Biomarker and Translational Prostate Cancer Research

The existing clinical biomarkers for prostate cancer (PCa) are not ideal, since they cannot specifically differentiate between those patients who should be treated immediately and those who should avoid overtreatment. Current screening techniques lack specificity, and a decisive diagnosis of PCa is based on prostate biopsy. Although PCa screening is widely utilized nowadays, two-thirds of the biopsies performed are still unnecessary. Thus, the discovery of noninvasive PCa biomarkers remains an urgent unmet medical need. Once metastasized, there is still no curative therapy. A better understanding of sustained androgen receptor signalling in castration resistant prostate cancer (CRPC) has now led to the development of more effective therapies. We need a better understanding of the molecular and cellular aspects of prostate carcinogenesis and progression. Identification of cancer initiating cells and therapies against these populations is a promising way forward to fight this disease

DNA Analysis and the Confrontation Clause: “Special Needs” Category for DNA Testimonial Evidence

This Comment examines three recent U.S. Supreme Court decisions dealing with forensic evidence and how its use is affected by the Confrontation Clause. The Confrontation Clause provides a defendant with the right to confront adverse witnesses. Notably, in Williams v. Illinois, Justice Breyer pointed out that the Court has explicitly not addressed the “outer limits of the “testimonial statements” rule set forth in Crawford v. Washington.” Specifically, Justice Breyer asked how “the Confrontation Clause [applies] to the panoply of crime laboratory reports and underlying technical statements written by (or otherwise made by) laboratory technicians?” This question, while left unanswered, could have major implications in future criminal cases and could affect how prosecutors prepare for and conduct their trials. This Comment addresses an open question regarding where the “outer limits” of testimonial evidence truly are. Part I of this Comment presents a brief legal background on the Confrontation Clause. It specifically details recent Supreme Court cases involving the impact of the Confrontation Clause on the use of forensic evidence. Part II presents a scientific background on DNA, the complexity of its analysis, and specific advances that may further complicate its relationship with the Confrontation Clause and the need for in-court testimony. Part III proposes a solution that would incorporate aspects of the three recent Supreme Court opinions and provide a workable way for prosecutors to admit scientific evidence, while allowing defense attorneys the opportunity to cross-examine appropriate witnesses. In essence, the Court should adopt a “special needs” category for DNA forensic testimonial evidence. This category would allow for judicial discretion when balancing the benefits of DNA evidence to the prosecution with the defendant’s right to confront adverse witnesses. This would present a solution to Justice Breyer’s concerns about requiring the confrontation of every possible person that worked on a DNA sample, but it would still allow a defendant to adequately cross-examine knowledgeable witnesses

Characterization of TAP Ambr250 disposable bioreactors as a reliable scale-down model for biologics process development

In recent years, biologic drugs such as antibodies, biosimilars and fusion proteins have continued to enter into the pharmaceutical pipeline. To shorten cell culture process development and accelerate clinical trials and regulatory filing, the disposable Advanced Microscale Bioreactors (Ambr 250) has burgeoned to be a useful tool due to the advantages of highly automated control and short turnaround. However, the traditional early stage upstream process development is normally conducted in 3L or 5L bioreactors. The usage of Ambr 250 instead of 5L bioreactors in the development has many benefits, but also brings necessity to establish a scale-down model of Ambr 250 to mimic 5L bioreactors. In our study, a comprehensive kLa characterization of Ambr 250 was conducted to define optimal operational conditions. Three different scale-down approaches, i.e. dimensionless volumetric flow rate (vvm), Power per unit volume (P/V) and kLa models have been evaluated using different cell lines. Since Design of Experiments (DoE) is often used in upstream process development, the response of Ambr 250 bioreactors to process parameters such as temperature, pH, seeding density, feeding strategy were compared to those of 5L bioreactors. In addition to process development, the suitability of Ambr 250 in the clone selection, which is traditionally conducted in 5L bioreactors, was investigated using six different clones. These studies showed that Ambr 250 generates similar profiles of cell growth and protein production to 5L and 1000L bioreactors. The data suggest that Ambr 250 can be used for early stage clone selection and process development as the replacement for traditional glass 5L bioreactors, and it has great potential applications in late stage process validation and process characterizatio

Use of the Ambr 250 to enable rapid clone selection and process development for large scale manufacturing processes

Currently, widely used bench scale bioreactor systems require much user manipulation, a large amount of raw materials, and have a long turnaround time for reactor cleaning and rebuilding. New technologies such as robotic disposable bioreactor systems provide a solution that is miniaturized, high throughput, and substantially automated. The Ambr® 250 offers such a solution, with 24x250mL bioreactors controlled independently. Although this new technology is rapidly being adopted by several groups as a way to increase efficiency and speed within upstream development, it remains to be proven that these systems are complete models for process characterization. We have shown that Ambr 250 is a good scale down model for multiple cell line systems. The aim of this work is to further characterize the engineering environment of the Ambr® 250 with a view of defining its role in industrial cell culture process development and scale-up. CFD modeling of the Ambr 250 mammalian vessel with validation via Particle Image Velocimetry (PIV) was conducted to simulate the hydrodynamic environment in the vessel. These findings were evaluated against current benchtop models and manufacturing scales. Cultures were run utilizing different engineering parameters (vvm, P/V, kLa) to assess the scalability of the current system. Cell growth, production, and product quality were compared across to recommend operating conditions for the Ambr® 250 that best match manufacturing scale reactors. Multiple CHO host cell lines were examined in order to find optimal operating conditions for the Ambr® 250 system

Using a smartphone application to promote healthy dietary behaviours and local food consumption

Smartphone “apps” are a powerful tool for public health promotion, but unidimensional interventions have been ineffective at sustaining behavioural change. Various logistical issues exist in successful app development for health intervention programs and for sustaining behavioural change. This study reports on a smartphone application and messaging service, called “SmartAPPetite,” which uses validated behaviour change techniques and a behavioural economic approach to “nudge” users into healthy dietary behaviours. To help gauge participation in and influence of the program, data were collected using an upfront food survey, message uptake tracking, experience sampling interviews, and a follow-up survey. Logistical and content-based issues in the deployment of the messaging service were subsequently addressed to strengthen the effectiveness of the app in changing dietary behaviours. Challenges included creating relevant food goal categories for participants, providing messaging appropriate to self-reported food literacy and ensuring continued participation in the program. SmartAPPetite was effective at creating a sense of improved awareness and consumption of healthy foods, as well as drawing people to local food vendors with greater frequency. This work serves as a storehouse of methods and best practices for multidimensional local food-based smartphone interventions aimed at improving the “triple bottom line” of health, economy, and environment

Examining the correlates of adolescent food and nutrition knowledge

Food literacy is a set of skills and knowledge that are integral to diet. It is common among teenagers to not have basic food literacy skills needed to consume a healthy diet. This study examined: (1) the current state of food and nutrition knowledge among adolescents 13–19 years of age in the census metropolitan area of London, ON, Canada; and (2) correlates of food knowledge and nutrition knowledge among adolescents. Data for this study were drawn from baseline youth and parent survey data collected from a larger population health intervention study. Statistical analysis of the survey data indicates that higher parental education and higher median neighbourhood family income, the use of mobile health applications, liking to cook, as well as confidence in reading and understanding food labels were all consistently associated with increased food and nutrition knowledge. Findings may help guide future research towards optimal methods for delivering food literacy interventions to effectively educate teenagers. Results of this study may help guide policy makers, researchers, and public health professionals in developing appropriate food and nutrition programs and curriculums to combat the decline in food literacy skills