Glial and neuronal dysfunction in streptozotocin-induced diabetic rats

Neuronal dysfunction has been noted very soon after the induction of diabetes by streptozotocin injection in rats. It is not clear from anatomical evidence whether glial cell dysfunction accompanies the well-documented neuronal deficit. Here, we isolate the Müller cell driven slow-P3 component of the full-field electroretinogram and show that it is attenuated at 4 weeks following the onset of streptozotocin-hyperglycaemia. We also found a concurrent reduction in the sensitivity of the phototransduction cascade, as well as in the components of the electroretinogram known to indicate retinal ganglion cell and amacrine cell integrity. Our data support the idea that neuronal and Müller cell dysfunction occurs at the same time in streptozotocin-induced hyperglycaemia.

Physical activity, sedentary behaviour and fetal macrosomia in uncomplicated pregnancies: A prospective cohort study

Objective: to explore maternal energy balance, incorporating free living physical activity and sedentary behaviour, in uncomplicated pregnancies at risk of macrosomia.

Methods: a parallel-group cross-sectional analysis was conducted in healthy pregnant women predicted to deliver infants weighing Z4000 g (study group) or o4000 g (control group). Women were recruited in a 1:1 ratio from antenatal clinics in Northern Ireland. Women wore a SenseWears Body Media Pro3 physical activity armband and completed a food diary for four consecutive days in the third trimester. Physical activity was measured in Metabolic Equivalent of Tasks (METs) where 1 MET¼1 kcal per kilogram of body weight per hour. Analysis of covariance (ANCOVA) was employed using the General Linear Model to adjust for potential confounders.

Findings: of the 112 women recruited, 100 complete datasets were available for analysis. There was no significant difference in energy balance between the two groups. Intensity of free living physical activity (average METs) of women predicted to deliver macrosomic infants (n¼50) was significantly lower than that of women in the control group (n¼50) (1.3 (0.2) METs (mean, standard deviation) versus 1.2 (0.2) METs; difference in means 0.1 METs (95% confidence interval: 0.19, 0.01); p¼0.021). Women predicted to deliver macrosomic infants also spent significantly more time in sedentary behaviour (r1 MET) than the control group (16.1 (2.8) hours versus 13.8 (4.3) hours; 2.0 hours (0.3, 3.7), p¼0.020).

Key conclusions and implications for practice: although there was no association between predicted fetal macrosomia and energy balance, those women predicted to deliver a macrosomic infant exhibited increased sedentary behaviour and reduced physical activity in the third trimester of pregnancy. Professionals caring for women during pregnancy have an important role in promoting and supporting more active lifestyles amongst women who are predicted to deliver a macrosomic infant given the known associated risks.

Search for the Return of Activity in Active Asteroid 176P/LINEAR

We present the results of a search for the reactivation of active asteroid 176P/LINEAR during its 2011 perihelion passage using deep optical observations obtained before, during, and after that perihelion passage. Deep composite images of 176P constructed from data obtained between 2011 June and 2011 December show no visible signs of activity, while photometric measurements of the object during this period also show no significant brightness enhancements similar to that observed for 176P between 2005 November and 2005 December when it was previously observed to be active. An azimuthal search for dust emission likewise reveals no evidence for directed emission (i.e., a tail, as was previously observed for 176P), while a one-dimensional surface brightness profile analysis shows no indication of a spherically symmetric coma at any time in 2011. We conclude that 176P did not in fact exhibit activity in 2011, at least not on the level on which it exhibited activity in 2005, and suggest that this could be due to the devolatization or mantling of the active site responsible for its activity in 2005.

A high resolution study of complex organic molecules in hot cores

We present the results of a line identification analysis using data from the IRAM Plateau de Bure Inferferometer, focusing on six massive star-forming hot cores: G31.41+0.31, G29.96-0.02, G19.61-0.23, G10.62-0.38, G24.78+0.08A1 and G24.78+0.08A2. We identify several transitions of vibrationally excited methyl formate (HCOOCH$_3$) for the first time in these objects as well as transitions of other complex molecules, including ethyl cyanide (C$_2$H$_5$CN), and isocyanic acid (HNCO). We also postulate a detection of one transition of glycolaldehyde (CH$_2$(OH)CHO) in two new hot cores. We find G29.96-0.02, G19.61-0.23, G24.78+0.08A1 and 24.78+0.08A2 to be chemically very similar. G31.41+0.31, however, is chemically different: it manifests a larger chemical inventory and has significantly larger column densities. We suggest that it may represent a different evolutionary stage to the other hot cores in the sample, or it may surround a star with a higher mass. We derive column densities for methyl formate in G31.41+0.31, using the rotation diagram method, of $\times$10$^{17}$ cm$^{-2}$ and a T$_{rot}$ of $\sim$170 K. For G29.96-0.02, G24.78+0.08A1 and G24.78+0.08A2, glycolaldehyde, methyl formate and methyl cyanide all seem to trace the same material and peak at roughly the same position towards the dust emission peak. For G31.41+0.31, however, glycolaldehyde shows a different distribution to methyl formate and methyl cyanide and seems to trace the densest, most compact inner part of hot cores.

Distal volcanic ash layers in the Lateglacial Interstadial (GI-1): problems of stratigraphic discrimination

A new Icelandic ash layer has been detected in mid-Interstadial sediments in a number of Scottish Lateglacial sequences and has been named the Penifiler Tephra. It is rhyolitic in composition and possesses a chemistry, which is similar to the Borrobol Tephra of early Lateglacial Interstadial age, which also occurs in a number of these same sequences. Where the Borrobol Tephra has been identified in these sequences it consistently exhibits a diffuse distribution accompanied in some cases by stratigraphic bimodality. A number of sedimentological and taphonomic factors are considered in order to account for this distribution. One possibility is that these distributions are produced by taphonomic factors. Another possibility is that the Borrobol Tephra may not be the product of a single Icelandic eruption, but of two events closely spaced in time. In at least two of the sequences investigated in this study, basaltic shards were found in association with the Penifiler and Borrobol tephras, suggesting either a basaltic phase associated with these eruptions, or coincident eruptions from a separate basaltic volcanic centre. The discovery of the new Penifiler Tephra makes a contribution to the regional tephrostratigraphic framework, and provides an additional isochron for assessing the synchroneity of palaeoenvironmental changes during the Interstadial. The true stratigraphic nature and age of the Borrobol Tephra, however, remains unresolved and, therefore, its use as an isochron is more problematic. The possible occurrence of basaltic populations may strengthen correlations with basaltic tephras recently detected in the NGRIP ice-core.

Electronic voting in the French legislative elections of 2012

This chapter presents an analysis of the unprecedented use of electronic voting by expatriates during the French 2012 legislative elections, when they elected their own representatives (referred to here as ‘deputies’), to the National Assembly in Paris for the first time, in 11 newly created overseas constituencies.
The study is presented within the broader perspective of electronic voting in France more generally, and in the historical context of extra-territorial voting by French expatriates. The authors discuss the main issues and controversies that arose during the 2012 elections, and in a final section analyse the results. The authors conclude by drawing attention to recent developments in electronic voting in France since the 2012 elections, which suggest that although there was much criticism expressed by experts of electronic voting as to the security and transparency of the system used, the official discourse that acclaimed the experience as a success, appears to have convinced its target audience.

Community structure, diversity and spatial organization of enchytraeids in Mediterranean urban holm oak stands

There is a strong northern bias in Europe as regards enchytraeid community ecology, particularly in urban settings. We approached the enchytraeid assemblages of urban holm oak stands in Naples and Siena adopting a high intensity sampling that, for the first time in the Mediterranean climate zone, would ensure that the data collected be representative of the target populations. Structural parameters (diversity and evenness, biomass, size classes, aggregation) were compared across different spatial (regional, urban district, within habitat) and temporal scales (season and year). Species richness was found to change significantly only at regional scale; background data suggest that this may depend on the higher environmental heterogeneity occurring at Naples. Differences in size class structure were significant only on a seasonal scale and within either city separately. With one exception (Fridericia bulbosa s.s.), the patterns of spatial aggregation of the common species were fairly robust and the total range of patchiness was consistent with previous studies, despite the different sampling methodologies. The size of the sampling unit, the number of replicates per plot and the number of plots proposed in this study appear suitable to obviate the difficulties of evaluating Mediterranean enchytraeid communities.

Three Types of Temporal Perspective: Characterizing Developmental Changes in Temporal Thought

This paper provides an outline of the development of temporal thinking that is underpinned by the idea that temporal cognition shifts from being event dependent to event independent over the preschool period. I distinguish between three different ways in which it may be possible to have a perspective on time: (1) a perspective that is grounded in script-like representations of repeated events; (2) a more sophisticated perspective that brings in an fundamental categorical distinction between events that have already happened and events that are yet to come; and (3) a mature temporal perspective that involves orienting oneself in time using a linear temporal framework, with a grasp of the distinctions between past, present, and future. I propose that, with development, children possess each of these types of perspective in turn, and that only the last of these involves being able to represent time in an event-independent way.

Scyphozoan jellyfish provide short-term reproductive habitat for hyperiid amphipods in a temperate near-shore environment

Hyperiid amphipods (Order Amphipoda, Suborder Hyperiidea) are known to infest gelatinous zooplankton. However, the temporal backdrop to these associations is less clear, given that data are often gathered during discrete sampling events rather than over time. In general, hyperiids are considered to be pelagic: however, for individuals associated with metagenic jellyfishes in temperate shallow shelf seas, this may not always be the case, as the majority of their gelatinous hosts are present in the water column from spring to the onset of autumn. Here, we explored the temporal patterns of colonisation and overall duration of the association between Hyperia galba and 3 scyphozoan jellyfish species (Aurelia aurita, Cyanea capillata and C. lamarckii) in a temperate coastal system (Strangford Lough, Northern Ireland) during 2010 and 2012. Concomitantly, we used carbon and nitrogen stable isotope ratios to examine whether hyperiid infestation represented a permanent association with their host or was part of a more complex life history. We found that jellyfish were colonised by H. galba ca. 2 mo after they are first observed in the lough and that H. galba reached 100% prevalence in the different jellyfish species shortly before the medusae of each species disappeared from the water column. It is possible that some jellyfish overwintered in deeper water, prolonging the association between H. galba and their hosts. However, all the medusae sampled during the spring and early summer (whether they were newly emerged or had overwintered from the previous season) were not infected with hyperiids, suggesting that such behaviour was uncommon or that individuals had become dissociated from their host during the winter. Further evidence of temporary association came from stable isotope data, where δ13C and δ15N isotope ratios were indicative of feeding outside of their host prior to jellyfish colonisation. In combination, these findings suggest alternating habitat associations for H. galba, with the amphipods spending the majority of the year outside of the 3 scyphozoan species considered here.

Beyond Financialisation? Transformative Strategies for More Sustainable Financial Markets in the European Union

The global financial crisis has led many regulators and lawmakers to a rethinking about current versus optimum financial market structures and activities that include a variety and even radical ideas about delevaraging and downsizing finance. This paper focuses on the flaws and shortcomings of regulatory reforms of finance and on the necessity of and scope for more radical transformative strategies. With 'crisis economics' back, the most developed countries, including the EU member states, are still on the edge of disaster and confronted with systemic risk. Changes in financial regulation adopted in the aftermath of the financial meltdown have not been radical enough to transform the overall system of finance-driven capitalism towards a more sustainable system with a more embedded finance. The paper discusses financialisation in order to understand the development trends in finance over the past decades and examines various theories to describe the typical trends and patterns in financial regulation. By focusing on a limited number of regulatory reforms in the European Union, the limitations of current reforms and the need for additional transformative strategies necessary to overcome the finance-driven accumulation regime are explored. Finally, the regulatory space for such transformative strategies and for taming finance in times of crisis, austerity, and increased public protest potential is analysed.

Application of Asymmetric Marcus-Hush Theory to Voltammetry in Room-Temperature Ionic Liquids

Asymmetric MarcusHush (AMH) theory is applied for the first time in ionic solvents to model the voltammetric reduction of oxygen in 1-butyl-1-methylpyrrolidinium bis-(trifluoromethylsulfonyl)-imide and of 2-nitrotoluene (2-NT), nitrocyclopentane (NCP), and 1-nitro-butane (BuN) in trihexyltetradecylphosphonium tris(pentafluoroethyl)trifluorophosphate on a gold microdisc electrode. An asymmetry parameter, gamma, was estimated for all systems as -0.4 for the reduction of oxygen and -0.05, 0.25, and 0 +/- 0.05 for the reductions of 2-NT, NCP, and BuN, respectively, which suggests equal force constants of reactants and products in the case of 2-NT and BuN and unequal force constants for oxygen and NCP where the force constants of the oxidized species are greater than the reduced species in the case of oxygen and less than the reduced species in the case of NCP. Previously measured values for a, the Butler-Volmer transfer coefficient, reflect this in each case. Where appreciable asymmetry occurs, AMH theory was seen to parametrize the experimental data better than either Butler-Volmer or symmetric Marcus-Hush theory, allowing additionally the extraction of reorganization energy. This is the first study to provide key physical insights into electrochemical systems in room-temperature ionic liquids using AMH theory, allowing elucidation of the reorganization energies and the relative force constants of the reactants and products in each reaction.

Late-Pleistocene palaeoclimate and glacial activity recorded from lake sediments in the Eastern Alps

Greenland ice core data show that the last glaciation in the Northern Hemisphere was characterized by relatively short and rapid warming-cooling cycles. While the Last Glacial Maximum (LGM) and the following Late Glacial are well documented in the Eastern Alps, continuous and well dated records of the time period preceding the LGM are only known from stalagmites. Although most of the sediment that filled the Alpine valleys prior to the LGM was eroded, thick successions have been locally preserved as terraces along the flanks of large longitudinal valleys. The Inn valley in Tyrol (Austria) offers the most striking examples of Pleistocene terraces in the Eastern Alps. A large number of drill cores provides the opportunity to study these sediments for the first time in great detail. Our study focuses on the river terrace of Unterangerberg near Wörgl, where LGM gravel and till were deposited on top of (glacio)lacustrine sediments. The cores comprise mostly silty material, ranging from organic-rich to organic-poor and dropstone-rich beds. A diamictic layer classified as basal till is present at the bottom of the lake sediments. Radiocarbon ages of plant macro remains from the lake sequences indicate deposition between ~40 and >50 cal. ka BP. Luminescence ages obtained from fine-grain polymineral (4-11 μm) samples suggest an age of the lake deposits between ~40 to 60 ka and are consistent with the radiocarbon dates. Sedimentological analyses indicate that sedimentation in these palaeolakes was driven by local processes, but also by climatically induced changes in nearby glacier activity. These observations strongly hint towards a significant ice advance in the Eastern Alps during the early last glacial and subsequent mild interstadial conditions, supporting a local coniferous forest vegetation.

Towards core outcome set (COS) development: a follow-up descriptive survey of outcomes in Cochrane reviews

BACKGROUND: A core outcome set (COS) can address problems of outcome heterogeneity and outcome reporting bias in trials and systematic reviews, including Cochrane reviews, helping to reduce waste. One of the aims of the international Core Outcome Measures in Effectiveness Trials (COMET) Initiative is to link the development and use of COS with the outcomes specified and reported in Cochrane reviews, including the outcomes listed in the summary of findings (SoF) tables. As part of this work, an earlier exploratory survey of the outcomes of newly published 2007 and 2011 Cochrane reviews was performed. This survey examined the use of COS, the variety of specified outcomes, and outcome reporting in Cochrane reviews by Cochrane Review Group (CRG). To examine changes over time and to explore outcomes that were repeatedly specified over time in Cochrane reviews by CRG, we conducted a follow-up survey of outcomes in 2013 Cochrane reviews.

METHODS: A descriptive survey of outcomes in Cochrane reviews that were first published in 2013. Outcomes specified in the methods sections and reported in the results section of the Cochrane reviews were examined by CRG. We also explored the uptake of SoF tables, the number of outcomes included in these, and the quality of the evidence for the outcomes.

RESULTS: Across the 50 CRGs, 375 Cochrane reviews that included at least one study specified a total of 3142 outcomes. Of these outcomes, 32 % (1008) were not reported in the results section of these reviews. For 23 % (233) of these non-reported outcomes, we did not find any reason in the text of the review for this non-report. Fifty-seven percent (216/375) of reviews included a SoF table.

CONCLUSIONS: The proportion of specified outcomes that were reported in Cochrane reviews had increased in 2013 (68 %) compared to 2007 (61 %) and 2011 (65 %). Importantly, 2013 Cochrane reviews that did not report specified outcomes were twice as likely to provide an explanation for why the outcome was not reported. There has been an increased uptake of SoF tables in Cochrane reviews. Outcomes that were repeatedly specified in Cochrane reviews by CRG in 2007, 2011, and 2013 may assist COS development.

Integration of copy number and transcriptomics provides risk stratification in prostate cancer: A discovery and validation cohort study

BACKGROUND: Understanding the heterogeneous genotypes and phenotypes of prostate cancer is fundamental to improving the way we treat this disease. As yet, there are no validated descriptions of prostate cancer subgroups derived from integrated genomics linked with clinical outcome.

METHODS: In a study of 482 tumour, benign and germline samples from 259 men with primary prostate cancer, we used integrative analysis of copy number alterations (CNA) and array transcriptomics to identify genomic loci that affect expression levels of mRNA in an expression quantitative trait loci (eQTL) approach, to stratify patients into subgroups that we then associated with future clinical behaviour, and compared with either CNA or transcriptomics alone.

FINDINGS: We identified five separate patient subgroups with distinct genomic alterations and expression profiles based on 100 discriminating genes in our separate discovery and validation sets of 125 and 103 men. These subgroups were able to consistently predict biochemical relapse (p = 0.0017 and p = 0.016 respectively) and were further validated in a third cohort with long-term follow-up (p = 0.027). We show the relative contributions of gene expression and copy number data on phenotype, and demonstrate the improved power gained from integrative analyses. We confirm alterations in six genes previously associated with prostate cancer (MAP3K7, MELK, RCBTB2, ELAC2, TPD52, ZBTB4), and also identify 94 genes not previously linked to prostate cancer progression that would not have been detected using either transcript or copy number data alone. We confirm a number of previously published molecular changes associated with high risk disease, including MYC amplification, and NKX3-1, RB1 and PTEN deletions, as well as over-expression of PCA3 and AMACR, and loss of MSMB in tumour tissue. A subset of the 100 genes outperforms established clinical predictors of poor prognosis (PSA, Gleason score), as well as previously published gene signatures (p = 0.0001). We further show how our molecular profiles can be used for the early detection of aggressive cases in a clinical setting, and inform treatment decisions.

INTERPRETATION: For the first time in prostate cancer this study demonstrates the importance of integrated genomic analyses incorporating both benign and tumour tissue data in identifying molecular alterations leading to the generation of robust gene sets that are predictive of clinical outcome in independent patient cohorts.