Variants Identified Through Tumor Genomic Profiling: Assessing Genetic Counseling Outcomes.

Purpose: As tumor genomic profiling (TGP) is increasingly used to help guide cancer treatment, variants, which may or may not be reflective of the germline genome, are being identified. As TGP use increases, it is becoming an important tool for referral to genetic counseling and identifying patients with hereditary cancer syndromes such as hereditary breast and ovarian cancer. This study explores genetic counseling referral patterns and germline implications of patients found to have pathogenic variants identified through TGP.

A Monte Carlo framework for managing biological variability in manufacture of autologous cell therapy from mesenchymal stromal cells therapies.

Manufacturing processes for autologous cell therapy need to reproducibly generate in specification (quality and quantity) clinical product. However, patient variability prevents the level of control of cell input material that could be achieved in a cell line or allogeneic-based process. We have applied literature data on bone marrow-derived mesenchymal stromal cells variability to estimate probability distributions for stem cell yields given underlying truncated normal distributions in total nucleated cell concentration, stem cell percentage and plausible aspirate volumes.

Immobilisation of Delta-like 1 ligand for the scalable and controlled manufacture of hematopoietic progenitor cells in a stirred bioreactor.

Background: Umbilical cord blood provides a source of hematopoietic stem cells for transplantation with immunological and availability advantages over conventional bone marrow sources. Limited cell numbers and slower engraftment from umbilical cord blood units has led to the clinical development of immobilised Notch ligand Delta-Like 1 to promote ex vivo expansion of a rapidly engrafting cell population. However, current immobilisation methods are not simple to scale in a controlled manner.

Safety evaluation of orally administered afoxolaner and milbemycin oxime in eight-week-old dogs.

The safety profile of afoxolaner (an isoxazoline molecule) when combined with milbemycin oxime (a macrocyclic lactone) was evaluated according to the regulatory requirements when administered six times orally in a soft chewable formulation at a dose of at least 1×, 3×, or 5× the maximum exposure dose in 8-week-old Beagle dogs. Thirty-two healthy puppies (16 males and 16 females) were enrolled and allocated randomly to one of four treatment groups. Three doses were administered at 28-day intervals (Days 0, 28, and 56), followed by three additional doses administered with 14-day intervals (Days 84, 98, and 112).

The intravenous and oral pharmacokinetics of afoxolaner and milbemycin oxime when used as a combination chewable parasiticide for dogs.

The pharmacokinetics of afoxolaner and milbemycin oxime (A3 and A4 forms) in dogs were evaluated following the oral administration of NexGard Spectra (Merial), a fixed combination chewable formulation of these two active pharmaceutical ingredients. Absorption of actives was rapid at levels that provide the minimum effective doses of 2.5 mg/kg and 0.