Crafting representations of rare disease: collage as qualitative inquiry.

BACKGROUND: Collage is a modality of expression which involves repurposing and juxtaposing fragments. Our aim was to explore both how and what collage, as an arts-based research method, might contribute to enlivening understandings of the experiences of families affected by rare conditions. METHODS: During 10 weeks of collaging workshops participants created artistic representations of their experiences. The methodology produced a convivial atmosphere where participants talked openly about everyday challenges. RESULTS: The collages and conversations produced offer a means through which to consider the complex and multiple positions which families affected by rare disease interpolate. Particularly, the collages prompt cross-cutting thematic reflections on motherhood and care, the challenges of being heard, and balancing family life alongside medicalisation. CONCLUSIONS: The opportunity to convey topics and feelings through a medium which was both tentatively open yet conceptually complex allowed the broaching of sensitive and elusive themes in a safe, expressive, and non-threatening manner.

Rapid Development of an Integrated Network Infrastructure to Conduct Phase 3 COVID-19 Vaccine Trials.

Importance: The COVID-19 pandemic has caused millions of infections and deaths and resulted in unprecedented international public health social and economic crises. As SARS-CoV-2 spread across the globe and its impact became evident, the development of safe and effective vaccines became a priority. Outlining the processes used to establish and support the conduct of the phase 3 randomized clinical trials that led to the rapid emergency use authorization and approval of several COVID-19 vaccines is of major significance for current and future pandemic response efforts. Observations: To support the rapid development of vaccines for the US population and the rest of the world, the National Institute of Allergy and Infectious Diseases established the COVID-19 Prevention Network (CoVPN) to assist in the coordination and implementation of phase 3 efficacy trials for COVID-19 vaccine candidates and monoclonal antibodies. By bringing together multiple networks, CoVPN was able to draw on existing clinical and laboratory infrastructure, community partnerships, and research expertise to quickly pivot clinical trial sites to conduct COVID-19 vaccine trials as soon as the investigational products were ready for phase 3 testing. The mission of CoVPN was to operationalize phase 3 vaccine trials using harmonized protocols, laboratory assays, and a single data and safety monitoring board to oversee the various studies. These trials, while staggered in time of initiation, overlapped in time and course of conduct and ultimately led to the successful completion of multiple studies and US Food and Drug Administration-licensed or -authorized vaccines, the first of which was available to the public less than 1 year from the discovery of the virus. Conclusions and Relevance: This Special Communication describes the design, geographic distribution, and underlying principles of conduct of these efficacy trials and summarizes data from 136 382 prospectively followed-up participants, including more than 2500 with documented COVID-19. These successful efforts can be replicated for other important research initiatives and point to the importance of investments in clinical trial infrastructure integral to pandemic preparedness.

When 'cultures of care' meet: entanglements and accountabilities at the intersection of animal research and patient involvement in the UK.

A good culture of care, empowering individuals within organisations to care and reflecting wider social expectations about care, is now a well-documented aspiration in managing practices of laboratory animal research and establishing priorities for patient and public health. However, there is little attention to how different institutional cultures of care interact and what happens to the accountabilities of caring roles and the entanglements of caring practices when institutional cultures meet. Drawing on research exploring the increasing practices of patient and public involvement (PPI) within animal research in the UK, we identify three ways in which cultures of care are changing in encounters between biomedical researchers and people affected by health conditions. Firstly, patient involvement in animal research brings additional bodies to care for within research facilities. Secondly, patient and public groups are seen as an increasingly important group to convey a culture of care to. Thirdly, involvement brings opportunities for patients and publics to connect care for both human and animals. However, more attention is required to understand how shifts towards cultures of care distribute power and responsibility to care within institutions and at their boundaries, where responsibilities to care may be disconnected from the power to effect meaningful changes.

Une culture du care de qualité, qui donne aux personnes au sein des organisations les moyens de prodiguer des soins et reflète des attentes sociales plus larges concernant la notion de care, est maintenant une aspiration bien documentée dans les pratiques de gestion de la recherche sur les animaux en laboratoire et l'établissement des priorités pour les patients et la santé publique. On accorde cependant peu d'attention à la manière dont les différentes cultures institutionnelles du care interagissent et ce qu'il advient des responsabilités des rôles de soins et des intrications des pratiques de care quand les cultures institutionnelles se rencontrent. En nous appuyant sur des recherches explorant l'augmentation de la pratique de participation des patients et du public (patient and public involvement ­ PPI) dans la recherche sur les animaux au Royaume-Uni, nous identifions trois manières dont les cultures du care sont en train de changer dans les rencontres entre des chercheurs biomédicaux et des personnes touchées par des problèmes de santé. Premièrement, la participation des patients dans la recherche sur les animaux amène plus d'êtres vivants à qui prodiguer des soins dans les centres de recherche. Deuxièmement, on considère que les groupes de patients et du public forment une cohorte à qui il est de plus en plus important de communiquer une culture du care. Troisièmement, cette participation donne aux patients et au public des opportunités de lier le care pour les humains et pour les animaux. Il faudra cependant du travail plus approfondi pour comprendre comment les changements vers les cultures du care distribuent les pouvoirs et les responsabilités dans les institutions aussi bien qu'à leurs frontières, où les responsabilités du care peuvent être déconnectées du pouvoir pour engendrer des changements significatifs.

Una buena cultura de la atención, que empodera a las personas en organizaciones hacia el cuidado y que refleja expectativas sociales más amplias sobre la atención, es ahora una aspiración bien documentada en la gestión de prácticas de investigación con animales de laboratorio y el establecimiento de prioridades para la salud pública y del paciente. Sin embargo, se presta poca atención a cómo interactúan las diferentes culturas institucionales de cuidado y qué sucede con los roles de cuidado y los enredos de las prácticas de cuidado cuando las culturas institucionales se encuentran. Basándonos en la investigación que explora las prácticas de participación del paciente y del público (PPI) dentro de la investigación con animales en el Reino Unido, identificamos tres formas en las que las culturas del cuidado están cambiando en los encuentros entre investigadores biomédicos y personas afectadas por problemas de salud. En primer lugar, la participación de los pacientes en la investigación con animales aporta organismos adicionales que cuidar dentro de las instalaciones de investigación. En segundo lugar, los grupos de pacientes y públicos se consideran un grupo cada vez más importante al que transmitir una cultura de cuidado. En tercer lugar, la participación brinda oportunidades para que los pacientes y el público conecten el cuidado tanto para humanos como para animales. Sin embargo, se requiere más atención para comprender cómo los cambios hacia las culturas del cuidado distribuyen el poder y la responsabilidad del cuidado dentro de las instituciones y en sus límites, donde las responsabilidades del cuidado pueden estar desconectadas del poder de efectuar cambios significativos.

Writing the worlds of genomic medicine: experiences of using participatory-writing to understand life with rare conditions.

The diagnostic and treatment possibilities made possible by the development and subsequent mainstreaming of clinical genomics services have the potential to profoundly change the experiences of families affected by rare genetic conditions. Understanding the potentials of genomic medicine requires that we consider the perspectives of those who engage with such services; there are substantial social implications involved. There are increasing calls to think more creatively, and draw on more participatory approaches, in evoking rich accounts of lived experience. In this article, we discuss our rationale for, and experiences of, using 'participatory-writing' to understand the diverse, variable and multilayered everyday lives of families and how these correspond with the emerging, rapidly changing and complex field of genomic medicine. Participatory-writing has many benefits as a method for social inquiry. Writing can be expressive and self-revelatory, providing insight into personal and sensitive topics. Writing together produces new conversations and relationships. Pieces written by participants have the potential to affect readers, evoking and enlivening research and prompting professional change. Working with a writing tutor, we organised a participatory-writing programme for families touched by genetic conditions. This involved a series of workshops with an emphasis on building confidence in expressing lived experience through experimenting with different writing techniques. Afterwards we arranged reflective interviews with participants. We drew on dialogical narrative analysis to engage with participants' written pieces, and highlight what everyday life is like for the people who live with, and care for, those with genetic conditions. The stories produced through our writing-groups unfold the implications of new genomic technologies, illuminating how genomics acts to (and likewise, fails to) reconfigure aspects of people's lives outside of the clinic, while simultaneously existing as a sociotechnical frame that can eclipse the wider contexts, challenges and liveliness of life with rare genetic conditions.

"Perhaps something of beauty can grow:" experiences of care farming for grief.

Care farming has been used to alleviate distress and increase wellbeing in various populations. This study provides an overview of how bereaved adults (N = 115) experienced a grief-specific care farm through a content analysis of open-ended survey questions. The care farm's nature spaces and interactions with animals emerged as important components of the experience, interacting with grief-related activities and experiences. Together, the spaces and species of the care farm provided a supportive context for integrating grief, processing emotions, and receiving compassionate support. Some participants also experienced changes in how they viewed their grief and improvements in interpersonal relationships.

The social aspects of genome editing: publics as stakeholders, populations and participants in animal research.

The application of genome editing to animal research connects to a wide variety of policy concerns and public conversations. We suggest focusing narrowly on public opinion of genome editing is to overlook the range of positions from which people are brought into relationships with animal research through these technologies. In this paper, we explore three key roles that publics are playing in the development of genome editing techniques applied to animals in biomedical research. First, publics are positioned by surveys and focus groups as stakeholders with opinions that matter to the development of research technologies. Learning lessons from controversies over genetically modified food in Europe, these methods are used to identify problems in science-society relations that need to be managed. Second, people are recruited into research projects through participating in biobanks and providing data, where their contributions are encouraged by appeals to the public good and maintained by public confidence. Thirdly, patients are increasingly taking positions within research governance, as lay reviewers on funding panels, where their expertise helps align research priorities and practices with public expectations of research. These plural publics do not easily aggregate into a simple or singular public opinion on genome editing. We conclude by suggesting more attention is needed to the multiple roles that different publics expect - and are expected - to play in the future development of genomic technologies.

Multi-species dementia studies: Contours, contributions and controversies.

Developed via an online collaborative writing project involving members of the Multi-species Dementia International Research Network, this article seeks to refocus "the lens of the dementia debate" (Bartlett & O'Connor, 2007) by bringing dementia's complicated relations with the more-than-human world into sharper relief. Specifically, the article explores four thematic areas (contours) within contemporary dementia studies (Care & Caring; Illness Experience & Disease Pathology; Environment, Self & Sustainability; Power, Rights & Social Justice) where the application of multi-species theories and concepts has potential to foster innovation and lead to new ways of thinking and working. Whilst incorporating multi-species perspectives within dementia studies can create new ways of responding and new spaces of response-ability, the potential for conflict and controversy remains high. It is imperative, therefore, that the field of dementia studies not only becomes a site within which multi-species perspectives can flourish, but that dementia studies also becomes a vehicle through which multi-species concepts may be refined.

The Activate Test of Embodied Cognition (ATEC): Reliability, concurrent validity and discriminant validity in a community sample of children using cognitively demanding physical tasks related to executive functioning.

Embodied cognition assessment may be more closely related to how children function than standard measures of executive functioning (EF) that require little body movement. Activate Test of Embodied Cognition (ATEC) measures cognitive functioning based on cognitively demanding physical tasks assessed using an automated administration with motion capture technology. This study evaluated the psychometrics of ATEC.Children ages 5-11 years were recruited from the community (N = 55). ATEC was performed twice for a subsample, approximately 2 weeks apart. Motion capture data were collected and converted into ATEC Total Score. Concurrent measures included scores from NIH Toolbox for EF (Flanker, Working Memory, Go/No-Go task, Balloon Analogue Risk Task (BART)), and parent reports (Child Behavior Checklist (CBCL), Behavioral Rating Inventory of Executive Function (BRIEF-2) and Swanson, Nolan, and Pelham Rating Scale (SNAP-IV) for ADHD).ATEC Total Score was significantly correlated with concurrent measures of EF and showed significant discriminant validity between At-Risk children and Normal Range children on CBCL Competency, CBCL ADHD Combined score, BRIEF-2 Global Executive Composite, BRIEF-2 Cognitive Regulation Index and SNAP-IV ADHD Combined Score. Regression analyses showed that ATEC Total score was a better predictor of CBCL Competency than any of the standard EF assessments. ATEC Total Score had excellent test-retest reliability, (ICC = .945, df = 27, p < .001) with a small practice effect (Cohen's d = 0.33). ATEC Total Score correlated with age (r = .42, p < .003) suggesting improvement with normal development. ATEC produces reliable scores that may identify children at risk for EF impairments.

Randomized Trial of a Vaccine Regimen to Prevent Chronic HCV Infection.

BACKGROUND: A safe and effective vaccine to prevent chronic hepatitis C virus (HCV) infection is a critical component of efforts to eliminate the disease. METHODS: In this phase 1-2 randomized, double-blind, placebo-controlled trial, we evaluated a recombinant chimpanzee adenovirus 3 vector priming vaccination followed by a recombinant modified vaccinia Ankara boost; both vaccines encode HCV nonstructural proteins. Adults who were considered to be at risk for HCV infection on the basis of a history of recent injection drug use were randomly assigned (in a 1:1 ratio) to receive vaccine or placebo on days 0 and 56. Vaccine-related serious adverse events, severe local or systemic adverse events, and laboratory adverse events were the primary safety end points. The primary efficacy end point was chronic HCV infection, defined as persistent viremia for 6 months. RESULTS: A total of 548 participants underwent randomization, with 274 assigned to each group. There was no significant difference in the incidence of chronic HCV infection between the groups. In the per-protocol population, chronic HCV infection developed in 14 participants in each group (hazard ratio [vaccine vs. placebo], 1.53; 95% confidence interval [CI], 0.66 to 3.55; vaccine efficacy, -53%; 95% CI, -255 to 34). In the modified intention-to-treat population, chronic HCV infection developed in 19 participants in the vaccine group and 17 in placebo group (hazard ratio, 1.66; 95% CI, 0.79 to 3.50; vaccine efficacy, -66%; 95% CI, -250 to 21). The geometric mean peak HCV RNA level after infection differed between the vaccine group and the placebo group (152.51×103 IU per milliliter and 1804.93×103 IU per milliliter, respectively). T-cell responses to HCV were detected in 78% of the participants in the vaccine group. The percentages of participants with serious adverse events were similar in the two groups. CONCLUSIONS: In this trial, the HCV vaccine regimen did not cause serious adverse events, produced HCV-specific T-cell responses, and lowered the peak HCV RNA level, but it did not prevent chronic HCV infection. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT01436357.).

Improving patient informed consent for haemophilia gene therapy: the case for change.

Adeno-associated virus-based gene therapy points to a coming transformation in the treatment of people living with haemophilia, promising sustained bleed control and potential improvement in quality of life. Nevertheless, the consequences of introducing new genetic material are not trivial. The perceived benefits should not minimise the challenges facing patients in understanding the long-term risks and providing a valid and meaningful informed consent, whether in a research or clinical setting. Informed consent is a fundamentally important doctrine in both medical ethics and health law, upholding an individual's right to define their personal goals and make their own autonomous choices. Patients should be enabled to recognise their clinical situation, understand the implications of treatment and integrate every facet of their life into their decision. This review describes informed consent processes for haemophilia gene therapy clinical trials, factors affecting patients' decision making and the availability of patient-centred decision support interventions, to ensure that patients' interests are being protected. Regulatory guidance has been published for physicians and manufacturers in haemophilia on informed consent, including for gene therapy, while best-practice recommendations for patient-physician discussions are available. In all settings, however, communicating and presenting highly technical and complex therapeutic information is challenging, especially where multiple barriers to scientific knowledge and health literacy exist. We propose several evidence-informed strategies to enhance the consent procedure, such as utilising validated literacy and knowledge assessment tools as well as participatory learning environments over an extended period, to ensure that patients are fully cognisant of the consent they give or deny. Further research is needed to define new, creative approaches for patient education and the upholding of ethical values in the informed consent process for gene therapy. The lessons learnt and approaches developed within haemophilia could set the gold standard for good practice in ensuring ethical preparedness amidst advances in genetic therapies. Plain language summary: Improving the informed consent process for people living with haemophilia considering gene therapy. Gene therapy is the process of replacing faulty genes with healthy ones. In haemophilia, gene therapy involves introducing a working copy of the gene for the clotting factor that patients are missing. Following treatment, patients should begin producing their own clotting factor normally. However, people living with haemophilia (PwH) need to be fully informed regarding the potential benefits and risks of gene therapy and what this means for them, whether as part of a research study or routine medical care.Patients must be respected and supported to make decisions about their own health and wellbeing, recognising their legal and moral right to set personal goals and make treatment choices. For this to happen in practice, patients should be aware of their individual health needs, understand the effects of treatment and consider lifestyle preferences in relation to their decisions. This article attempts to describe how informed consent is obtained in haemophilia gene therapy clinical trials, what affects a patient's ability to make decisions and the availability of information and support to respect and protect the interests of PwH.Regulators responsible for approving medical products have published guidance on informed consent for physicians and pharmaceutical manufacturers in haemophilia, including for gene therapy. Recommendations have been made about the best ways for PwH to discuss gene therapy with their physicians. Yet, poor communication of complex topics, such as gene therapy, can be problematic, especially if patients lack the skills and confidence to understand and discuss the science, or for physicians with limited time in clinic.We propose strategies to improve the consent process, so patients can feel more able to make informed decisions about new treatments. Further research is needed to find new, creative approaches for educating patients and ensuring that the informed consent process for gene therapy in haemophilia is ethical.

Evaluating care farming as a means to care for those in trauma and grief.

The interrelationships between nature, health, and wellbeing are increasingly recognized and incorporated into therapeutic interventions. Care farming, the concept of utilizing agricultural places and practices for providing care, therapy, and rehabilitation, is a paradigmatic example of this shift. This mixed method study empirically evaluates the efficacy of care farming as an intervention for individuals affected by traumatic grief, a complex experiential condition. Both quantitative and qualitative results suggest this care farm intervention was beneficial, yielding significant reductions in subjective distress to grief intensity. The study's findings add to the growing body of evidence on care farming and support green care as a therapeutic potential for individuals affected by traumatic grief.

Animal research nexus: a new approach to the connections between science, health and animal welfare.

Animals used in biological research and testing have become integrated into the trajectories of modern biomedicine, generating increased expectations for and connections between human and animal health. Animal research also remains controversial and its acceptability is contingent on a complex network of relations and assurances across science and society, which are both formally constituted through law and informal or assumed. In this paper, we propose these entanglements can be studied through an approach that understands animal research as a nexus spanning the domains of science, health and animal welfare. We introduce this argument through, first, outlining some key challenges in UK debates around animal research, and second, reviewing the way nexus concepts have been used to connect issues in environmental research. Third, we explore how existing social sciences and humanities scholarship on animal research tends to focus on different aspects of the connections between scientific research, human health and animal welfare, which we suggest can be combined in a nexus approach. In the fourth section, we introduce our collaborative research on the animal research nexus, indicating how this approach can be used to study the history, governance and changing sensibilities around UK laboratory animal research. We suggest the attention to complex connections in nexus approaches can be enriched through conversations with the social sciences and medical humanities in ways that deepen appreciation of the importance of path-dependency and contingency, inclusion and exclusion in governance and the affective dimension to research. In conclusion, we reflect on the value of nexus thinking for developing research that is interdisciplinary, interactive and reflexive in understanding how accounts of the histories and current relations of animal research have significant implications for how scientific practices, policy debates and broad social contracts around animal research are being remade today.

Atlantic Horseshoe Crabs and Endotoxin Testing: Perspectives on Alternatives, sustainable Methods, and the 3Rs (Replacement, Reduction, and Refinement).

Endotoxin testing is a vital part of quality and safety control in pharmaceutical production. The primary method for this testing in North America and Europe is the limulus amebocyte lysate (LAL) test, a critical component of which is the blood of Atlantic horseshoe crabs (Limuius poiyphemus). Procuring blood for LAL testing involves capturing and bleeding over 500,000 crabs from wild marine populations each year. Whilst efforts are made by manufacturers to return crabs to the sea following the collection of blood, there is a level of mortality and sub-lethal impact involved, prompting increasing discussions about welfare and ethics. The 3Rs - the ambition to where possible, replace, reduce, and refine the use of animals - are established and accepted worldwide as the best framework for governing animal-dependent science. However, the biomedical utilization of horseshoe crabs to produce the LAL test has rarely been viewed through a 3Rs framework. More recently, there has been a renewed attention on sustainable methods and alternatives to the LAL test. Drawing on in-depth qualitative interviews, this article examines stakeholder perspectives on opportunities for thinking with the 3Rs, considering current appetites to replace, refine, and reduce contemporary biomedical reliance on horseshoe crabs. The shape of conversations about the biomedical utilization of horseshoe crabs has shifted significantly in recent years, and the 3Rs are an important driver of change, offering the potential to advance the use of more sustainable methods, and realize the welfare considerations increasingly expected across science and society.

What's in it for the animals? Symbiotically considering 'therapeutic' human-animal relations within spaces and practices of care farming.

Human-animal relations are increasingly imbricated, encountered and experienced in the production of medicine and health. Drawing on an empirical study of care farms in the UK, this article uses the language of symbiosis to develop a framework for critically considering the relationships enrolled within interspecies therapeutic practices. Care farming is an emerging paradigm that aims to deploy farming practices as a form of therapeutic intervention, with human-animal relations framed as providing important opportunities for human health. This article moves to attend to multispecies therapeutic interventions and relationships from a more-than-human perspective, drawing attention to the often-troubling anthropocentrism in which such practices are framed and performed. Attempting to perform and realise human imaginations of 'therapeutic' affects, spaces and relationships can rely on processes that reduce animals' own opportunities for flourishing. Yet, the therapeutic use of other species does not have to be forever anthropocentric or utilitarian. The article explores whether relations between humans and animals might result in a level of mutual proliferation of affective capacities, reciprocally beneficial. These human-animal entanglements highlight opportunities to think more critically about how to practice interspecies relationships and practices in ways that are less parasitic, and instead framed more by attempts at producing opportunities for mutualistic flourishing.

Thinking critically about health and human-animal relations: Therapeutic affect within spaces of care farming.

This article draws on a more-than-representational approach to reconsider how geographers engage with ideas of 'health'. Health can be understood as the constant reshaping of an individual's capacity to affect and be affected, the way in which a body's powers to act are dynamically augmented or diminished by different affective relations. The article also addresses calls for health geography to engage with the more-than-human. The article mobilises a qualitative study of 'care farming' within England and Wales to highlight the generative potential of human-animal relations in (re)shaping the diverse affective relations gathered together to produce new bodily capacities. The article demonstrates how animal presence and agency can break down barriers, allowing people to navigate and negotiate adverse contexts and access support in a manner and space in which they feel comfortable. Additionally, human-animal relations are shown to produce affective experiences that act to re-place identities, understandings, and ways of 'being-with' the world that can enact what different actants may become. Human-animal relations matter for health.

The prognostic utility of baseline alpha-fetoprotein for hepatocellular carcinoma patients.

INTRODUCTION: Alpha-fetoprotein (AFP) has a valuable role in postoperative surveillance for hepatocellular carcinoma (HCC) recurrence. The utility of pretreatment or baseline AFP remains controversial. The present study hypothesized that elevated baseline AFP levels are associated with worse overall survival in HCC patients. METHODS: Adult HCC patients were identified using the National Cancer Database (2004-2013). Patients were stratified according to baseline AFP measurements into the following groups: Negative (<20), Borderline (20-199), Elevated (200-1999), and Highly Elevated (>2000). The primary outcome was overall survival (OS), which was analyzed by log-rank test and graphed using Kaplan-Meier method. Multivariate regression modeling was used to determine hazard ratios (HR) for OS. RESULTS: Of 41 107 patients identified, 15 809 (33.6%) were Negative. Median overall survival was highest in the Negative group, followed by Borderline, Elevated, and Highly Elevated (28.7 vs 18.9 vs 8.8 vs 3.2 months; P < 0.001). On multivariate analysis, overall survival hazard ratios for the Borderline, Elevated, and Highly Elevated groups were 1.18 (P = 0.267), 1.94 (P < 0.001), and 1.77 (P = 0.007), respectively (reference Negative). CONCLUSION: Baseline AFP independently predicted overall survival in HCC patients regardless of treatment plan. A baseline AFP value is a simple and effective method to assist in expected survival for HCC patients.