How demanding is the revealed preference approach to demand

A well known problem with revealed preference methods is that when data are found to satisfy their restrictions it is hard to know whether this should be viewed as a triumph for economic theory, or a warning that these conditions are so undemanding that almost anything goes. This paper allows researchers to make this distinction. Our approach builds on theoretical support in the form of an axiomatic cardinal characterisation of a measure of predictive success due to Selten(1991). We illustrate the idea using a large, nationally representative panel survey of Spanish consumers with broad commodity coverage. The results show that this approach to revealed preference methods can lead us radically to reassess our view of the empirical performance of economic theory.

Web-Based Psychological Interventions for People Living With and Beyond Cancer:Meta-Review of What Works and What Does Not for Maximizing Recruitment, Engagement, and Efficacy

BACKGROUND: Despite high levels of psychological distress experienced by many patients with cancer, previous research has identified several barriers to accessing traditional face-to-face psychological support. Web-based psychosocial interventions have emerged as a promising alternative. OBJECTIVE: This meta-review aimed to synthesize evidence on recruitment challenges and enablers, factors that promote engagement and adherence to web-based intervention content, and factors that promote the efficacy of web-based psychosocial interventions for patients with cancer and cancer survivors. METHODS: We conducted a systematic search of previous reviews that investigated the recruitment, engagement, and efficacy of web-based and app-based psychosocial interventions in adult patients with cancer and cancer survivors. We searched PubMed, CINAHL, PsycINFO, and the Cochrane Library database for relevant literature. The search terms focused on a combination of topics pertaining to neoplasms and telemedicine. Two independent authors conducted abstract screening, full text screening, and data extraction for each identified article. RESULTS: A total of 20 articles met eligibility criteria. There was inconsistency in the reporting of uptake and engagement data; however, anxiety about technology and perceived time burden were identified as 2 key barriers. Web-based psychosocial oncology interventions demonstrated efficacy in reducing depression and stress but reported weak to mixed findings for distress, anxiety, quality of life, and well-being. Although no factors consistently moderated intervention efficacy, preliminary evidence indicated that multicomponent interventions and greater communication with a health care professional were preferred by participants and were associated with superior effects. CONCLUSIONS: Several consistently cited barriers to intervention uptake and recruitment have emerged, which we recommend future intervention studies address. Preliminary evidence also supports the superior efficacy of multicomponent interventions and interventions that facilitate communication with a health care professional. However, a greater number of appropriately powered clinical trials, including randomized trials with head-to-head comparisons, are needed to enable more confident conclusions regarding which web-based psychosocial oncology interventions work best and for whom. TRIAL REGISTRATION: PROSPERO CRD42020202633; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=20263

Dual membrane-spanning anti-sigma factors regulate vesiculation in Bacteroides thetaiotaomicron

Bacteroidota are abundant members of the human gut microbiota that shape the enteric landscape by modulating host immunity and degrading dietary- and host-derived glycans. These processes are mediated in part b

Enterotoxigenic Escherichia coli heat-labile toxin drives enteropathic changes in small intestinal epithelia

Enterotoxigenic E. coli (ETEC) produce heat-labile (LT) and/or heat-stable (ST) enterotoxins, and commonly cause diarrhea in resource-poor regions. ETEC have been linked repeatedly to sequelae in children including enteropathy, malnutrition, and growth impairment. Although cellular actions of ETEC enterotoxins leading to diarrhea are well-established, their contributions to sequelae remain unclear. LT increases cellular cAMP to activate protein kinase A (PKA) that phosphorylates ion channels driving intestinal export of salt and water resulting in diarrhea. As PKA also modulates transcription of many genes, we interrogated transcriptional profiles of LT-treated intestinal epithelia. Here we show that LT significantly alters intestinal epithelial gene expression directing biogenesis of the brush border, the major site for nutrient absorption, suppresses transcription factors HNF4 and SMAD4 critical to enterocyte differentiation, and profoundly disrupts microvillus architecture and essential nutrient transport. In addition, ETEC-challenged neonatal mice exhibit substantial brush border derangement that is prevented by maternal vaccination with LT. Finally, mice repeatedly challenged with toxigenic ETEC exhibit impaired growth recapitulating the multiplicative impact of recurring ETEC infections in children. These findings highlight impacts of ETEC enterotoxins beyond acute diarrheal illness and may inform approaches to prevent major sequelae of these common infections including malnutrition that impact millions of children

Sperm design and variation in the New World blackbirds (Icteridae)

Post-copulatory sexual selection (PCSS) is thought to be one of the evolutionary forces responsible for the rapid and divergent evolution of sperm design. However, whereas in some taxa particular sperm traits are positively associated with PCSS, in other taxa, these relationships are negative, and the causes of these different patterns across taxa are poorly understood. In a comparative study using New World blackbirds (Icteridae), we tested whether sperm design was influenced by the level of PCSS and found significant positive associations with the level of PCSS for all sperm components but head length. Additionally, whereas the absolute length of sperm components increased, their variation declined with the intensity of PCSS, indicating stabilizing selection around an optimal sperm design. Given the diversity of, and strong selection on, sperm design, it seems likely that sperm phenotype may influence sperm velocity within species. However, in contrast to other recent studies of passerine birds, but consistent with several other studies, we found no significant link between sperm design and velocity, using four different species that vary both in sperm design and PCSS. Potential reasons for this discrepancy between studies are discussed

Central retinal thickness is positively correlated with macular pigment optical density. Exp. Eye Res.

Abstract Macular pigment (MP) has been suggested to have a protective role in age-related macular degeneration by reducing the amount of oxidative stress on the retina. MP levels peak at the foveal center, where it is found predominantly in the receptor axon and inner plexiform layers of the retina. The purpose of this study was to investigate the relationship between central retinal thickness and macular pigment optical density in a group of healthy subjects. We report that macular pigment optical density (MPOD) has a significant and positive relationship with central retinal thickness as measured by optical coherence tomography. The strength of the observed relationship (rw0.30) was independent of the technique used to measure MPOD, whether heterochromatic flicker photometry (HFP) or 2-wavelength autofluorescence (AF). Of note, there was no statistically demonstrable relationship between MPOD at an eccentricity of 1-or 2-degrees and central retinal thickness. This finding has important implications for future studies investigating MPOD, and its response to dietary modification/supplementation.

Heritability of Macular Pigment: A Twin Study

PURPOSE. Several studies have reported higher levels of macular pigment (MP) in association with reduced risk for age-related macular degeneration (ARMD), a disease to which there is a genetic predisposition. A classic twin study was performed to determine the heritability of MP in the healthy eye. METHODS. One hundred fifty twin pairs (76 monozygotic [MZ] and 74 dizygotic [DZ]), aged 18 to 50 years, participated. MP optical density was measured psychophysically with heterochromatic flicker photometry (HFP) and also with an imaging method involving fundus autofluorescence (AF). The covariance of MP within MZ and DZ twin pairs was compared, and genetic modeling techniques were used to determine the relative contributions of genes and environment to the variation in MP. RESULTS. The mean MP optical density, measured using HFP, was 0.43 Ϯ 0.21. Using AF, the mean MP optical density, measured at 1°eccentricity, was 0.28 Ϯ 0.11. MP optical densities correlated more highly in MZ twins than in DZ twins, according to both HFP (MZ: 0.65; DZ: 0.24) and AF (MZ: 0.83; DZ: 0.50). A model combining additive genetic and unique environmental effects provided the best fit and resulted in MP heritability estimates of 0.67 (95% CI, 0.52-0.77) and 0.85 (95% CI, 0.78 -0.90) for HFP and AF readings, respectively. CONCLUSIONS. This classic twin study demonstrates that genetic background is an important determinant of MP optical density, reflected in heritability estimates of 0.67 and 0.85 for HFP and AF measures, respectively. (Invest Ophthalmol Vis Sci. 2005; 46:4430 -4436

Beyond aggression: Androgen-receptor blockade modulates social interaction in wild meerkats

In male vertebrates, androgens are inextricably linked to reproduction, social dominance, and aggression, often at the cost of paternal investment or prosociality. Testosterone is invoked to explain rank-related reproductive differences, but its role within a status class, particularly among subordinates, is underappreciated. Recent evidence, especially for monogamous and cooperatively breeding species, suggests broader androgenic mediation of adult social interaction. We explored the actions of androgens in subordinate, male members of a cooperatively breeding species, the meerkat (Suricata suricatta). Although male meerkats show no rank-related testosterone differences, subordinate helpers rarely reproduce. We blocked androgen receptors, in the field, by treating subordinate males with the antiandrogen, flutamide. We monitored androgen concentrations (via baseline serum and time-sequential fecal sampling) and recorded behavior within their groups (via focal observation). Relative to controls, flutamide-treated animals initiated less and received more high-intensity aggression (biting, threatening, feeding competition), engaged in more prosocial behavior (social sniffing, grooming, huddling), and less frequently initiated play or assumed a ‘dominant’ role during play, revealing significant androgenic effects across a broad range of social behavior. By contrast, guarding or vigilance and measures of olfactory and vocal communication in subordinate males appeared unaffected by flutamide treatment. Thus, androgens in male meerkat helpers are aligned with the traditional trade-off between promoting reproductive and aggressive behavior at a cost to affiliation. Our findings, based on rare endocrine manipulation in wild mammals, show a more pervasive role for androgens in adult social behavior than is often recognized, with possible relevance for understanding tradeoffs in cooperative systems

Gamma secretase inhibition promotes hypoxic necrosis in mouse pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDA) is a highly lethal disease that is refractory to medical intervention. Notch pathway antagonism has been shown to prevent pancreatic preneoplasia progression in mouse models, but potential benefits in the setting of an established PDA tumor have not been established. We demonstrate that the gamma secretase inhibitor MRK003 effectively inhibits intratumoral Notch signaling in the KPC mouse model of advanced PDA. Although MRK003 monotherapy fails to extend the lifespan of KPC mice, the combination of MRK003 with the chemotherapeutic gemcitabine prolongs survival. Combination treatment kills tumor endothelial cells and synergistically promotes widespread hypoxic necrosis. These results indicate that the paucivascular nature of PDA can be exploited as a therapeutic vulnerability, and the dual targeting of the tumor endothelium and neoplastic cells by gamma secretase inhibition constitutes a rationale for clinical translation