Molecular pathology - The value of an integrative approach

Molecular Pathology (MP) is at the heart of modern diagnostics and translational research, but the controversy on how MP is best developed has not abated. The lack of a proper model or trained pathologists to support the diagnostic and research missions makes MP a rare commodity overall. Here we analyse the scientific and technology areas, in research and diagnostics, which are encompassed by MP of solid tumours; we highlight the broad overlap of technologies and analytical capabilities in tissue research and diagnostics; and we describe an integrated model that rationalizes technical know-how and pathology talent for both. The model is based on a single, accredited laboratory providing a single standard of high-quality for biomarker discovery, biomarker validation and molecular diagnostics.

Digital pathology and image analysis in tissue biomarker research

Digital pathology and the adoption of image analysis have grown rapidly in the last few years. This is largely due to the implementation of whole slide scanning, advances in software and computer processing capacity and the increasing importance of tissue-based research for biomarker discovery and stratified medicine. This review sets out the key application areas for digital pathology and image analysis, with a particular focus on research and biomarker discovery. A variety of image analysis applications are reviewed including nuclear morphometry and tissue architecture analysis, but with emphasis on immunohistochemistry and fluorescence analysis of tissue biomarkers. Digital pathology and image analysis have important roles across the drug/companion diagnostic development pipeline including biobanking, molecular pathology, tissue microarray analysis, molecular profiling of tissue and these important developments are reviewed. Underpinning all of these important developments is the need for high quality tissue samples and the impact of pre-analytical variables on tissue research is discussed. This requirement is combined with practical advice on setting up and running a digital pathology laboratory. Finally, we discuss the need to integrate digital image analysis data with epidemiological, clinical and genomic data in order to fully understand the relationship between genotype and phenotype and to drive discovery and the delivery of personalized medicine.

Neuromusculature of Macrogyrodactylus congolensis, a monogenean skin parasite of the Nile catfish Clarias gariepinus

Phalloidin fluorescence technique, enzyme cytochemistry and immunocytochemistry, in conjunction with confocal scanning laser microscopy, were used to describe the neuromusculature of the monogenean skin parasite Macrogyrodactylus congolensis from the Nile catfish Clarias gariepinus. The body wall muscles are composed of an outer layer of compactly arranged circular fibres, an intermediate layer of paired longitudinal fibres and an inner layer of well-spaced bands of diagonal fibres arranged in two crossed directions. The central nervous system consists of paired cerebral ganglia from which three pairs of longitudinal ventral, lateral and dorsal nerve cords arise. The nerve cords are connected at intervals by many transverse connectives. Both central and peripheral nervous systems are bilaterally symmetrical and better developed ventrally than laterally and dorsally. Structural and functional correlates of the neuromusculature of the pharynx, haptor and reproductive tracts were examined. Results implicate acetylcholine, FMRFamide-related peptides and serotonin in sensory and motor function. The results were compared with those of Macrogyrodactylus clarii, a gill parasite of the same host fish C. gariepinus.

Secular trends in reported portion size of food and beverages consumed by Irish adults

The present analysis aimed to investigate the changes in the reported portion sizes (PS) of foods and beverages commonly consumed by Irish adults (18-64 years) from the North South Ireland Food Consumption Survey (NSIFCS) (1997-2001) and the National Adult Nutrition Survey (NANS) (2008-10). Food PS, which are defined as the weight of food (g) consumed per eating occasion, were calculated for comparable foods and beverages in two nationally representative cross-sectional Irish food consumption surveys and were published in NSIFCS and NANS. Repeated measure mixed model analysis compared reported food PS at the total population level as well as subdivided by sex, age, BMI and social class. A total of thirteen commonly consumed foods were examined. The analysis demonstrated that PS significantly increased for five foods ('white sliced bread', 'brown/wholemeal breads', 'all meat, cooked', 'poultry, roasted' and 'milk'), significantly decreased for three ('potatoes', 'chips/wedges' and 'ham, sliced') and did not significantly change for five foods ('processed potato products', 'bacon/ham', 'cheese', 'yogurt' and 'butter/spreads') between the NSIFCS and the NANS. The present study demonstrates that there was considerable variation in the trends in reported food PS over this period.

Distal tephrochronology in volcanic regions: Challenges and insights from Kamchatkan lake sediments

Kamchatka is one of the world’s most active volcanic regions and has hosted many explosive eruptions during the Holocene. These eruptions had the potential to disperse tephra over wide areas, forming time-synchronous markers wherever those tephras are found. Recent research in Kamchatka has begun to focus on the geochemical analysis of individual glass shards in order to characterise tephra layers. We have applied this approach to the study of visible tephras from three lakes – one in central and two in northern Kamchatka – with the aim of identifying key tephras and potential issues in the application of distal (>100 km from an active volcano) tephra in volcanically complex regions. In total, 23 tephras from 22 tephra beds have been geochemically analysed, representing products from at least four volcanic systems in Kamchatka. We demonstrate that distal lake sediments in the region can yield reliable tephrostratigraphies, capturing tephra from eruptions that have the greatest potential to disperse volcanic ash beyond the region. We draw attention to issues relating to correlating and distinguishing key marker horizons from the highly active Shiveluch Volcano, namely the need to ensure inter-lab comparability of geochemical data and good chronological control of the proximal and distal tephras. Importantly, we have also extended the known distribution of two key tephra isochrons from the Ksudach volcano. Our work contributes valuable glass geochemical on data several key marker beds that will facilitate future tephra and palaeoenvironmental research within and beyond Kamchatka.

PICan: An integromics framework for dynamic cancer biomarker discovery

Modern cancer research on prognostic and predictive biomarkers demands the integration of established and emerging high-throughput technologies. However, these data are meaningless unless carefully integrated with patient clinical outcome and epidemiological information. Integrated datasets hold the key to discovering new biomarkers and therapeutic targets in cancer. We have developed a novel approach and set of methods for integrating and interrogating phenomic, genomic and clinical data sets to facilitate cancer biomarker discovery and patient stratification. Applied to a known paradigm, the biological and clinical relevance of TP53, PICan was able to recapitulate the known biomarker status and prognostic significance at a DNA, RNA and protein levels.

Exceptionally Long Distance Transport of Volcanic Ash: Implications for Stratigraphy, Hazards and the Sourcing of Distal Tephra Deposits

Cryptotephras (tephra not visible to the naked eye) form the foundation of the tephrostratigraphic frameworks used in Europe to date and correlate widely distributed geologic, paleoenvironmental and archaeological records. Pyne-O'Donnell et al. (2012) established the potential for developing a similar crypto-tephrostratigraphy across eastern North America by identifying multiple tephra, including the White River Ash (east; WRAe), St. Helens We and East Lake, in a peat core located in Newfoundland. Following on from this work, several ongoing projects have examined additional peat cores from Michigan, New York State, Maine, Nova Scotia and Newfoundland to build a tephrostratigraphic framework for this region. Using the precedent set by recent research by Jensen et al.(in press) that correlated the Alaskan WRAe to the European cryptotephra AD860B, unknown tephras identified in this work were not necessarily assumed to be from "expected" source areas (e.g. the Cascades). Here we present several examples of the preservation of tephra layers with an intercontinental distribution (i.e. WRAe and Ksudach 1), from relatively small magnitude events (i.e. St. Helens layer T, Mono Crater), and the first example of a Mexican ash in the NE (Volcan Ceboruco, Jala pumice). There are several implications of the identification of these units. These far-travelled ashes: (1) highlight the need to consider "ultra" distal source volcanoes for unknown cryptotephra deposits,. (2) present an opportunity for physical volcanologists to examine why some eruptions have an exceptional distribution of ash that is not necessarily controlled by the magnitude of the event. (3) complicate the idea of using tephrostratigraphic frameworks to understand the frequency of eruptions towards aiding hazard planning and prediction (e.g. Swindles et al., 2011). (4) show that there is a real potential to link tropical and mid to high-latitude paleoenvironmental records. Jensen et al. (in press) Transatlantic correlation of the Alaskan White River Ash. Geology. Pyne-O'Donnell et al. (2012). High-precision ultra-distal Holocene tephrochronology in North America. Quaternary Science Reviews, 52, 6-11. Swindles et al. (2011). A 7000 yr perspective on volcanic ash clouds affecting northern Europe. Geology, 39, 887-890.