The contribution of X-linked coding variation to severe developmental disorders

Abstract: Over 130 X-linked genes have been robustly associated with developmental disorders, and X-linked causes have been hypothesised to underlie the higher developmental disorder rates in males. Here, we evaluate the burden of X-linked coding variation in 11,044 developmental disorder patients, and find a similar rate of X-linked causes in males and females (6.0% and 6.9%, respectively), indicating that such variants do not account for the 1.4-fold male bias. We develop an improved strategy to detect X-linked developmental disorders and identify 23 significant genes, all of which were previously known, consistent with our inference that the vast majority of the X-linked burden is in known developmental disorder-associated genes. Importantly, we estimate that, in male probands, only 13% of inherited rare missense variants in known developmental disorder-associated genes are likely to be pathogenic. Our results demonstrate that statistical analysis of large datasets can refine our understanding of modes of inheritance for individual X-linked disorders

Thinking beyond the Cure : a constructive design research investigation into the patient experience of radiotherapy

This constructive design research dissertation aims to understand how design can be used as part of a composite research approach to generate knowledge about how complex phenomena are composed through their interactions and relationships with various actors, both human and non-human. It has done this by investigating a single phenomenon, the patient experience of radiotherapy. Through the purposeful selection and application of methods, theories, and existing research from design, nursing, and STS, this thesis utilizes a mixed-method approach comprised of qualitative, quantitative methods, and design experimentation, across multiple research sites and patient populations, in three research projects – PERT, DUMBO, and POIS – to generate rich and layered knowledge of the patient experience. Experience prototypes are used to challenge, through intervention or provocation, the relationships between the various radiotherapy actors identified through the empirical methods. Together, the research generated in PERT, DUMBO, and POIS construct a map of the networked, interdependent actors which shape the patient’s emotional experience of radiotherapy: the staff, technology, information, environment, and institutions. It also calls attention to the problematic relationship between radiotherapy patients and the technologies used to treat them, which can lead to anxiety, worry, and fear. This thesis offers contributions related to both improving patient experience and designing for complex social issues. First, this research suggests that individuals, other than primary users, need to be acknowledged in the design of medical technologies. It proposes calling attention to patients by naming them as interactors in their relationships with the aforementioned technologies, removing them from the role of implicated actor. Second, this thesis problematizes treating the actors within a network as independent entities, which medical research and user-centered design often does, and calls for a new type of design practice which attends to these networked relationships. Third, this thesis suggests two ways in which design research practice should be shifted methodologically if it wants to engage with and design for complex social issues like patient experience; widening the researcher’s perspective on the issue through the use of a composite methodology, and having the researcher maintain this scope by remaining closely connected to their research context. The implications of this work concern how design research, design education, and design practice might shift their approaches to fully acknowledge and attend to the complexity of systems like healthcare

Why ‘design research practice’ is not design as we know it

Is there a difference between design practice and design research practice? Building on recent discussions within design research about whether the design practice which occurs within design research is distinct and separate from the design practice which occurs within the design profession, this paper presents a case where constructive design practice was employed within a research project, using this example to study the nature of the design process in research. Through a thorough analysis of the designs generated, the motivations behind their development, their use as research tools, and the knowledge they generated, we identified three ways in which the design process was altered when it was imported into the research. First, the degree of development of the designs shifted from fully functional to functional enough. Second, the designs were developed in order to ask questions rather than trying to solve a problem. And finally, the failure of the design was equally able to contribute to generating knowledge as its success. We argue that these shifts in values clearly distinguish design research practice from professional design practice, but come with very real consequences that challenge the core measures we use to assess design

Wellbeing in healthcare environments : a human-centered design research approach to improving the cancer patient experience during radiation therapy

Healthcare and medical products are often designed with the singular focus of providing the best treatment available to patients. However, research has shown that this treatment-based approach does not result in quality care. There are many factors that play into making a healthcare experience patient-centered, and this paper explores the use of human-centered design research to understand this experience. This paper presents a case-study of a Radiotherapy Department at a University Hospital, where we used patient survey, observational, and narrative data to gain awareness into the patient experience during radiation therapy. Our research shows how the current radiotherapy environment is anxiety provoking to the patient, and how insights gained from the written and visual stories of the patients’ experiences were used to develop a design solution that improves the patient view in the treatment room with the intent to make this space more patient-centered and inviting. In conclusion, this paper argues that designing for the patient experience and their emotional wellbeing is a crucial aspect of any healthcare service

Thinking beyond the cure : a case for human-centered design in cancer care

In this paper we explore how human-centered design can expand the solution space surrounding patient experience in healthcare, looking specifically at patient emotional wellbeing. The findings presented here are taken from our ethnographic research of cancer patients undergoing radiotherapy treatment; we investigated these individuals' emotional experiences during their time in the treatment facility. Building upon previous findings within the field of nursing concerned with the prevalence of anxiety in cancer patients and the importance of person-centered care, we implement a human-centered design research approach to investigate the situational triggers of patient anxiety within the radiotherapy treatment experience. Through 'quick ethnography', we recognize that the fixation technology used within radiotherapy is a key trigger for anxiety in patients. Application of theory from the field of science and technology studies to our analysis of this technologically-mediated anxiety suggests that the fixation device confines the patient to a passive, disempowered role within its interactions due to it being embedded with the socially scripted 'sick role'. Summarizing our insights, we find that human-centered design is capable of looking holistically at patient experience to discover new solutions spaces for mediating and preventing situational anxiety, and turning person-centered care within Radiotherapy into a pre-emptive practice instead of a responsive one

Thinking beyond the cure : a case for human-centered design in cancer care

In this paper we explore how human-centered design can expand the solution space surrounding patient experience in healthcare, looking specifically at patient emotional wellbeing. The findings presented here are taken from our ethnographic research of cancer patients undergoing radiotherapy treatment; we investigated these individuals' emotional experiences during their time in the treatment facility. Building upon previous findings within the field of nursing concerned with the prevalence of anxiety in cancer patients and the importance of person-centered care, we implement a human-centered design research approach to investigate the situational triggers of patient anxiety within the radiotherapy treatment experience. Through 'quick ethnography', we recognize that the fixation technology used within radiotherapy is a key trigger for anxiety in patients. Application of theory from the field of science and technology studies to our analysis of this technologically-mediated anxiety suggests that the fixation device confines the patient to a passive, disempowered role within its interactions due to it being embedded with the socially scripted 'sick role'. Summarizing our insights, we find that human-centered design is capable of looking holistically at patient experience to discover new solutions spaces for mediating and preventing situational anxiety, and turning person-centered care within Radiotherapy into a pre-emptive practice instead of a responsive one

The influence of a department's psychosocial climate and treatment environment on cancer patients' anxiety during radiotherapy

PURPOSE: The objective of this study is to determine whether there is a relationship between cancer patients' perceptions of the person-centeredness of their treatment experience and their anxiety levels during treatment. METHOD: A questionnaire was distributed to adult cancer patients going through external beam radiotherapy (RT) with curative intent at a university hospital in Sweden (n = 892), which included two surveys, the State Trait Anxiety Inventory-state specific questions (STAI-S), and the Patient-centered Climate Questionnaire (PCQ) and additional treatment-specific questions. Eligible patients were provided with the questionnaire on their seventh day of RT by an RT-nurse. RESULTS: Statistical analysis showed a significant negative relationship between STAI-S scores and PCQ scores, and a significant positive relationship between the Treatment Environment questions and the STAI-S scores. Multivariate regression modeling found the PCQ subscale of safety to have the strongest negative association with STAI-S scores, showing that a climate of safety can significantly decrease patient situational anxiety levels. On the other hand, difficulty tolerating the overall treatment experience, worry about the treatment equipment, or feelings of isolation or claustrophobia within the treatment room all significantly factor into increases in patient-reported situational anxiety levels. CONCLUSION: Both the treatment environment and the psychosocial climate of the RT clinic significantly impact cancer patient state anxiety levels. These findings suggest that actively employing a person-centered approach during RT, and designing the treatment environment to be more attentive to the patient experience can both play a significant role in decreasing patient situational anxiety during treatment

Children's experiences and responses towards an intervention for psychological preparation for radiotherapy.

BACKGROUND: Children can experience distress when undergoing radiotherapy as a reaction to being scared of and unfamiliar with the procedure. The aim was to evaluate children's experiences and responses towards an intervention for psychological preparation for radiotherapy. METHODS: A case control design with qualitative content analysis of semi-structured interviews and statistical analysis of anxiety ratings were used for evaluating a strategy for psychological preparation and distraction. Fifty-seven children aged 2 to 18 years and their parents participated - 30 children in the baseline group and 27 in the intervention group. Child interviews were performed and the child and their parents rated the child's anxiety. RESULTS: The intervention was most appropriate for the younger children, who enjoyed the digital story, the stuffed animal and training with their parents. There were some technical problems and the digital story was not detailed enough to fit exactly with various cancer diagnoses. Children described suggestions for improvement of the intervention. The ratings of the child's anxiety during radiation treatment showed no differences between the baseline group and the intervention group. CONCLUSIONS: The children of all the age groups experienced their interventions as positive. The strength of the intervention was that it encouraged interaction within the family and provided an opportunity for siblings and peers to take part in what the child was going through. Future research on children's experiences to interventions should be encouraged. The intervention and the technical solutions could improve by further development.De två första författarna delar på förstaförfattarskapet.</p