Photometry of supernovae in an image series : methods and application to the Supernova Legacy Survey (SNLS)

We present a technique to measure lightcurves of time-variable point sources on a spatially structured background from imaging data. The technique was developed to measure light curves of SNLS supernovae in order to infer their distances. This photometry technique performs simultaneous PSF photometry at the same sky position on an image series. We describe two implementations of the method: one that resamples images before measuring fluxes, and one which does not. In both instances, we sketch the key algorithms involved and present the validation using semi-artificial sources introduced in real images in order to assess the accuracy of the supernova flux measurements relative to that of surrounding stars. We describe the methods required to anchor these PSF fluxes to calibrated aperture catalogs, in order to derive SN magnitudes. We find a marginally significant bias of 2 mmag of the after-resampling method, and no bias at the mmag accuracy for the non-resampling method. Given surrounding star magnitudes, we determine the systematic uncertainty of SN magnitudes to be less than 1.5 mmag, which represents about one third of the current photometric calibration uncertainty affecting SN measurements. The SN photometry delivers several by-products: bright star PSF flux mea- surements which have a repeatability of about 0.6%, as for aperture measurements; we measure relative astrometric positions with a noise floor of 2.4 mas for a single-image bright star measurement; we show that in all bands of the MegaCam instrument, stars exhibit a profile linearly broadening with flux by about 0.5% over the whole brightness range.Comment: Accepted for publication in A&A. 20 page

Measurement and conceptualization of maternal PTSD following childbirth: Psychometric properties of the City Birth Trauma Scale-French Version (City BiTS-F).

The City Birth Trauma Scale (City BiTS) assesses posttraumatic stress disorder symptoms following childbirth (PTSD-FC). Recent studies investigating the latent factor structure of PTSD-FC in women reported mixed results. No validated French questionnaire exists to measure PTSD-FC symptoms. Therefore, this study first aimed to validate the French version of the City BiTS (City BiTS-F). Second, it aimed to establish the latent factor structure of PTSD-FC. French-speaking women with infants aged 1 to 12 months old (n = 541) completed an online cross-sectional survey. Questionnaires included the City BiTS-F, the PTSD Checklist, the Edinburgh Postnatal Depression Scale, and the anxiety subscale of the Hospital Anxiety and Depression Scale. Additionally, sociodemographic and medical data were collected. The two-factor model with birth-related symptoms (BRS) and general symptoms (GS) fit the data well, whereas the four-factor model was not confirmed. The bifactor model with a general factor and the BRS and GS gave the best fit to the data, suggesting that use of the total score in addition to the BRS and GS subscales scores is justified. High reliability (α = .88 to .90) and good convergent and divergent validity were obtained. Discriminant validity was calculated with weeks of gestation, gravidity, history of traumatic childbirth and event, and mode of delivery. The City BiTS-F is a reliable and valid measure of PTSD-FC symptoms in French-speaking women. Both total score and BRS or GS subscale scores can be calculated. This psychometric tool is of importance for clinical and research purposes. (PsycInfo Database Record (c) 2021 APA, all rights reserved)

Extracellular Vesicles in HIV, Drug Abuse, and Drug Delivery

Extracellular vesicles (EVs) are known to perform important biological functions and have been implicated in multiple disease pathogeneses, including HIV and drugs of abuse. EVs can carry biological molecules via biofluids such as plasma and cerebrospinal fluids (CSF) from healthy or disease organs to distant organs and deliver biomolecules to recipient cells that subsequently alter the physiology of the recipient organs. As biocarriers, EVs have the potential to be developed as non-invasive biomarkers for disease pathogenesis and drug abuse, as the level of specific EV components can be altered under disease/drug abuse conditions. Since many drugs don’t cross the blood-brain barrier, EVs have shown the potential to encapsulate small drug molecules, including nucleotides, and carry these drugs to brain cells and enhance brain drug bioavailability. Through this special issue, we have covered several studies related to the role of EVs in altering biological functions via cell-cell interactions in healthy, HIV, and drug of abuse conditions. We have also included studies on the role of EVs as potential biomarkers for HIV pathogenesis and drugs of abuse. Further, the potential role of EVs in drug delivery in the CNS for diseases, including HIV-associated neurocognitive disorders and other neurological disorders, are covered in this issue

Maghemite nanoparticles bearing di(amidoxime) groups for the extraction of uranium from wastewaters

Polyamidoximes (pAMD) are known to have strong affinities for uranyl cations. Grafting pAMD onto the surface of functionalized maghemite nanoparticles (MNP) leads to a nanomaterial with high capacities in the extraction of uranium from wastewaters by magnetic sedimentation. A diamidoxime (dAMD) specifically synthesized for this purpose showed a strong affinity for uranyl: Ka = 105 M-1 as determined by Isothermal Titration Calorimetry (nano-ITC). The dAMD was grafted onto the surface of MNP and the obtained sorbent (MNP-dAMD) was characterized. The nanohybrids were afterward incubated with different concentrations of uranyl and the solid phase recovered by magnetic separation. This latter was characterized by zeta-potential measurements, X-Ray Photoelectron Spectroscopy (XPS) and X-Ray Fluorescence spectroscopy (XRF), whereas the supernatant was analyzed by Inductively Coupled Plasma coupled to Mass Spectrometry (ICP-MS). All the data fitted the models of Langmuir, Freundlich and Temkin isotherms very well. These isotherms allowed us to evaluate the efficiency of the adsorption of uranium by MNP-dAMD. The saturation sorption capacity (qmax) was determined. It indicates that MNP-dAMD is able to extract up to 120 mg of uranium per gram of sorbent. Spherical aberration (Cs)-corrected High-Resolution Scanning Transmission Electron Microscopy (HRSTEM) confirmed these results and clearly showed that uranium is confined at the surface of the sorbent. Thus, MNP-dAMD presents a strong potential for the extraction of uranium from wastewaters

Impacts of feeding less food-competing feedstuffs to livestock on global food system sustainability

Funding Christian Schader, Adrian Muller, Nadia El-Hage Scialabba, Judith Hecht, Anne Isensee, Harinder P.S. Makkar, Peter Klocke, Florian Leiber, Matthias Stolze, Urs Niggli thank FAO for funding this research. K.E. gratefully acknowledges funding from ERC-2010-Stg-263522 LUISE. Additional data and method details are provided in the supplementary materials. The contribution of P.S. is supported by funding from the Belmont Forum-FACCE-JPI Project ‘Delivering Food on Limited Land’ (DEVIL), with the UK contribution supported by NERC (NE/M021327/1).Peer reviewedPublisher PD

Enhanced insulin sensitivity associated with provision of mono and polyunsaturated fatty acids in skeletal muscle cells involves counter modulation of PP2A

International audienceAims/Hypothesis: Reduced skeletal muscle insulin sensitivity is a feature associated with sustained exposure to excess saturated fatty acids (SFA), whereas mono and polyunsaturated fatty acids (MUFA and PUFA) not only improve insulin sensitivity but blunt SFA-induced insulin resistance. The mechanisms by which MUFAs and PUFAs institute these favourable changes remain unclear, but may involve stimulating insulin signalling by counter-modulation/repression of protein phosphatase 2A (PP2A). This study investigated the effects of oleic acid (OA; a MUFA), linoleic acid (LOA; a PUFA) and palmitate (PA; a SFA) in cultured myotubes and determined whether changes in insulin signalling can be attributed to PP2A regulation. Principal Findings: We treated cultured skeletal myotubes with unsaturated and saturated fatty acids and evaluated insulin signalling, phosphorylation and methylation status of the catalytic subunit of PP2A. Unlike PA, sustained incubation of rat or human myotubes with OA or LOA significantly enhanced Akt-and ERK1/2-directed insulin signalling. This was not due to heightened upstream IRS1 or PI3K signalling nor to changes in expression of proteins involved in proximal insulin signalling, but was associated with reduced dephosphorylation/inactivation of Akt and ERK1/2. Consistent with this, PA reduced PP2Ac demethylation and tyrosine 307 phosphorylation-events associated with PP2A activation. In contrast, OA and LOA strongly opposed these PA-induced changes in PP2Ac thus exerting a repressive effect on PP2A.Conclusions/Interpretation: Beneficial gains in insulin sensitivity and the ability of unsaturated fatty acids to oppose palmitate-induced insulin resistance in muscle cells may partly be accounted for by counter-modulation of PP2A

Efficacy of adjuvant chemotherapy according to hormone receptor status in young patients with breast cancer: a pooled analysis

Introduction Breast cancer at a young age is associated with an unfavorable prognosis. Very young patients with breast cancer therefore are advised to undergo adjuvant chemotherapy irrespective of tumor stage or grade. However, chemotherapy alone may not be adequate in young patients with hormone receptor-positive breast cancer. Therefore, we studied the effect of adjuvant chemotherapy in young patients with breast cancer in relation to hormone receptor status. Methods Paraffin-embedded tumor material was collected from 480 early-stage breast cancer patients younger than 41 years who participated in one of four European Organization for Research and Treatment of Cancer trials. Using immunohistochemistry on the whole series of tumors, we assessed estrogen receptor (ER) status and progesterone receptor (PgR) status in a standardized way. Endpoints in this study were overall survival (OS) and distant metastasis-free survival (DMFS). The median follow-up period was 7.3 years. Results Overall, patients with ER-positive tumors had better OS rates (hazard ratio [HR] 0.63; P = 0.02) compared with those with ER-negative tumors. However, in the subgroup of patients who received chemotherapy, no significant difference in OS (HR 0.87; P = 0.63) and DMFS (HR 1.36; P = 0.23) was found between patients with ER-positive tumors or those with ER-negative tumors. These differences were similar for PgR status. Conclusion Young patients with hormone receptor-positive tumors benefit less from adjuvant systemic chemotherapy than patients with hormone receptor-negative tumors. These results confirm that chemotherapy alone cannot be considered optimal adjuvant systemic treatment in breast cancer patients 40 years old or younger with hormone receptor-positive tumors

Exploring venlafaxine pharmacokinetic variability with a phenotyping approach, a multicentric french-swiss study (MARVEL study).

It is well known that the standard doses of a given drug may not have equivalent effects in all patients. To date, the management of depression remains mainly empirical and often poorly evaluated. The development of a personalized medicine in psychiatry may reduce treatment failure, intolerance or resistance, and hence the burden and costs of mood depressive disorders. The Geneva Cocktail Phenotypic approach presents several advantages including the "in vivo" measure of different cytochromes and transporter P-gp activities, their simultaneous determination in a single test, avoiding the influence of variability over time on phenotyping results, the administration of low dose substrates, a limited sampling strategy with an analytical method developed on DBS analysis. The goal of this project is to explore the relationship between the activity of drug-metabolizing enzymes (DME), assessed by a phenotypic approach, and the concentrations of Venlafaxine (VLX) + O-demethyl-venlafaxine (ODV), the efficacy and tolerance of VLX. This study is a multicentre prospective non-randomized open trial. Eligible patients present a major depressive episode, MADRS over or equal to 20, treatment with VLX regardless of the dose during at least 4 weeks. The Phenotype Visit includes VLX and ODV concentration measurement. Following the oral absorption of low doses of omeprazole, midazolam, dextromethorphan, and fexofenadine, drug metabolizing enzymes activity is assessed by specific metabolite/probe concentration ratios from a sample taken 2 h after cocktail administration for CYP2C19, CYP3A4, CYP2D6; and by the determination of the limited area under the curve from the capillary blood samples taken 2-3 and 6 h after cocktail administration for CYP2C19 and P-gp. Two follow-up visits will take place between 25 and 40 days and 50-70 days after inclusion. They include assessment of efficacy, tolerance and observance. Eleven french centres are involved in recruitment, expected to be completed within approximately 2 years with 205 patients. Metabolic ratios are determined in Geneva, Switzerland. By showing an association between drug metabolism and VLX concentrations, efficacy and tolerance, there is a hope that testing drug metabolism pathways with a phenotypical approach would help physicians in selecting and dosing antidepressants. The MARVEL study will provide an important contribution to increasing the knowledge of VLX variability and in optimizing the use of methods of personalized therapy in psychiatric settings. ClinicalTrials.gov NCT02590185 (10/27/2015). This study is currently recruiting participants

Heterogeneity of patients with functional/dissociative seizures: three multidimensional profiles

Objective Current concepts highlight the neurological and psychological heterogeneity of functional/dissociative seizures (FDS). However, it remains uncertain whether it is possible to distinguish between a limited number of subtypes of FDS disorders. We aimed to identify profiles of distinct FDS subtypes by cluster analysis of a multidimensional dataset without any a priori hypothesis. Methods We conducted an exploratory, prospective multicenter study of 169 patients with FDS. We collected biographical, trauma (childhood and adulthood traumatic experiences), semiological (seizure characteristics), and psychopathological data (psychiatric comorbidities, dissociation, and alexithymia) through psychiatric interviews and standardized scales. Clusters were identified by the Partitioning Around Medoids method. The similarity of patients was computed using Gower distance. The clusters were compared using analysis of variance, chi-squared, or Fisher exact tests. Results Three patient clusters were identified in this exploratory, hypothesis-generating study and named on the basis of their most prominent characteristics: 1. A “No/Single Trauma” group (31.4%), with more male patients, intellectual disabilities, and nonhyperkinetic seizures, and a low level of psychopathology; 2. A “Cumulative Lifetime Traumas” group (42.6%), with clear female predominance, hyperkinetic seizures, relatively common comorbid epilepsy, and a high level of psychopathology; and 3. A “Childhood Traumas” group (26%), commonly with comorbid epilepsy, history of childhood sexual abuse (75%), and posttraumatic stress disorder, but also with a high level of anxiety and dissociation. Significance Although our cluster analysis was undertaken without any a priori hypothesis, the nature of the trauma history emerged as the most important differentiator between three common FDS disorder subtypes. This subdifferentiation of FDS disorders may facilitate the development of more specific therapeutic programs for each patient profile