Developmental neurotoxicity of environmentally relevant pharmaceuticals and mixtures thereof in a zebrafish embryo behavioural test

Humans are exposed daily to complex mixtures of chemical substances via food intake, inhalation, and dermal contact. Developmental neurotoxicity is an understudied area and entails one of the most complex areas in toxicology. Animal studies for developmental neurotoxicity (DNT) are hardly performed in the context of regular hazard studies, as they are costly and time consuming and provide only limited information as to human relevance. There is a need for a combination of in vitro and in silico tests for the assessment of chemically induced DNT in humans. The zebrafish (Danio rerio) embryo (ZFE) provides a powerful model to study DNT because it shows fast neurodevelopment with a large resemblance to the higher vertebrate, including the human system. One of the suitable readouts for DNT testing in the zebrafish is neurobehaviour (stimulus-provoked locomotion) since this provides integrated information on the functionality and status of the entire nervous system of the embryo. In the current study, environmentally relevant pharmaceuticals and their mixtures were investigated using the zebrafish light-dark transition test. Zebrafish embryos were exposed to three neuroactive compounds of concern, carbamazepine (CBZ), fluoxetine (FLX), and venlafaxine (VNX), as well as their main metabolites, carbamazepine 10,11-epoxide (CBZ 10,11E), norfluoxetine (norFLX), and desvenlafaxine (desVNX). All the studied compounds, except CBZ 10,11E, dose-dependently inhibited zebrafish locomotor activity, providing a distinct behavioural phenotype. Mixture experiments with these pharmaceuticals identified that dose addition was confirmed for all the studied binary mixtures (CBZ-FLX, CBZ-VNX, and VNX-FLX), thereby supporting the zebrafish embryo as a model for studying the cumulative effect of chemical mixtures in DNT. This study shows that pharmaceuticals and a mixture thereof affect locomotor activity in zebrafish. The test is directly applicable in environmental risk assessment; however, further studies are required to assess the relevance of these findings for developmental neurotoxicity in humans

Cosmology from Cross-Correlation of ACT-DR4 CMB Lensing and DES-Y3 Cosmic Shear

Cross-correlation between weak lensing of the Cosmic Microwave Background (CMB) and weak lensing of galaxies offers a way to place robust constraints on cosmological and astrophysical parameters with reduced sensitivity to certain systematic effects affecting individual surveys. We measure the angular cross-power spectrum between the Atacama Cosmology Telescope (ACT) DR4 CMB lensing and the galaxy weak lensing measured by the Dark Energy Survey (DES) Y3 data. Our baseline analysis uses the CMB convergence map derived from ACT-DR4 and $\textit{Planck}$ data, where most of the contamination due to the thermal Sunyaev Zel'dovich effect is removed, thus avoiding important systematics in the cross-correlation. In our modelling, we consider the nuisance parameters of the photometric uncertainty, multiplicative shear bias and intrinsic alignment of galaxies. The resulting cross-power spectrum has a signal-to-noise ratio $= 7.1$ and passes a set of null tests. We use it to infer the amplitude of the fluctuations in the matter distribution ($S_8 \equiv \sigma_8 (\Omega_{\rm m}/0.3)^{0.5} = 0.782\pm 0.059$) with informative but well-motivated priors on the nuisance parameters. We also investigate the validity of these priors by significantly relaxing them and checking the consistency of the resulting posteriors, finding them consistent, albeit only with relatively weak constraints. This cross-correlation measurement will improve significantly with the new ACT-DR6 lensing map and form a key component of the joint 6x2pt analysis between DES and ACT.Comment: 26 pages, 30 figures (including appendices). Data associated with this article is available at https://github.com/itrharrison/actdr4kappa-x-desy3gamma-dat

Transcriptome analysis of secondary cell wall development in Medicago truncatula

This article describes a transcriptome microarray assay and high through-put quantitative real time PCR analysis of Medicago truncatula

Cosmology from cross-correlation of ACT-DR4 CMB lensing and DES-Y3 cosmic shear

Cross-correlation between weak lensing of the Cosmic Microwave Background (CMB) and weak lensing of galaxies offers a way to place robust constraints on cosmological and astrophysical parameters with reduced sensitivity to certain systematic effects affecting individual surveys. We measure the angular cross-power spectrum between the Atacama Cosmology Telescope (ACT) DR4 CMB lensing and the galaxy weak lensing measured by the Dark Energy Survey (DES) Y3 data. Our baseline analysis uses the CMB convergence map derived from ACT-DR4 and Planck data, where most of the contamination due to the thermal Sunyaev Zel’dovich effect is removed, thus avoiding important systematics in the cross-correlation. In our modelling, we consider the nuisance parameters of the photometric uncertainty, multiplicative shear bias and intrinsic alignment of galaxies. The resulting cross-power spectrum has a signal-to-noise ratio = 7.1 and passes a set of null tests. We use it to infer the amplitude of the fluctuations in the matter distribution (S8 ≡ σ8(Ωm/0.3)0.5 = 0.782 ± 0.059) with informative but well-motivated priors on the nuisance parameters. We also investigate the validity of these priors by significantly relaxing them and checking the consistency of the resulting posteriors, finding them consistent, albeit only with relatively weak constraints. This cross-correlation measurement will improve significantly with the new ACT-DR6 lensing map and form a key component of the joint 6×2pt analysis between DES and ACT

Higher Preoperative Weight loss Is Associated with Greater Weight Loss up to 12 Months After Bariatric Surgery

BACKGROUND: Prior research suggested presurgical weight loss is associated with greater total weight loss, resulting in a more effective bariatric intervention. We aimed to assess whether preoperative weight loss is a predictor for total weight loss, and which patient factors are associated with successful weight loss.METHODS: All patients (N = 773) that underwent primary bariatric surgery between June 2017 and August 2019 were included in this single-center retrospective study. Outcome measures were preoperative weight loss (%preopWL) and total weight loss (%TWL) up to 1 year postoperatively. Patients were divided into 4 groups based on quartiles of %preopWL.RESULTS: Total weight loss after 1, 6, and 12 months for the upper quartile was 16.9%, 33.4%, and 37.8%, and for the lower quartile 11.8%, 28.9%, and 35.2%, respectively (p &lt; 0.001). Seven hundred fourteen patients (92.4%) were available for the 1-year follow-up. Preoperative weight loss was not associated with the incidence of complications. Independent factors predicting increased %preopWL were mandated preoperative weight loss program (MWP) (p &lt; 0.001), older age (p = 0.005), weight measurement in the week before surgery (p = 0.031), and non-diabetic status (p = 0.010). Predictors for superior %TWL were MWP (p = 0.014), younger age (p = 0.001), non-diabetic status (p = 0.005), female gender (p = 0.001), higher Body Mass Index (p = 0.006), and banded gastric bypass (p = 0.001).CONCLUSION: Higher preoperative weight loss is associated with persisting greater weight loss up to at least 12 months post-surgery. In order to optimize preoperative weight loss, we recommend extra preoperative support to younger and diabetic patients. We advise nutritional counseling and additional weight measurement in the week before surgery.</p

The Simons Observatory: impact of bandpass, polarization angle and calibration uncertainties on small-scale power spectrum analysis

We study the effects due to mismatches in passbands, polarization angles, and temperature and polarization calibrations in the context of the upcoming cosmic microwave background experiment Simons Observatory (SO). Using the SO multi-frequency likelihood, we estimate the bias and the degradation of constraining power in cosmological and astrophysical foreground parameters assuming different levels of knowledge of the instrumental effects. We find that incorrect but reasonable assumptions on the values of all the systematics examined here can have important effects in cosmological analyses, hence requiring marginalization approaches at likelihood level. When doing so, we find that the most relevant effect is due to bandpass shifts. When marginalizing over them, the posteriors of parameters describing astrophysical microwave foregrounds (such as radio point sources or dust) get degraded, while cosmological parameters constraints are not significantly affected. Marginalization over polarization angles with up to 0.25∘ uncertainty causes an irrelevant bias ≲0.05σ in all parameters. Marginalization over calibration factors in polarization broadens the constraints on the effective number of relativistic degrees of freedom Neff by a factor 1.2, interpreted here as a proxy parameter for non standard model physics targeted by high-resolution CMB measurements