Validation of Next Generation Sequencing Technologies in Comparison to Current Diagnostic Gold Standards for BRAF, EGFR and KRAS Mutational Analysis

Next Generation Sequencing (NGS) has the potential of becoming an important tool in clinical diagnosis and therapeutic decision-making in oncology owing to its enhanced sensitivity in DNA mutation detection, fast-turnaround of samples in comparison to current gold standard methods and the potential to sequence a large number of cancer-driving genes at the one time. We aim to test the diagnostic accuracy of current NGS technology in the analysis of mutations that represent current standard-of-care, and its reliability to generate concomitant information on other key genes in human oncogenesis. Thirteen clinical samples (8 lung adenocarcinomas, 3 colon carcinomas and 2 malignant melanomas) already genotyped for EGFR, KRAS and BRAF mutations by current standard-of-care methods (Sanger Sequencing and q-PCR), were analysed for detection of mutations in the same three genes using two NGS platforms and an additional 43 genes with one of these platforms. The results were analysed using closed platform-specific proprietary bioinformatics software as well as open third party applications. Our results indicate that the existing format of the NGS technology performed well in detecting the clinically relevant mutations stated above but may not be reliable for a broader unsupervised analysis of the wider genome in its current design. Our study represents a diagnostically lead validation of the major strengths and weaknesses of this technology before consideration for diagnostic use.

Improving MTM-UAS to predetermine automotive maintenance times

The preventive knowledge of serviceability times is a critical factor for the quantification of after-sales services costs of a vehicle. Predetermined motion time system are frequently used to set labor rates in industry by quantifying the amount of time required to perform specific tasks. The first such system is known as Methods-time measurement (MTM). Several variants of MTM have been developed differing from each other on their level of focus. Among them MTM-UAS is suitable for processes that average around 1-3 min. However experimental tests carried out by the authors in Elasis (Research Center of FIAT Group) demonstrate that MTM-UAS is not the optimal approach to measure serviceability times. The reason is that it doesn't take into account ergonomic factors. In the present paper the authors propose to correct the MTM-UAS method including in the task analysis the study of human postures and efforts. The proposed approach allows to estimate with an "acceptable" error the time needed to perform maintenance tasks since the first phases of product design, by working on Digital Mock-up and human models in virtual environment. As a byproduct of that analysis, it is possible to obtain a list of maintenance times in order to preventively set after-sales service costs. © 2012 Springer-Verlag.

First steps: study protocol for a randomized controlled trial of the effectiveness of the Group Family Nurse Partnership (gFNP) program compared to routine care in improving outcomes for high-risk mothers and their children and preventing abuse

Background: Evidence from the USA suggests that the home-based Family Nurse Partnership program (FNP), extending from early pregnancy until infants are 24 months, can reduce the risk of child abuse and neglect throughout childhood. FNP is now widely available in the UK. A new variant, Group Family Nurse Partnership (gFNP) offers similar content but in a group context and for a shorter time, until infants are 12 months old. Each group comprises 8 to 12 women with similar expected delivery dates and their partners. Its implementation has been established but there is no evidence of its effectiveness.

Methods/Design: The study comprises a multi-site randomized controlled trial designed to identify the benefits of gFNP compared to standard care. Participants (not eligible for FNP) must be either aged <20 years at their last menstrual period (LMP) with one or more previous live births, or aged 20 to 24 at LMP with low educational qualifications and no previous live births. 'Low educational qualifications' is defined as not having both Maths and English Language GCSE at grade C or higher or, if they have both, no more than four in total at grade C or higher. Exclusions are: under 20 years and previously received home-based FNP and, in either age group, severe psychotic mental illness or not able to communicate in English. Consenting women are randomly allocated (minimized by site and maternal age group) when between 10 and 16 weeks pregnant to either to the 44 session gFNP program or to standard care after the collection of baseline information. Researchers are blind to group assignment. The primary outcomes at 12 months are child abuse potential based on the revised Adult-Adolescent Parenting Inventory and parent/infant interaction coded using the CARE Index based on a video-taped interaction. Secondary outcomes are maternal depression, parenting stress, health related quality of life, social support, and use of services.

Discussion: This is the first study of the effectiveness of gFNP in the UK. Results should inform decision-making about its delivery alongside universal services, potentially enabling a wider range of families to benefit from the FNP curriculum and approach to supporting parenting.

Improving the Semantics of Conceptual-Modeling Grammars:A New Perspective on an Old Problem

A core activity in information systems development involves understanding the
conceptual model of the domain that the information system supports. Any conceptual model is ultimately created using a conceptual-modeling (CM) grammar. Accordingly, just as high quality conceptual models facilitate high quality systems development, high quality CM grammars facilitate high quality conceptual modeling. This paper seeks to provide a new perspective on improving the quality of CM grammar semantics. For the past twenty years, the leading approach to this topic has drawn on ontological theory. However, the ontological approach captures just half of the story. It needs to be coupled with a logical approach. We show how ontological quality and logical quality interrelate and we outline three contributions of a logical approach: the ability to see familiar conceptualmodeling problems in simpler ways, the illumination of new problems, and the ability to prove the benefit of modifying CM grammars.

Using mixed-methods to examine teachers’ attitudes to educational change:The case of the Skills for Life strategy for improving adult literacy and numeracy skills in England.

This paper reports on a longitudinal study that examines how a national reform introduced in England in the field of adult literacy, language, and numeracy is affecting teachers. The paper focuses on the use of a mixed methodology to explore teachers' attitudes to the reform and how these change over time. The quantitative strand includes the construction and use of a Likert-type instrument for measuring the attitudes of a panel of 1,500 teachers. The qualitative strand builds on the quantitative results and includes focus groups and in-depth interviews with a subsample of teachers in the panel. As the study is still in its initial phase, the purpose is not to present findings, but to discuss how quantitative and qualitative evidence can be combined in evaluation research.

Supporting group work in Scottish primary classrooms:Improving the quality of collaborative dialogue

A large body of research has demonstrated the value of fostering peer interaction in the context of collaborative group work as an effective strategy to facilitate learning. The present study attempted to enable teachers in a varied sample of 24 Scottish primary classrooms to improve the quality of collaborative group work interaction among their pupils. Observations were carried out at three time points during the year of the intervention, both during whole class teaching and planned group work activity. A global rating instrument was also used to evaluate the overall quality of classroom environment created by participating class teachers to support group work sessions. The results showed significant increases both in the observed frequencies of children's collaborative dialogue and in the rated quality of classroom learning environments over the course of the study. The implications of these results are discussed in the context of current curricular reform.