Assessing the clinical value of targeted massively parallel sequencing in a longitudinal, prospective population-based study of cancer patients

INTRODUCTION: Recent discoveries in cancer research have revealed a plethora of clinically actionable mutations that provide therapeutic, prognostic and predictive benefit to patients. The feasibility of screening mutations as part of the routine clinical care of patients remains relatively unexplored as the demonstration of massively parallel sequencing (MPS) of tumours in the general population is required to assess its value towards the health-care system. METHODS: Cancer 2015 study is a large-scale, prospective, multisite cohort of newly diagnosed cancer patients from Victoria, Australia with 1094 patients recruited. MPS was performed using the Illumina TruSeq Amplicon Cancer Panel. RESULTS: Overall, 854 patients were successfully sequenced for 48 common cancer genes. Accurate determination of clinically relevant mutations was possible including in less characterised cancer types; however, technical limitations including formalin-induced sequencing artefacts were uncovered. Applying strict filtering criteria, clinically relevant mutations were identified in 63% of patients, with 26% of patients displaying a mutation with therapeutic implications. A subset of patients was validated for canonical mutations using the Agena Bioscience MassARRAY system with 100% concordance. Whereas the prevalence of mutations was consistent with other institutionally based series for some tumour streams (breast carcinoma and colorectal adenocarcinoma), others were different (lung adenocarcinoma and head and neck squamous cell carcinoma), which has significant implications for health economic modelling of particular targeted agents. Actionable mutations in tumours not usually thought to harbour such genetic changes were also identified. CONCLUSIONS: Reliable delivery of a diagnostic assay able to screen for a range of actionable mutations in this cohort was achieved, opening unexpected avenues for investigation and treatment of cancer patients

Microscopic Charcoal Signal in Archaeological Contexts

The recovery of archaeological wood charcoals from combustion features provides insights into the exploitation and use of wood fuel resources and past landscapes. The quality of our interpretation based on wood charcoals, however, depends on reliable information about the charcoal assemblages resulting from taphonomy. Charcoal is very fragile in comparison to other combustion residues such as burnt bones. In archaeological contexts, charcoal can easily be fragmented into small pieces (<0.25 mm) due to their fragile property. The investigation of small fragments and particles is particularly important for the interpretation of combustion residues when large pieces of charcoal are rare or apparently absent in archaeological sites, which is mainly true for many European Palaeolithic sites. Here, archaeologists get incomplete information when only the largest pieces and fragments are considered. In this chapter, we present a method for extracting and quantifying charcoal pieces, fragments, and particles. This approach can be considered as a strategy to minimize the impact of sample incompleteness and biases related to combustion residues in archaeological contexts. We further provide (1) a definition of what the charcoal signal means in an archaeological context; (2) an overview of taphonomy that causes charcoal fragmentation; (3) a review of charcoal sampling, extraction, observation and quantification protocols; (4) a manual (pictures and descriptions) for the observation of charcoal, from large pieces to the smallest particles; and (5) a discussion about why the charcoal signal is useful for archaeologists. By taking into account the consequences of taphonomy, the microscopic charcoal analysis in archaeological contexts provides a reliable assessment of firewood and fuel management practices and the related resilience of societies through time. The microscopic charcoal analysis can further offer additional information about the intensity of taphonomical processes and dating

Episode-centered guidelines for teacher belief change toward technology integration

Teachers' episodic memories influence their beliefs. The investigation of episodic memories can help identify the teacher beliefs that limit technology-integration. We propose the Episode-Centered Belief Change (ECBC) model that utilizes teachers' episodic memories for changing beliefs impeding effective technology integration. We also propose guidelines for using ECBC model in professional development to promote teacher belief change for effective technology integration. A preliminary study was conducted to apply the ECBC model in a teacher education course. The findings suggest that the ECBC model was effective in changing teacher beliefs regarding technology integration. Finally, the implications of the ECBC model and guidelines for research and practice are discussed

The ECORS-Truc Vert’08 nearshore field experiment: Presentation of a three-dimensional morphologic system in a macro-tidal environment during consecutive extreme storm conditions

A large multi-institutional nearshore field experiment was conducted at Truc Vert, on the Atlantic coast of France in early 2008. Truc Vert’08 was designed to measure beach change on a long, sandy stretch of coast without engineering works with emphasis on large winter waves (offshore significant wave height up to 8 m), a three-dimensional morphology, and macro-tidal conditions. Nearshore wave transformation, circulation and bathymetric changes involve coupled processes at many spatial and temporal scales thus implying the need to improve our knowledge for the full spectrum of scales to achieve a comprehensive view of the natural system. This experiment is unique when compared with existing experiments because of the simultaneous investigation of processes at different scales, both spatially (from ripples to sand banks) and temporally (from single swash events to several spring-neap tidal cycles, including a major storm event). The purpose of this paper is to provide background information on the experiment by providing detailed presentation of the instrument layout and snapshots of preliminary results.Hydraulic EngineeringCivil Engineering and Geoscience

Timber exploitation during the 5th–3rd millennia BCE at Arslantepe (Malatya, Turkey). Environmental constraints and cultural choices

A considerable amount of charcoal remains from the archaeological site of Arslantepe (Eastern Anatolia) has been analysed. The anthracological assemblage comes from seven archaeological periods, ranging from the Late Chalcolithic 1–2 (mid-5th millennium BCE) to the Early Bronze Age III (late 3rd millennium BCE). The woody taxa exploited by the local communities appeared to have only mi- nor changes throughout the investigated periods. For the eval- uation of wood use practices, charcoal was chronologically grouped according to depositional context. The categories of depositional context identified differentiate between the uses of wood for structural parts of buildings, object manufacture, fuel, refuse, and wood found in outdoor areas or in burial contexts. Communities at Arslantepe, characterized by different cultural and socio-economic traits, appeared overall to select timber de- pending on its use: hydrophilous plants prevail in building mate- rial, with the exception of the 2900–2500 BCE period when environmental constraints probably motivate the dominance of woodland-steppe plants. The differential occurrence of Electronic supplementary material The online version of this article (doi:10.1007/s12520-017-0499-0) contains supplementary material, which is available to authorized users. taxa in the diverse depositional contexts highlighted cases of under/overestimation of remains, in particular in relation to the woods for construction. Finally, taxa have been attributed to different ecological groups. The interpretation of results and the comparison with other available palaeoenvironmental data point out that climatic factors play only a secondary role in the choice of wood exploitation in the area. Human choice may vary even with constant environmental records