'Seeing' the Difference: The Importance of Visibility and Action as a Mark of 'Authenticity' in Co-production ; Comment on “Collaboration and Co-production of Knowledge in Healthcare: Opportunities and Challenges”

The Rycroft-Malone paper states that co-production relies on ‘authentic’ collaboration as a context for action. Our commentary supports and extends this assertion. We suggest that ‘authentic’ co-production involves processes where participants can ‘see’ the difference that they have made within the project and beyond. We provide examples including: the use of design in health projects which seek to address power issues and make contributions visible through iteration and prototyping; and the development of ‘actionable outputs’ from research that are the physical embodiment of coproduction. Finally, we highlight the elements of the Collaboration for Leadership in Applied Health Research and Care (CLAHRC) architecture that enables the inclusion of such collaborative techniques that demonstrate visible co-production. We reinforce the notion that maintaining collaboration requires time, flexible resources, blurring of knowledge produceruser boundaries, and leaders who promote epistemological tolerance and methodological exploration Keywords: Co-production, Knowledge Mobilisation, Design Approaches in Healthcare, Research Impact, Actionable Tool

“Seeing” the Difference: The Importance of Visibility and Action as a Mark of “Authenticity” in Co-production Comment on “Collaboration and Co-production of Knowledge in Healthcare: Opportunities and Challenges”

The Rycroft-Malone paper states that co-production relies on ‘authentic’ collaboration as a context for action. Our commentary supports and extends this assertion. We suggest that ‘authentic’ co-production involves processes where participants can ‘see’ the difference that they have made within the project and beyond. We provide examples including: the use of design in health projects which seek to address power issues and make contributions visible through iteration and prototyping; and the development of ‘actionable outputs’ from research that are the physical embodiment of coproduction. Finally, we highlight the elements of the Collaboration for Leadership in Applied Health Research and Care (CLAHRC) architecture that enables the inclusion of such collaborative techniques that demonstrate visible co-production. We reinforce the notion that maintaining collaboration requires time, flexible resources, blurring of knowledge produceruser boundaries, and leaders who promote epistemological tolerance and methodological exploratio

Dual Mechanisms of LYN Kinase Dysregulation Drive Aggressive Behavior in Breast Cancer Cells

The SRC-family kinase LYN is highly expressed in triple-negative/basal-like breast cancer (TNBC) and in the cell of origin of these tumors, c-KIT-positive luminal progenitors. Here, we demonstrate LYN is a downstream effector of c-KIT in normal mammary cells and protective of apoptosis upon genotoxic stress. LYN activity is modulated by PIN1, a prolyl isomerase, and in BRCA1 mutant TNBC PIN1 upregulation activates LYN independently of c-KIT. Furthermore, the full-length LYN splice isoform (as opposed to the Δaa25-45 variant) drives migration and invasion of aggressive TNBC cells, while the ratio of splice variants is informative for breast cancer-specific survival across all breast cancers. Thus, dual mechanisms-uncoupling from upstream signals and splice isoform ratios-drive the activity of LYN in aggressive breast cancers

Minimum Target Prices for Production of Direct-Acting Antivirals and Associated Diagnostics to Combat Hepatitis C Virus

Combinations of direct-acting antivirals (DAAs) can cure hepatitis C virus (HCV) in the majority of treatment-na€ ıve patients. Mass treatment programs to cure HCV in developing countries are only feasible if the costs of treatment and laboratory diagnostics are very low. This analysis aimed to estimate minimum costs of DAA treatment and associated diagnostic monitoring. Clinical trials of HCV DAAs were reviewed to identify combinations with consistently high rates of sustained virological response across hepatitis C genotypes. For each DAA, molecular structures, doses, treatment duration, and components of retrosynthesis were used to estimate costs of large-scale, generic production. Manufacturing costs per gram of DAA were based upon treating at least 5 million patients per year and a 40% margin for formulation. Costs of diagnostic support were estimated based on published minimum prices of genotyping, HCV antigen tests plus full blood count/clinical chemistry tests. Predicted minimum costs for 12-week courses of combination DAAs with the most consistent efficacy results were: US$122 per person for sofosbuvir1daclatasvir

Experience of Subjective Symptoms in Euthymic Patients with Bipolar Disorder

Bipolar patients often experience subjective symptoms even if they do not have active psychotic symptoms in their euthymic state. Most studies about subjective symptoms are conducted in schizophrenia, and there are few studies involving bipolar patients. We examined the nature of the subjective symptoms of bipolar patients in their euthymic state, and we also compared it to that of schizophrenia and normal control. Thirty bipolar patients, 25 patients with schizophrenia, and 21 normal control subjects were included. Subjective symptoms were assessed using the Korean version of the Frankfurter Beschwerde Fragebogen (K-FBF) and the Symptom Check List 90-R (SCL90-R). Euthymic state was confirmed by assessing objective psychopathology with the Positive and Negative Syndrome scale of Schizophrenia (PANSS), the Young Mania Rating Scale (YMRS), and the Montgomery Asberg Depression Rating Scale (MADRS). K-FBF score was significantly higher in bipolar patients than in normal controls, but similar to that in schizophrenia patients (F=5.86, p=0.004, R2=2033.6). In contrast, SCL90-R scores did not differ significantly among the three groups. Euthymic bipolar patients experience subjective symptoms that are more confined to cognitive domain. This finding supports the hypothesis that subtle cognitive impairments persists in euthymic bipolar patients

Leading co-production in five UK collaborative research partnerships (2008–2018): responses to four tensions from senior leaders using auto-ethnography

Background: Despite growing enthusiasm for co-production in healthcare services and research, research on co-production practices is lacking. Multiple frameworks, guidelines and principles are available but little empirical research is conducted on ‘how to do’ co-production of research to improve healthcare services. This paper brings together insights from UK-based collaborative research partnerships on leading co-production. Its aim is to inform practical guidance for new partnerships planning to facilitate the co-production of applied health research in the future. Methods: Using an auto-ethnographic approach, experiential evidence was elicited through collective sense making from recorded conversations between the research team and senior leaders of five UK-based collaborative research partnerships. This approach applies a cultural analysis and interpretation of the leaders’ behaviours, thoughts and experiences of co-production taking place in 2008–2018 and involving academics, health practitioners, policy makers and representatives of third sector organisations. Results: The findings highlight a variety of practices across CLAHRCs, whereby the intersection between the senior leaders’ vision and local organisational context in which co-production occurs largely determines the nature of co-production process and outcomes. We identified four tensions in doing co-production: (1) idealistic, tokenistic vs realistic narratives, (2) power differences and (lack of) reciprocity, (3) excluding vs including language and communication, (4) individual motivation vs structural issues. Conclusions: The tensions were productive in helping collaborative research partnerships to tailor co-production practices to their local needs and opportunities. Resulting variation in co-production practices across partnerships can therefore be seen as highly advantageous creative adaptation, which makes us question the utility of seeking a unified ‘gold standard’ of co-production. Strategic leadership is an important starting point for finding context-tailored solutions; however, development of more distributed forms of leadership over time is needed to facilitate co-production practices between partners. Facilitating structures for co-production can enable power sharing and boost capacity and capability building, resulting in more inclusive language and communication and, ultimately, more credible practices of co-production in research. We provide recommendations for creating more realistic narratives around co-production and facilitating power sharing between partners

Progress in Spacecraft Environment Interactions: International Space Station (ISS) Development and Operations

The set of spacecraft interactions with the space flight environment that have produced the largest impacts on the design, verification, and operation of the International Space Station (ISS) Program during the May 2000 to May 2007 time frame are the focus of this paper. In-flight data, flight crew observations, and the results of ground-based test and analysis directly supporting programmatic and operational decision-making are reported as are the analysis and simulation efforts that have led to new knowledge and capabilities supporting current and future space explorations programs. The specific spacecraft-environment interactions that have had the greatest impact on ISS Program activities during the first several years of flight are: 1) spacecraft charging, 2) micrometeoroids and orbital debris effects, 3) ionizing radiation (both total dose to materials and single event effects [SEE] on avionics), 4) hypergolic rocket engine plume impingement effects, 5) venting/dumping of liquids, 6) spacecraft contamination effects, 7) neutral atmosphere and atomic oxygen effects, 8) satellite drag effects, and 9) solar ultraviolet effects. Orbital inclination (51.6deg) and altitude (nominally between 350 km and 460 km) determine the set of natural environment factors affecting the performance and reliability of materials and systems on ISS. ISS operates in the F2 region of Earth s ionosphere in well-defined fluxes of atomic oxygen, other ionospheric plasma species, solar UV, VUV, and x-ray radiation as well as galactic cosmic rays, trapped radiation, and solar cosmic rays. The micrometeoroid and orbital debris environment is an important determinant of spacecraft design and operations in any orbital inclination. The induced environment results from ISS interactions with the natural environment as well as environmental factors produced by ISS itself and visiting vehicles. Examples include ram-wake effects, hypergolic thruster plume impingement, materials out-gassing, venting and dumping of fluids, and specific photovoltaic (PV) power system interactions with the ionospheric plasma. Vehicle size (L) and velocity (v), combined with the magnitude and direction of the geomagnetic field (B) produce operationally significant magnetic induction voltages (VxB.L) in ISS conducting structure during high latitude flight (>+/- 45deg) during each orbit. In addition, ISS is a large vehicle and produces a deep wake structure from which both ionospheric plasma and neutrals species are largely excluded. ISS must fly in a very limited number of approved flight attitudes, so that exposure of a particular material or system to environmental factors depends upon: 1) location on ISS, 2) ISS flight configuration, 3) ISS flight attitude, and 4) variation of solar exposure (Beta angle), and hence thermal environment, with time. Finally, an induced ionizing radiation environment is produced by trapped radiation and solar/cosmic ray interactions with the relatively massive ISS structural shielding

Leading co-production in five UK collaborative research partnerships (2008-2018): responses to four tensions from senior leaders using auto-ethnography

BackgroundDespite growing enthusiasm for co-production in healthcare services and research, research on co-production practices is lacking. Multiple frameworks, guidelines and principles are available but little empirical research is conducted on ‘how to do’ co-production of research to improve healthcare services. This paper brings together insights from UK-based collaborative research partnerships on leading co-production. Its aim is to inform practical guidance for new partnerships planning to facilitate the co-production of applied health research in the future. MethodsUsing an auto-ethnographic approach, experiential evidence was elicited through collective sense making from recorded conversations between the research team and senior leaders of five UK-based collaborative research partnerships. This approach applies a cultural analysis and interpretation of the leaders’ behaviours, thoughts, and experiences of co-production taking place in 2008-2018 and involving academics, health practitioners, policy makers, and representatives of third sector organisations. ResultsThe findings highlight a variety of practices across CLAHRCs, whereby the intersection between the senior leaders’ vision and local organisational context in which co-production occurs largely determines the nature of co-production process and outcomes. We identified four tensions in doing co-production: 1) idealistic, tokenistic vs realistic narratives, 2) power differences and (lack of) reciprocity, 3) excluding vs including language and communication, 4) individual motivation vs structural issues.ConclusionsThe tensions were productive in helping collaborative research partnerships to tailor co-production practices to their local needs and opportunities. Resulting variation in co-production practices across partnerships can therefore be seen as highly advantageous creative adaptation, which makes us question the utility of seeking a unified ‘gold standard’ of co-production. Strategic leadership is an important starting point for finding context-tailored solutions; however, development of more distributed forms of leadership over time is needed to facilitate co-production practices between partners. Facilitating structures for co-production can enable power sharing and boost capacity and capability building, resulting in more inclusive language and communication and, ultimately, more credible practices of co-production in research. We provide recommendations for creating more realistic narratives around co-production and facilitating power sharing between partners