Tissue biomarker development in a multicentre trial context: a feasibility study on the PETACC3 stage II and III colon cancer adjuvant treatment trial.

Purpose: We evaluated the feasibility of biomarker development in the context of multicenter clinical trials.

Experimental Design: Formalin-fixed, paraffin-embedded (FFPE) tissue samples were collected from a prospective adjuvant colon cancer trial (PETACC3). DNA was isolated from tumor as well as normal tissue and used for analysis of microsatellite instability, KRAS and BRAF genotyping, UGT1A1 genotyping, and loss of heterozygosity of 18 q loci. Immunohistochemistry was used to test expression of TERT, SMAD4, p53, and TYMS. Messenger RNA was retrieved and tested for use in expression profiling experiments.

Results: Of the 3,278 patients entered in the study, FFPE blocks were obtained from 1,564 patients coming from 368 different centers in 31 countries. In over 95% of the samples, genomic DNA tests yielded a reliable result. Of the immmunohistochemical tests, p53 and SMAD4 staining did best with reliable results in over 85% of the cases. TERT was the most problematic test with 46% of failures, mostly due to insufficient tissue processing quality. Good quality mRNA was obtained, usable in expression profiling experiments.

Conclusions: Prospective clinical trials can be used as framework for biomarker development using routinely processed FFPE tissues. Our results support the notion that as a rule, translational studies based on FFPE should be included in prospective clinical trials.

Archiving Qualitative Data in the Context of a Society Coming out of Conflict: Some Lessons from Northern Ireland.

ARK (‘Access Research Knowledge’) was set up with a single goal: to make social science information on Northern Ireland available to the widest possible audience. The most well-known and widely used part of the ARK resource is CAIN (Conflict Archive on the INternet), which is one of the largest on-line collections of source material and information and about the Northern Ireland conflict. The compilation of CAIN's new Remembering: Victims, Survivors and Commemoration section raised issues related to the sensitivity of the material, as it feeds into the fundamental debate on the legacy of the Northern Ireland conflict. It also fundamentally raises the question to what extent archiving is a neutral or political activity and necessitates a discourse on responsibility and ethics among social researchers. Experiences from the establishment of the Northern Ireland Qualitative Archive (NIQA) shed light on future possibilities with regard to qualitative archives on the Northern Ireland conflict.

Social support, network heterogeneity, and smoking behavior in women: The 10-town study

Purpose. Examine the associations among social support, network heterogeneity, and smoking behavior in a large sample of Finnish female municipal employees.

Comparative tracing experiments to investigate epikarst structural and compositional heterogeneity

Comparative tracer testing may be used to evaluate the vulnerability of groundwater to specific contaminants by comparing reactive tracer response to that of a simultaneously injected non-reactive “conservative” substance. Conversely, knowledge of tracer reaction with specific materials permits information about subsurface heterogeneity to be inferred. A series of tests completed in the vadose zone overlying a limestone aquifer employed a cocktail of particles along with reactive and non-reactive solute tracers to investigate transport rates between the ground surface and monitoring points approximately 10 m below ground. Short pulse tests revealed both solutes and particulate contaminants could travel at rates of over 10 m/h. Comparison of particle (microorganisms) and non-reactive solute tracer breakthrough revealed that particle tracers experience pore exclusion resulting in higher peak relative concentrations which arrive earlier than those of the solute. Prolonged tracer injection during subsequent experiments confirmed the response observed and illustrated that over 40 % of flow paths between injection and monitoring points were inaccessible to particles, but could allow solutes to pass through them. Similarly, the difference in response between various reactive tracers demonstrated tracers reached monitoring points via multiple flow paths and suggests geochemical heterogeneity plays an important role in influencing tracer behaviour. The results of this investigation highlight the complexity of water flow through the epikarst and the vulnerability of groundwater in karst aquifers to contamination when soil cover is thin to absent.