Does promoting plant-based products in Veganuary lead to increased sales, and a reduction in meat sales? A natural experiment in a supermarket setting.

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.

Sparking Change: Evaluating the effectiveness of a multi-component intervention at encouraging more sustainable food behaviors.

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.

Cortical amplification models of experience-dependent development of selective columns and response sparsification.

The development of direction-selective cortical columns requires visual experience, but the neural circuits and plasticity mechanisms that are responsible for this developmental transition are unknown. To gain insight into the mechanisms that could underlie experience-dependent increases in selectivity, we explored families of cortical amplifier models that enhance weakly biased feedforward signals. Here we focused exclusively on possible contributions of cortico-cortical connections and took feedforward input to be constant. We modeled pairs of interconnected columns that received equal and oppositely biased inputs. In a single-element model of cortical columns, we found two ways that cortical columns could receive biased feedforward input and exhibit strong but unselective responses to stimuli: 1) within-column recurrent excitatory connections could be strong enough to amplify both strong and weak feedforward input, or 2) columns that received differently biased inputs could have strong excitatory cross-connections that destroy selectivity. A Hebbian plasticity rule combined with simulated experience with stimuli weakened these strong cross-connections across cortical columns, allowing the individual columns to respond selectively to their biased inputs. In a model that included both excitatory and inhibitory neurons in each column, an additional means of obtaining selectivity through the cortical circuit was uncovered: cross-column suppression of inhibition-stabilized networks. When each column operated as an inhibition-stabilized network, cross-column excitation onto inhibitory neurons forced competition between the columns but in a manner that did not involve strong null-direction inhibition, consistent with experimental measurements of direction selectivity in visual cortex. Experimental predictions of these possible contributions of cortical circuits are discussed.NEW & NOTEWORTHY Sensory circuits are initially constructed via mechanisms that are independent of sensory experience, but later refinement requires experience. We constructed models of how circuits that receive biased feedforward inputs can be initially unselective and then be modified by experience and plasticity so that the resulting circuit exhibits increased selectivity. We propose that neighboring cortical columns may initially exhibit coupling that is too strong for selectivity. Experience-dependent mechanisms decrease this coupling so individual columns can exhibit selectivity.

Exploring chronic airways disease patients' perspectives on self-management topics.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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 Forecasting & Air Quality Index (n = 29). 141 participants' responses were categorised during the second stage. CONCLUSIONS: 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. PRACTICE IMPLICATIONS: Findings may illuminate potential areas to investigate communication gaps among CAD patients; further investigation is warranted among non-specialty care patients.

National Trends in Extended Criteria Donor Utilization and Outcomes for Lung Transplantation.

BACKGROUND: Extended criteria donor (ECD) for lung transplantation (LTx) have been implemented due to the donor organ shortage. The impact on recipient survival is under investigation. We report trends in the use of extended criteria lungs in the modern era and its association with survival outcomes using a large national database. METHODS: We performed a retrospective analysis of all adult LTx from May 2005 to December 2018 using the United Network for Organ Sharing database. ECD were defined by 2 or more variances from standard criteria: age ≥ 55 years, pO2 ≤ 300, pack years ≥ 20, diabetes, purulent bronchoscopy, blood infection, or abnormal chest radiographs. Transplant centers were dichotomized based on volume. Recipient survival was analyzed using lung allocation score as a covariate. RESULTS: Of 24,888 LTx, 80% had extended criteria; 42% had 2 or more extensions and were deemed ECD in this analysis. Both LTx volume (2005: 1352; 2018: 2495) and use of ECD (2005: 27% ECD, 2018: 50% ECD) have increased over the study period. Survival of LTx recipients has steadily increased (2005: 82% 1-year survival in 2005; 2017: 90% 1-year survival). High-volume centers (>47 annual LTx) utilized ECD in 46% of transplants compared with 40% ECD among other centers. Recipients of ECD and standard criteria organs had no difference in 1-year survival. CONCLUSIONS: Donor supply limits the number of LTx performed. Extension of donor criteria has occurred alongside increased overall LTx volume. Use of ECD did not compromise 30-day, 90-day, nor 1-year survival. Further studies are warranted to define long-term outcomes.

Facilitating Positive Spillover Effects: New Insights From a Mixed-Methods Approach Exploring Factors Enabling People to Live More Sustainable Lifestyles.

Positive spillover occurs when changes in one behavior influence changes in subsequent behaviors. Evidence for such spillover and an understanding of when and how it may occur are still limited. This paper presents findings of a 1-year longitudinal behavior change project led by a commercial retailer in the United Kingdom and Ireland to examine behavior change and potential spillover of pro-environmental behavior, and how this may be associated with changes in environmental identity and perceptions of ease and affordability as well as perceptions of how participation in the project has helped support behavior change. We draw on both quantitative and qualitative data. Study 1 examines quantitative data from the experimental and a matched control group. Study 2 reports qualitative findings from a follow up interview study with participants of the experimental group. As expected, we found significant changes in reported pro-environmental behavior and identity in the experimental group as well as some indications of behavioral spillover. These changes were not significantly associated with changes in environmental identity. The interviews suggested that group dynamics played an important role in facilitating a sense of efficacy and promoting sustained behavior change and spillover. Moreover, the support by a trusted entity was deemed to be of crucial importance.

Establishing state of motion through two-dimensional foot and shoe print analysis: A pilot study.

According to the College of Podiatry, footprints rank among the most frequent forms of evidence found at crime scenes, and the recent ascension of forensic podiatry reflects the importance of footwear and barefoot traces in contemporary forensic practice. In this context, this pilot study focused on whether it is possible to distinguish between walking and running states using parameters derived from two-dimensional foot or shoe prints. Eleven subjects moved along four tracks (barefoot walking; barefoot running; footwear walking; footwear running) while having their bare feet or footwear stained with artificial blood and their footstep patterns recorded. Contact stains and associated bloodstain patterns were collected, and body movements were recorded through three-dimensional motion capture. Barefoot walking prints were found to be larger than barefoot static prints (1.789±0.481cm; p<0.001) and barefoot running prints (0.635±0.405cm; p=0.006). No correlation was observed for footwear prints. Running trials were more associated with the presence of both passive and cast off stains than walking trials, and the quantity of additional associated stains surrounding individual foot and shoe prints was also higher in running states. Furthermore, a previously proposed equation predicted speed with a high degree of accuracy (within 6%) and may be used for clinical assessment of walking speed. Contact stains, associated bloodstain patterns and stride length measurements may serve to ascertain state of motion in real crime scene scenarios, and future studies may be capable of designing statistical frameworks which could be used in courts of law.

Does experience provide a permissive or instructive influence on the development of direction selectivity in visual cortex?

In principle, the development of sensory receptive fields in cortex could arise from experience-independent mechanisms that have been acquired through evolution, or through an online analysis of the sensory experience of the individual animal. Here we review recent experiments that suggest that the development of direction selectivity in carnivore visual cortex requires experience, but also suggest that the experience of an individual animal cannot greatly influence the parameters of the direction tuning that emerges, including direction angle preference and speed tuning. The direction angle preference that a neuron will acquire can be predicted from small initial biases that are present in the naïve cortex prior to the onset of visual experience. Further, experience with stimuli that move at slow or fast speeds does not alter the speed tuning properties of direction-selective neurons, suggesting that speed tuning preferences are built in. Finally, unpatterned optogenetic activation of the cortex over a period of a few hours is sufficient to produce the rapid emergence of direction selectivity in the naïve ferret cortex, suggesting that information about the direction angle preference that cells will acquire must already be present in the cortical circuit prior to experience. These results are consistent with the idea that experience has a permissive influence on the development of direction selectivity.

Reactivation of the p90RSK-CDC25C Pathway Leads to Bypass of the Ganetespib-Induced G2-M Arrest and Mediates Acquired Resistance to Ganetespib in KRAS-Mutant NSCLC.

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.

Acquired Resistance to the Hsp90 Inhibitor, Ganetespib, in KRAS-Mutant NSCLC Is Mediated via Reactivation of the ERK-p90RSK-mTOR Signaling Network.

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.

Perfluorinated alkyl acids in plasma of American alligators (Alligator mississippiensis) from Florida and South Carolina.

The present study aimed to quantitate 15 perfluoroalkyl acids (PFAAs) in 125 adult American alligators at 12 sites across the southeastern United States. Of those 15 PFAAs, 9 were detected in 65% to 100% of samples: perfluorooctanoic acid, perfluorononanoic acid, perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnA), perfluorododecanoic acid, perfluorotridecanoic acid (PFTriA), perfluorotetradecanoic acid, perfluorohexanesulfonic acid (PFHxS), and perfluorooctane sulfonate (PFOS). Males (across all sites) showed significantly higher concentrations of 4 PFAAs: PFOS (p = 0.01), PFDA (p = 0.0003), PFUnA (p = 0.021), and PFTriA (p = 0.021). Concentrations of PFOS, PFHxS, and PFDA in plasma were significantly different among the sites in each sex. Alligators at both Merritt Island National Wildlife Refuge (FL, USA) and Kiawah Nature Conservancy (SC, USA) exhibited some of the highest PFOS concentrations (medians of 99.5 ng/g and 55.8 ng/g, respectively) in plasma measured to date in a crocodilian species. A number of positive correlations between PFAAs and snout-vent length were observed in both sexes, suggesting that PFAA body burdens increase with increasing size. In addition, several significant correlations among PFAAs in alligator plasma may suggest conserved sources of PFAAs at each site throughout the greater study area. The present study is the first to report PFAAs in American alligators, to reveal potential PFAA hot spots in Florida and South Carolina, and to provide a contaminant of concern when assessing anthropogenic impacts on ecosystem health. Environ Toxicol Chem 2017;36:917-925. Published 2016 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.

Sympathetic sudomotor disturbance in early type 1 diabetes mellitus is linked to lipid peroxidation.

The present study was performed to determine whether increased lipid peroxidation, as assessed from malondialdehyde (MDA) excretion, is associated with deterioration in peripheral nerve function in early type 1 diabetes mellitus. These parameters were measured annually for 3 years in 36 patients who entered the study less than 2 years after the diagnosis of diabetes. Malondialdehyde excretion was 1.51 +/- 0.20 micromol/g creatinine in the controls, and 2.43 +/- 0.21, 2.39 +/- 0.22, and 1.93 +/- 0.21 micromol/g creatinine at the first, second, and third evaluations, respectively (P < .005). The increased MDA was seen only in the female participants. Malondialdehyde excretion was increased in those with high vs low hemoglobin Alc across all years (P < .05). Malondialdehyde excretion correlated negatively with sudomotor function below the waist. The mean sweat production from the 3 evaluations correlated with mean MDA excretion across all years in the proximal leg (r = -0.42, P < .005) and distal leg (r = -0.40, P < .01). Below the waist, sweating correlated with MDA (r = -0.40, P < .01) as did total sweat (r = -0.38, P < .01). The response amplitudes of the peroneal nerves correlated negatively with MDA excretion (for the mean values at the second 2 evaluations, P < .005, r = -0.45). Tests of sensory function correlated inconsistently with MDA excretion. In summary, lipid peroxidation, as assessed from malondialdehyde excretion, is associated with sudomotor dysfunction in early diabetes.

Perfluorinated alkyl acids in the plasma of South African crocodiles (Crocodylus niloticus).

Perfluorinated alkyl acids (PFAAs) are environmental contaminants that have been used in many products for over 50 years. Interest and concern has grown since 2000 on the widespread presence of PFAAs, when it was discovered that PFAAs were present in wildlife samples around the northern hemisphere. Since then, several studies have reported PFAAs in wildlife from many locations, including the remote regions of Antarctica and the Arctic. Although there are a multitude of studies, few have reported PFAA concentrations in reptiles and wildlife in the Southern Hemisphere. This study investigated the presence of PFAAs in the plasma of Nile crocodiles (Crocodylus niloticus) from South Africa. Crocodiles were captured from five sites in and around the Kruger National Park, South Africa, and plasma samples examined for PFAAs. Perfluorooctane sulfonate (PFOS) was the most frequent PFAA detected; with median values of 13.5 ng/g wet mass in crocodiles. In addition to PFOS, long chain perfluorinated carboxylic acids were also detected. Correlations between total length and PFAA load were investigated, as were differences in PFAA accumulation between sexes. No correlations were seen between crocodile size, nor were there sex-related differences. Spatial differences were examined and significant differences were observed in samples collected from the different sites (p < 0.05). Flag Boshielo Dam had the highest PFOS measurements, with a median concentration of 50.3 ng/g wet mass, when compared to the other sites (median concentrations at other sites below 14.0 ng/g wet mass). This suggests a point source of PFOS in this area.

Nitrosative stress, uric Acid, and peripheral nerve function in early type 1 diabetes.

The present study was performed to determine whether nitric oxide overproduction is associated with deterioration in peripheral nerve function in type 1 diabetes. We measured peripheral nerve function and biochemical indicators of nitrosative stress annually for 3 years in 37 patients with type 1 diabetes. Plasma nitrite and nitrate (collectively NO(x)) were 34.0 +/- 4.9 micro mol/l in the control subjects and 52.4 +/- 5.1, 50.0 +/- 5.1, and 49.0 +/- 5.2 in the diabetic patients at the first, second, and third evaluations, respectively (P < 0.01). Nitrotyrosine (NTY) was 13.3 +/- 2.0 micro mol/l in the control subjects and 26.8 +/- 4.4, 26.1 +/- 4.3, and 32.7 +/- 4.3 in the diabetic patients (P < 0.01). Uric acid was suppressed by 20% in the diabetic patients (P < 0.001). Composite motor nerve conduction velocity for the median, ulnar, and peroneal nerves was decreased in patients with high versus low NTY (mean Z score -0.522 +/- 0.25 versus 0.273 +/- 0.22; P < 0.025). Patients with high NO(x) had decreased sweating, and those with suppressed uric acid had decreased autonomic function. In conclusion, nitrosative stress in early diabetes is associated with suppressed uric acid and deterioration in peripheral nerve function.