Distant X-ray Galaxies: Insights from the Local Population

A full understanding of the origin of the hard X-ray background requires a complete and accurate census of the distant galaxies that produce it. Unfortunately, distant X-ray galaxies tend to be very faint at all wavelengths, which hinders efforts to perform this census. This chapter discusses the insights that can be obtained through comparison of the distant population to local X-ray galaxies, whose properties are well characterized. Such comparisons will ultimately aid investigations into the cosmic evolution of supermassive black holes and their environments.Comment: 19 pages, 10 figures, to appear as Chapter 7 in "Supermassive Black Holes in the Distant Universe" (2004), ed. A. J. Barger, Kluwer Academic Publishers, in pres

Ferritins: furnishing proteins with iron

Ferritins are a superfamily of iron oxidation, storage and mineralization proteins found throughout the animal, plant, and microbial kingdoms. The majority of ferritins consist of 24 subunits that individually fold into 4-α-helix bundles and assemble in a highly symmetric manner to form an approximately spherical protein coat around a central cavity into which an iron-containing mineral can be formed. Channels through the coat at inter-subunit contact points facilitate passage of iron ions to and from the central cavity, and intrasubunit catalytic sites, called ferroxidase centers, drive Fe2+ oxidation and O2 reduction. Though the different members of the superfamily share a common structure, there is often little amino acid sequence identity between them. Even where there is a high degree of sequence identity between two ferritins there can be major differences in how the proteins handle iron. In this review we describe some of the important structural features of ferritins and their mineralized iron cores and examine in detail how three selected ferritins oxidise Fe2+ in order to explore the mechanistic variations that exist amongst ferritins. We suggest that the mechanistic differences reflect differing evolutionary pressures on amino acid sequences, and that these differing pressures are a consequence of different primary functions for different ferritins

Bronchoalveolar lavage in infants with recurrent lower respiratory symptoms

Background: Few data are available about the inflammatory cytokine profile of bronchoalveolar lavage (BAL) from young children with frequent wheeze. The first aim was to investigate the BAL cellular and cytokine profiles in infants with recurrent lower respiratory symptoms in whom bronchoscopy was indicated for clinical symptom evaluation. The second aim was to relate the BAL results with the histological findings of the endobronchial carina biopsies. Methods: Thirty-nine infants (median age 0.9 years) underwent lung function testing by whole-body plethysmography prior to the bronchoscopy. The BAL differential cell counts and cytokine levels were quantified. These findings were compared with the histological findings of the endobronchial carina biopsies. Results: The differential cytology reflected mainly that described for healthy infants with lymphocyte counts at the upper range level. A positive association between BAL CD8+ lymphocytes and neutrophils and endobronchial reticular basement membrane was found. Detectable levels of pro-inflammatory cytokine proteins IL-1 beta, IL-17A, IL-18, IL-23, and IL-33 were found, whereas levels of Th2-type cytokine proteins were low. Frequent wheeze was the only clinical characteristic significantly related to detectable combined pro-inflammatory cytokine profile. Lung function did not correlate with any cytokine. Conclusions: A positive association between BAL CD8+ lymphocytes and neutrophils and endobronchial reticular basement thickness was found. Detectable production of pro-inflammatory cytokines associated positively with frequent wheeze.Peer reviewe

Solar fusion cross sections. II. The pp chain and CNO cycles

We summarize and critically evaluate the available data on nuclear fusion cross sections important to energy generation in the Sun and other hydrogen-burning stars and to solar neutrino production. Recommended values and uncertainties are provided for key cross sections, and a recommended spectrum is given for 8B solar neutrinos. We also discuss opportunities for further increasing the precision of key rates, including new facilities, new experimental techniques, and improvements in theory. This review, which summarizes the conclusions of a workshop held at the Institute for Nuclear Theory, Seattle, in January 2009, is intended as a 10-year update and supplement to Reviews of Modern Physics 70 (1998) 1265.Comment: 54 pages, 20 figures, version to be published in Reviews of Modern Physics; various typos corrected and several updates mad

Physicochemical analysis of rotavirus segment 11 supports a 'modified panhandle' structure and not the predicted alternative tRNA-like structure (TRLS)

.Rotaviruses are a major cause of acute gastroenteritis, which is often fatal in infants. The viral genome consists of 11 double-stranded RNA segments, but little is known about their cis-acting sequences and structural elements. Covariation studies and phylogenetic analysis exploring the potential structure of RNA11 of rotaviruses suggested that, besides the previously predicted "modified panhandle" structure, the 5' and 3' termini of one of the isoforms of the bovine rotavirus UKtc strain may interact to form a tRNA-like structure (TRLS). Such TRLSs have been identified in RNAs of plant viruses, where they are important for enhancing replication and packaging. However, using tRNA mimicry assays (in vitro aminoacylation and 3'- adenylation), we found no biochemical evidence for tRNA-like functions of RNA11. Capping, synthetic 3' adenylation and manipulation of divalent cation concentrations did not change this finding. NMR studies on a 5'- and 3'-deletion construct of RNA11 containing the putative intra-strand complementary sequences supported a predominant panhandle structure and did not conform to a cloverleaf fold despite the strong evidence for a predicted structure in this conserved region of the viral RNA. Additional viral or cellular factors may be needed to stabilise it into a form with tRNA-like properties

Building development and roads: implications for the distribution of stone curlews across the Brecks

Background: Substantial new housing and infrastructure development planned within England has the potential to conflict with the nature conservation interests of protected sites. The Breckland area of eastern England (the Brecks) is designated as a Special Protection Area for a number of bird species, including the stone curlew (for which it holds more than 60% of the UK total population). We explore the effect of buildings and roads on the spatial distribution of stone curlew nests across the Brecks in order to inform strategic development plans to avoid adverse effects on such European protected sites. Methodology: Using data across all years (and subsets of years) over the period 1988 – 2006 but restricted to habitat areas of arable land with suitable soils, we assessed nest density in relation to the distances to nearest settlements and to major roads. Measures of the local density of nearby buildings, roads and traffic levels were assessed using normal kernel distance-weighting functions. Quasi-Poisson generalised linear mixed models allowing for spatial auto-correlation were fitted. Results: Significantly lower densities of stone curlew nests were found at distances up to 1500m from settlements, and distances up to 1000m or more from major (trunk) roads. The best fitting models involved optimally distance-weighted variables for the extent of nearby buildings and the trunk road traffic levels. Significance : The results and predictions from this study of past data suggests there is cause for concern that future housing development and associated road infrastructure within the Breckland area could have negative impacts on the nesting stone curlew population. Given the strict legal protection afforded to the SPA the planning and conservation bodies have subsequently agreed precautionary restrictions on building development within the distances identified and used the modelling predictions to agree mitigation measures for proposed trunk road developments

Strategies to reduce sample sizes in Alzheimer’s disease primary and secondary prevention trials using longitudinal amyloid PET imaging

BACKGROUND: Detecting subtle-to-moderate biomarker changes such as those in amyloid PET imaging becomes increasingly relevant in the context of primary and secondary prevention of Alzheimer's disease (AD). This work aimed to determine if and when distribution volume ratio (DVR; derived from dynamic imaging) and regional quantitative values could improve statistical power in AD prevention trials. METHODS: Baseline and annualized % change in [11C]PIB SUVR and DVR were computed for a global (cortical) and regional (early) composite from scans of 237 cognitively unimpaired subjects from the OASIS-3 database ( www.oasis-brains.org ). Bland-Altman and correlation analyses were used to assess the relationship between SUVR and DVR. General linear models and linear mixed effects models were used to determine effects of age, sex, and APOE-ε4 carriership on baseline and longitudinal amyloid burden. Finally, differences in statistical power of SUVR and DVR (cortical or early composite) were assessed considering three anti-amyloid trial scenarios: secondary prevention trials including subjects with (1) intermediate-to-high (Centiloid > 20.1), or (2) intermediate (20.1 < Centiloid ≤ 49.4) amyloid burden, and (3) a primary prevention trial focusing on subjects with low amyloid burden (Centiloid ≤ 20.1). Trial scenarios were set to detect 20% reduction in accumulation rates across the whole population and in APOE-ε4 carriers only. RESULTS: Although highly correlated to DVR (ρ = .96), cortical SUVR overestimated DVR cross-sectionally and in annual % change. In secondary prevention trials, DVR required 143 subjects per arm, compared with 176 for SUVR. Both restricting inclusion to individuals with intermediate amyloid burden levels or to APOE-ε4 carriers alone further reduced sample sizes. For primary prevention, SUVR required less subjects per arm (n = 855) compared with DVR (n = 1508) and the early composite also provided considerable sample size reductions (n = 855 to n = 509 for SUVR, n = 1508 to n = 734 for DVR). CONCLUSION: Sample sizes in AD secondary prevention trials can be reduced by the acquisition of dynamic PET scans and/or by restricting inclusion to subjects with intermediate amyloid burden or to APOE-ε4 carriers only. Using a targeted early composite only leads to reductions of sample size requirements in primary prevention trials. These findings support strategies to enable smaller Proof-of-Concept Phase II clinical trials to better streamline drug development

Strategies to reduce sample sizes in Alzheimer’s disease primary and secondary prevention trials using longitudinal amyloid PET imaging

BACKGROUND: Detecting subtle-to-moderate biomarker changes such as those in amyloid PET imaging becomes increasingly relevant in the context of primary and secondary prevention of Alzheimer's disease (AD). This work aimed to determine if and when distribution volume ratio (DVR; derived from dynamic imaging) and regional quantitative values could improve statistical power in AD prevention trials. METHODS: Baseline and annualized % change in [11C]PIB SUVR and DVR were computed for a global (cortical) and regional (early) composite from scans of 237 cognitively unimpaired subjects from the OASIS-3 database ( www.oasis-brains.org ). Bland-Altman and correlation analyses were used to assess the relationship between SUVR and DVR. General linear models and linear mixed effects models were used to determine effects of age, sex, and APOE-ε4 carriership on baseline and longitudinal amyloid burden. Finally, differences in statistical power of SUVR and DVR (cortical or early composite) were assessed considering three anti-amyloid trial scenarios: secondary prevention trials including subjects with (1) intermediate-to-high (Centiloid > 20.1), or (2) intermediate (20.1 < Centiloid ≤ 49.4) amyloid burden, and (3) a primary prevention trial focusing on subjects with low amyloid burden (Centiloid ≤ 20.1). Trial scenarios were set to detect 20% reduction in accumulation rates across the whole population and in APOE-ε4 carriers only. RESULTS: Although highly correlated to DVR (ρ = .96), cortical SUVR overestimated DVR cross-sectionally and in annual % change. In secondary prevention trials, DVR required 143 subjects per arm, compared with 176 for SUVR. Both restricting inclusion to individuals with intermediate amyloid burden levels or to APOE-ε4 carriers alone further reduced sample sizes. For primary prevention, SUVR required less subjects per arm (n = 855) compared with DVR (n = 1508) and the early composite also provided considerable sample size reductions (n = 855 to n = 509 for SUVR, n = 1508 to n = 734 for DVR). CONCLUSION: Sample sizes in AD secondary prevention trials can be reduced by the acquisition of dynamic PET scans and/or by restricting inclusion to subjects with intermediate amyloid burden or to APOE-ε4 carriers only. Using a targeted early composite only leads to reductions of sample size requirements in primary prevention trials. These findings support strategies to enable smaller Proof-of-Concept Phase II clinical trials to better streamline drug development

A Prospective Study of the Association of Metacognitive Beliefs and Processes with Persistent Emotional Distress After Diagnosis of Cancer

Two hundred and six patients, diagnosed with primary breast or prostate cancer completed self-report questionnaires on two occasions: before treatment (T1) and 12 months later (T2). The questionnaires included: the Hospital Anxiety and Depression Scale; Impact of Events Scale; the Metacognitions Questionnaire-30 (MCQ-30) and the Illness Perceptions Questionnaire-revised. A series of regression analyses indicated that metacognitive beliefs at T1 predicted between 14 and 19 % of the variance in symptoms of anxiety, depression and trauma at T2 after controlling for age and gender. For all three outcomes, the MCQ-30 subscale ‘negative beliefs about worry’ made the largest individual contribution with ‘cognitive confidence’ also contributing in each case. For anxiety, a third metacognitive variable, ‘positive beliefs about worry’ also predicted variance in T2 symptoms. In addition, hierarchical analyses indicated that metacognitive beliefs explained a small but significant amount of variance in T2 anxiety (2 %) and T2 depression (4 %) over and above that explained by demographic variables, T1 symptoms and T1 illness perceptions. The findings suggest that modifying metacognitive beliefs and processes has the potential to alleviate distress associated with cancer

Rural Development Programme measures on cultivated land in Europe to mitigate greenhouse gas emissions – regional ‘hotspots’ and priority measures

© 2016 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.Agriculture is a significant source of GHG emissions, contributing 10% of total emissions within the EU-28. Emissions from European agriculture have been reduced, albeit at the expense of crop yield and the risk of production displacement (the transfer of production, and associated emissions, to land outside of Europe). This article assesses the impact on GHG emissions of selected European Rural Development Program measures, representative of a diversity of management strategies implemented on cultivated land, within nine European Member States. Climatic zone and underlying spatial environmental variables were accounted for using a novel technique, “Regional Variation Categories,” developed with European-scale GIS data sets. Production displacement is assessed with two benchmarks: (1) compared with existing crop production and (2) relative to a “minimum requirement” land management scenario, where an emissions reduction of less than this does not constitute mitigation. Most measures reduce emissions relative to the baseline crop scenario; however, many do not reduce emissions beyond the “minimum requirement,” this being limited to measures such as catch crops and within-field grass areas to prevent soil erosion. The selection and targeting of measures to maximize agricultural GHG mitigation on cultivated land within Europe is discussed...Peer reviewedFinal Published versio