Age and its impact on crisis management performance and learning after simulation-based education by acute care physicians: a multicentre prospective cohort study.

Background: Physiological changes associated with ageing could negatively impact the crisis resource management skills of acute care physicians. This study was designed to determine whether physician age impacts crisis resource management skills, and crisis resource management skills learning and retention using full-body manikin simulation training in acute care physicians.

Methods: Acute care physicians at two Canadian universities participated in three 8-min simulated crisis (pulseless electrical activity) scenarios.

Generalizability of clinical trial efficacy results to a real-world population: An example in migraine prevention.

Background: Health care decision makers are often concerned about the external validity of randomized controlled trials (RCTs), as their results may not apply to certain patients in the real world who intend to receive treatment.

Objective: To demonstrate a methodology for assessing the generalizability of clinical trial results to a real-world population, before sufficient and appropriate real-world effectiveness data are available, using individual patient-level data from an RCT and aggregated baseline data from a real-world French registry in migraine.

Methods: The analyses were conducted in 2 steps.

EPH receptor tyrosine kinases phosphorylate the PAR-3 scaffold protein to modulate downstream signaling networks.

EPH receptors (EPHRs) constitute the largest family among receptor tyrosine kinases in humans. They are mainly involved in short-range cell-cell communication events that regulate cell adhesion, migration, and boundary formation. However, the molecular mechanisms by which EPHRs control these processes are less understood.

SRC homology 3 domains: multifaceted binding modules.

The assembly of complexes following the detection of extracellular signals is often controlled by signaling proteins comprising multiple peptide binding modules. The SRC homology (SH)3 family represents the archetypical modular protein interaction module, with ~300 annotated SH3 domains in humans that regulate an impressive array of signaling processes. We review recent findings regarding the allosteric contributions of SH3 domains host protein context, their phosphoregulation, and their roles in phase separation that challenge the simple model in which SH3s are considered to be portable domains binding to specific proline-rich peptide motifs.

Cardiovascular Profile of Patients with Type 2 Diabetes in France Based on REWIND CVOT Inclusion Criteria: A Real-World Retrospective Study.

Introduction: The REWIND study demonstrated a cardiovascular (CV) benefit of dulaglutide treatment in patients with type 2 diabetes (T2D) with or without established cardiovascular disease (CVD). The current study aims to describe similarities and differences between characteristics of patients with T2D in France and the REWIND population.

Methods: A retrospective, observational study was conducted in France using primary care IQVIA electronic medical records.

Conversations and reactions around severe hypoglycemia (CRASH) global survey of people with type 1 diabetes or insulin-treated type 2 diabetes and caregivers: Findings from the French cohort.

Aim: The objective of the CRASH (Conversations and Reactions Around Severe Hypoglycemia) survey was to further our understanding of the characteristics, experience, behavior and conversations with healthcare professionals (HCPs) of people with diabetes (PWD) receiving insulin, and of caregivers (CGs) caring for such people, concerning hypoglycemia requiring external assistance (severe hypoglycemic events [SHEs]).

Methods: CRASH was an online cross-sectional survey conducted across eight countries. PWD with self-reported type 1 (T1D) or insulin-treated type 2 (T2D) diabetes were aged≥18 years and had experienced one or more SHEs in the past 3 years; CGs were non-medical professionals aged ≥18 years, caring for PWD meeting all the above criteria except for PWD age (≥4 rather than ≥18 years).

Hyphenation of capillary electrophoresis with MC-ICP-MS - A novel tool for uranium age dating.

Capillary electrophoresis (CE) was hyphenated to multi-collector inductively coupled plasma mass spectrometry (MC-ICP-MS) to determine the model age of a highly enriched uranium (HEU) sample using the U/Th radiochronometer. The use of hydroxymethylbutyric acid (HMBA) as the CE electrolyte was investigated, and a complexation stacking method was developed to increase the thorium signal obtained. The age of the material was determined by measuring the Th content of the HEU sample using isotope dilution in conjunction with the CE-MC-ICP-MS protocol.

A new method for determining U/U isotope ratios in environmental samples by means OF ICP-MS/MS.

The U/U isotope ratio is a widely used tracer, which provides information on source identification for safeguard purposes, nuclear forensic studies and environmental monitoring. This paper describes an original approach to determine U/U ratios, below 10, in environmental samples by combination of ICP-MS/MS for U/U ratio and multiple collector ICPMS measurements for U/U and U/U isotope ratios. Since the hydride form of UO (UOH) is less prone to occur than UH, we were focused on the oxidised forms of uranium in order to reduce hydride based-interferences in ICP-MS/MS.

Isotopic variations of copper at the protein fraction level in neuronal human cells exposed in vitro to uranium.

The study of isotopic variations of endogenous and toxic metals in fluids and tissues is a recent research topic with an outstanding potential in biomedical and toxicological investigations. Most of the analyses have been performed so far in bulk samples, which can make the interpretation of results entangled, since different sources of stress or the alteration of different metabolic processes can lead to similar variations in the isotopic compositions of the elements in bulk samples. The downscaling of the isotopic analysis of elements at the sub-cellular level, is considered as a more promising alternative.

Impact of uranium uptake on isotopic fractionation and endogenous element homeostasis in human neuron-like cells.

The impact of natural uranium (U) on differentiated human neuron-like cells exposed to 1, 10, 125, and 250 µM of U for seven days was assessed. In particular, the effect of the U uptake on the homeostatic modulation of several endogenous elements (Mg, P, Mn, Fe, Zn, and Cu), the U isotopic fractionation upon its incorporation by the cells and the evolution of the intracellular Cu and Zn isotopic signatures were studied. The intracellular accumulation of U was accompanied by a preferential uptake of U for cells exposed to 1 and 10 µM of U, whereas no significant isotopic fractionation was observed between the extra- and the intracellular media for higher exposure U concentrations.

Proteomic Analysis of NCK1/2 Adaptors Uncovers Paralog-specific Interactions That Reveal a New Role for NCK2 in Cell Abscission During Cytokinesis.

Signals from cell surface receptors are often relayed via adaptor proteins. NCK1 and NCK2 are Src-Homology (SH) 2 and 3 domain adaptors that regulate processes requiring a remodeling of the actin cytoskeleton. Evidence from gene inactivation in mouse suggests that NCK1 and NCK2 are functionally redundant, although recent reports support the idea of unique functions for NCK1 and NCK2.

Evaluation of superficially and fully porous particles for HILIC separation of lanthanide-polyaminocarboxylic species and simultaneous coupling to ESIMS and ICPMS.

In this work, amide-bonded columns packed with fully porous particles (FPP) and superficially porous particles (SPP) were evaluated to separate lanthanide-polyaminocarboxylic species by hydrophilic interaction liquid chromatography (HILIC), using two model samples of interest in nuclear and other industrial applications. We assessed the gains achieved by reducing the dimensions of the columns along with the size of the FPPs to sub-2 μm and by using sub-3 μm SPP-packed columns. The FPP-packed Acquity column (100 × 2.

Precise U and Pu Isotope Ratio Measurements in Nuclear Samples by Hyphenating Capillary Electrophoresis and MC-ICPMS.

Precise isotopic and elemental characterization of spent nuclear fuel is a major concern for the validation of the neutronic calculation codes and waste management strategy in the nuclear industry. Generally, the elements of interest, particularly U and Pu which are the two major elements present in spent fuel, are purified by ion exchange or extractant resins before off-line measurements by thermal ionization mass spectrometry. The aim of the present work was to develop a new analytical approach based on capillary electrophoresis (CE) hyphenated to a multicollector inductively coupled plasma mass spectrometer (MC-ICPMS) for online isotope ratio measurements.

Direct Phosphorylation of SRC Homology 3 Domains by Tyrosine Kinase Receptors Disassembles Ligand-Induced Signaling Networks.

Phosphotyrosine (pTyr) signaling has evolved into a key cell-to-cell communication system. Activated receptor tyrosine kinases (RTKs) initiate several pTyr-dependent signaling networks by creating the docking sites required for the assembly of protein complexes. However, the mechanisms leading to network disassembly and its consequence on signal transduction remain essentially unknown.

Resource Use and Cost of Alzheimer's Disease in France: 18-Month Results from the GERAS Observational Study.

Background: There is little longitudinal data on resource use and costs associated with Alzheimer's disease (AD) in France.

Objectives: To evaluate resource use and societal costs associated with AD in a French cohort of patients and their caregivers and the effect of patient cognitive decline on costs over an 18-month period.

Methods: Community-dwelling patients with mild, moderate, or moderately severe/severe AD dementia (n = 419) were followed-up for 18 months.

A new procedure for high precision isotope ratio determinations of U, Cu and Zn at nanogram levels in cultured human cells: What are the limiting factors?

The monitoring of isotopic fractionations in in vitro cultured human cell samples is a very promising and under-exploited tool to help identify the metabolic processes leading to disease-induced isotopic fractionations or decipher metabolic pathways of toxic metals in these samples. One of the limitations is that the analytes are often present at small amounts, ranging from tens to hundreds of ng, thus making challenging low-uncertainty isotope ratio determinations. Here we present a new procedure for U, Cu and Zn purification and isotope ratio determinations in cultured human neuron-like cells exposed to natural U.

The Cost-effectiveness of Dulaglutide 1.5mg versus Exenatide QW for the Treatment of Patients with Type 2 Diabetes Mellitus in France.

Introduction: Dulaglutide is a novel onceweekly administered glucagon-like peptide 1 receptor agonist (GLP-1 RA) for the management of type 2 diabetes mellitus (T2DM). The objective of this analysis was to estimate the cost-effectiveness of dulaglutide 1.5 mg versus exenatide QW for the management of T2DM in France.

Multi-elemental Nd, Sm, Eu, Gd isotope ratio measurements by stop-flow isotachophoresis coupled to MC-ICPMS.

In this study, a new analytical procedure based on isotachophoresis (ITP) coupled to a multi collector inductively coupled plasma mass spectrometer named Stop-Flow-ITP-MC-ICPMS is developed for exhaustive and high-precision multi-elemental isotopic characterization. We demonstrate that Stop-Flow-ITP makes it possible to stop the analytes migration several times for a duration compatible with the detector configuration changes without losing the separation performance. With this procedure, isotope ratio measurements of four lanthanides of interest for nuclear applications (Nd, Sm, Eu and Gd) were obtained with a reproducibility better than 0.

MPZL1 forms a signalling complex with GRB2 adaptor and PTPN11 phosphatase in HER2-positive breast cancer cells.

HER2/ErbB2 is overexpressed in a significant fraction of breast tumours and is associated with a poor prognosis. The adaptor protein GRB2 interacts directly with activated HER2 and is sufficient to transmit oncogenic signals. However, the consequence of HER2 activation on global GRB2 signalling networks is poorly characterized.

Follow-up study of patients treated with olanzapine pamoate in France in real-life treatment situation.

Objective: To characterize patients treated with olanzapine pamoate in French centers and investigate the conditions of use of olanzapine pamoate in real-life treatment situation.

Methods: Data came from French sites participating in an international post-authorization safety study. In this observational study, patients diagnosed with schizophrenia were receiving commercially available olanzapine pamoate, in accordance with their physician's usual standard of care.

Evidence of isotopic fractionation of natural uranium in cultured human cells.

The study of the isotopic fractionation of endogen elements and toxic heavy metals in living organisms for biomedical applications, and for metabolic and toxicological studies, is a cutting-edge research topic. This paper shows that human neuroblastoma cells incorporated small amounts of uranium (U) after exposure to 10 µM natural U, with preferential uptake of the U isotope with regard to U. Efforts were made to develop and then validate a procedure for highly accurate n(U)/n(U) determinations in microsamples of cells.

Multi-elemental Gd, Eu, Sm, Nd isotope ratio measurements by liquid chromatography coupled to MC-ICPMS with variable Faraday cup configurations during elution.

The high-precision isotopic characterization of actinides and fission products in nuclear samples is fundamental for various applications such as the management of spent nuclear fuel or the validation of neutronic calculation codes. However multi-elemental isotope ratio measurements by mass spectrometric techniques are hampered by the presence of both spectral and non-spectral interferences as complex sample matrices are encountered in such topics, but also due to the lack of high precision mass spectrometers able to cover the entire mass spectrum. This work describes a new LC-MC-ICPMS approach allowing simultaneous high-precision and multi-elemental isotope ratio measurements of four fission products of interest for nuclear issues (Nd, Sm, Eu, Gd) within a single elution run.

Prasugrel Use in Real Life: A Report From the Outpatient Setting in France.

The objective of this study was to provide descriptive statistics on patterns of prasugrel usage in the outpatient setting in France. This retrospective study was conducted to describe treatment patterns for prasugrel in the outpatient setting in France using the Intercontinental Marketing Services (IMS) Disease Analyzer database, which collates electronic medical records updated by a nationally representative database of 1200 French general practitioners (GPs). Anonymous data were collected prospectively at each follow-up visit.