Resolving Structures of Paramagnetic Systems in Chemistry and Materials Science by Solid-State NMR: The Revolving Power of Ultra-Fast MAS.

Ultra-fast magic-angle spinning (100+kHz) has revolutionized solid-state NMR of biomolecular systems but has so far failed to gain ground for the analysis of paramagnetic organic and inorganic powders, despite the potential rewards from substantially improved spectral resolution. The principal blockages are that the smaller fast-spinning rotors present significant barriers for sample preparation, particularly for air/moisture-sensitive systems, and are associated with low sensitivity from the reduced sample volumes. Here, we demonstrate that the sensitivity penalty is less severe than expected for highly paramagnetic solids and is more than offset by the associated improved resolution.

Geometry and electronic structure of Yb(III)[CH(SiMe)] from EPR and solid-state NMR augmented by computations.

Characterization of paramagnetic compounds, in particular regarding the detailed conformation and electronic structure, remains a challenge, and - still today it often relies solely on the use of X-ray crystallography, thus limiting the access to electronic structure information. This is particularly true for lanthanide elements that are often associated with peculiar structural and electronic features in relation to their partially filled f-shell. Here, we develop a methodology based on the combined use of state-of-the-art magnetic resonance spectroscopies (EPR and solid-state NMR) and computational approaches as well as magnetic susceptibility measurements to determine the electronic structure and geometry of a paramagnetic Yb(III) alkyl complex, Yb(III)[CH(SiMe)], a prototypical example, which contains notable structural features according to X-ray crystallography.

Canadian Association of Radiologists Thoracic Imaging Referral Guideline.

The Canadian Association of Radiologists (CAR) Thoracic Expert Panel consists of radiologists, respirologists, emergency and family physicians, a patient advisor, and an epidemiologist/guideline methodologist. After developing a list of 24 clinical/diagnostic scenarios, a rapid scoping review was undertaken to identify systematically produced referral guidelines that provide recommendations for one or more of these clinical/diagnostic scenarios. Recommendations from 30 guidelines and contextualization criteria in the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) for guidelines framework were used to develop 48 recommendation statements across the 24 scenarios.

Quantitative Li NMR Investigations of Silicon Anode Evolution during Fast Charging and Extended Cycling.

The development and optimization of fast battery charging protocols require detailed information regarding lithium speciation inside a battery. Nuclear magnetic resonance (NMR) spectroscopy has the unique capability of identifying the Li phases formed in an anode during Li-ion cell operation and quantifying their relative amounts. In addition, both Li metal films and dendrites are readily detected and quantified.

Fluorinated Rocksalt Cathode with Ultra-high Active Li Content for Lithium-ion Batteries.

The key to increasing the energy density of lithium-ion batteries is to incorporate high contents of extractable Li into the cathode. Unfortunately, this triggers formidable challenges including structural instability and irreversible chemistry under operation. Here, we report a new kind of ultra-high Li compound: Li MoO F (1≤x≤3) for cathode with an unprecedented level of electrochemically active Li (>3 Li per formula), delivering a reversible capacity up to 438 mAh g .

Adaptive Behavior in Young Autistic Children: Associations with Irritability and ADHD Symptoms.

Attention-deficit/hyperactivity disorder (ADHD) symptoms affect 40-60% of autistic children and have been linked to differences in adaptive behavior. It is unclear whether adaptive behavior in autistic youth is directly impacted by co-occurring ADHD symptoms or by another associated feature of both autism and ADHD, such as increased irritability. The current study examined relationships between irritability, ADHD symptoms, and adaptive behavior in 3- to 7-year-old autistic children.

Balovaptan vs Placebo for Social Communication in Childhood Autism Spectrum Disorder: A Randomized Clinical Trial.

Importance: There are no approved medications for the core symptoms of autism spectrum disorder (ASD), socialization and communication difficulties.

Objective: To evaluate the efficacy and safety of balovaptan, an oral selective vasopressin 1a receptor antagonist, compared with placebo in children and adolescents with ASD.

Design, Setting, And Participants: The aV1ation study was a randomized, double-blind, 24-week, parallel-group, placebo-controlled phase 2 trial.

Large multicenter randomized trials in autism: key insights gained from the balovaptan clinical development program.

Background: Autism spectrum disorder (ASD) is a common and heterogeneous neurodevelopmental condition that is characterized by the core symptoms of social communication difficulties and restricted and repetitive behaviors. At present, there is an unmet medical need for therapies to ameliorate these core symptoms in order to improve quality of life of autistic individuals. However, several challenges are currently faced by the ASD community relating to the development of pharmacotherapies, namely in the conduct of clinical trials.

Proton-detected fast-magic-angle spinning NMR of paramagnetic inorganic solids.

Fast (60 kHz) magic angle spinning solid-state NMR allows very sensitive proton detection in highly paramagnetic organometallic powders. We showcase this technique with the complete assignment of H and C resonances in a high-spin Fe(ii) polymerisation catalyst with less than 2 mg of sample at natural abundance.

Efficacy and safety of balovaptan for socialisation and communication difficulties in autistic adults in North America and Europe: a phase 3, randomised, placebo-controlled trial.

Background: There are no approved pharmacological therapies to support treatment of the core communication and socialisation difficulties associated with autism spectrum disorder in adults. We aimed to assess the efficacy, safety, and pharmacokinetics of balovaptan, a vasopressin 1a receptor antagonist, versus placebo in autistic adults.

Methods: V1aduct was a phase 3, randomised, placebo-controlled, double-blind trial, conducted at 46 sites across six countries (the USA, the UK, France, Italy, Spain, and Canada).

Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder.

Background: Experimental studies and small clinical trials have suggested that treatment with intranasal oxytocin may reduce social impairment in persons with autism spectrum disorder. Oxytocin has been administered in clinical practice to many children with autism spectrum disorder.

Methods: We conducted a 24-week, placebo-controlled phase 2 trial of intranasal oxytocin therapy in children and adolescents 3 to 17 years of age with autism spectrum disorder.

Agitation in a Microcarrier-based Spinner Flask Bioreactor Modulates Homeostasis of Human Mesenchymal Stem Cells.

Human mesenchymal stem cells (hMSCs) are well known in cell therapy due to their secretion of trophic factors, multipotent differentiation potential, and ability for self-renewal. As a result, the number of clinical trials has been steadily increasing over the last decade highlighting the need for in vitro systems capable of producing large quantities of cells to meet growing demands. However, hMSCs are highly sensitive to microenvironment conditions, including shear stress caused by dynamic bioreactor systems, and can lead to alteration of cellular homeostasis.

SARS-CoV-2 variant B.1.1.7 is susceptible to neutralizing antibodies elicited by ancestral spike vaccines.

All current vaccines for COVID-19 utilize ancestral SARS-CoV-2 spike with the goal of generating protective neutralizing antibodies. The recent emergence and rapid spread of several SARS-CoV-2 variants carrying multiple spike mutations raise concerns about possible immune escape. One variant, first identified in the United Kingdom (B.

A parallel-plate RF probe and battery cartridge for Li ion battery studies.

A new parallel-plate resonator for Li ion cell studies is introduced along with a removable cartridge-like electrochemical cell for lithium ion battery studies. This geometry separates the RF probe from the electrochemical cell permitting charge/discharge of the cell outside the magnet and introduces the possibility of multiplexing samples under test. The new cell has a geometry that is similar to that of a real battery, unlike the majority of cells employed for MR/MRI studies to this point.

SARS-CoV-2 variant B.1.1.7 is susceptible to neutralizing antibodies elicited by ancestral Spike vaccines.

The SARS-CoV-2 Spike glycoprotein mediates virus entry and is a major target for neutralizing antibodies. All current vaccines are based on the ancestral Spike with the goal of generating a protective neutralizing antibody response. Several novel SARS-CoV-2 variants with multiple Spike mutations have emerged, and their rapid spread and potential for immune escape have raised concerns.

Picometer Resolution Structure of the Coordination Sphere in the Metal-Binding Site in a Metalloprotein by NMR.

Most of our understanding of chemistry derives from atomic-level structures obtained with single-crystal X-ray diffraction. Metal centers in X-ray structures of small organometallic or coordination complexes are often extremely well-defined, with errors in the positions on the order of 10-10 Å. Determining the metal coordination geometry to high accuracy is essential for understanding metal center reactivity, as even small structural changes can dramatically alter the metal activity.

Rationale, design, and methods of the Autism Centers of Excellence (ACE) network Study of Oxytocin in Autism to improve Reciprocal Social Behaviors (SOARS-B).

Objective: To describe the rationale, design, and methods of the Autism Centers of Excellence (ACE) network Study of Oxytocin in Autism to improve Reciprocal Social Behaviors (SOARS-B).

Method: This phase 2 clinical trial was designed to evaluate the use of intranasal oxytocin treatment to improve social difficulties in individuals with autism spectrum disorder (ASD). In total, 290 participants ages 3 to 17 years with a DSM-5 diagnosis of ASD were enrolled to receive 24 weeks of treatment with either oxytocin or a matched placebo at one of seven collaborating sites.

Addressing Challenging Behavior During Hospitalizations for Children with Autism: A Pilot Applied Behavior Analysis Randomized Controlled Trial.

This study evaluated the feasibility, acceptance, and potential clinical benefit of brief applied behavior analysis (ABA)-based interventions for children and adolescents with autism spectrum disorder (ASD) displaying challenging behaviors during hospitalizations. Participants included 36 children diagnosed with ASD, 6-17 years of age, who were medically or psychiatrically hospitalized. Children in the intervention group received a brief ABA intervention and were compared to children in the evaluation and monitoring-only group.

Surgical tracheostomies in Covid-19 patients: important considerations and the "5Ts" of safety.

The coronavirus disease (covid19) pandemic (caused by the SARS-CoV-2 virus) is the greatest healthcare challenge in a generation. Clinicians are modifying the way they approach day-to-day procedures. Safety and reduction of transmission risk is paramount.

Pharmacogenetics of Metformin for Medication-Induced Weight Gain in Autism Spectrum Disorder.

We recently found that metformin attenuated weight gain due to mixed dopamine and serotonin receptor antagonists, commonly termed atypical antipsychotics, in children and adolescents with autism spectrum disorder (ASD). Previous studies have found that genetic variation predicts response to metformin in diabetes. In this study, we aimed to assess whether response to metformin for weight gain in this population is associated with variants in five genes previously implicated in metformin response in diabetes.

Inpatient Psychiatric Treatment of Serious Behavioral Problems in Children with Autism Spectrum Disorder (ASD): Specialized Versus General Inpatient Units.

Psychiatric hospitalization of children with autism spectrum disorder (ASD) is common, but there is little comparative information available on different psychiatric hospital treatment models. Children with ASD ages 4-20 were enrolled upon admission to either a specialized (N = 53) or a general child psychiatric unit (N = 27). Caregivers completed the Aberrant Behavioral Checklist-Irritability Sub-scale (ABC-I) at admission, discharge, and 2 months post-discharge and reported information on crisis service utilization 2 months post-discharge.

Effects of Metformin on Spatial and Verbal Memory in Children with ASD and Overweight Associated with Atypical Antipsychotic Use.

Objectives: Studies in humans and rodents suggest that metformin, a medicine typically used to treat type 2 diabetes, may have beneficial effects on memory. We sought to determine whether metformin improved spatial or verbal memory in children with autism spectrum disorder (ASD) and overweight associated with atypical antipsychotic use.

Methods: We studied the effects of metformin (Riomet) concentrate on spatial and verbal memory in 51 youth with ASD, ages 6 through 17 years, who were taking atypical antipsychotic medications, had gained significant weight, and were enrolled in a trial of metformin for weight management.

A Randomized, Placebo-Controlled Trial of Metformin for the Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorder: Open-Label Extension.

Objective: A previous study reported on a 16-week placebo-controlled, randomized clinical trial (RCT) of metformin for weight stabilization in 61 children and adolescents 6 to 17 years old with autism spectrum disorder who were prescribed atypical antipsychotics. The present study describes the results of a 16-week open-label extension.

Method: Fifty-two participants from the acute trial (85%) entered the extension; 22 had been on metformin during the initial RCT and 30 had been on placebo.