EuroClonality/BIOMED-2 guidelines for interpretation and reporting of Ig/TCR clonality testing in suspected lymphoproliferations.

PCR-based immunoglobulin (Ig)/T-cell receptor (TCR) clonality testing in suspected lymphoproliferations has largely been standardized and has consequently become technically feasible in a routine diagnostic setting. Standardization of the pre-analytical and post-analytical phases is now essential to prevent misinterpretation and incorrect conclusions derived from clonality data. As clonality testing is not a quantitative assay, but rather concerns recognition of molecular patterns, guidelines for reliable interpretation and reporting are mandatory. Here, the EuroClonality (BIOMED-2) consortium summarizes important pre- and post-analytical aspects of clonality testing, provides guidelines for interpretation of clonality testing results, and presents a uniform way to report the results of the Ig/TCR assays. Starting from an immunobiological concept, two levels to report Ig/TCR profiles are discerned: the technical description of individual (multiplex) PCR reactions and the overall molecular conclusion for B and T cells. Collectively, the EuroClonality (BIOMED-2) guidelines and consensus reporting system should help to improve the general performance level of clonality assessment and interpretation, which will directly impact on routine clinical management (standardized best-practice) in patients with suspected lymphoproliferations.

Multi-purpose utility of circulating plasma DNA testing in patients with advanced cancers.

Tumor genomic instability and selective treatment pressures result in clonal disease evolution; molecular stratification for molecularly targeted drug administration requires repeated access to tumor DNA. We hypothesized that circulating plasma DNA (cpDNA) in advanced cancer patients is largely derived from tumor, has prognostic utility, and can be utilized for multiplex tumor mutation sequencing when repeat biopsy is not feasible. We utilized the Sequenom MassArray System and OncoCarta panel for somatic mutation profiling. Matched samples, acquired from the same patient but at different time points were evaluated; these comprised formalin-fixed paraffin-embedded (FFPE) archival tumor tissue (primary and/or metastatic) and cpDNA. The feasibility, sensitivity, and specificity of this high-throughput, multiplex mutation detection approach was tested utilizing specimens acquired from 105 patients with solid tumors referred for participation in Phase I trials of molecularly targeted drugs. The median cpDNA concentration was 17 ng/ml (range: 0.5-1600); this was 3-fold higher than in healthy volunteers. Moreover, higher cpDNA concentrations associated with worse overall survival; there was an overall survival (OS) hazard ratio of 2.4 (95% CI 1.4, 4.2) for each 10-fold increase in cpDNA concentration and in multivariate analyses, cpDNA concentration, albumin, and performance status remained independent predictors of OS. These data suggest that plasma DNA in these cancer patients is largely derived from tumor. We also observed high detection concordance for critical 'hot-spot' mutations (KRAS, BRAF, PIK3CA) in matched cpDNA and archival tumor tissue, and important differences between archival tumor and cpDNA. This multiplex sequencing assay can be utilized to detect somatic mutations from plasma in advanced cancer patients, when safe repeat tumor biopsy is not feasible and genomic analysis of archival tumor is deemed insufficient. Overall, circulating nucleic acid biomarker studies have clinically important multi-purpose utility in advanced cancer patients and further studies to pursue their incorporation into the standard of care are warranted.

Developing an engineering approach for migrating from prescriptive to performance-based specification for concrete

The integral variability of raw materials, lack of awareness and appreciation of the technologies for achieving quality control and lack of appreciation of the micro and macro environmental conditions that the structures will be subjected, makes modern day concreting a challenge. This also makes Designers and Engineers adhere more closely to prescriptive standards developed for relatively less aggressive environments. The data from exposure sites and real structures prove, categorically, that the prescriptive specifications are inadequate for chloride environments. In light of this shortcoming, a more pragmatic approach would be to adopt performance-based specifications which are familiar to industry in the form of specification for mechanical strength. A recently completed RILEM technical committee made significant advances in making such an approach feasible.
Furthering a performance-based specification requires establishment of reliable laboratory and on-site test methods, as well as easy to perform service-life models. This article highlights both laboratory and on-site test methods for chloride diffusivity/electrical resistivity and the relationship between these tests for a range of concretes. Further, a performance-based approach using an on-site diffusivity test is outlined that can provide an easier to apply/adopt practice for Engineers and asset managers for specifying/testing concrete structures.

Testing the psychometric properties of two self-report clinical competence scales for nursing students.

Background: It is important to assess the clinical competence of nursing students to gauge their educational needs. Competence can be measured by self-assessment tools; however, Anema and McCoy (2010) contend that currently available measures should be further psychometrically tested.
Aim: To test the psychometric properties of Nursing Competencies Questionnaire (NCQ) and Self-Efficacy in Clinical Performance (SECP) clinical competence scales.
Method: A non-randomly selected sample of n=248 2nd year nursing students completed NCQ, SECP and demographic questionnaires (June and September 2013). Mokken Scaling Analysis (MSA) was used to investigate structural validity and scale properties; convergent and discriminant validity and reliability were also tested for each scale.
Results: MSA analysis identified that the NCQ is a unidimensional scale with strong scale scalability coefficients Hs =0.581; but limited item rankability HT =0.367. The SECP scale MSA suggested that the scale could be potentially split into two unidimensional scales (SECP28 and SECP7), each with good/reasonable scalablity psychometric properties as summed scales but negligible/very limited scale rankability (SECP28: Hs = 0.55, HT=0.211; SECP7: Hs = 0.61, HT=0.049). Analysis of between cohort differences and NCQ/SECP scores produced evidence of discriminant and convergent validity; good internal reliability was also found: NCQ α = 0.93, SECP28 α = 0.96 and SECP7 α=0.89.

Discussion: In line with previous research further evidence of the NCQ’s reliability and validity was demonstrated. However, as the SECP findings are new and the sample small with reference to Straat and colleagues (2014), the SECP results should be interpreted with caution and verified on a second sample.
Conclusions: Measurement of perceived self-competence could start early in a nursing programme to support students’ development of clinical competence. Further testing of the SECP scale with larger nursing student samples from different programme years is indicated.

References:
Anema, M., G and McCoy, JK. (2010) Competency-Based Nursing Education: Guide to Achieving Outstanding Learner Outcomes. New York: Springer.
Straat, JH., van der Ark, LA and Sijtsma, K. (2014) Minimum Sample Size Requirements for Mokken Scale Analysis Educational and Psychological Measurement 74 (5), 809-822.