Development of a Control Strategy for Benzene Impurity in HPMCAS-Stabilized Spray-Dried Dispersion Drug Products Using a Science-Based and Risk-Based Approach.

Purpose: To develop a strategy to control benzene, an ICH Q3C Class 1 impurity that may be present in spray solvents at ppm concentration, in amorphous polymer-stabilized spray-dried dispersion (SDD) products.

Methods: Risk assessments included determining the probability for benzene concentration in primary spray solvents, the physical properties of volatiles, and the potential enrichment of benzene from solution to solid. Mechanistic understanding of benzene removal was gained through a benzene-spiked fate and tolerance (F&T) study simulating worst-case spray-drying conditions and application of diffusion models for secondary drying.

Community-wide assessment of protein-interface modeling suggests improvements to design methodology.

The CAPRI (Critical Assessment of Predicted Interactions) and CASP (Critical Assessment of protein Structure Prediction) experiments have demonstrated the power of community-wide tests of methodology in assessing the current state of the art and spurring progress in the very challenging areas of protein docking and structure prediction. We sought to bring the power of community-wide experiments to bear on a very challenging protein design problem that provides a complementary but equally fundamental test of current understanding of protein-binding thermodynamics. We have generated a number of designed protein-protein interfaces with very favorable computed binding energies but which do not appear to be formed in experiments, suggesting that there may be important physical chemistry missing in the energy calculations.

Approaches to the evaluation of outbreak detection methods.

Background: An increasing number of methods are being developed for the early detection of infectious disease outbreaks which could be naturally occurring or as a result of bioterrorism; however, no standardised framework for examining the usefulness of various outbreak detection methods exists. To promote comparability between studies, it is essential that standardised methods are developed for the evaluation of outbreak detection methods.

Methods: This analysis aims to review approaches used to evaluate outbreak detection methods and provide a conceptual framework upon which recommendations for standardised evaluation methods can be based.

Q fever vaccine uptake in South Australian meat processors prior to the introduction of the National Q Fever Management Program.

Despite the availability of a vaccine, the incidence of Q fever disease among populations at risk continues to be high. Q fever is an important cause of morbidity for workers, particularly in the meat and agricultural industries. Following an increase in 1998 in the number of Q fever notifications among meat processors to the Communicable Disease Control Branch, South Australia, a survey was conducted in the same year to assess the uptake of Q fever immunisation programs in meat processors and to identify barriers to offering these programs.

Reactive joint symptoms following an outbreak of Salmonella typhimurium phage type 135a.

Objective: To quantify the incidence and clinical features of reactive arthritis (ReA) developing in a cohort exposed to an outbreak of Salmonella typhimurium phage type 135a, and factors affecting host susceptibility to ReA.

Methods: A screening questionnaire was mailed to 493 patients with confirmed Salmonella infection. Musculoskeletal symptoms and extraarticular manifestations of ReA were quantified.

Introducing laparoscopic Roux-en-Y gastric bypass at a Veterans Affairs medical facility.

Background: Previous studies have shown that advanced age, diabetes, and male gender are associated with higher morbidity and mortality after bariatric surgery. Those risk factors are characteristic of patients in the Veterans Affairs (VA) health care system. Laparoscopic Roux-en-Y gastric bypass (RYGB) has become an established treatment modality for morbid obesity.