Prognostic and Predictive Biomarkers in Resected Colon Cancer: Current Status and Future Perspectives for Integrating Genomics into Biomarker Discovery

The number of agents that are potentially effective in the adjuvant treatment of locally advanced resectable colon cancer is increasing. Consequently, it is important to ascertain which subgroups of patients will benefit from a specific treatment. Despite more than two decades of research into the molecular genetics of colon cancer, there is a lack of prognostic and predictive molecular biomarkers with proven utility in this setting. A secondary objective of the Pan European Trials in Adjuvant Colon Cancer-3 trial, which compared irinotecan in combination with 5-fluorouracil and leucovorin in the postoperative treatment of stage III and stage II colon cancer patients, was to undertake a translational research study to assess a panel of putative prognostic and predictive markers in a large colon cancer patient cohort. The Cancer and Leukemia Group B 89803 trial, in a similar design, also investigated the use of prognostic and predictive biomarkers in this setting. In this article, the authors, who are coinvestigators from these trials and performed similar investigations of biomarker discovery in the adjuvant treatment of colon cancer, review the current status of biomarker research in this field, drawing on their experiences and considering future strategies for biomarker discovery in the postgenomic era. The Oncologist 2010; 15: 390-404

Monitoring and repair of an impact damaged prestressed bridge

This paper details the monitoring and repair of an impact damaged prestressed concrete bridge. The repair was required following an impact from a low-loader carrying an excavator while passing underneath the bridge. The repair was carried out by preloading the bridge in the vicinity of the damage to relieve some prestressing. This preload was removed following the hardening and considerable strength gain of the repair material. The true behaviour of damaged prestressed concrete bridges during repair is difficult to estimate theoretically due to lack of benchmarking and inadequacy of assumed damage models. A network of strain gauges at locations of interest was thus installed during the entire period of repair. Effects of various activities were qualitatively and quantitatively observed. The interaction and rapid, model-free calibration of damaged and undamaged beams, including identification of damaged gauges were also probed. This full scale experiment is expected to be of interest and benefit to the practising engineer and the researcher alike.

Verification of McCabe's Delta L Law for Growth of Lysozyme Crystals by Hanging Drop Method

Lysozyme is a naturally occurring enzyme in egg white and has high commercial importance due to its antimicrobial properties. The main objective of this work was to study the growth rate of lysozyme crystals isolated from egg for the first 72 hours and verify the results with McCabe’s constant crystal growth theory. Hanging drop crystallization method was used to form high purity lysozyme crystals from the embryonic stage. To this end, this work differs from an earlier work of Forsythe et al., who used seed crystals in the size range of 10 µm - 40 µm for face growth measurements at different pH values. The maximum crystal size recorded in the present work was 392.86 µm, which is within the typical size range of 50 µm - 500 µm for which constant crystal growth is expected to hold according to McCabe’s ?L law. Electron micrographs (SEM) revealed the structure and dimensions of the crystals while SDS-Page was used to measure the purity of the crystals. The SEM results showed that that lysozyme growth rate was linear and agreed with McCabe’s constant growth theory, producing a growth rate of 1.77 x 10-3 µm .s-1

Body size in ecological networks

Body size determines a host of species traits that can affect the structure and dynamics of food webs, and other ecological networks, across multiple scales of organization. Measuring body size provides a relatively simple means of encapsulating and condensing a large amount of the biological information embedded within an ecological network. Recently, important advances have been made by incorporating body size into theoretical models that explore food web stability, the patterning of energy fluxes, and responses to perturbations. Because metabolic constraints underpin bodysize scaling relationships, metabolic theory offers a potentially useful new framework within which to develop novel models to describe the structure and functioning of ecological networks and to assess the probable consequences of biodiversity change.

Association Testing of Previously Reported Variants in a Large Case-Control Meta-analysis of Diabetic Nephropathy

We formed the GEnetics of Nephropathy–an International Effort (GENIE) consortium to examine previously reported genetic associations with diabetic nephropathy (DN) in type 1 diabetes. GENIE consists of 6,366 similarly ascertained participants of European ancestry with type 1 diabetes, with and without DN, from the All Ireland-Warren 3-Genetics of Kidneys in Diabetes U.K. and Republic of Ireland (U.K.-R.O.I.) collection and the Finnish Diabetic Nephropathy Study (FinnDiane), combined with reanalyzed data from the Genetics of Kidneys in Diabetes U.S. Study (U.S. GoKinD). We found little evidence for the association of the EPO promoter polymorphism, rs161740, with the combined phenotype of proliferative retinopathy and end-stage renal disease in U.K.-R.O.I. (odds ratio [OR] 1.14, P = 0.19) or FinnDiane (OR 1.06, P = 0.60). However, a fixed-effects meta-analysis that included the previously reported cohorts retained a genome-wide significant association with that phenotype (OR 1.31, P = 2 × 10-9). An expanded investigation of the ELMO1 locus and genetic regions reported to be associated with DN in the U.S. GoKinD yielded only nominal statistical significance for these loci. Finally, top candidates identified in a recent meta-analysis failed to reach genome-wide significance. In conclusion, we were unable to replicate most of the previously reported genetic associations for DN, and significance for the EPO promoter association was attenuated.