrals, African American breast cancer support groups, and community agency referrals in a Midwest metropolitan area of the United States. In addition, recruitment flyers were placed in various community locations . The inclusion criteria were: (1) self-identifying as a Black/African American woman and currently living in the study area; (2) adults aged ≥18 years; (3) diagnosed with noninvasive (stage 0) or operable invasive breast carcinoma ; (4) not diagnosed with any other types of cancer; (5) finished “active” cancer treatment  in at least a six-month span; (6) ability to read and speak English; and (7) be accessible by telephone. Exclusion criteria included being currently pregnant or undergoing therapy for life-threatening illnesses. Written informed consent was obtained at the beginning of the focus group sessions.Recruitment, enrollment, and the focus groups occurred during 2016–2017. Focus groups were conducted in a small community-accessible conference room. Each group lasted approximately two hours and was audio recorded and moderated by a trained research assistant, who is an African American woman. The moderator followed a standardized group discussion guide. This study used a protocol starting with open-ended exploratory questions related to what it means to be an African American woman who survived breast cancer in general and within the African American community. The interview guide was developed in alignment with the BFT theory to reflect AAWBCS’ lived experiences at multiple intersections of oppression, including race, class, gender, and sexual oppression ,5. Then,Audio recordings were transcribed verbatim and analyzed thematically. Qualitative analyses were implemented using computer-assisted coding and memos . Qualitative data analysis procedures were based on the framework analysis methodology by Krueger and Casey . The anaA total of 30 survivors participated in seven focus groups, with an average of four participants per group. Of the 30 participants, 70% percent were 55 or older. Based on self-reported marital status, twelve (40%) had never been married. In regard to educational attainment, 23.3% of participants had completed some high school, 23% were high school graduates, 37% had completed some college or technical school, and 16.7% were college graduates. Regarding income, more than half of the participants (56.7%) reported an annual household income of less than $20,000.Four themes emerged in the analysis of data: (1) caregiving roles provide both support and challenges for survivors, (2) the “strong Black woman” is inherent in survivor experiences, (3) intersectionality impacts survivorship, (4) African American women resist oppression through culturally specific supports and advocacy. Incorporating these themes, the PEN-3 cultural model provides culturally responsive recommendations for health promotion programming.Traditional gender roles may position women to take on more caregiving in their families, which include cooking, cleaning, and caring for parents, children, and grandchildren. These roles emerged as both motivators for survivorship and challenges in maintaining health. Survivors expressed that caring for their families provided them with purpose, self-worth, and motivation. One participant stated:“Because I tell my grand babies I live for them. They is what gives me joy. They is what give me the strength I need because when I feel depressed, I feel lonely, I feel like I don’t want to go outside, I don’t want to make no phone call, I got to keep it real … And then when I get that phone call or they just pop up at my door, there it is. It’s like … something just click. You know what I’m saying? And my grandkids is what give me life. And I tell them that all the time, ‘I live for y’all. Y’all give me the strength, the joy that I need to keep keeping on.’”Another participant shared experiences caregiving for her grandson in the morning. She explained his concern for her slipping in the cold while they waited for his bus:“‘Go back, grandma. You gonna fall out and who gonna pick you up! … Go back, grandma … it’s slick out here,’ he can tell me, ‘You gonna fall and who gonna pick you up?’ I said, ‘You gonna get me up…’ But I- it’s- that keeps me going.”While family demands are motivating, they can take a toll and impact on survivors’ physical and mental health. Survivors report exhaustion and fatigue in caregiving and little external social support to assist in these gender-defined roles. One participant shared:“Yup. I did, because I put my foot down with my son and told him … ‘You got to come get your kids. I’ve gotta bathe them, I gotta feed them. I’m getting old, tired, whatever.’ And I’m like that, getting so I can’t go through this … I can’t cuz I get too tired. I be so tired … I said, ‘Y’all gonna send me to my grave early.’”For those in heterosexual relationships, women rarely mentioned men assisting in caregiving roles, or shared that men presumed women would maintain their caregiving roles through their cancer recovery. As one participant expressed, expectations fell on her shoulders:“My stuff is always, my husband’s, nothin’s never wrong. They always pass it all on to me. Um. I don’t know. I work every day. I take care of my mom. She’s 94. And I’m not, I’m busy doin’ whatever I need to do. Drive. Do normal. Men think we’re invincible, so, you know, do what you have to do.”Previous researchers have labeled the construct that African American women use to describe their lives and experiences as the “strong Black woman”, which is characterized by the promotion of unfaltering toughness (strength), resilience, self-containment, and self-sacrificing  ,32. The “Because even through all this I’m goin through I still manage to be there for my sister, my family. You know, I’m doin that. Because I’m strong enough to do it. Even when I was like really sick and from like all we need to be, I was out there tryin to do somethin’.”Survivors were able to draw upon a strength identity and continue many aspects of their lives, sometimes without their family knowing they had breast cancer. Some women shared that they did not disclose their diagnosis to anyone. One woman waited a year to tell her children she had breast cancer, stating:“I didn’t want to hurt them. And I didn’t tell anybody in the family … Because I was afraid I would devastate them … And I lived with it for that year and then when I did tell them, that devastated them more.”While adhering to the strong Black woman role can cause self-denial of needs, seeking help was necessary to deal with struggles in survivorship, including social anxiety, depression, phobias, and panic attacks. This was reflected by one survivor who stated:“I couldn’t come out my house for almost two years … after that … I was having really panic attacks and instead like I would just get really hot. It felt like, you know how you could be in a, uh, the lunchroom, how you just hear voices, just you hear everything everybody is saying…”In line with emerging research, themes suggested that African American breast cancer survivors identify with the strong Black woman role and that adherence to this role may be both protective and detrimental to various aspects of survival and quality of life.The third theme is how intersectionality impacts survivorship. It is closely related to the fourth concept of BFT—that African American women live at the intersection of race, social class/socioeconomic status, and gender oppression. The oppression that comes from intersecting and marginalized identities can make survivorship for African American women more challenging. Survivors shared concerns related to finances, unsafe neighborhoods, health insurance, and access to healthy food. Having a low income left some survivors dependent on financial assistance/grants, and while many shared positive experiences, these support mechanisms were difficult to navigate and frequently provided only short-term solutions. The limited and short-term nature of financial assistance left some women constantly needing to seek assistance. However, dealing with disability from cancer made navigating these processes more difficult. Exacerbating these challenges, a few participants shared experiences of racial discrimination as an additional barrier to receiving services. As one participant shared:“I don’t mind exposing his name because he deserved exposing, Dr. XX at the time, was at the XYZ hospital but wouldn’t come and see me. And um, so I got out of the hospital and I went to his office and I asked why didn’t you come and see me. He said “Well, there’s nothing we can do for you.” And my husband was like “Man, you her doctor, why wouldn’t you come and at least check in on your patient, and we actually saw you walking around the hall and you totally ignored her.”Another participant shared her painful experience because the doctor did not acknowledge or know who she was:‘’I had that experience with one of my oncologists when I went through my cancer thing and it really, really hurt my feelings just the fact that he had, didn’t quite acknowledge me, um, you know when I was in his office getting chemo. One day I was sitting for some test that he had referred me to and he walked right past me like he didn’t even know who I was. And you know, seeing his face every day for chemo. So when he did that to me and he didn’t acknowledge the face and then every time I came with him with questions, he just like brushed it off. He- it’s like my family would ask him things about me and what I was going through and he just- he wouldn’t give us answers. He just basically just brushed it off.”Social class impacts where women live, and the intersection between race and social class positions people of color in racially segregated neighborhoods with more deprivation and less access to health and social services . Some wo“I don’t know, if you want to do something you have to go so far out, stores have moved out of the neighborhoods … Because it used to be, maybe it still, can you go, you used to be able to go to market, general hospital or whatever, but they’ve moved. All of those things, out of your neighborhood. You don’t have access to it.”The challenge of seeking resources is exacerbated by living at the intersections of oppression. If African American women did not live in racially oppressed and isolated neighborhoods, their services “would not be so far out”, and traveling further would not be as challenging if they were not survivors dealing with health impacts from cancer.African American women breast cancer survivors resist oppression through activism and advocacy within their community. Survivors mobilize in culturally relevant ways that allow them to thrive, particularly through spirituality and with their churches. They shared a desire to educate others about breast cancer, promote screening, and spread hope. Survivors participate in breast cancer walks, mentor others, and host their own events. As one participant shared:“Like my cousin, she throws a pink party every year, and it’s just for people in the family to come, and she has like brassieres and stuff like this just to inform them, educate, because, you know, back in the day it was something you didn’t really know about. You shied away. You thought it was something negative. But there’s more information now. And we have to be that support system. You don’t know who’s next? So you have to build each other up and inform. We’ve got to get this education.”This advocacy was further fueled by women’s attitudes and beliefs about survival, resiliency, and hope. This is embodied in the words of one participant:“You know, I’ma live or die, but so in the meanwhile, it’s full, the doors open for me to challenge whatever I face and my family faces and my community faces that I don’t think is right. So, it gave me a voice and that was the part about staying strong because in order to have a voice, you have to stay strong.”This qualitative study explored AAWBCS’ lived experiences and examined how the multiple intersecting factors of race, gender, social class/socioeconomic status, and cancer-related disability impact their quality of life. The findings of this study were also used to inform future health promotion programming that is culturally relevant to AAWBCS to improve their quality of life. This study contributes to the field by collectively applying the BFT intersectionality framework and the PEN-3 model.According to the BTF framework , the corAmong the few studies to use BFT as a paradigm for interpreting the unique experiences of AAWBCS, our findings are consistent with the recent study by Armour-Burton and colleagues , which iThe BFT intersectionality framework also helps explain the theme “strong Black woman” as it allows us to center AAWBCS’ challenges as we consider the ways in which racism and gender-based oppression shape survivors’ mental health outcomes. Their race-gender identity affects African American women’s stress experience, coping responses, and mental health. Consistent with our findings, previous studies indicated that the perception and endorsement that African American women are naturally strong, resilient, self-contained, and self-sacrificing provided African American women with protection against the numerous stressors they encounter daily and was reported as protecting them from the adverse health impacts of racial discrimination . HoweverThe PEN-3 cultural model provides recommendations for culturally relevant interventions. In applying the PEN-3 model, the findings provided “insightful” and culturally relevant recommendations that can be used to inform future health promotion programming specifically for AAWBCS. These recommendations reinforce strengths-based solutions. Based on focus group findings related to AAWBCS’ intersectionality of cultural identities, the intervention point of entry should be at the peer support group level and centered on family. Three primary recommendations are described that future health promotion programming with African American women breast cancer survivors should: (1) create space to discuss identity, strengths, and role adherence/stress; (2) center services around family and community context, acknowledging the unique roles of each family member ; and (3) acknowledge existing advocacy by survivors and promote these efforts.Our findings suggested that the intervention point of entry should be at the peer support group level. Emerging evidence suggests that peer support is an effective strategy for AAWBCS. Those who received peer support reported greater access to and utilization of support resources, an increased ability to manage breast cancer-related stress, and an improved quality of life compared to survivors without peer support . Data suThe focus on group reflection may be particularly crucial, as previous research indicates that women transitioning from active breast cancer treatments want to connect with other survivors after treatment when there is less support from the medical community ,41. FlanIn addition to creating space for peer support, we suggest interventions that consider a strengths-based and family-centered approach. Similar to previous research, our study revealed that some AAWBCS experience loving support from family while others lack family support . ResearcIn addition to building family bonds, health promotion programming may be improved by centering services around a community context. Program planners should consider and continue faith-based interventions . ProgramOur work reinforced a core tenant of BFT found in similar studies, which is that AAWBCS resist oppression through engagement in activism with their family, social network, and larger community . In factFirst, this study reveals the unique experiences of the AAWBCS who participated in the study and may not reflect the larger population of AAWBCS in the recruitment region or beyond. For example, the sample was mainly at the lower socioeconomic level and were all U.S.-born African Americans. As a result, findings may not be generalizable to all AAWBCS. Specifically, there may be differences in the lived experiences of African American women from different socioeconomic groups or Black participants who might not be U.S.-born. Second, information about gender identity or sexual orientation and other contextual, demographic information was unavailable to use in further interpreting findings. Third, social desirability bias is also inherent in the study design, as participants may have been hesitant to share their actual experiences, beliefs, or opinions in a group setting.This study is one of the few studies to use the BFT framework as a paradigm to interpret the unique experiences of AAWBCS. Guided by the BFT intersectionality framework and the PEN-3 model, our findings provide insights that can inform interventions for promoting the health and well-being of AAWBCS. The intervention point of entry should be at the peer support group level, center on family, and provide community-based support and services. Future research should move upstream to address social determinants of health , includi


Our objective in this letter is initially to analyze the terminology related to one of the main trends in exercise science and practice and then to propose a term that could be deemed preferable considering the comprehensive approach of this type of training.Recently, from the 2000's onwards, a new exercise trend emerged worldwide, driven mainly by a brand, to improve physical fitness through the optimization of several components, such as aerobic capacity, muscular strength and endurance, speed, coordination, agility, balance, flexibility, and stamina , high-intensity multimodal training (HIMT), functional fitness training (FFT), extreme conditioning program (ECP), and Mixed Modal Training.Several terms to denominate this type of training have been used both in science and practice. The terminology (terms) is provided in Despite this, according to Sharp et al. , there i*” in 6, “high-intensity multimodal training” and “Mixed Modal Training” showed no results. Below we will discuss some aspects of each of the terms, thus since 2000 additional terms have been used over time, as shown in In a quick search in the PubMed database to gain an overview of the number of studies , we observed different results according to the terms searched. We chose the terms in accordance with those discussed here. The search “crossfit” resulted in 101 documents, while “functional fitness” resulted in 75, “functional fitness training” in 2, “high-intensity functional training” in 29, “extreme conditioning program® is a company (CrossFit® LLC) founded in 2000, but its inception by Greg Glassman occurred in 1996 in the USA. According to Official CrossFit® Affiliate Map (2022) there are more than 11,000 affiliated gyms worldwide  and a network of licensed affiliates–the gyms that are unofficially called boxes , and the inclusion of a certified CrossFit trainer. The affiliation of a physical location used for training allows the owners to legally use the CrossFit® trademark subject to the fulfillment of several requirements, such as obtaining at least a Level 1 Certificate to teach, some personal factors , the cost of affiliation through a fee payment, as well as criteria related to location and insurance. If an individual or entity is using CrossFit's intellectual property  without a license, confidential reports can be submitted to the legal department.CrossFitiate Map  there arEdmonds, . RegardiEdmonds, . The key Edmonds  . Thus, the use of the terms HIFT and HIMT would be correct only when the authors referred to METCON performed at high-intensity and not the modality in a broad way, as it includes the development of power, strength, and cardiovascular fitness in both periodization and training sessions.Later, other groups of researchers adopted terms referring to high intensity, such as: HIFT ” as the preferable term, at the present to describe this comprehensive type of training, characterized by a variety of movement patterns  . A specific organization can provide support to fuel the growth of functional fitness as a sport. This is an organization which aims to implement a standardized rulebook and clear movement standards. In addition, this organization has written safety guidelines for event organizers and increased competitive opportunities for athletes, being composed of several committees . There are several current national federations recognized by the International Federation , totalizing 52 countries.Functional fitness training was also recognized and regarded as one of the Top 20 Worldwide Fitness Trends for 2022. This trend first appeared in the ranking in 2007 and currently appears as trend n.14  of the preliminary text and of the article. RT: idea conception and writing (review and editing). AA: supervision. All authors made significant individual contributions to this manuscript.This research was funding by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brazil (CAPES) and FAPESC—Foundation for research and innovation support of the State of Santa Catarina—Grant Number 2019031000035 and call number N° 027/2020.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


This study aimed to discover and propose solutions to various decision-making problems, including obtaining consent, encountered by physicians when administering genetic testing to patients with disabilities. A preliminary survey and focus group interviews (FGIs) were conducted with 27 specialists who had 5–25 years of clinical experience in rehabilitation medicine, pediatrics, and obstetrics and gynecology, regarding their experience in providing genetic testing to people with developmental disabilities. This included the “role of medical staff in the patient’s decision-making process”, “difficulty of the consent process for genetic testing”, and so forth. Some limitations were identified in the genetic testing communication process for patients with disabilities. Although providing information corresponding to the level of understanding of each person and accurately evaluating the correct consenting ability is important, the usage rate of auxiliary tools, such as booklets and videos, was only 50.0%. Additionally, there were concerns regarding the marriage prospects of people with disabilities. For people with developmental disabilities to provide consent for genetic testing, legal consent forms and explanation aids that consider individual characteristics are necessary. Moreover, education on disability awareness throughout society, including cost support, is needed. Modern society has entered the fourth industrial revolution, presenting new opportunities in the medical field. Rapid advancements in medical technology have led to the introduction of innovative methods of diagnosing and treating diseases or disorders with previously unidentifiable causes .Since the enactment and enforcement of the new medical technology evaluation law in 2007 .Disability is defined as “difficulty encountered as a result of impairment, activity limitation, or participation restriction” . DisabilPeople with disabilities face various barriers, including social stigma and restricted mobility. Moreover, individuals with developmental disabilities, who face various constraints regarding communication and access to medical services, require greater attention and assistance to live a healthy life . GeneticHowever, despite these positive effects, if people with developmental disabilities cannot easily access or use this technology, then the gap between people with and without disabilities will widen. Therefore, to guarantee the benefits of medical technology for people with developmental disabilities, social and institutional devices should be tailored to the characteristics of people with developmental disabilities. This will allow them to access and properly utilize the relevant medical services. If these existing problems are resolved, people with developmental disabilities will be able to exercise voluntary decision-making and maximize participation in the process of receiving new medical technology ,7,8.In December 2017, the “Act on Guarantee of Right to Health and Access to Medical Services for Persons with Disabilities”  was enacted in Korea. The Act of H&APWD stipulates that access to healthcare services for persons with disabilities should be improved to ensure equality, regardless of the existence of a disability, type and degree of the disability, and gender. This resulted in the establishment of a national system to ensure that persons with disabilities have not only the right but also equal access to optimal healthcare and protection. This act is currently being recommended at the national and local levels by the Korean government .Moreover, 152 countries participated in the UN’s “Convention on the Rights of Persons with Disabilities”. The convention emphasized the importance of new medical technology to increase the independence and social participation of people with disabilities, calling for national investments and efforts to ensure accessibility. Furthermore, information on new technologies will increase the accessibility of systems and services to people with disabilities. This will help maintain their freedom to accept information, express opinions, and receive rehabilitation. Therefore, to realize the healthcare rights of people with disabilities, accurate and prompt access to information on new medical technologies is necessary .Genetic testing is sought after by people with developmental disabilities. However, they may lack knowledge about genetic testing and have limited access to relevant information. The process of obtaining consent is necessary for cooperative decision-making between patients and doctors in patient-centered medical care. However, few studies have investigated the difficulties faced by people with developmental disabilities while undergoing genetic testing. Furthermore, few studies have determined whether the process for rational decision-making regarding genetic testing is applicable to people with developmental disabilities .Therefore, we conducted a preliminary study on the experiences of medical staff conducting genetic testing on people with developmental disabilities. We aimed to suggest measures to resolve the issues related to performing genetic testing at the actual treatment site.This study was conducted among 27 medical doctors who had experience in recommending or performing genetic testing while providing healthcare for patients with developmental delays. The number of participants was set considering the minimum number required for a typical preliminary study, which ranges between 12 and 30 participants [In order to investigate the obstacles faced by doctors and their process of performing genetic tests on patients with disabilities, a questionnaire was developed based on a review of previous studies ,15,16,17The survey was analyzed by dividing the items into multiple-choice and open-ended questions. The multiple-choice questions were examined through frequency analysis, while the open-ended type questions were examined using a qualitative analysis method. Three expert researchers conducted the qualitative analysis after sufficient discussion. In order to protect the privacy of the study participants, no personally identifiable information  was collected. Furthermore, the questionnaire was only administered to those who provided voluntary consent for study participation after receiving an explanation of the study’s purposes. This study was conducted after receiving approval from the Institutional Review Board of Kyung Hee University ).All 27 study participants diligently responded to the questionnaire. The participants majored in rehabilitation medicine , pediatrics , and gynecology . Participants’ general characteristics, including their selected majors, specializations, and years of experience, are presented in Participants were asked if they had any experience providing genetic testing and responded “yes/no” to four questionnaire items. They could also provide a brief explanation of their responses to some questions. Most of their responses were positive .Participants rated the usefulness of genetic testing for patients with developmental delay on a 5-point Likert scale . All items received positive responses .Factors that should be considered while conducting genetic testing of patients with developmental delay were discussed in previous studies ,15,16,17In addition, physicians were asked how concerned they were about the following items in the actual clinical setting. The developed items as the results are presented in Most respondents (77.8%) were “not concerned at all” or “slightly concerned” about the “side effects of testing”. In total, respondents who were “concerned” or “very concerned” about the “lack of resources” and “lack of applicable therapeutic method” were 55.5% and 62.9%, respectively. Meanwhile, 37.0%, 33.3%, and 33.3% of participants were “concerned” or “very concerned” about “misusing test results”, “impact on health insurance”, and “genetic counseling”, respectively. Some respondents were not concerned about issues regarding the “ability to provide consent”, “genetic counseling”, “side effects of testing”, “misusing test results”, and “impact on health insurance”.The implementation items were developed based on previous studies ,15,16,17The following items were thus formulated: “providing information on indications for genetic testing”, “assessment for dysmorphic features”, “genetic counseling”, “assessment of the patients’ or caregivers’ ability to provide consent”, “conducting genetic testing”, “interpretation of test results”, and “providing feedback to patients or caregivers”. The degree of physicians’ implementation of each item is depicted in Overall, each step was diligently performed while conducting genetic testing. However, the percentage differed by item for those who responded: “performed ”. All items were performed well, considering the percentage of “mostly performed” and “completely performed” responses: “providing information on indications for genetic testing” (92.0%), “assessment for dysmorphic features” (72.0%), “genetic counseling” (60.0%), “assessment of the patients’ or caregivers’ ability to provide consent” (68.0%), “conducting genetic testing” (56.0%), “interpretation of test results” (64.0%), and “providing feedback to patients or caregivers” (76.0%). Meanwhile, regarding “perform genetic testing”, 4.0% of respondents answered, “not performed at all”. We investigated the reasons physicians recommended genetic testing for patients with developmental delay and identified the obstacles they faced. Some of the responses given during the FGIs are described below.(1)Predict, prepare, and family planning“If you know the name of the disease of the child, you can predict and prepare for the child’s future. There are certain genetic diseases that have a specific treatment method, so testing is absolutely necessary. It is also important for additional family planning.”(Participant 11)“First, if confirmed through genetic testing, comorbidities can be diagnosed and treated early. Second, the prognosis of the patient can be identified so that medical resource allocation can be discussed. Third, it can predict hereditary potential and serve as a resource for genetic counseling in case the patient or their relative has a child.”(Participant 20)(2)Child rearing“When a child has symptoms such as developmental delay, motor abnormality, or muscle weakness of unknown cause, a diagnosis can be determined via genetic testing. Accordingly, medications that can control the symptoms can be prescribed. In addition, genetic testing can provide the basis for preparing for a future at home, once the prognosis is determined, in terms of how much can be achieved after understanding the circumstances for rehabilitation. All this can be determined merely in response to a child falling behind at school. So, I always recommend genetic testing.”(Participant 24)(1)High cost and lack of auxiliary tools“The high cost of the test and the patient’s economic status may result in hesitation to undergo the test. I think the explanation of the test is conveyed mostly through the informed consent form, and an easy-to-understand information sheet is needed.”(Participant 1)“Chromosomal microarray analysis, which is performed as a primary test for developmental delay, may be covered by insurance, but there is the economic burden of additional tests that may need to be performed. The lack of understanding by the parents about genetic testing and the lack of auxiliary explanatory tools may be reasons for their hesitance.”(Participant 13)“Reasons for hesitance among disabled patients could include their economic status, the degree of understanding of the caregiver, lack of proper explanation, lack of auxiliary tools, lack of time, and lack of compensation for the time taken for proper explanation by the medical staff, and lack of experts who can provide repeated explanations.”(Participant 16)(2)Stigmatizing effect“Parents are concerned that disability may affect their children’s prospects of marriage (stigma effect). First, elderly patients or their spouses are often afraid of confirmation through genetic testing due to concerns about their children’s marriage. Second, young adult patients also often postpone genetic testing until they are married. Third, in the case of patients with disabilities, if the test is not covered by insurance, the cost burden is high. Fourth, although there are various genetic diseases, it is difficult to obtain auxiliary tools, such as well-written brochures, with which patients can explain to their caregivers the purpose and benefits of genetic tests.”(Participant 21)This study aimed to discover and propose solutions for various on-site decision-making problems encountered by physicians in administering genetic testing to persons with disabilities. These problems include obtaining consent and voluntary participation in decision-making. A preliminary survey was thus conducted among physicians with experience in treating individuals with developmental disabilities.Our findings revealed that various considerations were necessary when conducting genetic testing on people with developmental disabilities in the treatment setting. For various reasons, the physicians’ levels of concern differed regarding the problems encountered. There were also differences between some of the items under implementation. This may have emerged from issues related to the environment outside the treatment setting, as well as the diagnostic process, such as a lack of communication tools, lack of materials, and high medical costs.Few studies have examined the access of persons with disabilities to healthcare services and the genetic testing experience among this population. Conversely, however, this population will benefit the most from genetic testing, which is now covered by insurance or DTC projects recently promoted by the government. Our findings indicated that the reasons for conducting genetic testing on people with developmental disabilities included determining the diagnosis and treatment with the aim of identifying the cause of congenital disability in the individual’s DNA. Another reason was for family planning at the request of patients with disabilities to identify the likelihood of potential disability in their future children. The purpose of genetic testing is to provide a better quality of life for patients with disabilities. However, when conducting genetic testing on this population, the medical staff must consider the various issues identified in this study see . HoweverMoreover, the difficulties experienced by physicians while conducting genetic testing on patients with disabilities can be largely divided into problems during and beyond the diagnostic process. Regarding problems during the diagnostic process, 27 physicians identified various obstacles to each step of the genetic testing process. In terms of clinical aspects, providing information on genetic testing, assessment for dysmorphic features, and providing test feedback had a high implementation rate. However, genetic counseling and the assessment of the patients’ or caregivers’ ability to provide consent showed a relatively lower rate of implementation among some physicians. Patients with developmental delay may lack understanding due to their impaired cognitive ability; thus, their ability to provide consent should be assessed to determine whether they can adequately understand and consent to the test. Simultaneously, information should be provided that is suited to their level of understanding. If persons with disabilities cannot provide consent, then their caregivers can usually provide consent on their behalf when making a decision that involves the selection of medical services . HoweverProblems beyond the diagnostic process include a lack of communication tools that can supplement sufficient explanation on genetic testing for the patients with developmental disabilities or a lack of materials that can aid their understanding. Thus, problems in the treatment setting mentioned above do not arise because of physicians’ inabilities to assess patients’ ability to provide consent. As demonstrated by our results, the currently used legal forms ,21 in reThe counseling process and the difficulty physicians face in assessing patients’ ability to provide consent, as well as the lack of communication tools, present obstacles for patients with developmental disabilities and their families in understanding genetic testing. This ultimately hinders their ability to make decisions with sufficient information about their medical care.Therefore, it is necessary to improve various systems for individuals with developmental disabilities while creating communication tools that consider their individual characteristics. This will enable them to exercise their right to make decisions in receiving genetic testing. First, communication tools and materials that are developed to cater to their level of understanding, the severity of their disability, and age must be made available. Furthermore, regarding genetic testing, a system that can communicate according to the characteristics of the disorder should be established. It will thus be necessary to understand disabilities and learn how to communicate with individuals with disabilities via the domestic medical curriculum . Second, regarding problems beyond the diagnostic process, 55.5% of experts in this study responded that “lack of resources” was a major obstacle for patients with disabilities in using genetic testing. Compared to their able-bodied counterparts, people with disabilities have a relatively high burden of medical costs and are typically financially strained due to the loss of working ability. When the medical costs are not entirely covered by the government, the costs of genetic testing can be an additional burden. Although this group can benefit the most from genetic testing, it is difficult for people with disabilities to fully utilize these services. Therefore, it is necessary to consider ways to subsidize the cost of testing so that people with disabilities can easily undergo genetic testing according to their medical needs. Furthermore, in Korea, there is a stigma surrounding disability. Some parents try to postpone genetic testing because they believe that disability can affect their child’s prospects of marriage. In order to address this, the predominantly negative perception of disabilities in Korean society must be transformed. Thus, it is necessary to address these issues in the “Education for Disability Awareness” program propagated by the government ,23,24.Although this study was conducted among specialists with experience in providing genetic testing services to people with disabilities, our findings cannot be generalized, as the sample size was small. However, it is of significance because the study examined the difficulties of people with disabilities regarding genetic testing from the physician’s perspective; this is the first study to do so in Korea. Moreover, it outlined the factors required for cooperative decision-making between the patient and physician. Further research should be conducted among people with disabilities and their families to identify measures to increase accessibility to genetic testing among this population.An auxiliary tool that explains the details of genetic testing must be developed to achieve patient-centered medical care through cooperative decision-making between patients with disabilities and physicians. Moreover, a policy should be introduced to reduce medical costs and increase the accessibility of genetic testing for patients with disabilities. It is also necessary to decrease testing costs and thereby reduce the financial burden of patients with disabilities who wish to undergo genetic testing according to their medical needs. Finally, the “Education for Disability Awareness” program in Korea should address the stigma surrounding persons with disabilities, especially among those who are getting married.


Herein, we present an option to the traditional way of performing lifespan studies by using a novel method that generates high-quality data and allows for the inclusion of excluded animals, even animals removed at early signs of disease. This Survival-span method is designed to be feasibly done with simple means by any researcher and strives to improve the quality of aging studies and increase animal welfare.Lifespan analyses are important for advancing our understanding of the aging process. There are two major issues in performing lifespan studies: 1) late-stage animal lifespan analysis may include animals with non-terminal, yet advanced illnesses, which can pronounce indirect processes of aging rather than the aging process  This is particularly important in homogenous cohorts, for example inbred mice, that are more prone to develop specific diseases due to homozygosity rather than heterogeneous populations such as humans. Thus, by excluding animals that show overt signs of decreased health, variance within the remaining cohort is less likely due to an effect of illness or disease. Although necropsies can provide clarity as to the health state of an animal, insights from this postmortem approach cannot be applied ex post facto. This quandary has led the quest for better discernment between aging versus disease. From a study design perspective, however, the removal of diseased animals from a lifespan analysis can be problematic because it: 1) selects for some aged animals, and not all aged animals, 2) decreases the power of the study, and 3) might provide misleading data on actual aging.Aging is a complex process that affects virtually all organisms and tissues, and is a major risk factor for developing diseased states, such as forms of cancer, cardiovascular diseases, and neurodegenerative diseases. Thus, a better understanding of the mechanisms of aging is of major importance for most, if not all, medical fields . Aging sIn a previously published behavioral aging study, we devised a novel method that can be used for lifespan analysis, herein coined “Survival-span method”. This method allows for the inclusion of euthanized animals together with animals that died from “natural causes” . The SurThe Survival-span method was first performed using hybrid mice in our previous study, though this method is applicable to all animal lifespan analyses. The interval of median lifespan in our C57BL/6N×BALB/c F2 male hybrids was very similar (789 ± 130 compared to 742–826 days) to the four-way cross UM-HET3 male mice , and was slightly lower in females  The time until observation for each subject must be clearly defined and precisely measured. Having a clear starting point is optimal to reduce the risk of left-censoring, which can skew results. For example, if survival time of a specific subject group is studied, left-censoring can be a result of inclusion criteria dependent on vague diagnosis, making the actual starting point difficult to obtain. In lifespan studies, left-censoring is not an issue if the animal’s exact birth date is used.2) Every observation must fit into one of the two different states: “event” or “censored”. In lifespan studies, the observation is animal fate and can be either “event” (death) or “censored” (removed from study).3) The two states should be independent of each other and subjects should not be categorized as “censored” if the risk of an “event” occurring is increased. The Kaplan-Meier analysis assumes that censored data behaves as uncensored data beyond the time of censoring and if the prognosis of censored subjects relates to the event, this introduces a bias. However, in aging studies this assumption is difficult to adhere to since diseased subjects have an increased risk of dying and should not be either censored or removed from the study. The Survival-span method addresses this bias by including both possible fates and not selecting one fate above the other. Using both possible fates results in two lifespan calculations, one being an underestimation and the other an overestimation of an animal’s “true” lifespan.The requirements to perform this method are a spreadsheet program  and a statistical program  in which Kaplan-Meier survival analysis can be done. The Kaplan-Meier nonparametric test revolutionized survival analyses when presented in 1958 because it allowed, for the first time, the inclusion of incomplete observations in survival statistics. To correctly run the Kaplan-Meier analysis, specific criteria  regarding the dataset need to be acquired as indicated below .1) The t2) for each group for each event time and summarizes the results. Similar to the Kaplan-Meier test assumptions, the log-rank test requires that the comparison groups include similar degrees of censoring and that survival probability is the same regardless of when subjects were included in the study. The log-rank test should not be used on datasets with overlapping survival curves  test, but depending on the dataset other tests may be more appropriate. The log-rank test is nonparametric and calculates the chi-square (χl curves . In contl curves .1) Procedure: For each subject, log the date of birth and the number of days the birth date differs from the start of the study, as shown in To perform the Survival-span method, follow these instructions. Steps 1–3 are done in a spreadsheet , and steps 4–5 in a statistical program .2) Procedure: Monitor animals on a regular basis and remove animals with significantly decreased health.Rationale: To adhere to the assumption of exactness of time until an event is recorded, it is important to log the date of birth and days of lifespan. At the time of starting a lifespan study, animals typically would not be born on the same day. Thus, one should register each animal’s date of birth and the number of days differing for all animals to obtain a precise time until fate. In addition, a reference calendar for days of the lifespan study should be created. This enables knowing the exact study day for each animal.3) Procedure: Log the fate of each animal in the lifespan study. Code animals that died from “natural causes” with “1” for both minimum and maximum survival boxes. Euthanized animals are coded with “1” in the minimum survival log and with “0” in the maximum survival log, as shown in Rationale: Follow the animal research permit of the study per institutional guidelines. If using mice, animals should be checked at least twice per week when less than 24 months of age, and daily when older than 24 months of age. Symptoms indicating significant decreased health in mice may include, for example: hunched shoulders, shabby fur, rapid decrease in activity, decreased eating/drinking, tumors.4) Procedure: Transfer Rationale: To prepare data for statistical analysis, the fates need to be converted into “1”and “0” so that statistical programs can run the Kaplan-Meier analysis. In the Kaplan-Meier analysis “1” signifies an event and “0” signifies censored subject. It is the coding of the euthanized subjects that differs in the two lifespan curves.5) Procedure: Run the statistical analyses and obtain results.Rationale: Enables a statistical program to run the Kaplan-Meier analysis.Rationale: The Kaplan-Meier Survival analysis will generate data of survival  and graphs for visualization of lifespan see . Some stIn addition to the median (50%) survival, it can be helpful to estimate additional survival times  in order to compare the lifespan data with other aging studies. These additional survival percentages can be extrapolated from the Kaplan-Meier analysis and visualized as shown in In traditionally conducted lifespan studies, the strategy to generate a lifespan with the closest proximity to the exact lifespan is to, ideally, not interfere with the fate of subjects, but this may introduce variations due to disease and may not be compatible with ethical considerations of animal welfare. During aging, variation in cohorts of animals can increase; however, the removal of animals with evident signs of decreased health assists in decreasing some of the variation introduced by the reduced health state. Using the Survival-span method, all animals are included in the lifespan analyses regardless of when they might be removed due to decreased health. In per se, skew lifespan of group B, since in this example the subjects in group B that do not die early from disease are in fact just as long-lived as the subjects in group A.For comparison of survival intervals between different groups, we recommend performing a log-rank test (if Kaplan-Meier assumptions are met) for all minimum survival curves amongst cohorts and then repeating these analyses for all maximum survival curves. Analyzing the minimum and maximum survival curves separately allows for adhering to the assumption of similarity of censoring. In addition, comparing the minimum and maximum survival curves can result in valuable lifespan observations, such as if there were significant differences in minimum survival but not maximum survival, as illustrated in In general, researchers need to have clear and consistent censorship criteria when conducting animal lifespan studies. These criteria become even more important for survival analyses when applying the Survival-span method. Causes for euthanization may differ depending on the animal species, disease model, therapeutic treatment, researcher, institution, or country, all which can affect outcomes of the Survival-span method, highlighting a possible limitation of the method. We thus recommend researchers to standardize the criteria for the removal of animals in their lifespan studies. Notably, even in animals that appear healthy, full necropsy can show otherwise, thus the existence of disease can be concealed in animals that are not removed. A limitation related to the removal of animals is reflected in disease presentation that could potentially introduce removal inconsistencies. For example, an animal with a visible tumor may be euthanized earlier than an animal with an internal tumor, with the latter possibly not euthanized until signs of secondary effects from the tumor. In this scenario, these two animals would most likely be removed from the study at different degrees of disease. Taken together, the limitations of the Survival-span method can be considered relatively minor, but important to take into consideration.Lifespan studies are a crucial element to aging research and have been used to identify genes or pathways important in the regulation of lifespan, such as insulin/insulin-like growth factor 1 (IGF-1) signaling , mitochoHere, we present a novel approach to the Kaplan-Meier survival analysis, the Survival-span method, which generates a lifespan analysis model to address these central issues of aging studies. Our method utilizes the assumption of independence for censoring of events (Kaplan-Meier assumption 3), and allows removed subjects to be designated as either “natural death” or “censored”, which creates an under- and overestimation of true lifespan. Importantly, and as demonstrated by examples presented herein and recently published , the Surper se, which could affect conclusions of studies applicable to humans. In addition, how the removal of animals is statistically maneuvered impacts lifespan studies aiming to understand molecular mechanisms of aging. The Survival-span method is the first model to integrate an effect of decreased health into a survival analysis and this gives important biological information which may have been previously overlooked. For example, a recent aging study reported that overexpression of SIRT6, but not SIRT1, extended healthy lifespan; however, the mice that were euthanized were considered equal to mice that died from “natural causes”  on lifespan, the authors showed an increase on lifespan and reduction of frailty in male, but not female mice . In our In addition to distinguishing decreasing health due to diseased states from actual aging, using the Survival-span method also promotes animal welfare. Beyond the field of aging, this method can be applied to any study across disciplines, such as the effects of various treatments on cancer. We hope that this method will be used as a standard for survival estimation in future lifespan studies as it provides a way to: 1) include all enrolled animals, 2) perform lifespan analysis while considering animal welfare, and 3) increase the quality of behavioral/biochemical analyses of the aging process.


Finnegans Wake present a normless environment for its female characters, specifically Anna Livia Plurabelle (ALP). This paper explores ALP’s normlessness in her social interactions using Karen Horney’s theory of neurosis as a methodological device to reveal ALP’s detached personality. Horney considers normlessness a trend of “Moving Away from People,” also known as a detached personality. According to Horney, “self-sufficiency,” “perfection,” and “narrow limits in life” are the three neurotic factors that produce a detached personality, all of which are apparent in ALP’s personality. In this novel, ALP is portrayed as neurotic to demonstrate her dependence on men and how she coopts male power in favor of her needs.The complex structure and characterization of James Joyce’s  Ulysses (1922) and Finnegans Wake (1939) not pervert but more neurotic in style. The theory of neurosis, later on, was elucidated and explained by Horney (1885–1952).Norms are behavioral standards and obligational states that individuals must adhere to. They are expectations of an individual’s behaviors, which take “the form of a rule that is socially rather than formally enforced” . AccordiHorney, in her theory of neurosis, describes this situation as a trend of “moving away from people,” also known as a detached personality. According to Horney, people with detached personalities must not love, hate, cooperate with others, or become involved in any way. Their driving principle is never to become so attached to people or objects that they become indispensable, as “[t]hat would jeopardize aloofness; better to have nothing matter much” . Unlike Finnegans Wake, Anna Livia Plurabelle (ALP), the wife of Humphrey Chimpden Earwicker (HCE), is the river-woman, who opens the novel and her monolog concludes the book and frequently transforms throughout the novel in different forms of “mythic, natural, cultural, and historical human manifestations across time and space, even as she is unbound by time or space” .In this case, a woman serves as the conduit for the male creator and the practice of teaching letter writing to women serves only to allow men to recreate themselves: “man’s enterprise to teach a woman how to write his desire is also an acknowledgment of her exile from language” . Thus, JFinnegans Wake, ALP feels superior to other women and tries to distance herself from them. Her sexual conducts present her as the “waters of babalong” , ALP overtly associates herself with an infinite and omnipotent masculine deity, in which the incessant demand for heterosexuality proves her normlessness and neurotic personality. Since she may become anxious if she cannot satisfy her desire for a man to support her, she needs to replace her husband, whose death is imminent, with another man.Thus, Joyce wants to show the normality of life’s continuation through the normlessness of ALP’s need for heterosexuality. Similar to Molly’s belief in the deity in the Penelope episode of Finnegans Wake includes the complete text of a letter ALP writes to the world about her husband’s innocence. However, Philip Herring believes that “[t]he effect of ALP’s letter is precisely the opposite of her intent […] the more ALP defends her husband in her letter, the more scandal attaches to him” (196). Patrick McCarthy also claims that “[i]t is appropriate that the waters of the Liffey, representing Anna Livia, are washing away the evidence of Earwicker’s sins, […] for she takes on her husband’s guilt and redeems him; alternately she is tainted with his crimes and regarded as an accomplice” .Now changed, ALP reconciles these opposites by maximizing both, which is “a real hat trick, especially in connection with death” . As an eRegretting life’s typical changes is the second result of failed attempts at self-reliance. Such regret leads to normlessness and alienation. Joyce portrays ALP as a universal character representing motherhood, wifehood, and femininity. ALP is strong enough to defy norms despite the resulting failures. Although ALP wishes to appear strong to cope with her past and future responsibilities and problems, she fails to achieve this strength. ALP is unable to depend on her own strength during normal life because she cannot cope with life’s changes. Insisting on the stability of life, she takes her husband on a journey of her body from past to present. Although they romantically march across her body’s landscape during lovemaking, even ALP’s “littleeasechapel”  is a watFinnegans Wake, ALP moves away from humanity to attain salvation. At the beginning of the novel, it appears that ALP, as a “riverrun” woman, is capable of reaching the ocean as her final salvation. Therefore, we acknowledge her reason for feeling superior to others and accept her reliance on her own strength to maintain this superiority. However, as the novel progresses, ALP’s powerlessness to fulfill this wish becomes apparent. Joyce shows us that ALP “at the moment of reaching her epiphany-like self-realization in individual and non-fearful identity, even throwing off the Eden sponsored fear of death”  the amniotic waters of her reincarnation mother” (Joyce advances lost salvation as the third and final outcome of a frustrated attempt at self-reliance. Salvation denotes a means, cause, or source of being protected or saved from harm. In religious terms, it also entails the restoration or ascension of the natural world to a higher realm or state. Joyce demonstrates that, if using self-reliance to achieve salvation is doomed by supernatural elements, an individual can easily become normless relative to her religion and society. In f death” . This is mother” .As a result, ALP is defeated because of her normless trust in her own power to reach salvation and ultimate freedom. Joyce represents this failure through ALP’s fall into a bay instead of an ocean. ALP is neurotically detached from humanity as she cannot accomplish the duties that her society assigns her. However, ALP insists on her failure since a neurotic person refuses to recognize his or her real self and abilities. Therefore, she struggles and ultimately fails to take on her husband’s duties in raising her children. In addition, ALP fails to concede to life’s normal changes and to realize her inability to attain salvation through her own power, condemning her to reincarnation instead. These three elements pave the way for the failure of her over-stated self-reliance. The resulting collapse demonstrates ALP’s detached, neurotic personality and alienation.Finnegans Wake, ALP’s detached personality restricts her duties and responsibilities to relieve the pressure that affects her detachedness. If ALP wishes to alienate herself to lead a solitary life, she must limit the anxieties caused by other people. For example, her indifference to serious issues such as her husband’s sexual crime proves her inability to deal with her frustration. Likewise, her avoidance of any violence or conflict limits her life. Finally, by prioritizing herself or her daughter on any issue, ALP limits her life by distancing herself from her other family members. Thus, ALP narrowly limits her life to ease her anxiety and attain peace.Placing narrow limits on one’s life might allow an individual to feel less responsible for herself and other people. In Ulysses, who appears incapable of dealing with his wife’s infidelity, Alp becomes indifferent to her husband’s sexual scandals. When ALP understands that “he is not what he used to be” (Indifference to marital normlessness arises initially from the neurotic need to limit one’s life and is represented as “a diminished quality of life” . Maritald to be” , ALP doed to be” , erotic d to be” , and letd to be” .In terms of sexual demands, ALP might understand just how “polymorphously perverse he is and how, if it is to be revived, his sexuality must be addressed at a level beneath differentiation” . As a stFinnegans Wake, Joyce represents ALP as someone who washes away controversy and conflict because she cannot tolerate the anxiety that accompanies social or family conflicts. In addition to ALP’s indifference toward her husband’s crime, she is also apathetic and helpless to intervene in the conflicts of her children, Shem and Shaun. ALP, like a river, flows between her children as if they are riverbanks and cannot bring “their opposition into unity, nor does she erase their differences. Rather, the difference is placed under erasure: it is scored through in to present condition only to underscore, to highlight and embrace, another logic of dissimilarity” (Finnegans Wake, Joyce argues that avoidance of social conflict may result in an individual’s desire to distance herself from anything that provokes anxiety.Moreover, the need to wash away life’s challenges arises from the desire to limit one’s life. To remove dirt, one must wash it away. Throughout the first seven chapters of ilarity” . TherefoPrioritizing certain behaviors in one’s children also demonstrates the neurotic need for limited space to reduce the responsibility of sharing affection. Despite her rejection of femininity, ALP favors her daughter, Issy, over her sons. Issy is like a young ALP “whose showers feed the streams that form the Liffey and who is more knowing than her young years” . ALP focIn conclusion, Joyce creates a female character, who is neurotic and normless, rather than perverse. Drawn upon Horney’s theory of neurosis, we can conclude that the neurotic ALP is the product of the cultural and societal elements of masculinity, power, and prestige, which played significant roles in the early twentieth-century Ireland. In order to find peace, ALP, relying heavily on male power, attempts to demonstrate her superiority and self-sufficiency and give limits to her life to distance herself from others; however, these issues only increase ALP’s anxiety and psychological conflict. This conflict prevents her from satisfying her needs, as fulfilling those needs requires her to avoid social bonds. This approach-avoidance conflict increases her alienation and normlessness in both public and private life.The original contributions presented in this study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.


Gene expression is supposed to be an intermediate between DNA and the phenotype, and it can be measured. Thus, for a trait, we may have intermediate measures, which are in fact a series of genetically controlled traits. Similarly, several traits may be measured or predicted using infrared spectra, accelerometers, and similar high-throughput measures that we will call “omics.” Although these measurements have errors, many of them are heritable, and they may be more accurate or easier to record than the trait of interest. It is therefore important to develop methods to use intermediate measurements in selection. Here, we present methods and perspectives for selection based on massively recorded intermediate traits (omics). Recent developments allow a hierarchical integrated framework for prediction, in which a trait is partially controlled by omics. In addition, the omics measures are themselves partly controlled by genetics  and partly by environment or residual factors. Thus, a part of the genetic determinism of a trait is mediated by omics, whereas the remaining part is not mediated, which results in “residual breeding values.” In such a framework, genetic evaluations consist of 2 nested genomic BLUP-based models. In the first, the effect of omics on the trait (which can be seen as an improved estimate of the phenotype) and the residual breeding values are estimated. The second model extracts the mediated breeding values from the improved estimate of the phenotype, considering that omics themselves are heritable. The whole procedure is called GOBLUP (genomics omics BLUP) and it allows measures in only some individuals; that is, it is a “single-step”-like method. In this model, heritability is split into “mediated” and “not mediated” parts. This decomposition allows us to predict how accurate the omics measure of the trait would be compared with the direct measure. The ideal omics measure is heritable and explains a large part of the phenotypic variation of the trait. Ideally, this could be the case for some traits with low heritability. However, even if the omics measure explains only a small part of the phenotypic variation, when omics measurement themselves are heritable, the use of such a model would lead to more accurate selection. Expressions for upper bounds of reliability given omics measurements are also presented. More studies are needed to confirm the usefulness of omics or high-throughput prediction. Usefulness of the technology likely needs to be checked on a case-by-case basis. Before the genomic selection era, collecting phenotypes was an arduous experience, and adding new traits to the breeding objective implied a cost-benefit consideration unless those traits were recorded for management purposes . The breToday, the situation is different for several reasons. First, breeding objectives are becoming more diverse  and theyBV) or PTA is, literally, an expectation on random events .Assume then than we can do excellent work of predicting traits from a myriad of closer or indirect omics measures, whether these are gene transcripts, operational taxonomic unit counts in rumen or feces, accelerometer data, or milk spectra. How can these be converted into something usable for selection? A phenotype per se cannot directly be used to select animals. A fundamental principle in genetics  is that an animal transmits half its genotype to its offspring. This is the reason why natural and artificial selection act additively. Anything that is not contained in the DNA or cytoplasm of the female is not transmitted. For instance, the transcriptome may explain a large portion of a given phenotype such as growth. However, this transcriptome may be affected by environmental factors , which are not transmitted. Second, only a random gamete, half of the genotype, is transmitted—all dominant or epistatic combinations are lost, and many possible gametes exist. Thus, the breeding value  present a sketch of the theory and how it can be used for BV prediction, (2) discuss the circumstances in which the use of omics is advantageous with respect to current prediction based on phenotypes, (3) present some illustrative examples of omics use in plant and animal breeding, and (4) present some thoughts on selection schemes that use omics features. This review does not contain any studies with human or animal subjects and did not require animal care approval.The development here is taken and condensed from a is an overall BV andm) that define the outcome of a trait (y), a basic model for individual i ismi contains  omics measures for individual i and α contains their effects; we say that trait y is “mediated” by omics m. In addition, iε is a residual, the part unexplained by omics. Note that iε is different fromra , leading tom are transmitted to offspring. Thus, omics (mi) themselves need a decomposition into a genetic and a residual part, which leads to a another step in the hierarchy of models:A trait is classically decomposed asi,jg of omics j to the phenotype is i,jαjg, whereas the contribution of the residual i,je of omics j to the phenotype is i,jαje. Thus, we can define an “omics-mediated” BV, m(i)a, as a sum over omics of i,jαjg:m(i)u. So, for each individual, there is a single omics-mediated value m(i)u and a “residual” BV r(i)a that explains the genetic variation of the phenotype part not mediated by omics; the same individual i has, for each omics i,jm, a BV i,jg; and the sum of the BVs for omics ig times their effects α gives the mediated BVThe contribution of the BV ra and ma. This can be understood as follows. If gene A has action on the omics and the omics contribute to the trait, then gene A contributes to the genetic variation of ma, but not to that of ra. If gene B has no action on the omics yet it contributes to the trait , then gene B contributes to the genetic variation of ra, but not to that of ma. However, there is a correlation between each component m, ara, and overall a, as shown later. Finally, the overall residual after discounting BV isIt is worth noting that assumptions of the model lead to uncorrelated m) can be seen as multiple traits, but instead of using massive multiple trait models with unstructured covariance matrices, we use a hierarchical model, which is actually a recursive model  based on 2 successive mixed model equations (MME). This is not an approximation, because the information from each MME is disjoined.In the first step, omics effects on data are estimated, either by estimating omics effects (similar to SNP-BLUP) or using omics similarities (similar to GBLUP):X and Z incidence matrices,H is a genetic relationship . Parameters arey and omics M, and can be seen as “y with less environmental noise,” or as a predictor trait such as SCS, which is a predictor of subclinical mastitis.For  not new . These ey . The notion of using a predictor of a trait instead of a direct measure is very old and is used, for example, for protein content (measured through milk spectra) or subclinical mastitis (measured through SCC). However, in contrast to these well-established uses, these phenotype predictionsIn the second step, once the phenotype predictorsThe whole procedure is called GOBLUP. Thus, the basic machinery for omics-based selection is there, even if omics features have not (yet?) been massively produced, with the possible exception of those in crop plants . The nexFirst, the linear model above with the simplifying assumptions explains the variance decomposition of 2 more popular models. First, GBLUP, withanscript  withyi=iability  andhr2=variance . Still, Use of SNP chips for selection raises no questions in dairy cattle, but for species with a lower ratio of reproducer value to genotype cost, its use had to be considered. Similarly, we need to evaluate whether omics-based selection is useful given the cost of omics phenotyping and selection plans. In other words, is this a technology worth betting on?The case for omics-based selection is similar to that for SNP-based selection. The breeder wants a measurement of the BV that is either more accurate or available earlier. Note that this is somehow different from plants or other uses  where one is interested in the prediction of phenotype.First, we want to know whether the omics-predicted phenotype is a good predictor of the actual phenotype; to give an example, can we predict phenotype of feed intake based on phenotypes of MIR spectra ? The squma and the overall BV a,In other words, whenm are obtained. Plugging in estimates of omics effectsy,y and also BV prediction. We use this framework to characterize in which cases the omics feature is of interest using selection index theory. Assume that the unobserved omics trait u can be perfectly “predicted” conditionally on m; in other words, every iα is perfectly estimated. This will be the case, loosely speaking, when the producty has been recorded in a large number of individuals, and these individuals cover a large variation of the breed across herds, regions, and background genetics. In this case (α being perfectly estimated), phenotype prediction has reliabilityAfter an individual is phenotyped for omics, the omics measurements  content .To get some perspective on reliability using omics data, we derived upper bounds of reliabilities considering simple examples of single animals. Ultimately, accuracies of bulls with daughters are a function of the number of daughters and the accuracies of these daughters; the same applies for marker estimates.y. Reliability of the EBV is simplyy but has been properly phenotyped for omics, and α values are exactly known, so we have a perfect measure of u. The reliability of the phenotype prediction isu is actually the heritability of omics measurementsy is the reliability of the EBV for u, which is actually its heritability,Cow Artxueta has a single record for m is more reliable than measuring y is as follows:α was correctly estimated anyway.In this case, we can see that the space in which recording omics mRel) for a low heritability (h2 = 0.10), in which case, yRel = 0.10. The space in which omics are more accurate than the observation of the trait is wider whenThese ideas are reflected in y and the (perfect) prediction for u. According to selection index theory  will change microbiota composition , whereas selecting residual BV (ra) “will likely improve the trait by improved metabolic efficiency” . These aspects could be taken into account for the construction of selection indices.Another interesting use of prediction with intermediate features is to select differently for the mediated and not-mediated components of the trait. For instance, Overall, using omics or high-throughput measures may not be a “one size fits all” method but we consider it worth further exploration. The theory presented in this paper for BV prediction and the theory sketched for reliability of such predictions can help researchers determine when using omics or high-throughput measures is worthwhile for selection.