Life Options Research Articles

The body as an obstacle and the “other”. How patients with chronic inflammatory bowel diseases view their body, self and the good life

BackgroundTreatment of chronic inflammatory bowel disease (IBD) aims to improve patients’ quality of life and the extent of treatment success is measured via patient reported outcomes (PROs). However, questionnaires used to collect PROs often include scales that are not specific to IBDs. Improving these scales requires a deeper understanding of patients’ lived experience. With this study we give first insights and develop hypotheses on how patients with IBDs experience their body and self and how they adjust their life plans in the context of precision medicine (PM). The guiding question is to understand what they need to achieve a good life, while facing their disease.MethodsWe developed a conception of the “good life” that draws on Philippa Foot’s “naturalized” approach and distinguishes six different dimensions that are relevant for a good life. This conception guided us as we conducted 10 qualitative interviews with patients suffering from IBD who were in precision medicine clinical research settings. The interviews aimed to gain insights for answering our research question: How do body experiences affect the good life of patients with IBD? We analyzed the interviews with interpretative phenomenological analysis (IPA).ResultsFive group experiential themes emerged: (i) Life options and plans, (ii) other people’s responses, (iii) strategies to deal with others’ responses, (iv) perception of the body and self, and (v) perception of life as good despite suffering. We report here on three of them (i, iv and v), which are primarily relevant for evaluating the outcomes of PM care. Whereas with “life options and plans (i),” our study predominantly confirmed previous research, with “perception of the body and self (iv),” we found that some of the patients changed their relationship to their body and themselves. They perceived the body or the disease as the “other” and their self appears divorced from their own body. Although this might be an avoidance strategy patients use to assign responsibility for their condition and its “disgusting” symptoms to the “other,” it is important to include it in patient reported outcome (PRO) assessments.ConclusionsWe conclude with the insight that the multi-dimensional approach based on Foot’s concept of a good life is well-suited as a basis for investigating the quality of life of people with IBD. Interviews based on this concept produced results that go beyond the understanding of health-related quality of life (HRQoL). Additionally, we offer some considerations about patients’ opportunities for achieving a good life and suggestions for further developing patient reported outcome scales.

Early detection of side effects in patients with metastatic melanoma receiving immune checkpoint inhibitors by investigation of CD8+ immune infiltrate with [89Zr] crefmirlimab berdoxam PET.

TPS9601 Background: Immune checkpoint inhibitors (ICI) improved outcomes of patients (pts) with advanced melanoma. Nevertheless, a significant number have immune-mediated adverse event (iAE). Due to the impact on quality of life and other therapeutic options, early identification of pts with increased risk of iAE is needed. CD8 immuno-PET with [89Zr] crefmirlimab berdoxam (Zr-Df-IAB22M2C) has shown to be a specific tool to visualize CD8+ T cells mediating both anti-tumor immune response and inflammatory adverse effects rendering this an innovative evaluation method in the field of immuno-oncology. Methods: Trial design: Open-label, single-arm, single center study to determine if CD8+ T-cell infiltration evaluated by immune-PET provides diagnostic gain in early detection of severe iAE. Pts with irresectable stage III/IV melanoma receiving nivolumab + ipilimumab (NIVO+IPI) may be included. Primary objective: Feasibility of early detection of iAE by semiquantitative assessment of CD8+ T-cell infiltration using immune-PET. Secondary objectives: 1) Prediction of iAE using immuno-PET for semiquantitative assessment of CD8+ T-cell infiltration; 2) Correlation between CD8+ T-cell infiltration in metastasis and lymphoid organs and response. Baseline Imaging. To assess glucose metabolism in metastases, primary and secondary lymphatic organs [18F] FDG PET/CT (60 min p.i. 1.5 MBq/KG/BW) is performed on a high sensitivity PET/CT with large field of view (Siemens Vision Quadra). Immediately after PET/CT data acquisition, pts are injected with [89Zr] crefmirlimab berdoxam (37 MBq ±20%) and undergo immuno-PET/CT 24 hours p.i. to detect CD8+ T-cells in metastases and lymphoid organs. NIVO+IPI is administered immediately after completion of [89Zr] crefmirlimab berdoxam-PET/CT. Blood samples are taken for immune cell composition analysis, activation state, proteomic investigation (cytokine/chemokines) as well as metabolic profile. Therapy Phase Imaging: Three weeks after first ICI cycle and before second cycle, follow-up PET/CT are performed with both radiotracers [18F]FDG and [89Zr] crefmirlimab berdoxam following the identical protocol described above. Clinical trial information: EudraCT number - 2021-004328-13 .

From distress to anger to shame: Gender violence, empowerment, and emotional states in Ecuador

AbstractChanging discourses and laws related to women's rights and intimate partner violence (IPV) in rural Ecuador have profoundly reshaped how local women experience and respond to violence. Women once understood violence as one strand of social suffering embedded in everyday rural life, and they resisted and managed this violence through various collective idioms of distress. Over the last two decades, however, state and non‐governmental organization (NGO) campaigns have isolated gender violence as a discrete phenomenon, emphasizing the “wrongness” of IPV, the validity of righteous anger, and the importance of a legal response to secure the separation of “liberated” women. In this article, I draw on 20 years of fieldwork to discuss how emotional responses to gender violence have shifted in tandem with changing state and transnational discourses and policies in the coastal region of Las Colinas. A deep disjuncture between neoliberal discourses of feminist empowerment and the material reality of rural women's life options leaves many women experiencing new forms of shame when they are unable to turn anger into liberation and escape gender violence in their families and communities. Focusing on the emotional states that states create reveals how political‐economic and discursive shifts are mediated through emotions and collective idioms.

Fatigue crack growth simulation by extended finite element method: A review of case studies

AbstractNumerical simulation of fatigue crack growth (FCG) is presented, based on the application of the extended finite element method (XFEM). Couple of case studies are presented, as a review of recent experience of the Belgrade school of XFEM simulations, established at the Faculty of Mechanical Engineering. Case studies comprised Charpy specimen with initial crack at the notch tip, oil rig pipe with an axial surface crack, pressure vessels with a crack at the welded joint with connecting pipe, turbine shaft with a crack at the transition radius, optimization of a wing spar in respect to FCG, the effect of mesh size on fatigue life estimation of a stringer panel, fatigue life estimation of wing‐to‐fuselage connecting lug, geometry effect on fatigue life of orthopedic plates and fatigue life of hip implant. Based on these case studies, XFEM is discussed in respect to its accuracy and efficiency. It is concluded that XFEM is a versatile tool for simulation of FCG, providing an excellent option for precise and reliable fatigue life of a cracked component.

Study Notion: Edtech Web Application using MERN Stack

One of the pivotal roles of technology in education lies in its capacity to equalize opportunities among students. Technology serves as a potent instrument for revolutionizing learning, fostering stronger connections between educators and students, reimagining learning methods and teamwork, diminishing persistent disparities in equity and accessibility, and tailoring learning experiences to cater to the requirements of every learner. Study Notion is an innovative online learning web application built using the MERN stack. It is designed to offer a comprehensive educational experience for students and educators alike. It provides a user-friendly interface, allowing seamless navigation through its diverse features, including a well-organized course management system that facilitates the creation and delivery of educational content. Study Notion fosters collaboration among users through its integrated communication tools, such as discussion forums and live chat options. The platform caters to individual learning needs by offering personalized learning paths, adaptive technologies, and tailored recommendations. It ensures a robust assessment and feedback mechanism, allowing for various forms of evaluation and timely student performance tracking. Study Notion seamlessly integrates with various third-party tools and services, enhancing its functionality and enriching the overall learning experience for its users. Key Words: edtech, study notion, MERN stack, collaboration, web application.

Moral dumbfounding and imaginative resistance

ABSTRACT Moral dumbfounding and imaginative resistance have both spawned important literatures that intersect moral psychology. Moral dumbfounding, rooted in Jonathan Haidt’s empirical work, has been taken to be evidence of the epistemic and cognitive shallowness of many of our moral emotions and beliefs. Opinions about imaginative resistance, on the other hand, have treated it as something between a psychological curiosity and an ethical spandrel. This essay argues that the two are related and that teasing out this relation is important for understanding each phenomenon. For positions or practices that our moral communities treat as inadmissible, we do not naturally deliberate about the truth of such positions or imagine what the world would be like if we adopted those practices so much as we resist treating them as live options for moral consideration. As we near the perceived boundary of appropriate moral discourse, we switch from moral deliberation to the rehearsal of stock reasons for why the boundaries of deliberation are fixed where they are or to resisting uptake of reasons for doing what is perceived as morally deviant. Likewise, when asked to imagine a world in a way that invites situating the boundaries of what is morally inadmissible in our world differently, we switch from a willingness to suspend disbelief and accept a narrative on its own terms to explicitly bracketing or actively resisting the story.

Varied-Frequency CC–CV Inductive Wireless Power Transfer with Efficiency-Regulated EV Charging for an Electric Golf Cart

Wireless electric vehicle (EV) charging is an important operation for valuable EV options in modern life. Inductive wireless EV charging needs constant current and voltage (CC–CV) charge controllers. This paper presents 750 W variable frequency CC–CV inductive wireless charging for an e-golf cart 50 Ah 72 V Li-ion battery. Due to this system’s low power, the system’s efficiency may be weak; the secondary-side (SS) maximum efficiency-controlled (MEC) converter was validated. The golf cart’s battery characteristics were evaluated to design and experiment with inductive wireless power transfer (IPT) coils and an integration system for a 42 kHz resonant frequency. The CC–CV charged control is an infrastructural part of the H-bridge inverter at varied frequencies from 50 kHz to 56 kHz when the DC input voltage is 310 V, and in the range of 44 kHz to 46 kHz at the 155 V input. The results found the charging of 9 A CC, 82 V CV and 730 W. The 310 V input voltage system without the SS MEC converter’s efficiencies was 62% to 72% and it was improved to 65% to 81% using the SS MEC converter. Finally, the best cases were validated at the 155 V DC input voltage and the system with the SS MEC converter had 76% to 86% efficiency.

Mass determination and model prediction of retired blades from wind turbine repowering or dismantling using a GIS database

Existing estimations of waste from wind energy infrastructure that is headed for, flowing through, or having reached the terminus of various post-processing pathways have primarily relied on reported capacity to extrapolate the material weight of turbine components. This data can be used to project future streams of composite blade material coming from wind farm repowering and decommissioning and inform policies to optimize or improve certain blade End of Life (EoL) options. However, rated capacity alone is insufficient to quantify or characterize the dynamics of US wind fleet retirement, since turbines are often repowered with new blades but their capacity remains the same. This research demonstrates an alternative method, comparing various mass estimation techniques and identifying blade models that have been retired or are soon to enter waste pathways due to turbine repowering by spatiotemporal comparison of periodic versions of the United States Geological Survey (USGS) Wind Turbine Database (USWTDB). These analyses are used to compile a list of turbine and blade models that will be at the forefront of national repowering and decommissioning movements in the near future. Mass of future waste flows are totalled and can help inform protocols and frameworks for blade material EoL processes.

Probabilistic design life selection procedure for a steel bridge

AbstractNumerous bridges and viaducts built in Western Europe in the middle of the 20th century are now in service for more than 50 years. Aging and changes in societal demands result in a gradual decline of their technical and functional performance. This consequently forces responsible authorities to replace the obsolete infrastructure in the coming decades.Large‐scale renovation programs together with further development of the highway network require a lot of resources and make a significant environmental impact. The assumed design life of bridges affects structural solutions and the choice of materials. Therefore, there is an opportunity for more efficient use of resources and reduction of the environmental impact if the design life of new bridges is optimized with respect to life cycle costs and CO2 equivalent emissions.As multiple design life options exist for any bridge, it is essential to have a consistent approach capable of indicating the favorable option. Therefore, a procedure has been developed for comparison of various design life options based on lifecycle costs and lifecycle CO2 equivalent emissions. The procedure accounts for different traffic growth and traffic load development scenarios and it considers probabilities of these scenarios to happen in the future. This allows to assess the effect of uncertainty in functional parameters resulting in probabilistic lifecycle costs and emissions, which indicate a proper design life option.The procedure is applied to a large span steel bridge over a river. Two design life alternatives, namely 100 years and 200 years, are considered. This paper summarizes the results of this study and it offers a discussion on limitations and perspectives of the suggested procedure.

Platelet status in cancer cachexia progression in ApcMin/+ mice.

Cachexia, a complex wasting syndrome, significantly affects the quality of life and treatment options for cancer patients. Studies have reported a strong correlation between high platelet count and decreased survival in cachectic individuals. Therefore, this study aimed to investigate the immunopathogenesis of cancer cachexia using the ApcMin/+ mouse model of spontaneous colorectal cancer. The research focused on identifying cellular elements in the blood at different stages of cancer cachexia, assessing inflammatory markers and fibrogenic factors in the skeletal muscle, and studying the behavioral and metabolic phenotype of ApcMin/+ mice at the pre-cachectic and severely cachectic stages. Platelet measurements were also obtained from other animal models of cancer cachexia - Lewis Lung Carcinoma and Colon 26 adenocarcinoma. Our study revealed that platelet number is elevated prior to cachexia development in ApcMin/+ mice and can become activated during its progression. We also observed increased expression of TGFβ2, TGFβ3, and SMAD3 in the skeletal muscle of pre-cachectic ApcMin/+ mice. In severely cachectic mice, we observed an increase in Ly6g, CD206, and IL-10 mRNA. Meanwhile, IL-1β gene expression was elevated in the pre-cachectic stage. Our behavioral and metabolic phenotyping results indicate that pre-cachectic ApcMin/+ mice exhibit decreased physical activity. Additionally, we found an increase in anemia at pre-cachectic and severely cachectic stages. These findings highlight the altered platelet status during early and late stages of cachexia and provide a basis for further investigation of platelets in the field of cancer cachexia.

Linear programming approach to design bio-based plastics strategies for Japan: Integration of material characteristics, product applications, and end of life options

There is a growing interest in bio-based plastics for mitigating climate change; however, it remains unclear as to which products should be produced using bio-based plastics and how such plastics should be disposed of to minimize their environmental impact. To investigate the degree to which bio-based plastics can be applied toward the mitigation of climate change based on material characteristics, product applications, and end of life (EoL) options, we developed a linear-programming-based model to represent a plastic system of nine types of fossil-based plastics and 12 types of bio-based plastics in Japan. We found that introducing bio-based plastics could reduce life cycle greenhouse gas (LCGHG) emissions, provided that an appropriate EoL is coupled. Specifically, the ‘drop-in’ plastics were dominantly selected with feedstock recycling when only material property was constrained, and the LCGHG emissions from the system was −15.5 million t-CO2eq/year.

The Hegemonic Character of Techno-Functional Neo-Immanentism and Its Relationship with Culture Wars

This paper analyzes the social processes that have led to the consolidation of a technocratic secular order and the type of cultural struggle that has made this possible. To this end, it first proposes a reconstruction of the technocratic consciousness in the course of the secularization process that culminates in the technological determinism or technological solutionism of the social present; then, the analysis focuses on the neo-immanentist tendency of techno-functionalism, in which the secular context and the text of secularization become one and deplete a social explanation; thirdly, it reflects on and deals with the open nature of secular life, in which context does not determine social texts (inter-actions) and opens the way to the existence of different life options that compete with each other and even turn on—rebel against—institutional design. This reflection, then, focuses on the specific features of the culture wars in Western Judeo-Christian culture and its globalizing tendency. Finally, the document closes with a conclusion that analyzes the road travelled and introduces the new challenges arising from the arguments presented.

An Epistemic Approach to Ground

AbstractRecent enthusiasm for grounding often begins by observing that inquiry in metaphysics (and other areas) features a distinctive species of noncausal explanation. Having labeled this species “grounding explanation,” it’s a short step to the conclusion that we need a philosophical theory of grounding itself: an allegedly fundamental relation of metaphysical dependency between facts, such that a “grounding explanation” of some fact succeeds by providing information about what “grounds” that fact. This short step is hasty. For another live option is to accept that grounding explanation is a legitimate form of explanation, but to give it a thoroughly epistemic treatment, one that does not see it as involving any sort of special metaphysical relationship or structure at all. This paper sketches such a treatment, drawing inspiration from reflections on explanatory structure in mathematics.

Contempt, Withdrawal and Equanimity in the Zhuangzi

The Zhuangzi, a 4th century BCE Daoist text, is sceptical about the political culture of its time. Those who debated conceptions of a good life were hostile to the views of others. They were intolerant and at times contemptuous of others who did not embody their values. In contrast to such negativity, the Zhuangzi promotes equanimity. The equanimity of the sagely person is grounded in a balance she maintains between engagement and withdrawal. Engaging critically, she problematises the lack of diversity in their options for a good life. By withdrawing, she refuses to be party to the squabbles that perpetuate intolerance. The paper aims to show how equanimity is possible, thereby articulating a new angle on emotions in the Zhuangzi.

Oversimplification of Systems Engineering Goals, Processes, and Criteria in NASA Space Life Support

AbstractThis paper investigates the oversimplification of the inherently complex systems engineering process in space life support. The standard systems engineering process steps are described. The International Space Station (ISS) life support system is explained with its goals and performance criteria. Although it is not usually emphasized, the essential function of developing a hierarchy of systems and subsystems is to simplify the design process. The System Complexity Metric (SCM) shows how this divide‐and‐conquer approach also reduces the system complexity. The complete systems engineering process has many detailed steps. It is often simplified because of the effort required and the human limitations on working memory and decision span. Systems analysis demands slow, logical, and focused thinking but is often bypassed in favor of quick, intuitive, subconscious “gut feel.” A study of 100 system designs found examples of 12 specific mental mistakes, such as ignoring stakeholder needs, and these mistakes are essentially oversimplifications of the systems engineering process. An analysis of space life support goals, options, criteria, and processes found 11 examples of oversimplifications in systems engineering, such as neglecting safety and cost. All these 11 oversimplifications could be traced to one or more of the 12 previously identified mental mistakes or other well‐known ones, such as ignoring sunk costs. Oversimplification of the systems engineering process is rarely noticed but is a common and harmful problem. A study of failures in 50 different space systems found that problems in systems engineering caused failures and often led to errors in design, development, and test that further contributed to failure. It seems that more diligent systems engineering could prevent many project problems and failures, but projects seem to be more guided by “gut feel” based on tradition, authority, and consensus than on the logical, rational systems engineering approach.

Sodium thiosulfate ameliorates atopic dermatitis via inhibiting the activation of NLRP3 inflammasome

Atopic dermatitis (AD) is a common disease with a considerable impact on the patient's quality of life and limited treatment options. Sodium thiosulfate (STS) is a traditional medicine used in the rescue of cyanide poisoning, and some pruritus dermatosis. However, the exact efficacy and mechanism of its application on AD are not clear. In this work, comparing to other traditional therapy, STS was found to effectively improve the severity of skin lesions and the quality of life in AD patients with a dose-dependent manner. Mechanically, STS downregulated the expression of IL-4, IL-13, IgE in the serum of AD patients, as well as reduce the concentration of eosinophils. Furthermore, in the AD-like mice model triggered by ovalbumin (OVA) and calcitriol, STS was found to reduce the epidermal thickness, scratching times, and the infiltration of dermal inflammatory cells in AD mice, as well as the reactive oxygen species (ROS) production and the expression levels of inflammatory cytokines in the skin tissue. In HacaT cells, STS inhibited the accumulation of ROS and activation of NLRP3 inflammasome and its downstream IL-1β expression. Therefore, this study revealed that STS plays an important therapeutic role in AD, and the mechanism may be that STS inhibits the activation of NLRP3 inflammasome and the subsequent release of inflammatory cytokines. Thus, the role of STS in treating AD was clarified and the possible molecular mechanism was revealed.

Challenges and worries in life stories of women with bleeding disorders

Women with bleeding disorders have rarely been studied. Recently, thanks to the advancement in treatment options and the recognition that women can also suffer from haemo-philia, new research lines have been developed. This study investigated the experiences of women affected by bleeding disorders (patients, healthy or symptomatic carriers), specifically focussing on disease diagnosis and management in daily life, relational issues, and reproductive options. Age, family history, educational qualification and religiosity were also considered. Thirty-two women were interviewed, and their narratives were analysed with lexical-metric and qualitative content analysis. The results showed some key themes, which refer to cognitive, affective and behavioural responses to the disease. They included both sex-neutral and female-specific contents, offering a new reading of the phenomenon. Although the aware-ness of female bleeding disorders has increased in recent years, sick women stressed late di-agnosis paths and symptom underestimations, while female carriers discussed psychosexual issues and motherhood choices, with related implications on physical and psychological well-being, and relational life. Alongside commonalities, some differences emerged depending on women's socio-cultural situations. Overall, they suggested the importance of developing early patient-centred psycho-educational paths in order to tailor interventions to specific women's needs, promote disease and self-acceptance, and enhance effective management.

Whose Life Is It Anyway? Medical Aid in Dying and Its Legal, Medical, and Ethical Conundrums

Whose Life Is It Anyway? Medical Aid in Dying and Its Legal, Medical, and Ethical Conundrums

Osteogenesis and osteoclastogenesis on a chip: Engineering a self-assembling 3D coculture

Healthy bone is maintained by the process of bone remodeling. An unbalance in this process can lead to pathologies such as osteoporosis which are often studied with animal models. However, data from animals have limited power in predicting the results that will be obtained in human clinical trials. In search for alternatives to animal models, human in vitro models are emerging as they address the principle of reduction, refinement, and replacement of animal experiments (3Rs). At the moment, no complete in vitro model for bone-remodeling exists. Microfluidic chips offer great possibilities, particularly because of the dynamic culture options, which are crucial for in vitro bone formation. In this study, a scaffold free, fully human, 3D microfluidic coculture model of bone remodeling is presented. A bone-on-a-chip coculture system was developed in which human mesenchymal stromal cells differentiated into the osteoblastic lineage and self-assembled into scaffold free bone-like tissues with the shape and dimensions of human trabeculae. Human monocytes were able to attach to these tissues and to fuse into multinucleated osteoclast-like cells, establishing the coculture. Computational modeling was used to determine the fluid flow induced shear stress and strain in the formed tissue. Furthermore, a set-up was developed allowing for long-term (35 days) on-chip cell culture with benefits including continuous fluid-flow, low bubble formation risk, easy culture medium exchange inside the incubator and live cell imaging options. This on-chip coculture is a crucial advance towards developing in vitro bone remodeling models to facilitate drug testing.

Characteristics of Inclusive Web-Based Leisure Activities for Children With Disabilities: Qualitative Descriptive Study.

The participation of children with disabilities in leisure activities is a key determinant of their physical and mental health. The COVID-19 pandemic has limited participation in leisure activities for all children, particularly those with disabilities. As a result, children with disabilities may be less active while feeling more isolated and stressed. Web-based communities and activities have become increasingly important. Understanding how web-based activities include or exclude children with disabilities can contribute to the development of inclusive communities that may support participation after the pandemic. This study aimed to identify factors that may facilitate or prevent the participation of children with disabilities in web-based leisure activities. We adopted a qualitative descriptive interpretative methodology and conducted interviews with 2 groups of participants: service providers offering inclusive web-based leisure activities and parents of children with disabilities who have engaged in web-based leisure activities during the COVID-19 pandemic. A semistructured interview format was created based on the Theoretical Domains Framework. The questions focused on the description of the web-based activities offered by the service provider (eg, age range, frequency, cost, target population, and type of activity offered) and any adaptations to make the web-based activity accessible to children and youth with disabilities, and their perceptions and beliefs about what supported or deterred participation in the activities. A total of 17 participants described their experiences in participating in and creating web-based leisure programs and the factors preventing or facilitating children's participation in web-based activities. Environment and context factors included accommodations, the format of activities and the web-based setting, stakeholder involvement, and materials and resources available. Activities that had flexible schedules, both recorded and live options for joining, and that provided clear instructions and information were perceived as more accessible. Beliefs involved the characteristics of the child and the family environment, as well as the characteristics of the organizations providing the activity. Activity facilitators who were familiar with the web-based environment and knew the specific characteristics of the child facilitated their participation. Engagement in community champions and respect for children's individual preferences were perceived as positive. Access to technology, funding, and caregivers' ability to facilitate child engagement are crucial factors that must be considered when offering web-based programs. Web-based environments offer an accessible and safe option for leisure participation when public health conditions prevent children with disabilities from participating in in-person activities. However, to make web-based activities accessible to children with a variety of disabilities, there needs to be a clear plan toward universal web-based accessibility that accounts for individual needs and collective approaches to web-based leisure. Future work should consider developing and testing guidelines for web-based accessibility, equity, public policy, and programming considerations in offering these activities for all children.