Baseline Drug Clearance Predicts Outcomes in Children With Inflammatory Bowel Disease Treated With Vedolizumab: Results From the VedoKids Prospective Multicentre Study.

Background: The pharmacokinetics of biologic agents can differ between children and adults with inflammatory bowel disease (IBD), often necessitating modified paediatric dosing strategies.

Aims: To define the exposure-response relationship of vedolizumab in the paediatric IBD VedoKids cohort including the effect of baseline clearance on deep biochemical remission (normal C-reactive protein [CRP]/erythrocyte sedimentation rate [ESR] and steroid-free remission) at 30 weeks, and to use population pharmacokinetic models to find the best matches between adult and paediatric pharmacokinetic profiles.

Methods: We sought a pharmacokinetic model on 312 serum vedolizumab concentrations from 129 children, assisted by a published adult model as a Bayesian prior.

Revealing an unexpectedly low electron injection threshold via reinforced shock acceleration.

Collisionless shock waves, found in supernova remnants, interstellar, stellar, and planetary environments, and laboratories, are one of nature's most powerful particle accelerators. This study combines in situ satellite measurements with recent theoretical developments to establish a reinforced shock acceleration model for relativistic electrons. Our model incorporates transient structures, wave-particle interactions, and variable stellar wind conditions, operating collectively in a multiscale set of processes.

Structural insights into isoform-specific RAS-PI3Kα interactions and the role of RAS in PI3Kα activation.

Mutations in RAS and PI3Kα are major drivers of human cancer. Their interaction plays a crucial role in activating PI3Kα and amplifying the PI3K-AKT-mTOR pathway. Disrupting RAS-PI3Kα interaction enhances survival in lung and skin cancer models and reduces tumor growth and angiogenesis, although the structural details of this interaction remain unclear.

Maintenance treatment with vedolizumab in paediatric inflammatory bowel disease (VEDOKIDS): 54-week outcomes of a multicentre, prospective, cohort study.

Background: Infliximab and adalimumab are the only biologics thus far approved for paediatric patients with inflammatory bowel disease (IBD), so other biologics, such as vedolizumab, are prescribed off-label. Despite its frequent use, prospective data for vedolizumab treatment in children are available only for short-term induction outcomes. We aimed to evaluate the long-term efficacy and safety of maintenance therapy with vedolizumab in paediatric patients with IBD.

Frequency of Missing TNM Stage Data for Adults With Intellectual or Developmental Disabilities in a Provincial Cancer Registry-A Brief Report.

Background: Adults with intellectual or developmental disability (IDD) are at higher risk for incomplete cancer staging.

Aim: To compare unknown stage data between those with and without IDD.

Materials And Methods: We used the Ontario Cancer Registry linked to administrative health data between 2007 and 2019.