FGFR2 amplification in colorectal adenocarcinoma

FGFR2 is recurrently amplified in 5% of gastric cancers and 1%–4% of breast cancers; however, this molecular alteration has never been reported in a primary colorectal cancer specimen. Preclinical studies indicate that several FGFR tyrosine-kinase inhibitors (TKIs), such as AZD4547, have in vitro activity against the FGFR2-amplified colorectal cell line, NCI-H716. The efficacy of these inhibitors is currently under investigation in clinical trials for breast and gastric cancer. Thus, better characterizing colorectal tumors for FGFR2 amplification could identify a subset of patients who may benefit from FGFR TKI therapies. Here, we describe a novel FGFR2 amplification identified by clinical next-generation sequencing in a primary colorectal cancer. Further characterization of the tumor by immunohistochemistry showed neuroendocrine differentiation, similar to the reported properties of the NCI-H716 cell line. These findings demonstrate that the spectrum of potentially clinically actionable mutations detected by targeted clinical sequencing panels is not limited to only single-nucleotide polymorphisms and insertions/deletions but also to copy-number alterations.</jats:p

Nematicidal Effects of Carbofuran and GC-MS Analysis of its Residue in Pineapple Fruits

Concerns over the safety of food items from fields treated with nematicides had risen in recent times. In this study, two field experiments arranged in a Randomized Complete Block Design were conducted to assess the efficacy of poultry manure and carbofuran in suppressing nematode population and determine the residual presence of the nematicide in pineapple fruits. Three poultry manure rates (0, 20 and 25 metric tonnes per hectare) and carbofuran treatments (0, 3.0 kg a.i/ha and 3.4 kg a.i/ha) were applied to two naturally infested pineapple fields. Twenty core soil samples per plot were collected from plants rhizosphere at 3, 6, 9, 12, 15 and 18 months after planting. Fifty grams each of chopped pineapple samples from the carbofuran-treated and untreated plots was extracted with 20ml of ethyl acetate solution for fruit analysis to determine the residual presence of carbofuran using Gas Chromatography-Mass Spectrometry (GC-MS). The study indicated that poultry manure and carbofuran significantly (P� 0.05) suppressed nematode population in both locations and promoted crop yield. The GC-MS test showed that carbofuran and its metabolites were not detected in the pineapple fruits, suggesting that carbofuran is not likely to constitute dietary risks to consumers of fruits from treated plots. © 2015 Friends Science Publisher

An integrated approach to modelling the fluid-structure interaction of a collapsible tube

The well known collapsible tube experiment was conducted to obtain flow, pressure and materials property data for steady state conditions. These were then used as the boundary conditions for a fully coupled fluid-structure interaction (FSI) model using a propriety computer code, LS-DYNA. The shape profiles for the tube were also recorded. In order to obtain similar collapse modes to the experiment, it was necessary to model the tube flat, and then inflate it into a circular profile, leaving residual stresses in the walls. The profile shape then agreed well with the experimental ones. Two departures from the physical properties were required to reduce computer time to an acceptable level. One of these was the lowering of the speed of sound by two orders of magnitude which, due to the low velocities involved, still left the mach number below 0.2. The other was to increase the thickness of the tube to prevent the numerical collapse of elements. A compensation for this was made by lowering the Young's modulus for the tube material. Overall the results are qualitatively good. They give an indication of the power of the current FSI algorithms and the need to combine experiment and computer models in order to maximise the information that can be extracted both in terms of quantity and quality

Landscape approaches for ecosystem management in Mediterranean Islands

This book presents a series of essays, drawing on the twm concepts of ecosystem management and landscape approaches, to elucidate and reflect on the present situation and future evolution of Mediterranean islands. This publication brings together contributions from Mediterranean individuals, non-Mediterranean individuals, islanders and non-islanders there is, after all, no geographical limit on who and what we can learn from. The essays presented here each contribute a specific perspective on the future evolution of Mediterranean islands. This book presents a series of essays, drawing on the twin concepts of ecosystem management and landscape approaches, to elucidate and reflect on the present situation and future evolution of Mediterranean islands. This publication brings together contributions from Mediterranean individuals, non-Mediterranean individuals, islanders and non-islanders; there is, after all, no geographical limit on who and what we can learn from. The essays presented here each contribute a specific perspective on the future evolution of Mediterranean islands. Following this introductory chapter, the first section of the book focuses on the contributions that can be made by the discipline of landscape ecology. loannis Vogiatzakis and Geoffrey Griffiths first explain the concepts and relevance of landscape ecology, also presenting and discussing a range of applied tools that can facilitate landscape planning in Mediterranean islands. Louis F. Cassar then reviews the 'offshoot' discipline of restoration ecology, making a strong case for offsetting the environmental damage inflicted on natural ecosystems over millennia of human occupation, with constructive efforts to effectively restore and/or rehabilitate ecosystems. The two following chapters bring the socio-economic dimension into the discussion. Godfrey Baldacchino first presents two contrasting paradigms for the development of island territories, reviewing the dual influences of ecological and economic factors, and exploring ways in which the two can be brought together in successful development strategies. Gordon Cordina and Nadia Farrugia then address the demographic dimension of development, presenting a model to explain the economic costs of high population densities on islands. The third block of chapters expands on the relevance of social and cultural dynamics to the management of Mediterranean Islands. Isil Cakcï, Nur Belkayali and Ilkden Tazebay explain the evolution of the concept of a 'cultural landscape', focusing on the challenges of managing change in landscapes with strong heritage values. The chapter concludes with a case study on the Turkish island of Gökçeada (lmbros), which is experiencing major challenges in balancing the conservation of a cultural landscape on the one hand, and the management of inevitable change, on the other. Elisabeth Conrad then discusses the role of social capital in managing the landscape resources of Mediterranean islands, reviewing the potential for this intangible social fabric to facilitate or impede the sustainable evolution of island territories. The fourth section includes four chapters, each of which addresses a different aspect relevant to policy development and implementation in Mediterranean islands. Salvino Busuttil presents an essay outlining the political influences on the management of coastal landscapes, the latter so relevant to Mediterranean island territories. The essay derives from the author's professional experience in various policy-related institutions for environmental management within the Mediterranean region. Maggie Roe then reflects on issues of landscape sustainability, focusing on the neglected aspect of intelligence. She discusses ways in which landscape research, knowledge and understanding can feed directly into frameworks for 'sustainable' landscape planning. In the subsequent chapter, Adrian Phillips takes from his substantial experience with international landscape policy, reviewing the gradual emergence of international and national landscape 'tools', to draw out lessons for application in Mediterranean islands. In the final chapter of this section, Riccardo Priore and Damiano Galla present a comprehensive discussion of the European Landscape Convention, the first international instrument to focus exclusively on landscape. The authors explain the innovative character of this convention, and discuss its potential implementation in Mediterranean islands. The publication concludes with a series of case studies, highlighting specific constraints, experiences and opportunities in different Mediterranean islands. Theano Terkenli explores the landscapes of tourism in Mediterranean islands - perhaps no other industry has played such a fundamental role in shaping the evolution of Mediterranean landscapes in recent years. The author reviews the theoretical relationship between landscape and tourism across Mediterranean islands, before focusing on the specific case of the Greek Cycladic islands. In the following chapter, Alex Camilleri, Isabella Colombini and Lorenzo Chelazzi present an in-depth review of the context and challenges being faced on a number of minor Mediterranean islands, namely those of the Tuscan archipelago (Elba, Giglio, Capraia, Montecristo, Pianosa, Gorgona and Giannutri), and Comino, the latter forming part of the Maltese archipelago. The comparison between these various islands enables an appreciation of both commonalities across these islands, as well as considerations that are specific to the context of each in dividual island. JeremyBoissevain then adopts an anthropological lens to review the cautionary tale of landscape change in Malta, exploring underlying causes of landscape destruction and limited civil engagement. In the subsequent chapter, Jala Makhzoumi outlines the richness of Mediterranean islands' rural landscapes, focusing on olive landscapes in Cyprus. Her research demonstrates the economic and ecological robustness of various olive cultivation practices, and whilst warning of several threats to such sustainable regimes, she outlines strategies for reconfiguring our approach to rural heritage, in order to integrate such assets into sustainable development strategies. Finally, Stephen Morse concludes the section with an evaluation of sustainable development indicators, and the contribution that these can make towards enhancing the management of Mediterranean island territories. He illustrates his arguments with reference to the two island states of Malta and Cyprus. To conclude, in the final chapter of this publication, we review key insights emerging from the various chapters, and summarize considerations for ecosystem management and sustainable development in Mediterranean Islands. We truly hope that this publication makes some contribution towards safeguarding the "magic' of Mediterranean islands, whilst embracing their dynamic characteristics.Published under the patronage of UNESCO and with the support of the Maltese National Commission for UNESCOpeer-reviewe

Beyond carbon and nitrogen: how the microbial energy economy couples elemental cycles in diverse ecosystems

Microbial metabolism couples elemental reactions, driving biogeochemical cycles. Assimilatory coupling of elemental cycles, such as the carbon (C), nitrogen (N), and phosphorus cycles, occurs when these elements are incorporated into biomass or released through its decomposition. In addition, many microbes are capable of dissimilatory coupling, catalyzing energy-releasing reactions linked to transformations in the oxidation state of elements, and releasing the transformed elements to the environment. Different inorganic elements provide varying amounts of energy yield, and the interaction of these processes creates a microbial energy economy. Dissimilatory reactions involving C, N, iron, and sulfur provide particularly important examples where microbially mediated oxidation–reduction (redox) transformations affect nutrient availability for net primary production, greenhouse-gas emissions, levels of contaminants and natural toxic factors, and other ecosystem dynamics. Recent discoveries of previously unrecognized microbial dissimilatory processes are leading to reevaluation of traditional perceptions of biogeochemical cycles

Cis and Trans Effects of Human Genomic Variants on Gene Expression

This work was funded by the Louis-Jeantet Foundation (http://www.jeantet.ch/), the European Research Council (Grant ID: 260927 http://erc.europa.eu/), the Swiss National Foundation (Grant ID: 130342 http://www.snf.ch), NCCR Frontiers In Genetics (http://www.frontiers-in-genetics.org), the UK Medical Research Council (http://www.mrc.ac.uk) and the Wellcome Trust (Grant ID: 092731).

Garden and landscape-scale correlates of moths of differing conservation status: significant effects of urbanization and habitat diversity

Moths are abundant and ubiquitous in vegetated terrestrial environments and are pollinators, important herbivores of wild plants, and food for birds, bats and rodents. In recent years, many once abundant and widespread species have shown sharp declines that have been cited by some as indicative of a widespread insect biodiversity crisis. Likely causes of these declines include agricultural intensification, light pollution, climate change, and urbanization; however, the real underlying cause(s) is still open to conjecture. We used data collected from the citizen science Garden Moth Scheme (GMS) to explore the spatial association between the abundance of 195 widespread British species of moth, and garden habitat and landscape features, to see if spatial habitat and landscape associations varied for species of differing conservation status. We found that associations with habitat and landscape composition were species-specific, but that there were consistent trends in species richness and total moth abundance. Gardens with more diverse and extensive microhabitats were associated with higher species richness and moth abundance; gardens near to the coast were associated with higher richness and moth abundance; and gardens in more urbanized locations were associated with lower species richness and moth abundance. The same trends were also found for species classified as increasing, declining and vulnerable under IUCN (World Conservation Union) criteria

A point-of-care clinical trial comparing insulin administered using a sliding scale versus a weight-based regimen

Background Clinical trials are widely considered the gold standard in comparative effectiveness research (CER) but the high cost and complexity of traditional trials and concerns about generalizability to broad patient populations and general clinical practice limit their appeal. Unsuccessful implementation of CER results limits the value of even the highest quality trials. Planning for a trial comparing two standard strategies of insulin administration for hospitalized patients led us to develop a new method for a clinical trial designed to be embedded directly into the clinical care setting thereby lowering the cost, increasing the pragmatic nature of the overall trial, strengthening implementation, and creating an integrated environment of research-based care

Complex structural rearrangements are present in high-grade dysplastic Barrett\u27s oesophagus samples

Background: Oesophageal adenocarcinoma (EAC) incidence is increasing and has a poor survival rate. Barrett’s oesophagus (BE) is a precursor condition that is associated with EAC and often occurs in conjunction with chronic gastro-oesophageal reflux, however many individuals diagnosed with BE never progress to cancer. An understanding of the genomic features of BE and EAC may help with the early identification of at-risk individuals. Methods: In this study, we assessed the genomic features of 16 BE samples using whole-genome sequencing. These included non-dysplastic samples collected at two time-points from two BE patients who had not progressed to EAC over several years. Seven other non-dysplastic samples and five dysplastic BE samples with high-grade dysplasia were also examined. We compared the genome profiles of these 16 BE samples with 22 EAC samples. Results: We observed that samples from the two non-progressor individuals had low numbers of somatic single nucleotide variants, indels and structural variation events compared to dysplastic and the remaining non-dysplastic BE. EAC had the highest level of somatic genomic variations. Mutational signature 17, which is common in EAC, was also present in non-dysplastic and dysplastic BE, but was not present in the non-progressors. Many dysplastic samples had mutations in genes previously reported in EAC, whereas only mutations in CDKN2A or in the fragile site genes appeared common in non-dysplastic samples. Rearrangement signatures were used to identify a signature associated with localised complex events such as chromothripsis and breakage fusion-bridge that are characteristic of EACs. Two dysplastic BE samples had a high contribution of this signature and contained evidence of localised rearrangements. Two other dysplastic samples also had regions of localised structural rearrangements. There was no evidence for complex events in non-dysplastic samples. Conclusions: The presence of complex localised rearrangements in dysplastic samples indicates a need for further investigations into the role such events play in the progression from BE to EAC