Frequent mutations of KRAS in addition to BRAF in colorectal serrated adenocarcinoma

Aims: To define the occurrence of KRAS and BRAF mutations, microsatellite instability (MSI), and MGMT and hMLH1 methylation and expression in colorectal serrated adenocarcinoma. Methods and results: KRAS codon 12 ⁄ 13 and 59 ⁄ 61 and BRAF V600E mutations, MSI, and MGMT and hMLH1 methylation and expression in 42 serrated adenocarcinomas and 17 serrated adenomas were compared with those in 59 non-serrated colorectal carcinomas (CRCs) and nine adenomas. KRAS and BRAF mutations were observed in 45 % and 33 % of serrated adenocarcinomas and in 27 % and 0 % of nonserrated CRCs (P < 0.001). The KRAS c12G fi A transition was the predominant type of mutation in serrated adenocarcinomas. Forty-two per cent of BRAFmutate

Synthesis and Characterization of Temperature-Sensitive and Chemically Cross-Linked Poly(N-isopropylacrylamide)/Photosensitizer Hydrogels for Applications in Photodynamic Therapy

Copyright © 2018 American Chemical Society. A novel poly(N-isopropylacrylamide) (PNIPAM) hydrogel containing different photosensitizers (protoporphyrin IX (PpIX), pheophorbide a (Pba), and protoporphyrin IX dimethyl ester (PpIX-DME)) has been synthesized with a significant improvement in water solubility and potential for PDT applications compared to the individual photosensitizers (PSs). Conjugation of PpIX, Pba, and PpIX-DME to the poly(N-isopropylacrylamide) chain was achieved using the dispersion polymerization method. This study describes how the use of nanohydrogel structures to deliver a photosensitizer with low water solubility and high aggregation tendencies in polar solvents overcomes these limitations. FT-IR spectroscopy, UV-vis spectroscopy, 1 H NMR, fluorescence spectroscopy, SEM, and DLS analysis were used to characterize the PNIPAM-photosensitizer nanohydrogels. Spectroscopic studies indicate that the PpIX, Pba, and PpIX-DME photosensitizers are covalently conjugated to the polymer chains, which prevents aggregation and thus allows significant singlet oxygen production upon illumination. Likewise, the lower critical solution temperature was raised to ∼44 °C in the new PNIPAM-PS hydrogels. The PNIPAM hydrogels are biocompatible with > 90% cell viability even at high concentrations of the photosensitizer in vitro. Furthermore, a very sharp onset of light-dependent toxicity for the PpIX-based nanohydrogel in the nanomolar range and a more modest, but significant, photocytotoxic response for Pba-PNIPAM and PpIX-DME-PNIPAM nanohydrogels suggest that the new hydrogels have potential for applications in photodynamic therapy

Who speaks for the future of Earth? How critical social science can extend the conversation on the Anthropocene

This paper asks how the social sciences can engage with the idea of the Anthropocene in productive ways. In response to this question we outline an interpretative research agenda that allows critical engagement with the Anthropocene as a socially and culturally bounded object with many possible meanings and political trajectories. In order to facilitate the kind of political mobilization required to meet the complex environmental challenges of our times, we argue that the social sciences should refrain from adjusting to standardized research agendas and templates. A more urgent analytical challenge lies in exposing, challenging and extending the ontological assumptions that inform how we make sense of and respond to a rapidly changing environment. By cultivating environmental research that opens up multiple interpretations of the Anthropocene, the social sciences can help to extend the realm of the possible for environmental politics

An Analysis of Abatement Potential of Greenhouse Gas Emissions in Irish Agriculture 2021-2030

Teagasc SubmissionThis report has been prepared by the Teagasc Working Group on GHG Emissions, which brings together and integrates the extensive and diverse range of organisational expertise on agricultural greenhouse gases. The previous Teagasc GHG MACC was published in 2012 in response to both the EU Climate and Energy Package and related Effort Sharing Decision and in the context of the establishment of the Food Harvest 2020 production targets

Teagasc submission made in response to the Discussion document for the preparation of a National Policy Statement on the Bioeconomy

Teagasc SubmissionThis document is Teagasc’s response to the “Discussion Document for the Preparation of a National Policy Statement on the Bioeconomy” issued by the Department of the Taoiseach’s Economic Division in July 2017. It recognises the potential significance of the bioeconomy to Ireland, offers some policy and strategic insights from other countries, and identifies Teagasc’s role in supporting the development of the bioeconomy in Ireland

SPARC metrics provide mobility smoothness assessment in oldest-old with and without a history of falls : a case control study

Aging-related neuromuscular and neurocognitive decline induces unsmooth movements in daily functional mobility. Here, we used a robust analysis of linear and angular spectral arc length (SPARC) in the single and dual task instrumented timed up-and-go (iTUG) test to compare functional mobility smoothness in fallers and non-fallers aged 85 and older. 64 participants aged 85 and older took part in this case control study. The case group (fallers, n = 32) had experienced falls to the ground in the 6 months prior to the assessment. SPARC analyses were conducted in all phases of the single and dual task iTUGs. We also performed correlation mapping to test the relation of socio-demographic and clinical features on SPARC metrics. The magnitude of between-group differences was calculated using D-Cohen effect size (ES). SPARC was able to distinguish fallers during the single iTUG (ES ≈ 4.18). Turning while walking in the iTUG induced pronounced unsmooth movements in the fallers (SPARC ≈ −13; ES = 3.52) and was associated with the ability to maintain balance in the functional reach task. This information is of importance in the study of functional mobility in the oldest-old and to assess the efficacy of fall-prevention programs

Interferometric Observations of RS Ophiuchi and the Origin of the Near-IR Emission

We report observations of the recurrent nova RS Oph using long-baseline near-IR interferometry. We are able to resolve emission from the nova for several weeks after the February 2006 outburst. The near-IR source initially expands to a size of approximately 5 milli-arcseconds. However, beginning around day 10 the IR source appears to begin to shrink, reaching approximately 2 milli-arcseconds by day 100. We combine our measured angular diameters with previously available interferometric and photometric data to derive an emission measure for the source, and hence are able to determine the mass-loss rate of the nova in the days following the outburst.Comment: 17 pages, 4 figures. Accepted for publication in Ap

Permutation criteria to evaluate multiple clinical endpoints in a proof-of-concept study: lessons from Pre-RELAX-AHF

Clinically relevant endpoints cannot be routinely targeted with reasonable power in a small study. Hence, proof-of-concept studies are often powered to a primary surrogate endpoint. However, in acute heart failure (AHF) effects on surrogates have not translated into clinical benefit in confirmatory studies. Although observing an effect on one of many endpoints due to chance is likely, observing concurrent positive trends across several outcomes by chance is usually unlikely. Pre-RELAX-AHF, which compared 4 relaxin doses with placebo in AHF, has shown favourable trends versus placebo (one-sided P <0.10) on six of nine clinical endpoints in the 30 mu g/kg/day group. To illustrate evaluation of multiple, correlated clinical endpoints for evidence of efficacy and for dose selection, a permutation method was applied retrospectively. By randomly re-assigning the treatment group to the actual data for each of the 229 subjects, 20,000 permutation samples were constructed. The permutation P value for at least six favourable trends among nine endpoints in any dose groups was 0.0073 (99.9% CI 0.0053-0.0093). This is higher than would be expected if the endpoints were uncorrelated (0.00026), but much lower than the probability of observing one of nine comparisons significant at the traditional two-sided P <0.05 (0.74). Thus, the result was unlikely due to correlated endpoints or to chance. Examining consistency of effect across multiple clinical endpoints in a proof-of-concept study may identify efficacious therapies and enable dose selection for confirmatory trials. The merit of the approach described requires confirmation through prospective application in designing future studies