Is it time for studying real-life debiasing? Evaluation of the effectiveness of an analogical intervention technique.

The aim of this study was to initiate the exploration of debiasing methods applicable in real-life settings for achieving lasting improvement in decision making competence regarding multiple decision biases. Here, we tested the potentials of the analogical encoding method for decision debiasing. The advantage of this method is that it can foster the transfer from learning abstract principles to improving behavioral performance. For the purpose of the study, we devised an analogical debiasing technique for 10 biases (covariation detection, insensitivity to sample size, base rate neglect, regression to the mean, outcome bias, sunk cost fallacy, framing effect, anchoring bias, overconfidence bias, planning fallacy) and assessed the susceptibility of the participants (N = 154) to these biases before and 4 weeks after the training. We also compared the effect of the analogical training to the effect of 'awareness training' and a 'no-training' control group. Results suggested improved performance of the analogical training group only on tasks where the violations of statistical principles are measured. The interpretation of these findings require further investigation, yet it is possible that analogical training may be the most effective in the case of learning abstract concepts, such as statistical principles, which are otherwise difficult to master. The study encourages a systematic research of debiasing trainings and the development of intervention assessment methods to measure the endurance of behavior change in decision debiasing

Antichain cutsets of strongly connected posets

Rival and Zaguia showed that the antichain cutsets of a finite Boolean lattice are exactly the level sets. We show that a similar characterization of antichain cutsets holds for any strongly connected poset of locally finite height. As a corollary, we get such a characterization for semimodular lattices, supersolvable lattices, Bruhat orders, locally shellable lattices, and many more. We also consider a generalization to strongly connected hypergraphs having finite edges.Comment: 12 pages; v2 contains minor fixes for publicatio

Mechanistic study of an immobilized molecular electrocatalyst by in situ gap-plasmon-assisted spectro-electrochemistry

Immobilized first-row transition metal complexes are potential low-cost electrocatalysts for selective CO2 conversion in the production of renewable fuels. Mechanistic understanding of their function is vital for the development of next-generation catalysts, although the poor surface sensitivity of many techniques makes this challenging. Here, a nickel bis(terpyridine) complex is introduced as a CO2 reduction electrocatalyst in a unique electrode geometry, sandwiched by thiol-anchoring moieties between two gold surfaces. Gap-plasmon-assisted surface-enhanced Raman scattering spectroscopy coupled with density functional theory calculations reveals that the nature of the anchoring group plays a pivotal role in the catalytic mechanism. Our in situ spectro-electrochemical measurement enables the detection of as few as eight molecules undergoing redox transformations in individual plasmonic hotspots, together with the calibration of electrical fields via vibrational Stark effects. This advance allows rapid exploration of non-resonant redox reactions at the few-molecule level and provides scope for future mechanistic studies of single molecules

Osteoporosis in young adults: pathophysiology, diagnosis, and management

Postmenopausal osteoporosis is mainly caused by increased bone remodeling resulting from estrogen deficiency. Indications for treatment are based on low areal bone mineral density (aBMD, T-score ≤ −2.5), typical fragility fractures (spine or hip), and more recently, an elevated 10-year fracture probability (by FRAX®). In contrast, there is no clear definition of osteoporosis nor intervention thresholds in younger individuals. Low aBMD in a young adult may reflect a physiologically low peak bone mass, such as in lean but otherwise healthy persons, whereas fractures commonly occur with high-impact trauma, i.e., without bone fragility. Furthermore, low aBMD associated with vitamin D deficiency may be highly prevalent in some regions of the world. Nevertheless, true osteoporosis in the young can occur, which we define as a T-score below −2.5 at spine or hip in association with a chronic disease known to affect bone metabolism. In the absence of secondary causes, the presence of fragility fractures, such as in vertebrae, may point towards genetic or idiopathic osteoporosis. In turn, treatment of the underlying condition may improve bone mass as well. In rare cases, a bone-specific treatment may be indicated, although evidence is scarce for a true benefit on fracture risk. The International Osteoporosis Foundation (IOF) convened a working group to review pathophysiology, diagnosis, and management of osteoporosis in the young, excluding children and adolescents, and provide a screening strategy including laboratory exams for a systematic approach of this conditio

Transcriptional co-activators YAP1-TAZ of Hippo signalling in doxorubicin-induced cardiomyopathy

Aims Hippo signalling is an evolutionarily conserved pathway that controls organ size by regulating apoptosis, cell proliferation, and stem cell self-renewal. Recently, the pathway has been shown to exert powerful growth regulatory activity in cardiomyocytes. However, the functional role of this stress-related and cell death-related pathway in the human heart and cardiomyocytes is not known. In this study, we investigated the role of the transcriptional co-activators of Hippo signalling, YAP and TAZ, in human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in response to cardiotoxic agents and investigated the effects of modulating the pathway on cardiomyocyte function and survival. Methods and results RNA-sequencing analysis of human heart samples with doxorubicin-induced end-stage heart failure and healthy controls showed that YAP and ERBB2 (HER2) as upstream regulators of differentially expressed genes correlated with doxorubicin treatment. Thus, we tested the effects of doxorubicin on hiPSC-CMs in vitro. Using an automated high-content screen of 96 clinically relevant antineoplastic and cardiotherapeutic drugs, we showed that doxorubicin induced the highest activation of YAP/TAZ nuclear translocation in both hiPSC-CMs and control MCF7 breast cancer cells. The overexpression of YAP rescued doxorubicin-induced cell loss in hiPSC-CMs by inhibiting apoptosis and inducing proliferation. In contrast, silencing of YAP and TAZ by siRNAs resulted in elevated mitochondrial membrane potential loss in response to doxorubicin. hiPSC-CM calcium transients did not change in response to YAP/TAZ silencing. Conclusions Our results suggest that Hippo signalling is involved in clinical anthracycline-induced cardiomyopathy. Modelling with hiPSC-CMs in vitro showed similar responses to doxorubicin as adult cardiomyocytes and revealed a potential cardioprotective effect of YAP in doxorubicin-induced cardiotoxicity

Bacterial expression of two human aryl sulfotransferases

The effect of replacing a single codon in the N-terminal of human aryl sulfotransferase (HAST) 1 and 3 with one that is more commonly found in E. coli genes was assessed. The pKK233-2 E. coli expression vector was employed and the polymerase chain reaction (PCR) was used to introduce the 5' nucleotide substitution, at the same time maintaining the fidelity of the amino acid sequence. The data indicates that this change had a minimal effect on protein production, subcellular localization or, in the case of HAST3, catalytic activity. In general, the pKK233-2 E. coli vector has been less than optimal for expressing human sulfotransferase cDNAs. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved

Signaling via PI3K/FOXO1A pathway modulates formation and survival of human embryonic stem cell-derived endothelial cells

Vascular derivatives of human embryonic stem cells (hESC) are being developed as sources of tissue-specific cells for organ regeneration. However, identity of developmental pathways that modulate the specification of endothelial cells is not known yet. We studied phosphatidylinositol 3-kinase (PI3K)-Forkhead box O transcription factor 1A (FOXO1A) pathways during differentiation of hESC toward endothelial lineage and on proliferation, maturation, and cell death of hESC-derived endothelial cells (hESC-EC). During differentiation of hESC, expression of FOXO1A transcription factor was linked to the expression of a cluster of angiogenesis- and vascular remodeling-related genes. PI3K inhibitor LY294002 activated FOXO1A and induced formation of CD31(+) hESC-EC. In contrast, differentiating hESC with silenced FOXO1A by small interfering RNA (siRNA) showed lower mRNA levels of CD31 and angiopoietin2. LY294002 decreased proliferative activity of purified hESC-EC, while FOXO1A siRNA increased their proliferation. LY294002 inhibits migration and tube formation of hESC-EC; in contrast, FOXO1A siRNA increased in vitro tube formation activity of hESC-EC. After in vivo conditioning of cells in athymic nude rats, cells retain their low FOXO1A expression levels. PI3K/FOXO1A pathway is important for function and survival of hESC-EC and in the regulation of endothelial cell fate. Understanding these properties of hESC-EC may help in future applications for treatment of injured organs