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In this study, we explored chronic airways disease (CAD) patients' responses to health literacy (HL) communication domain questions within disease self-management scenarios, as part of a larger CAD HL measurement tool development study.Adult asthma and chronic obstructive pulmonary disease (COPD) patients from specialty care respiratory clinics were initially presented with realistic disease management scenarios and asked to share information they would communicate. Participants' responses were grouped into response categories that were reviewed and verified by key informants. A new cohort of CAD patients then responded to the same scenarios and had their answers placed into the developed response categories by trained interviewers.19 initial stage participants' responses informed response categories for the following self-management topics: Inhaler Use (n = 20); Prednisone Use (n = 30); Flu (Influenza) (n = 35); and Weather ForecastingAir Quality Index (n = 29). 141 participants' responses were categorised during the second stage.Specialty care CAD patients displayed an understanding of key information to communicate across disease self-management topic. Our two-step, patient-driven approach may interest researchers investigating health-related communication from patients' perspectives.Findings may illuminate potential areas to investigate communication gaps among CAD patients; further investigation is warranted among non-specialty care patients.

Objective:To explore changes in plant-based and meat product sales during and after implementation of a multi-component in-store intervention implemented by a major UK food retailer. Secondary objectives included exploring differences by store format and area affluence.Design:The intervention increased the visibility, accessibility, affordability and availability of a selection of plant-based products. Unit sales of plant-based and meat products during the intervention (January 2021) were compared with pre- (November 2020) and post-intervention (February and March 2021). Non-meat product sales were assessed as a control. Negative binomial mixed models were used to explore sales changes and differences by store format or affluence.Setting:The intervention was applied in a real-world supermarket setting during Veganuary.Participants:Stores that applied the full intervention (n 154) were included for analysis. Weekly sales data for each store were obtained from the retailer.Results:Average weekly unit sales of plant-based products increased significantly (57 %) during the intervention period (incidence rate ratio (IRR) 1·52 (95 % CI1·51, 1·55)). Plant-based product sales decreased post-intervention but remained 15 % higher than pre-intervention (IRR 1·13 (95 % CI 1·12, 1·14)). There was no significant change in meat sales according to time period. The increase in plant-based product sales was greatest at superstores (58 %), especially those located in below average affluence areas (64 %).Conclusions:Results suggest that increasing visibility, accessibility, affordability and availability of plant-based products led to increased sales, with evidence of lasting effects. No significant changes in meat sales were observed. Variation according to store format and area affluence indicates targeted intervention approaches are needed.

Supplementary Figure S1: Acquired resistance to ganetespib in KRAS mutant NSCLC cell line, H460, leads to loss of ganetespib induced G2/M arrest; Supplementary Figure S2: p90RSK overexpression leads to bypass of ganetespib induced G2/M arrest in an isoform specific manner; Supplementary Figure S3: Pharmacological inhibition of p90RSK leads to dose dependent G2/M arrest; Supplementary Figure S4: Acquired resistance to ganetespib in KRAS mutant NSCLC cell lines leads to upregulation of several critical G2/M checkpoint regulators; Supplementary Figure S5: CDC25C overexpression in KRAS mutant NSCLC cell lines; Supplementary Figure S6: Genetic silencing of CDC25C in parental as well as GR KRAS mutant NSCLC cells; Supplementary Figure S7: Overexpression of CDC25C sensitizes KRAS mutant NSCLC cells to CDC25C inhibitors; Supplementary Figure S8: Additive combinatorial activity of ganetespib and NSC-663284 observed in A549 cells; Supplementary Figure S9: Ganetespib resistance induced by CDC25C overexpression leads to ERK/p90RSK dependence; Supplementary Figure S10: Additive combinatorial activity of ganetespib and Bi-D1870 observed in KRAS mutant NSCLC cell - H460; Supplementary Figure S11: Additive combinatorial activity of ganetespib and Bi-D1870 observed in KRAS mutant NSCLC cell - A549; Supplementary Figure S12: Combinatorial activities of p90RSK inhibitor (BI-D1870), ERK1/2 inhibitor (SCH7729), and CDC25C inhibitor (NSC-663284) in H460-GR10 cells; Supplementary Figure S13: Combinatorial activities of p90RSK inhibitor (BI-D1870), ERK1/2 inhibitor (SCH7729), and CDC25C inhibitor (NSC-663284) in A549-GR100 cells.

Approximately 25% of non–small cell lung cancer (NSCLC) patients have KRAS mutations, and no effective therapeutic strategy exists for these patients. The use of Hsp90 inhibitors in KRAS-mutant NSCLC appeared to be a promising approach, as these inhibitors target many KRAS downstream effectors; however, limited clinical efficacy has been observed due to resistance. Here, we examined the mechanism(s) of acquired resistance to the Hsp90 inhibitor, ganetespib, and identified novel and rationally devised Hsp90 inhibitor combinations, which may prevent and overcome resistance to Hsp90 inhibitors. We derived KRAS-mutant NSCLC ganetespib-resistant cell lines to identify the resistance mechanism(s) and identified hyperactivation of RAF/MEK/ERK/RSK and PI3K/AKT/mTOR pathways as key resistance mechanisms. Furthermore, we found that ganetespib-resistant cells are “addicted” to these pathways, as ganetespib resistance leads to synthetic lethality to a dual PI3K/mTOR, a PI3K, or an ERK inhibitor. Interestingly, the levels and activity of a key activator of the mTOR pathway and an ERK downstream target, p90 ribosomal S6 kinase (RSK), were also increased in the ganetespib-resistant cells. Genetic or pharmacologic inhibition of p90RSK in ganetespib-resistant cells restored sensitivity to ganetespib, whereas p90RSK overexpression induced ganetespib resistance in naïve cells, validating p90RSK as a mediator of resistance and a novel therapeutic target. Our studies offer a way forward for Hsp90 inhibitors through the rational design of Hsp90 inhibitor combinations that may prevent and/or overcome resistance to Hsp90 inhibitors, providing an effective therapeutic strategy for KRAS-mutant NSCLC. Mol Cancer Ther; 16(5); 793–804. ©2017 AACR.

Supplementary Table S1: Primary and secondary antibodies used in the study; Supplementary Table S2: Sequences for CDC25C shRNA (5' - 3'); Supplementary Table S3: IC50 values for in vitro cytotoxicity after 72 hours of treatment with different drugs in KRAS mutant NSCLC cell lines examined.

A subset of non–small cell lung cancers (NSCLC) are dependent upon oncogenic driver mutations, including the most frequently observed driver mutant KRAS, which is associated with a poor prognosis. As direct RAS targeting in the clinic has been unsuccessful to date, use of Hsp90 inhibitors appeared to be a promising therapy for KRAS-mutant NSCLC; however, limited clinical efficacy was observed due to rapid resistance. Furthermore, the combination of the Hsp90 inhibitor (Hsp90i), ganetespib, and docetaxel was tested in a phase III clinical trial and failed to demonstrate benefit. Here, we investigated the mechanism(s) of resistance to ganetespib and explored why the combination with docetaxel failed in the clinic. We have not only identified a critical role for the bypass of the G2–M cell-cycle checkpoint as a mechanism of ganetespib resistance (GR) but have also found that GR leads to cross-resistance to docetaxel. Reactivation of p90RSK and its downstream target, CDC25C, was critical for GR and mediated the bypass of a G2–M arrest. Overexpression of either p90RSK or CDC25C lead to bypass of G2–M arrest and induced ganetespib resistance in vitro and in vivo. Moreover, resistance was dependent on p90RSK/CDC25C signaling, as synthetic lethality to ERK1/2, p90RSK, or CDC25C inhibitors was observed. Importantly, the combination of ganetespib and p90RSK or CDC25C inhibitors was highly efficacious in parental cells. These studies provide a way forward for Hsp90 inhibitors through the development of novel rationally designed Hsp90 inhibitor combinations that may prevent or overcome resistance to Hsp90i. Mol Cancer Ther; 16(8); 1658–68. ©2017 AACR.

Six Figures

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To enable a transition to a more sustainable food future, it is crucial policymakers consider and address livestock production and meat consumption holistically. The concept of ‘less and better’ meat and dairy offers an alternative approach to industrial livestock production. This study explores perspectives of UK stakeholders engaged in political advocacy and implementation on policy priorities and specific policy measures aimed at facilitating a transition to ‘less and better’ meat in the UK. 16 UK experts on food and farming from the research, civil society, business and farming sectors were interviewed. Thematic analysis was conducted to identify convergence and divergence on views related to policy priorities and the potential for impact, political feasibility and unintended consequences of specific policy measures aimed at increasing the sustainability of livestock production or reducing meat consumption. Experts agreed on policy priorities but held divergent views on the potential for impact of specific policy measures. Economic structures including incentives, disincentives and food prices were highlighted as having the greatest influence over meat production and consumption practices.

Retailers can play an important role in facilitating a transition to sustainable diets in the UK. They have been implementing strategies aimed at helping customers make healthier choices and are now considering how to broaden this to include sustainability, which is a live discussion in the UK retail sector. Focusing on ‘less and better’ meat and dairy as a core component of sustainable diets, this study investigates retailer perceptions of sustainable diets and their strategies and challenges to provide and promote customer purchasing of ‘less and better’ meat and dairy. Results from a series of semi-structured interviews with senior health and sustainability professionals within the UK retail sector indicate that retailers have a diverse understanding of sustainable diets that seldom includes ‘less and better’ meat and dairy. Retailers are adopting a range of different strategies linked to ‘less and better’ meat and dairy – from improving the sustainability of their meat and dairy supply chains to influencing customer purchasing through ‘nudge’ interventions. While strategies related to ‘better’ meat and dairy are being adopted, no retailer is implementing interventions focused on reducing purchasing of meat products. The promotion of sustainable diets is seen by some retailers as a way of positively engaging with customers and improving brand loyalty, but there are external barriers to reducing purchasing of meat and dairy products that are beyond the direct control of the retailer.

While public bodies and civil society organisations play an important role in the transition towards a more sustainable society, there has been very limited research on how to make these institutions more sustainable. Therefore, the purpose of this study is to generate insights on processes and patterns of change towards sustainability, and to identify effective practices that might be transferred and adapted to different institutional contexts. The research followed an organisational change framework and a qualitative exploratory design. Six semi-structured interviews were conducted with experienced sustainability practitioners working at leading organisations in the UK. Thematic analysis of the data revealed three overarching themes: knowledge and reflection, support and engagement, and driving and enabling change. From this, a framework for effective practice was developed, highlighting the importance of (i) explicitly linking organisational understanding to working practices through frequent and deliberate reflection; (ii) developing a support base that provides expertise and legitimacy; and (iii) using context-specific strategies for implementing planned changes, as well as supporting emergent change throughout organisational sub-systems.

Several years ago, I had the rare experience of examining a short early film preserved in the BFI National Archive on nitrate stock. Getting to see it on the editing bench involved an elaborate rit...

The crisis of climate disruption and shortcomings in top-down approaches has focused attention on the effectiveness of governance to achieve climate goals. New sub-national governance models such as business alliances, city networks and NGO coalitions have emerged; such institutional ‘re-making’ is often motivated by frustration at national inaction, and by a belief thatlocal actors offer an effective ‘bottom-up’ approach. Literature on the emergence of climate-led multi-level and polycentric governance focuses primarily on cities; the role of urban-rural counties and of the micro-level of local government, and the challenges and opportunities before them, is less well studied. This paper draws on work in progress in a study exploring progress, challenges and failings in UK climate governance across multiple levels of county-based government: Surrey, an area of towns, peri-urban districts and countryside, is offered as a case study, with a focus on micro-level action in small towns and parishes. We find that despite a lack of national government orchestration or sub-regional frameworks, climate action is occurring voluntarily at all levels of governance. However, the nature of action is variable and irregular and there is little evidence as yet to demonstrate effectiveness. A fragmented form of multi-level governance is observed, with limited upward flows of ideas and no indication of national interest in micro-local climate lessons and experience. We identify the importance of ‘wilful actors’ and the need for greater coordination, information- and knowledge-sharing networks to achieve effective institutional ‘remaking’ for climate action.

HighlightsOrchestration requires political commitment and engagement on the basis of evidence, knowledge and progress-checking. Local actors face challenges in compiling carbon baselines that offer useful production and consumption emissions.

HighlightsThe commoning approach to climate action collectively claims, creates and stewards the net-zero infrastructure. Commoning invites people to participate in the transition, to have a stake, not just a say, and shape their response.

Facilitating the adoption of more sustainable food behaviors is key in order to reduce pressure on nature and improve public health. Food businesses that interact directly with consumers are well placed to enable a positive change in food behaviors. The present study evaluates the effectiveness of a 9-week multi-component behavioral intervention implemented by a large UK food retailer. Three food behaviors were explored: meat consumption, food waste and scratch cooking. Evaluation methods comprise of surveys issued pre-intervention, at intervention-end and at delayed follow-up (3 months after intervention end), and focus groups where participants were divided according to life-stage (pre-family, family, retired). Results show the intervention mitigated individual barriers to change and had a positive impact on awareness, intention and behavior which lasted beyond intervention-end. Participants reported reducing their meat consumption and food waste and cooking more frequently from scratch. Findings indicate that the online community, 'ask the expert' videos and product samples were the most impactful intervention components, while recipes and cook-alongs were less effective. This study provides an effective and feasible intervention which could be implemented and scaled by food companies. While behavioral interventions offer a positive opportunity for companies to drive consumer behavior change, structural and cultural changes to the food environment will be needed to facilitate long-term change at scale.

The physical mechanism for the production of fast gamma-ray variability in blazars remains debated. Plasmoids – magnetized quasi-circular structures of plasma formed self-consistently in reconnecting current sheets – are ideal candidates for the production of broadband variable non-thermal emission. Using state-of-the-art kinetic simulations of magnetic reconnection and radiative transfer calculations, we generate artificial gamma-ray light curves that would be observed with the Fermi Large Area Telescope (LAT). Our goal is to investigate if characteristic features of the theoretical light curves, such as the ultra-rapid gamma-ray flares predicted by the reconnection model, are detectable with the typical Fermi-LAT observations. A comparison with observed luminous and fast gamma-ray flares from flat spectrum radio quasars (FSRQs) reveals that magnetic reconnection events lead to comparable flux levels and variability patterns, especially when the reconnection layer is slightly misaligned with the line of sight. Emission from fast plasmoids moving close to the line of sight could explain fast variability on the time scales of minutes for which evidence has been found in observations of FSRQs. Our results motivate improvements in the existing reconnection model for blazars as well as dedicated searches for fast variability in LAT data as evidence for magnetic reconnection events.

The study of early cinema beyond Europe and North America is still sufficiently underdeveloped to make Rielle Navitski’s Public Spectacles of Violence a welcome addition. But it should also be of w...