Scoping potential routes to UK civil unrest via the food system: Results of a structured expert elicitation

We report the results of a structured expert elicitation to identify the most likely typesof potential food system disruption scenarios for the UK, focusing on routes to civil unrest. Wetake a backcasting approach by defining as an end-point a societal event in which 1 in 2000 peoplehave been injured in the UK, which 40% of experts rated as “Possible (20–50%)”, “More likely thannot (50–80%)” or “Very likely (>80%)” over the coming decade. Over a timeframe of 50 years, thisincreased to 80% of experts. The experts considered two food system scenarios and ranked theirplausibility of contributing to the given societal scenario. For a timescale of 10 years, the majorityidentified a food distribution problem as the most likely. Over a timescale of 50 years, the expertswere more evenly split between the two scenarios, but over half thought the most likely route tocivil unrest would be a lack of total food in the UK. However, the experts stressed that the variouscauses of food system disruption are interconnected and can create cascading risks, highlighting theimportance of a systems approach. We encourage food system stakeholders to use these results intheir risk planning and recommend future work to support prevention, preparedness, response andrecovery planning

Cancer-specific loss of p53 leads to a modulation of myeloid and T cell responses

Loss of p53 function contributes to the development of many cancers. While cell-autonomous consequences of p53 mutation have been studied extensively, the role of p53 in regulating the anti-tumor immune response is still poorly understood. Here, we show that loss of p53 in cancer cells modulates the tumor-immune landscape to circumvent immune destruction. Deletion of p53 promotes the recruitment and instruction of suppressive myeloid CD11b cells, in part through increased expression of CXCR3/CCR2-associated chemokines and macrophage colony-stimulating factor (M-CSF), and attenuates the CD4 T helper 1 (Th1) and CD8 T cell responses in vivo. p53-null tumors also show an accumulation of suppressive regulatory T (Treg) cells. Finally, we show that two key drivers of tumorigenesis, activation of KRAS and deletion of p53, cooperate to promote immune tolerance. [Abstract copyright: Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

Personalized Research on Diet in Ulcerative Colitis and Crohn\u27s Disease: A Series of N-of-1 Diet Trials

INTRODUCTION: Evidence about specific carbohydrate diet (SCD) for inflammatory bowel disease (IBD) is limited. We conducted 54 single-subject, double-crossover N-of-1 trials comparing SCD with a modified SCD (MSCD) and comparing each with the participant\u27s baseline, usual diet (UD). METHODS: Across 19 sites, we recruited patients aged 7–18 years with IBD and active inflammation. Following a 2-week baseline (UD), patients were randomized to 1 of 2 sequences of 4 alternating 8-week SCD and MSCD periods. Outcomes included fecal calprotectin and patient-reported symptoms. We report posterior probabilities from Bayesian models comparing diets. RESULTS: Twenty-one (39%) participants completed the trial, 9 (17%) completed a single crossover, and 24 (44%) withdrew. Withdrawal or early completion occurred commonly (lack of response [n = 11], adverse events [n = 11], and not desiring to continue [n = 6]). SCD and MSCD performed similarly for most individuals. On average, there was \u3c1% probability of a clinically meaningful difference in IBD symptoms between SCD and MSCD. The average treatment difference was −0.3 (95% credible interval −1.2, 0.75). There was no significant difference in the ratio of fecal calprotectin geometric means comparing SCD and MSCD (0.77, 95% credible interval 0.51, 1.10). Some individuals had improvement in symptoms and fecal calprotectin compared with their UD, whereas others did not. DISCUSSION: SCD and MSCD did not consistently improve symptoms or inflammation, although some individuals may have benefited. However, there are inherent difficulties in examining dietary changes that complicate study design and ultimately conclusions regarding effectiveness

Personalized Research on Diet in Ulcerative Colitis and Crohn\u27s Disease: A Series of N-of-1 Diet Trials

INTRODUCTION: Evidence about specific carbohydrate diet (SCD) for inflammatory bowel disease (IBD) is limited. We conducted 54 single-subject, double-crossover N-of-1 trials comparing SCD with a modified SCD (MSCD) and comparing each with the participant\u27s baseline, usual diet (UD). METHODS: Across 19 sites, we recruited patients aged 7–18 years with IBD and active inflammation. Following a 2-week baseline (UD), patients were randomized to 1 of 2 sequences of 4 alternating 8-week SCD and MSCD periods. Outcomes included fecal calprotectin and patient-reported symptoms. We report posterior probabilities from Bayesian models comparing diets. RESULTS: Twenty-one (39%) participants completed the trial, 9 (17%) completed a single crossover, and 24 (44%) withdrew. Withdrawal or early completion occurred commonly (lack of response [n = 11], adverse events [n = 11], and not desiring to continue [n = 6]). SCD and MSCD performed similarly for most individuals. On average, there was \u3c1% probability of a clinically meaningful difference in IBD symptoms between SCD and MSCD. The average treatment difference was −0.3 (95% credible interval −1.2, 0.75). There was no significant difference in the ratio of fecal calprotectin geometric means comparing SCD and MSCD (0.77, 95% credible interval 0.51, 1.10). Some individuals had improvement in symptoms and fecal calprotectin compared with their UD, whereas others did not. DISCUSSION: SCD and MSCD did not consistently improve symptoms or inflammation, although some individuals may have benefited. However, there are inherent difficulties in examining dietary changes that complicate study design and ultimately conclusions regarding effectiveness

Scoping Potential Routes to UK Civil Unrest via the Food System: Results of a Structured Expert Elicitation

Peer reviewed: TrueAcknowledgements: We are very grateful to the other participants not included as authors who took the survey, including Dan Crossley, Sue Davies, Katie Palmer, Anna Taylor, Alex Read and those who did not opt in to being named. Thank you to Adam Amara for helpful discussions about the framing of the study. We are grateful to Ben Dare for assistance in formatting and proofreading. The contents of this paper should not be taken to represent the views of the UK Government or the organisations to which the authors are affiliated.Publication status: PublishedFunder: Met Office Food, Farming and Natural Environment Climate ServiceFunder: Met Office Hadley Centre Climate ProgrammeFunder: DSITWe report the results of a structured expert elicitation to identify the most likely types of potential food system disruption scenarios for the UK, focusing on routes to civil unrest. We take a backcasting approach by defining as an end-point a societal event in which 1 in 2000 people have been injured in the UK, which 40% of experts rated as “Possible (20–50%)”, “More likely than not (50–80%)” or “Very likely (&gt;80%)” over the coming decade. Over a timeframe of 50 years, this increased to 80% of experts. The experts considered two food system scenarios and ranked their plausibility of contributing to the given societal scenario. For a timescale of 10 years, the majority identified a food distribution problem as the most likely. Over a timescale of 50 years, the experts were more evenly split between the two scenarios, but over half thought the most likely route to civil unrest would be a lack of total food in the UK. However, the experts stressed that the various causes of food system disruption are interconnected and can create cascading risks, highlighting the importance of a systems approach. We encourage food system stakeholders to use these results in their risk planning and recommend future work to support prevention, preparedness, response and recovery planning.</jats:p

Scoping Potential Routes to UK Civil Unrest via the Food System: Results of a Structured Expert Elicitation

We report the results of a structured expert elicitation to identify the most likely types of potential food system disruption scenarios for the UK, focusing on routes to civil unrest. We take a backcasting approach by defining as an end-point a societal event in which 1 in 2000 people have been injured in the UK, which 40% of experts rated as “Possible (20–50%)”, “More likely than not (50–80%)” or “Very likely (>80%)” over the coming decade. Over a timeframe of 50 years, this increased to 80% of experts. The experts considered two food system scenarios and ranked their plausibility of contributing to the given societal scenario. For a timescale of 10 years, the majority identified a food distribution problem as the most likely. Over a timescale of 50 years, the experts were more evenly split between the two scenarios, but over half thought the most likely route to civil unrest would be a lack of total food in the UK. However, the experts stressed that the various causes of food system disruption are interconnected and can create cascading risks, highlighting the importance of a systems approach. We encourage food system stakeholders to use these results in their risk planning and recommend future work to support prevention, preparedness, response and recovery planning