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.

Two-Stage Transmitter Precoding Based on Data-Driven Code Hopping and Partial Zero Forcing Beamforming for MC-DCMA Communications

This paper proposes a hybrid transmission technique based on adaptive code-to-user allocation and linear precoding for the downlink of phase shift keying (PSK) based multi-carrier code division multiple access (MC-CDMA) systems. The proposed scheme is based on the separation of the instantaneous multiple access interference (MAI) into constructive and destructive components taking into account the dependency on both the channel variation and the instantaneous symbol values of the active users. The first stage of the proposed technique is to adaptively distribute the available spreading sequences to the users on a symbol-by-symbol basis in the form of codehopping with the objective to steer the users' instantaneous crosscorrelations to yield a favourable constructive to destructive MAI ratio. The second stage is to employ a partial transmitter based zero forcing (ZF) scheme specifically designed for the exploitation of constructive MAI. The partial ZF processing decorrelates destructive interferers, while users that interfere constructively remain correlated. This results in a signal to interference-plus-noise ratio (SINR) enhancement without the need for additional power-per-user investment. It will be shown in the results section that significant bit error rate (BER) performance benefits can be achieved with this technique.

Factors influencing patients with stage 5 chronic kidney disease to opt for conservative management: a practitioner research study

Aims and objectives. This study explored decision-making experiences of patients with stage 5 chronic kidney disease when opting for conservative management of their renal failure.

Background. Dialysis is an invasive treatment, and for some older patients, there is an associated treatment burden of dialysis-related symptoms. An alternative choice is conservative management, but little is known about those who make this decision and how they are supported through the process.

Design. Qualitative practitioner research study.

Method. Data were generated from nine patients' naturally occurring clinic consultations with a renal clinical nurse specialist between May 2010 - July 2010. Interviews were transcribed verbatim and findings fed back at three multi-disciplinary meetings to check for relevance and resonance. Common themes were identified and codes applied.

Results. Patients reported age and having to travel three times a week to hospital for dialysis as reasons not to opt for treatment. Others felt well without dialysis not wanting to upset the 'status quo' or to burden loved ones. Most felt equipped to make the decision following explanation and discussion with the clinical nurse specialist in the renal clinic.

Conclusions. Patients opting for conservative management give numerous reasons for this including old age, travel limitations, feeling well without dialysis and not wanting to be a burden, but appear content with their decision. One-to-one discussions with the clinical nurse specialist appear helpful during the decision-making process presenting an opportunity for advancing nursing roles in the chronic kidney disease service.

Relevance to clinical practice. Understanding patients' reasons for refusing dialysis assists in supporting until death. There is an opportunity for developing nursing practice to meet the multi-faceted needs of this group.

Development and independent validation of a prognostic assay for stage ii colon cancer using formalin-fixed paraffin-embedded tissue

Purpose: Current prognostic factors are poor at identifying patients at risk of disease recurrence after surgery for stage II colon cancer. Here we describe a DNA microarray-based prognostic assay using clinically relevant formalin-fixed paraffin-embedded (FFPE) samples. Patients and Methods: A gene signature was developed from a balanced set of 73 patients with recurrent disease (high risk) and 142 patients with no recurrence (low risk) within 5 years of surgery. Results: The 634-probe set signature identified high-risk patients with a hazard ratio (HR) of 2.62 (P <.001) during cross validation of the training set. In an independent validation set of 144 samples, the signature identified high-risk patients with an HR of 2.53 (P <.001) for recurrence and an HR of 2.21 (P = .0084) for cancer-related death. Additionally, the signature was shown to perform independently from known prognostic factors (P <.001). Conclusion: This gene signature represents a novel prognostic biomarker for patients with stage II colon cancer that can be applied to FFPE tumor samples. © 2011 by American Society of Clinical Oncology.

Estimation of survival rate and extinction probability for stage-structured populations with overlapping life stages

The development of methods providing reliable estimates of demographic parameters (e. g., survival rates, fecundity) for wild populations is essential to better understand the ecology and conservation requirements of individual species. A number of methods exist for estimating the demographics of stage-structured populations, but inherent mathematical complexity often limits their uptake by conservation practitioners. Estimating survival rates for pond-breeding amphibians is further complicated by their complex migratory and reproductive behaviours, often resulting in nonobservable states and successive cohorts of eggs and tadpoles. Here we used comprehensive data on 11 distinct breeding toad populations (Bufo calamita) to clarify and assess the suitability of a relatively simple method [the Kiritani-Nakasuji-Manly (KNM) method] to estimate the survival rates of stage-structured populations with overlapping life stages. The study shows that the KNM method is robust and provides realistic estimates of amphibian egg and larval survival rates for species in which breeding can occur as a single pulse or over a period of several weeks. The study also provides estimates of fecundity for seven distinct toad populations and indicates that it is essential to use reliable estimates of fecundity to limit the risk of under- or overestimating the survival rates when using the KNM method. Survival and fecundity rates for B. calamita populations were then used to define population matrices and make a limited exploration of their growth and viability. The findings of the study recently led to the implementation of practical conservation measures at the sites where populations were most vulnerable to extinction. © 2010 The Society of Population Ecology and Springer.

Rate-determining stage in NOSCR with propane on low-exchanged Cu-ZSM-5 catalyst

The kinetics of the NO SCR with propane has been studied on a low-exchanged Cu-ZSM-5 catalyst. The study of the kinetics of individual reaction stages (2-nitrosopropane isomerization to acetone oxime and reaction of adsorbed acetone oxime with gaseous NO) has shown that the NO reaction with acetone oxime is the rate-determining stage in the whole chain of transformations leading to the formation of molecular nitrogen in the low-temperature region below 300 C-degrees. The kinetic analysis of the reaction has revealed that at the temperatures above 300(degrees)C propane plays a more important role.

Design considerations for the autism spectrum disorder-friendly Key Stage 1 classroom

There is a growing consensus that an appropriate classroom environment will aid the performance of the pupil with autism spectrum disorder (ASD). There are, however, very few design guidelines available when considering ASD and the school environment. Such guidelines that do exist tend only to be in general terms. Therefore, this article seeks to highlight design considerations specifically for the ASD-friendly Key Stage 1 (age five to eight) classroom. It will first highlight some of the challenges for those with autism spectrum disorder in a school environment and the triad of challenges faced by architects and designers when considering ASD-friendly classroom design. It will then go on to describe the findings and results of a two-year study carried out in conjunction with the ASD teaching staff of Northern Ireland's Southern Education and Library Board. These consist of 16 specific design considerations for the Key Stage 1 ASD-friendly classroom applicable to all classrooms for pupils between five and eight years of age.