Technical Evaluation of Commercial Mutation Analysis Platforms and Reference Materials for Liquid Biopsy Profiling

Molecular profiling from liquid biopsy, in particular cell-free DNA (cfDNA), represents an attractive alternative to tissue biopsies for the detection of actionable targets and tumor monitoring. In addition to PCR-based assays, Next Generation Sequencing (NGS)-based cfDNA assays are now commercially available and are being increasingly adopted in clinical practice. However, the validity of these products as well as the clinical utility of cfDNA in the management of patients with cancer has yet to be proven. Within framework of the Innovative Medicines Initiative (IMI) program CANCER-ID we evaluated the use of commercially available reference materials designed for ctDNA testing and cfDNA derived from Diagnostic Leukaphereses (DLA) for inter-and intra-assay as well as intra-and inter-laboratory comparisons. In three experimental setups, a broad range of assays including ddPCR, MassARRAY and various NGS-based assays were tested. We demonstrate that both reference materials with predetermined VAFs and DLA samples are extremely useful for the performance assessment of mutation analysis platforms. Moreover, our data indicate a substantial variability of NGS assays with respect to sensitivity and specificity

Call for emergency action to restore dietary diversity and protect global food systems in times of COVID-19 and beyond: Results from a cross-sectional study in 38 countries

Background: The COVID-19 pandemic has revealed the fragility of the global food system, sending shockwaves across countries' societies and economy. This has presented formidable challenges to sustaining a healthy and resilient lifestyle. The objective of this study is to examine the food consumption patterns and assess diet diversity indicators, primarily focusing on the food consumption score (FCS), among households in 38 countries both before and during the first wave of the COVID-19 pandemic. Methods: A cross-sectional study with 37 207 participants (mean age: 36.70 ± 14.79, with 77 % women) was conducted in 38 countries through an online survey administered between April and June 2020. The study utilized a pre-tested food frequency questionnaire to explore food consumption patterns both before and during the COVID-19 periods. Additionally, the study computed Food Consumption Score (FCS) as a proxy indicator for assessing the dietary diversity of households. Findings: This quantification of global, regional and national dietary diversity across 38 countries showed an increment in the consumption of all food groups but a drop in the intake of vegetables and in the dietary diversity. The household's food consumption scores indicating dietary diversity varied across regions. It decreased in the Middle East and North Africa (MENA) countries, including Lebanon (p < 0.001) and increased in the Gulf Cooperation Council countries including Bahrain (p = 0.003), Egypt (p < 0.001) and United Arab Emirates (p = 0.013). A decline in the household's dietary diversity was observed in Australia (p < 0.001), in South Africa including Uganda (p < 0.001), in Europe including Belgium (p < 0.001), Denmark (p = 0.002), Finland (p < 0.001) and Netherland (p = 0.027) and in South America including Ecuador (p < 0.001), Brazil (p < 0.001), Mexico (p < 0.0001) and Peru (p < 0.001). Middle and older ages [OR = 1.2; 95 % CI = [1.125–1.426] [OR = 2.5; 95 % CI = [1.951–3.064], being a woman [OR = 1.2; 95 % CI = [1.117–1.367], having a high education (p < 0.001), and showing amelioration in food-related behaviors [OR = 1.4; 95 % CI = [1.292–1.709] were all linked to having a higher dietary diversity. Conclusion: The minor to moderate changes in food consumption patterns observed across the 38 countries within relatively short time frames could become lasting, leading to a significant and prolonged reduction in dietary diversity, as demonstrated by our findings.Revisión por pare

Intuition and Reasoning in Choosing Ambiguous and Risky Lotteries

This paper focuses on information acquisition and individual decision making in ambiguous situations and presents a novel experimental design which may help to tackle open questions from a fresh perspective. Instead of giving subjects the choice between risky and ambiguous Ellsberg urns, we let them choose between a safe option and a risky lottery, whose risk is a priori unknown to subjects. By acquiring information about the probability distribution of the lottery's payoff s, subjects can reduce or even eliminate the ambiguity and turn the decision situation into one of risk. Under the assumption that an ambiguity averse subject should reduce ambiguity within a decision process we predicted that these subjects would request more information. Moreover, we investigate whether the relation between attitudes towards risk and ambiguity is linked to intuitive and deliberate thinking. Based on a detailed analysis of subjects' information acquisition and decision processes we do not find that those subjects showing ambiguity aversion in an urn experiment based on Halevy (2007) significantly reduce the ambiguity more than others. More intuitive subjects acquire less information and are more likely to avoid the risky lottery. Intuition seems to be negatively correlated with risk aversion, but not with ambiguity aversion. Moreover, we find a positive correlation between risk and ambiguity aversion.Die experimentelle Studie untersucht den Einfluss von Risiko- und Unsicherheitsaversion auf das individuelle Entscheidungsverhalten. Darüber hinaus wird der Einfluss von intuitivem Denken auf den Entscheidungsprozess betrachtet. Dabei stellt die Studie ein neues experimentelles Design vor, welches hilft, die offenen Fragen auf diesem Themengebiet aus einem neuen Blickwinkel zu betrachten. Anders als in der bestehenden Literatur ist der Grad an Unsicherheit in diesem Experiment endogen und kann durch die Probanden verringert werden. Entscheidungen zwischen einer sicheren Option und eingangs durch Unsicherheit charakterisierter Lotterien können somit durch Informationsgewinnung über die Wahrscheinlichkeitsstruktur der Lotterien zu Entscheidungssituationen unter Risiko verändert werden. Basierend auf detaillierten Analysen des Entscheidungsprozesses zeigen die Ergebnisse, dass Individuen mit höherem Grad an Unsicherheitsaversion, gemessen mit einem Testverfahren nach Halevy (2007), die Unsicherheit nicht signifikant mehr reduzieren als andere. Intuitiv denkende Individuen fragen weniger Informationen nach, vermeiden jedoch risikoreichere Lotterien. Die Studie findet eine positive Korrelation zwischen Intuition und Risikoaversion, aber keine zwischen Unsicherheitsaversion und Intuition. Darüber hinaus zeigen die Ergebnisse eine positive Korrelation zwischen Risiko- und Unsicherheitsaversion

Call for emergency action to restore dietary diversity and protect global food systems in times of COVID-19 and beyond: Results from a cross-sectional study in 38 countries

Background: The COVID-19 pandemic has revealed the fragility of the global food system, sending shockwaves across countries\u27 societies and economy. This has presented formidable challenges to sustaining a healthy and resilient lifestyle. The objective of this study is to examine the food consumption patterns and assess diet diversity indicators, primarily focusing on the food consumption score (FCS), among households in 38 countries both before and during the first wave of the COVID-19 pandemic. Methods: A cross-sectional study with 37 207 participants (mean age: 36.70 ± 14.79, with 77 % women) was conducted in 38 countries through an online survey administered between April and June 2020. The study utilized a pre-tested food frequency questionnaire to explore food consumption patterns both before and during the COVID-19 periods. Additionally, the study computed Food Consumption Score (FCS) as a proxy indicator for assessing the dietary diversity of households. Findings: This quantification of global, regional and national dietary diversity across 38 countries showed an increment in the consumption of all food groups but a drop in the intake of vegetables and in the dietary diversity. The household\u27s food consumption scores indicating dietary diversity varied across regions. It decreased in the Middle East and North Africa (MENA) countries, including Lebanon (p \u3c 0.001) and increased in the Gulf Cooperation Council countries including Bahrain (p = 0.003), Egypt (p \u3c 0.001) and United Arab Emirates (p = 0.013). A decline in the household\u27s dietary diversity was observed in Australia (p \u3c 0.001), in South Africa including Uganda (p \u3c 0.001), in Europe including Belgium (p \u3c 0.001), Denmark (p = 0.002), Finland (p \u3c 0.001) and Netherland (p = 0.027) and in South America including Ecuador (p \u3c 0.001), Brazil (p \u3c 0.001), Mexico (p \u3c 0.0001) and Peru (p \u3c 0.001). Middle and older ages [OR = 1.2; 95 % CI = [1.125–1.426] [OR = 2.5; 95 % CI = [1.951–3.064], being a woman [OR = 1.2; 95 % CI = [1.117–1.367], having a high education (p \u3c 0.001), and showing amelioration in food-related behaviors [OR = 1.4; 95 % CI = [1.292–1.709] were all linked to having a higher dietary diversity. Conclusion: The minor to moderate changes in food consumption patterns observed across the 38 countries within relatively short time frames could become lasting, leading to a significant and prolonged reduction in dietary diversity, as demonstrated by our findings

How Do Fair Value Measurements of Financial Instruments Affect Investments in Banks?

This paper experimentally investigates how fair value measurements of financial instruments affect the decision of nonprofessional investors to invest in a bank's shares. Specifically, we assess how investors respond to variations in net income resulting from fair value adjustments in trading assets and how the reliability of the fair value estimates affects their decision. We find that investment decreases as a result of transitions from the first to the third level and we even observe lower investments in case of positive changes in income. Investment decreases most if negative valuation adjustments are based on level 1 estimates suggesting that down pricing by the market is considered as a worse signal than model-based decreases in net income. For larger positive and negative adjustments the impact of valuation levels on investment turns out to be limited. Our results do not provide evidence that Fair Value Accounting per se induces pro-cyclical investment behavior.Die experimentelle Studie untersucht, wie die Bewertung zum Fair Value die Investitionsentscheidung nicht-professioneller Investoren beeinflusst. Dabei wird die Entscheidung, in Aktien einer Bank zu investieren, in Reaktion auf verschieden hohe Bewertungsänderungen der Aktiva Position 'Wertpapiere' der Bank untersucht. Es erfolgt des Weiteren eine differenzierte Betrachtung der Auswirkungen der Fair Value Hierarchie (Level 1-3) auf die Investitionsbereitschaft. Die Resultate zeigen, dass die Investitionsbereitschaft sowohl für negative als auch positive Bewertungsänderungen abnimmt. Die geringste Investitionsbereitschaft wird im Fall von negativen Bewertungsänderungen auf Grundlage beobachtbarer Marktpreise beobachtet (Level 1)

Reversal of Myocyte Hypertrophy by Ventricular Unloading: Cardiac Improvement Without Adrenergic Receptor Upregulation and Relocalization

In previous studies, we found that the improved contractile ability of cardiac myocytes from patients who have had left ventricular assist device (LVAD) support was due to a number of beneficial changes, most notably in calcium handling (increased sarcoplasmic reticulum calcium binding and uptake), improved integrity of cell membranes due to phospholipid reconstruction (reduced lysophospholipid content), and an upregulation of adrenoreceptors (increased adrenoreceptor numbers). However, in the case presented here, there was no increase in adrenoreceptor number, which is something that we usually find in core tissue at the time of LVAD removal or organ transplantation; also, there was no homogeneous postassist device receptor distribution. However, the patient was well maintained for 10 months following LVAD implantation, until a donor organ was available, regardless of the lack of adrenoreceptor improvement. We conclude from these studies that cardiac recovery is the result of the initiation of multiple repair mechanisms, and that the lack of expected changes, in this case increased adrenoreceptors, is not always an accurate indicator of anticipated outcome. We suggest that interventions and strategies have to consider multiple, beneficial changes due to unloading and target a number of biochemical and structural areas to produce improvement, even if not all of these improvements occur

The bacterial storage compound poly-β-hydroxybutyrate protects Artemia franciscana from pathogenic Vibrio campbellii

Infections caused by antibiotic-resistant luminescent Vibrios can cause dramatic losses in aquaculture. In this study, the short-chain fatty acid β-hydroxybutyrate and its polymer poly-β-hydroxybutyrate were investigated as possible new biocontrol agents. β-Hydroxybutyrate was shown to completely inhibit the growth of pathogenic Vibrio campbelli at 100 mM. Moreover, the addition of 100 mM of this fatty acid to the culture water of Artemia nauplii infected with the V. campbelli strain significantly increased the survival of the nauplii. As Artemia is a non-selective and particle filter feeder, we also investigated whether poly-β-hydroxybutyrate particles could be used to protect Artemia from the pathogenic V. campbellii. The addition of 100 mg l−1 poly-β-hydroxybutyrate or more to the Artemia culture water offered a preventive and curative protection from the pathogen as a significantly enhanced survival was noticed. If added as a preventive treatment, a complete protection of infected nauplii (no significant mortality compared with uninfected nauplii) was observed at 1000 mg l−1 poly-β-hydroxybutyrate. Our data indicate that the use of poly-β-hydroxybutyrate might constitute an ecologically and economically sustainable alternative strategy to fight infections in aquaculture

Wnt/β-catenin signaling induces axial elasticity patterns of Hydra extracellular matrix

Summary: The extracellular matrix (ECM) plays crucial roles in animal development and diseases. Here, we report that Wnt/β-catenin signaling induces the ECM remodeling during Hydra axis formation. We determined the micro- and nanoscopic arrangement of fibrillar type I collagen along Hydra’s body axis using high-resolution microscopy and X-ray scattering. Elasticity mapping of the ECM ex vivo revealed distinctive elasticity patterns along the body axis. A proteomic analysis of the ECM showed that these elasticity patterns correlate with a gradient-like distribution of metalloproteases along the body axis. Activation of the Wnt/β-catenin pathway in wild-type and transgenic animals alters these patterns toward low ECM elasticity patterns. This suggests a mechanism whereby high protease activity under control of Wnt/β-catenin signaling causes remodeling and softening of the ECM. This Wnt-dependent spatiotemporal coordination of biochemical and biomechanical cues in ECM formation was likely a central evolutionary innovation for animal tissue morphogenesis