Artists Don\u27t Get No Respect: Panel on Attribution and Integrity

When I was considering the question of the moral right to attribution and how unauthorized fan creativity relates to that concept, it struck me that there are two interesting issues from a theoretical perspective. The first is: who gets the credit? When I was in law school and discovered fan fiction, the reason why I got into intellectual property was because most of these stories had a disclaimer-no copyright infringement intended, these characters aren\u27t mine, I\u27m not making any money, please don\u27t sue. And as a student, my question was – does that work? Is that good enough? I was interested in these disclaimers because copyright law does not have an explicit place in the fair use test for evaluating disclaimers as a factor favoring a defense in the way that trademark law does. I, nonetheless, concluded that, in general, fan fiction was going to be fair use. It has yet to be litigated to any particular conclusion. Although cease and desist letters do so still go out, and fans still either comply or they say no, generally there is no result. That is, I think a lot of the copyright owners are unwilling to deal with the publicity and the possibility of finding this as fair use in a litigated case

Interactive digital interventions to promote self-management in adults with asthma : systematic review and meta-analysis

This paper presents independent research funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (Grant Reference Number (RP-PG- 1211–20001).Background: To identify, summarise and synthesise the evidence for using interactive digital interventions to support patient self-management of asthma, and determine their impact. Methods: Systematic review with meta-analysis. We searched MEDLINE, EMBASE, CINAHL, PsycINFO, ERIC, Cochrane Library, DoPHER, TROPHI, Social Science Citation Index and Science Citation Index. The selection criteria requirement was studies of adults (16 years and over) with asthma, interventions that were interactive digital interventions and the comparator was usual care. Outcomes were change in clinical outcomes, cost effectiveness and patient-reported measures of wellbeing or quality of life. Only Randomised Controlled Trials published in peer-reviewed journals in English were eligible. Potential studies were screened and study characteristics and outcomes were extracted from eligible papers independently by two researchers. Where data allowed, meta-analysis was performed using a random effects model. Results: Eight papers describing 5 trials with 593 participants were included, but only three studies were eligible for inclusion for meta-analysis. Of these, two aimed to improve asthma control and the third aimed to reduce the total dose of oral prednisolone without worsening control. Analyses with data from all three studies showed no significant differences and extremely high heterogeneity for both Asthma Quality of Life (AQLQ) (Standardised Mean Difference (SMD) 0.05; 95 % Confidence Interval (CI) 0.32 to -0.22: I2 96.8) and asthma control (SMD 0.21; 95 % CI -0.05 to .42; I2 = 87.4). The removal of the third study reduced heterogeneity and indicated significant improvement for both AQLQ (SMD 0.45; 95 % CI 0.13 to 0.77: I2 = 0.34) and asthma control (SMD 0.54; 95 % CI 0.22 to 0.86: I2 = 0.11). No evidence of harm was identified. Conclusion: Digital self-management interventions for adults with asthma show promise, with some evidence of small beneficial effects on asthma control. Overall, the evidence base remains weak due to the lack of large, robust trials.Publisher PDFPeer reviewe

Implementing resources to support the diagnosis and management of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) in primary care: a qualitative study

BACKGROUND: Previous research has highlighted that many GPs lack the confidence and knowledge to diagnose and manage people with CFS/ME. Following the development of an online training module for GPs, and an information pack and DVD for patients, this study explored the extent to which these resources can be implemented in routine primary care.METHODS: Semi structured qualitative interviews were completed with patients and GPs across North West England. All interviews were transcribed and analysed using open exploratory thematic coding. Following this thematic analysis, the authors conducted a further theory-driven analysis of the data guided by Normalisation Process Theory.RESULTS: When used in line with advice from the research team, the information resource and training were perceived as beneficial to both patients and GPs in the diagnosis and management of CFS/ME. However, 47 % of patients in this study did not receive the information pack from their GP. When the information pack was used, it was often incomplete, sent in the post, and GPs did not work with patients to discuss the materials. Only13 out of 21 practices completed the training module due to time pressures and the low priority placed on low prevalence, contentious, hard to manage conditions. When the module was completed, many GPs stated that it was not feasible to retain the key messages as they saw so few patients with the condition. Due to the complexity of the condition, GPs also believed that the diagnosis and management of CFS/ME should take place in a specialist care setting.CONCLUSION: While barriers to the implementation of training and resources for CFS/ME remain, there is a need to support CFS/ME patients to access reliable, evidence based information outside primary care. Our findings suggest that future research should develop an online resource for patients to support self-management

The notch regulator MAML1 interacts with p53 and functions as a coactivator.

Members of the evolutionarily conserved Mastermind (MAM) protein family, including the three related mammalian Mastermind-like (MAML) proteins MAML1-3, function as crucial coactivators of Notch-mediated transcriptional activation. Given the recent evidence of cross-talk between the p53 and Notch signal transduction pathways, we have investigated whether MAML1 may also be a transcriptional coactivator of p53. Indeed, we show here that MAML1 is able to interact with p53. We show that MAML1-p53 interaction involves the N-terminal region of MAML1 and the DNA-binding domain of p53, and we use a chromatin immunoprecipitation assay to show that MAML1 is part of the activator complex that binds to native p53-response elements within the promoter of the p53 target genes. Overexpression of wild-type MAML1 as well as a mutant, defective in Notch signaling, enhanced the p53-dependent gene induction in mammalian cells, whereas MAML1 knockdown reduced the p53-dependent gene expression. MAML1 increases the half-life of p53 protein and enhances its phosphorylation/acetylation upon DNA damage of cells. Finally, RNA interference-mediated knockdown of the single Caenorhabditis elegans MAML homolog, Lag-3, led to substantial abrogation of p53-mediated germ-cell apoptotic response to DNA damage and markedly reduced the expression of Ced-13 and Egl-1, downstream pro-apoptotic targets of the C. elegans p53 homolog Cep-1. Thus, we present evidence for a novel coactivator function of MAML1 for p53, independent of its function as a coactivator of Notch signaling pathway

Qualitative process study to explore the perceived burdens and benefits of a digital intervention for self-managing high blood pressure in Primary Care in the UK.

OBJECTIVES: Digital interventions can change patients' experiences of managing their health, either creating additional burden or improving their experience of healthcare. This qualitative study aimed to explore perceived burdens and benefits for patients using a digital self-management intervention for reducing high blood pressure. A secondary aim was to further our understanding of how best to capture burdens and benefits when evaluating health interventions. DESIGN: Inductive qualitative process study nested in a randomised controlled trial. SETTING: Primary Care in the UK. PARTICIPANTS: 35 participants taking antihypertensive medication and with uncontrolled blood pressure at baseline participated in semistructured telephone interviews. INTERVENTION: Digital self-management intervention to support blood pressure self-monitoring and medication change when recommended by the healthcare professional. ANALYSIS: Data were analysed using inductive thematic analysis with techniques from grounded theory. RESULTS: Seven themes were developed which reflected perceived burdens and benefits of using the intervention, including worry about health, uncertainty about self-monitoring and reassurance. The analysis showed how beliefs about their condition and treatment appeared to influence participants' appraisal of the value of the intervention. This suggested that considering illness and treatment perceptions in Burden of Treatment theory could further our understanding of how individuals appraise the personal costs and benefits of self-managing their health. CONCLUSIONS: Patients' appraisal of the burden or benefit of using a complex self-management intervention seemed to be influenced by experiences within the intervention (such as perceived availability of support) and beliefs about their condition and treatment (such as perceived control and risk of side effects). Developing our ability to adequately capture these salient burdens and benefits for patients could help enhance evaluation of self-management interventions in the future. Many participants perceived important benefits from using the intervention, highlighting the need for theory to recognise that engaging in self-management can include positive as well as negative aspects. TRIAL REGISTRATION NUMBER: ISRCTN13790648; Pre-results

Intervention planning for a digital intervention for self-management of hypertension: a theory-, evidence- and person-based approach.

BACKGROUND: This paper describes the intervention planning process for the Home and Online Management and Evaluation of Blood Pressure (HOME BP), a digital intervention to promote hypertension self-management. It illustrates how a Person-Based Approach can be integrated with theory- and evidence-based approaches. The Person-Based Approach to intervention development emphasises the use of qualitative research to ensure that the intervention is acceptable, persuasive, engaging and easy to implement. METHODS: Our intervention planning process comprised two parallel, integrated work streams, which combined theory-, evidence- and person-based elements. The first work stream involved collating evidence from a mixed methods feasibility study, a systematic review and a synthesis of qualitative research. This evidence was analysed to identify likely barriers and facilitators to uptake and implementation as well as design features that should be incorporated in the HOME BP intervention. The second work stream used three complementary approaches to theoretical modelling: developing brief guiding principles for intervention design, causal modelling to map behaviour change techniques in the intervention onto the Behaviour Change Wheel and Normalisation Process Theory frameworks, and developing a logic model. RESULTS: The different elements of our integrated approach to intervention planning yielded important, complementary insights into how to design the intervention to maximise acceptability and ease of implementation by both patients and health professionals. From the primary and secondary evidence, we identified key barriers to overcome (such as patient and health professional concerns about side effects of escalating medication) and effective intervention ingredients (such as providing in-person support for making healthy behaviour changes). Our guiding principles highlighted unique design features that could address these issues (such as online reassurance and procedures for managing concerns). Causal modelling ensured that all relevant behavioural determinants had been addressed, and provided a complete description of the intervention. Our logic model linked the hypothesised mechanisms of action of our intervention to existing psychological theory. CONCLUSION: Our integrated approach to intervention development, combining theory-, evidence- and person-based approaches, increased the clarity, comprehensiveness and confidence of our theoretical modelling and enabled us to ground our intervention in an in-depth understanding of the barriers and facilitators most relevant to this specific intervention and user population

Free Fatty Acids Rewire Cancer Metabolism in Obesity-Associated Breast Cancer via Estrogen Receptor and mTOR Signaling

Obesity is a risk factor for postmenopausal estrogen receptor alpha (ERα)-positive (ER+) breast cancer. Molecular mechanisms underlying factors from plasma that contribute to this risk and how these mechanisms affect ERα signaling have yet to be elucidated. To identify such mechanisms, we performed whole metabolite and protein profiling in plasma samples from women at high risk for breast cancer, which led us to focus on factors that were differentially present in plasma of obese versus nonobese postmenopausal women. These studies, combined with in vitro assays, identified free fatty acids (FFA) as circulating plasma factors that correlated with increased proliferation and aggressiveness in ER+ breast cancer cells. FFAs activated both the ERα and mTOR pathways and rewired metabolism in breast cancer cells. Pathway preferential estrogen-1 (PaPE-1), which targets ERα and mTOR signaling, was able to block changes induced by FFA and was more effective in the presence of FFA. Collectively, these data suggest a role for obesity-associated gene and metabolic rewiring in providing new targetable vulnerabilities for ER+ breast cancer in postmenopausal women. Furthermore, they provide a basis for preclinical and clinical trials where the impact of agents that target ERα and mTOR signaling cross-talk would be tested to prevent ER+ breast cancers in obese postmenopausal women

Home and Online Management and Evaluation of Blood Pressure (HOME BP) using a digital intervention in poorly controlled hypertension:Randomised controlled trial

Objective The HOME BP (Home and Online Management and Evaluation of Blood Pressure) trial aimed to test a digital intervention for hypertension management in primary care by combining self-monitoring of blood pressure with guided self-management. Design Unmasked randomised controlled trial with automated ascertainment of primary endpoint. Setting 76 general practices in the United Kingdom. Participants 622 people with treated but poorly controlled hypertension (&gt;140/90 mm Hg) and access to the internet. Interventions Participants were randomised by using a minimisation algorithm to self-monitoring of blood pressure with a digital intervention (305 participants) or usual care (routine hypertension care, with appointments and drug changes made at the discretion of the general practitioner; 317 participants). The digital intervention provided feedback of blood pressure results to patients and professionals with optional lifestyle advice and motivational support. Target blood pressure for hypertension, diabetes, and people aged 80 or older followed UK national guidelines. Main outcome measures The primary outcome was the difference in systolic blood pressure (mean of second and third readings) after one year, adjusted for baseline blood pressure, blood pressure target, age, and practice, with multiple imputation for missing values. Results After one year, data were available from 552 participants (88.6%) with imputation for the remaining 70 participants (11.4%). Mean blood pressure dropped from 151.7/86.4 to 138.4/80.2 mm Hg in the intervention group and from 151.6/85.3 to 141.8/79.8 mm Hg in the usual care group, giving a mean difference in systolic blood pressure of -3.4 mm Hg (95% confidence interval -6.1 to -0.8 mm Hg) and a mean difference in diastolic blood pressure of -0.5 mm Hg (-1.9 to 0.9 mm Hg). Results were comparable in the complete case analysis and adverse effects were similar between groups. Within trial costs showed an incremental cost effectiveness ratio of £11 ($15, €12; 95% confidence interval £6 to £29) per mm Hg reduction. Conclusions The HOME BP digital intervention for the management of hypertension by using self-monitored blood pressure led to better control of systolic blood pressure after one year than usual care, with low incremental costs. Implementation in primary care will require integration into clinical workflows and consideration of people who are digitally excluded. Trial registration ISRCTN13790648.</p