Poverty-related bandwidth constraints reduce the value of consumption.

Poverty confers many costs on individuals, primarily through direct material deprivation. We hypothesize that these costs may be understated: poverty may also reduce human welfare by decreasing the experiential value of what little the poor are able to consume via reduced bandwidth (cognitive resources)-exerting a de facto "tax" on the value of consumption. We test this hypothesis using a randomized controlled trial in which we experimentally simulate key aspects of poverty that impair bandwidth via methods commonly used in laboratory studies (e.g., memorizing sequences) and via introducing stressors commonly associated with life in poverty (e.g., thinking about financial security and experiencing thirst). Participants then engaged in consumption activities and were asked to rate their enjoyment of these activities. Consistent with our hypothesis, the randomly assigned treatments designed to reduce bandwidth significantly and meaningfully reduced ratings of the consumption activities, with the strongest effects on the consumption of food. Our results shed additional light on how the consequences of poverty on human welfare may compound and motivate future work on the full scope of returns to poverty alleviation efforts.

Facial expression modifies female body perception.

The judgment of female body appearance has been reported to be affected by a range of internal (e.g., viewers' sexual cognition) and external factors (e.g., viewed clothing type and colour). This eye-tracking study aimed to complement previous research by examining the effect of facial expression on female body perception and associated body-viewing gaze behaviour. We presented female body images of Caucasian avatars in a continuum of common dress sizes posing seven basic facial expressions (neutral, happiness, sadness, anger, fear, surprise, and disgust), and asked both male and female participants to rate the perceived body attractiveness and body size. The analysis revealed an evident modulatory role of avatar facial expressions on body attractiveness and body size ratings, but not on the amount of viewing time directed at individual body features. Specifically, happy and angry avatars attracted the highest and lowest body attractiveness ratings, respectively, and fearful and surprised avatars tended to be rated slimmer. Interestingly, the impact of facial expression on female body assessment was not further influenced by viewers' gender, suggesting a 'universal' role of common facial expressions in modifying the perception of female body appearance.

Mortality in 98 type 1 diabetes mellitus and type 2 diabetes mellitus: Foot ulcer location is an independent risk determinant.

INTRODUCTION: We previously demonstrated in both a longitudinal study and in meta-analysis (pooled relative-risk RR, 2.45) that all-cause mortality is significantly higher in people with diabetes foot ulceration (DFU) than with those without a foot ulcer. In this prospective study, we looked at the factors linked to mortality after presentation to podiatry with DFU. METHODS: Ninety-eight individuals recruited consecutively from the Salford Royal Hospital Multidisciplinary Foot Clinic in Spring 2016 were followed up for up to 48 months. Data concerning health outcomes were extracted from the electronic patient record (EPR). RESULTS: Seventeen people (17) had type 1 diabetes mellitus, and 81 had type 2 diabetes mellitus. Thirty-one were women. The mean age (range) was 63.6 (28-90) years with maximum diabetes duration 45 years. Mean HbA1c was 72 (95% CI: 67-77) mmol/mol; 97% had neuropathy (International Working Group on the Diabetic Foot (IWGDF) monofilament); 62% had vascular insufficiency (Doppler studies); 69% of ulcers were forefoot, and 23% of ulcers were hind foot in location. Forty of 98 (40%) patients died in follow-up with 27% of death certificates including sepsis (not foot-related) and 35% renal failure as cause of death. Multivariate regression analysis indicated a 6.3 (95% CI: 3.9-8.1) fold increased risk of death with hind foot ulcer, independent of age/BMI/gender/HbA1c/eGFR/total cholesterol level. CONCLUSION: This prospective study has indicated a very high long-term mortality rate in individuals with DFU, greater for those with a hind foot ulcer and shown a close relation between risk of sepsis/renal failure and DFU mortality, highlighting again the importance of addressing all risk factors as soon as people present with a foot ulcer.

Priority setting in health: development and application of a multi-criteria algorithm for the population of New Zealand's Waikato region.

BACKGROUND: Priority setting in a climate of diverse needs and limited resources is one of the most significant challenges faced by health care policymakers. This paper develops and applies a comprehensive multi-criteria algorithm to help determine the relative importance of health conditions that affect a defined population. METHODS: Our algorithm is implemented in the context of the Waikato District Health Board (WDHB) in New Zealand, which serves approximately 10% of the New Zealand population. Strategic priorities of the WDHB are operationalized into five criteria along which the algorithm is structured-scale of disease, household financial impact of disease, health equity, cost-effectiveness, and multimorbidity burden. Using national-level data and published literature from New Zealand, the World Health Organization, and other high-income Commonwealth countries, 25 health conditions in Waikato are identified and mapped to these five criteria. These disease-criteria mappings are weighted with data from an ordered choice survey administered to the general public of the Waikato region. The resulting output of health conditions ranked in order of relative importance is validated against an explicit list of health concerns, provided by the survey respondents. RESULTS: Heart disease and cancerous disorders are assigned highest priority rankings according to both the algorithm and the survey data, suggesting that our model is aligned with the primary health concerns of the general public. All five criteria are weighted near-equal across survey respondents, though the average health equity preference score is 9.2% higher for Maori compared to non-Maori respondents. Older respondents (50 years and above) ranked issues of multimorbidity 4.2% higher than younger respondents. CONCLUSIONS: Health preferences of the general population can be elicited using ordered-choice surveys and can be used to weight data for health conditions across multiple criteria, providing policymakers with a practical tool to inform which health conditions deserve the most attention. Our model connects public health strategic priorities, the health impacts and financial costs of particular health conditions, and the underlying preferences of the general public. We illustrate a practical approach to quantifying the foundational criteria that drive public preferences, for the purpose of relevant, legitimate, and evidence-based priority setting in health.

Bmi1 is required for the initiation of pancreatic cancer through an Ink4a-independent mechanism.

Epigenetic dysregulation is involved in the initiation and progression of many epithelial cancers. BMI1, a component of the polycomb protein family, plays a key role in these processes by controlling the histone ubiquitination and long-term repression of multiple genomic loci. BMI1 has previously been implicated in pancreatic homeostasis and the function of pancreatic cancer stem cells. However, no work has yet addressed its role in the early stages of pancreatic cancer development. Here, we show that BMI1 is required for the initiation of murine pancreatic neoplasia using a novel conditional knockout of Bmi1 in combination with a Kras(G12D)-driven pancreatic cancer mouse model. We also demonstrate that the requirement for Bmi1 in pancreatic carcinogenesis is independent of the Ink4a/Arf locus and at least partially mediated by dysregulation of reactive oxygen species. Our data provide new evidence of the importance of this epigenetic regulator in the genesis of pancreatic cancer.

The Economic Consequences of Increasing Sleep Among the Urban Poor.

The urban poor in developing countries face challenging living environments, which may interfere with good sleep. Using actigraphy to measure sleep objectively, we find that low-income adults in Chennai, India, sleep only 5.5 hours a night on average despite spending 8 hours in bed. Their sleep is highly interrupted, with sleep efficiency-sleep per time in bed-comparable to those with disorders such as sleep apnea or insomnia. A randomized three-week treatment providing information, encouragement, and improvements to home sleep environments increased sleep duration by 27 minutes a night by inducing more time in bed. Contrary to expert predictions and a large body of sleep research, increased nighttime sleep had no detectable effects on cognition, productivity, decision making, or well being, and led to small decreases in labor supply. In contrast, short afternoon naps at the workplace improved an overall index of outcomes by 0.12 standard deviations, with significant increases in productivity, psychological well-being, and cognition, but a decrease in work time.

Informing sleep policy through field experiments.

Evidence is particularly needed from poorer communities.

Multimodal Mapping of the Tumor and Peripheral Blood Immune Landscape in Human Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDA) is characterized by an immune-suppressive tumor microenvironment that renders it largely refractory to immunotherapy. We implemented a multimodal analysis approach to elucidate the immune landscape in PDA. Using a combination of CyTOF, single-cell RNA sequencing, and multiplex immunohistochemistry on patient tumors, matched blood, and non-malignant samples, we uncovered a complex network of immune-suppressive cellular interactions. These experiments revealed heterogeneous expression of immune checkpoint receptors in individual patient's T cells and increased markers of CD8+ T cell dysfunction in advanced disease stage. Tumor-infiltrating CD8+ T cells had an increased proportion of cells expressing an exhausted expression profile that included upregulation of the immune checkpoint TIGIT, a finding that we validated at the protein level. Our findings point to a profound alteration of the immune landscape of tumors, and to patient-specific immune changes that should be taken into account as combination immunotherapy becomes available for pancreatic cancer.

Pancreatic HIF2α Stabilization Leads to Chronic Pancreatitis and Predisposes to Mucinous Cystic Neoplasm.

BACKGROUND & AIMS: Tissue hypoxia controls cell differentiation in the embryonic pancreas, and promotes tumor growth in pancreatic cancer. The cellular response to hypoxia is controlled by the hypoxia-inducible factor (HIF) proteins, including HIF2α. Previous studies of HIF action in the pancreas have relied on loss-of-function mouse models, and the effects of HIF2α expression in the pancreas have remained undefined. METHODS: We developed several transgenic mouse models based on the expression of an oxygen-stable form of HIF2α, or indirect stabilization of HIF proteins though deletion of von Hippel-Lindau, thus preventing HIF degradation. Furthermore, we crossed both sets of animals into mice expressing oncogenic KrasG12D in the pancreas. RESULTS: We show that HIF2α is not expressed in the normal human pancreas, however, it is up-regulated in human chronic pancreatitis. Deletion of von Hippel-Lindau or stabilization of HIF2α in mouse pancreata led to the development of chronic pancreatitis. Importantly, pancreatic HIF1α stabilization did not disrupt the pancreatic parenchyma, indicating that the chronic pancreatitis phenotype is specific to HIF2α. In the presence of oncogenic Kras, HIF2α stabilization drove the formation of cysts resembling mucinous cystic neoplasm (MCN) in humans. Mechanistically, we show that the pancreatitis phenotype is linked to expression of multiple inflammatory cytokines and activation of the unfolded protein response. Conversely, MCN formation is linked to activation of Wnt signaling, a feature of human MCN. CONCLUSIONS: We show that pancreatic HIF2α stabilization disrupts pancreatic homeostasis, leading to chronic pancreatitis, and, in the context of oncogenic Kras, MCN formation. These findings provide new mouse models of both chronic pancreatitis and MCN, as well as illustrate the importance of hypoxia signaling in the pancreas.

Mutant p53R270H drives altered metabolism and increased invasion in pancreatic ductal adenocarcinoma.

Pancreatic cancer is characterized by nearly universal activating mutations in KRAS. Among other somatic mutations, TP53 is mutated in more than 75% of human pancreatic tumors. Genetically engineered mice have proven instrumental in studies of the contribution of individual genes to carcinogenesis. Oncogenic Kras mutations occur early during pancreatic carcinogenesis and are considered an initiating event. In contrast, mutations in p53 occur later during tumor progression. In our model, we recapitulated the order of mutations of the human disease, with p53 mutation following expression of oncogenic Kras. Further, using an inducible and reversible expression allele for mutant p53, we inactivated its expression at different stages of carcinogenesis. Notably, the function of mutant p53 changes at different stages of carcinogenesis. Our work establishes a requirement for mutant p53 for the formation and maintenance of pancreatic cancer precursor lesions. In tumors, mutant p53 becomes dispensable for growth. However, it maintains the altered metabolism that characterizes pancreatic cancer and mediates its malignant potential. Further, mutant p53 promotes epithelial-mesenchymal transition (EMT) and cancer cell invasion. This work generates new mouse models that mimic human pancreatic cancer and expands our understanding of the role of p53 mutation, common in the majority of human malignancies.

A Randomized Controlled Trial of Employer Matching of Employees' Monetary Contributions to Deposit Contracts to Promote Weight Loss.

PURPOSE: To test whether employer matching of employees' monetary contributions increases employees' (1) participation in deposit contracts to promote weight loss and (2) weight loss. DESIGN: A 36-week randomized trial. SETTING: Large employer in the northeast United States. PARTICIPANTS: One hundred thirty-two obese employees. INTERVENTIONS: Over 24 weeks, participants were asked to lose 24 pounds and randomized to monthly weigh-ins or daily weigh-ins with monthly opportunities to deposit $1 to $3 per day that was not matched, matched 1:1, or matched 2:1. Deposits and matched funds were returned to participants for each day they were below their goal weight. MEASURES: Rates of making ≥1 deposit, weight loss at 24 weeks (primary outcome), and 36 weeks. ANALYSIS: Deposit rates were compared using χ(2) tests. Weight loss was compared using t tests. RESULTS: Among participants eligible to make deposits, 29% made ≥1 deposit and matching did not increase participation. At 24 weeks, control participants gained an average of 1.0 pound, whereas 1:1 match participants lost an average of 5.3 pounds (P = .005). After 36 weeks, control participants gained an average of 2.1 pounds, whereas no match participants lost an average of 5.1 pounds (P = .008). CONCLUSION: Participation in deposit contracts to promote weight loss was low, and matching deposits did not increase participation. For deposit contracts to impact population health, ongoing participation will need to be higher.

Change isn't always better.

Maintaining the identity of acinar cells in the pancreas could help to prevent the development of pancreatic cancer.

Comparing the effectiveness of individualistic, altruistic, and competitive incentives in motivating completion of mental exercises.

This study examines the impact of individually oriented, purely altruistic, and a hybrid of competitive and cooperative monetary reward incentives on older adults' completion of cognitive exercises and cognitive function. We find that all three incentive structures approximately double the number of exercises completed during the six-week active experimental period relative to a no incentive control condition. However, the altruistic and cooperative/competitive incentives led to different patterns of participation, with significantly higher inter-partner correlations in utilization of the software, as well as greater persistence once incentives were removed. Provision of all incentives significantly improved performance on the incentivized exercises. However, results of an independent cognitive testing battery suggest no generalizable gains in cognitive function resulted from the training.

Novel tools for genetic manipulation of follicle stem cells in the Drosophila ovary reveal an integrin-dependent transition from quiescence to proliferation.

In many tissues, the presence of stem cells is inferred by the capacity of the tissue to maintain homeostasis and undergo repair after injury. Isolation of self-renewing cells with the ability to generate the full array of cells within a given tissue strongly supports this idea, but the identification and genetic manipulation of individual stem cells within their niche remain a challenge. Here we present novel methods for marking and genetically altering epithelial follicle stem cells (FSCs) within the Drosophila ovary. Using these new tools, we define a sequential multistep process that comprises transitioning of FSCs from quiescence to proliferation. We further demonstrate that integrins are cell-autonomously required within FSCs to provide directional signals that are necessary at each step of this process. These methods may be used to define precise roles for specific genes in the sequential events that occur during FSC division after a period of quiescence.

Canonical wnt signaling is required for pancreatic carcinogenesis.

Wnt ligand expression and activation of the Wnt/ß-catenin pathway have been associated with pancreatic ductal adenocarcinoma, but whether Wnt activity is required for the development of pancreatic cancer has remained unclear. Here, we report the results of three different approaches to inhibit the Wnt/ß-catenin pathway in a established transgenic mouse model of pancreatic cancer. First, we found that ß-catenin null cells were incapable of undergoing acinar to ductal metaplasia, a process associated with development of premalignant pancreatic intraepithelial neoplasia lesions. Second, we addressed the specific role of ligand-mediated Wnt signaling through inducible expression of Dkk1, an endogenous secreted inhibitor of the canonical Wnt pathway. Finally, we targeted the Wnt pathway with OMP-18R5, a therapeutic antibody that interacts with multiple Frizzled receptors. Together, these approaches showed that ligand-mediated activation of the Wnt/ß-catenin pathway is required to initiate pancreatic cancer. Moreover, they establish that Wnt signaling is also critical for progression of pancreatic cancer, a finding with potential therapeutic implications.

Drosophila Boi limits Hedgehog levels to suppress follicle stem cell proliferation.

Stem cells depend on signals from cells within their microenvironment, or niche, as well as factors secreted by distant cells to regulate their maintenance and function. Here we show that Boi, a Hedgehog (Hh)-binding protein, is a novel suppressor of proliferation of follicle stem cells (FSCs) in the Drosophila ovary. Hh is expressed in apical cells, distant from the FSC niche, and diffuses to reach FSCs, where it promotes FSC proliferation. We show that Boi is expressed in apical cells and exerts its suppressive effect on FSC proliferation by binding to and sequestering Hh on the apical cell surface, thereby inhibiting Hh diffusion. Our studies demonstrate that cells distant from the local niche can regulate stem cell function through ligand sequestration, a mechanism that likely is conserved in other epithelial tissues.

The psychology of nutrition messages.

The purpose of this paper is to explore consumer thinking about nutrition decisions and how firms can use consumers' awareness of the links between nutrients and health generated by public health messages to market products, including ones, which have little nutritional value. We approach this issue by tracking the development of public health messages based on scientific research, dissemination of those messages in the popular press, and use of nutrition claims in food advertisements to assess whether firms are timing the use of nutrition claims to take advantage of heuristic-based decision-making. Our findings suggest that the timing of the development of nutrition information, its dissemination in the press, and use in advertising accords well with a heuristic processing model in which firms take advantage of associations between nutrient information and health in their advertisements. However, the demonstrated relationships may not be causal. Further research will be needed to provide stronger and more comprehensive evidence regarding the proposed message hijacking process. If the message hijacking framework is borne out: (1) simple overall health rating scales could significantly improve consumer decision-making, (2) the impact of misleading advertisements could be mitigated by encouraging a multidimensional view of nutrition, and (3) more intensive regulation of product labeling could limit the impact of hijacked messages. Overall, this paper considers a novel hypothesis about the impact of public health messages on nutrition and health.