Genetic Evidence Implicates the Immune System and Cholesterol Metabolism in the Aetiology of Alzheimer's Disease

Background: Late Onset Alzheimer's disease (LOAD) is the leading cause of dementia. Recent large genome-wide association studies (GWAS) identified the first strongly supported LOAD susceptibility genes since the discovery of the involvement of APOE in the early 1990s. We have now exploited these GWAS datasets to uncover key LOAD pathophysiological processes. Methodology: We applied a recently developed tool for mining GWAS data for biologically meaningful information to a LOAD GWAS dataset. The principal findings were then tested in an independent GWAS dataset.

Spatial Mobility Intentions, the Labour Market and Incapacity Benefit Claimants Evidence from Northern Ireland

The paper analyses the work-related spatial mobility intentions of incapacity benefit (IB) claimants in Northern Ireland using a new survey dataset. Greater understanding of the prospective mobility of benefit claimants contributes to debates about employability, inclusion in the labour market and arguments about spatial mismatch. The analysis finds that IB claimants are not markedly less mobile than other population groups; that mobility is shaped by age, level of qualification, illness type, ability to drive and motivation; and that geography is important in several ways. The paper concludes by arguing that limited spatial mobility is a good indicator of disadvantage and that spatial mobility should be placed nearer the centre of the design and delivery of labour market policy

Replication of EPHA1 and CD33 associations with late-onset Alzheimer’s disease: a multi-centre case-control study

A recently published genome-wide association study (GWAS) of late-onset Alzheimer's disease (LOAD) revealed genome-wide significant association of variants in or near MS4A4A, CD2AP, EPHA1 and CD33. Meta-analyses of this and a previously published GWAS revealed significant association at ABCA7 and MS4A, independent evidence for association of CD2AP, CD33 and EPHA1 and an opposing yet significant association of a variant near ARID5B. In this study, we genotyped five variants (in or near CD2AP, EPHA1, ARID5B, and CD33) in a large (2,634 LOAD, 4,201 controls), independent dataset comprising six case-control series from the USA and Europe. We performed meta-analyses of the association of these variants with LOAD and tested for association using logistic regression adjusted by age-at-diagnosis, gender, and APOE e4 dosage.

No Evidence that Extended Tracts of Homozygosity are Associated with Alzheimer’s Disease.

We sought to investigate the contribution of extended runs of homozygosity in a genome-wide association dataset of 1,955 Alzheimer's disease cases and 955 elderly screened controls genotyped for 529,205 autosomal single nucleotide polymorphisms. Tracts of homozygosity may mark regions inherited from a common ancestor and could reflect disease loci if observed more frequently in cases than controls. We found no excess of homozygous tracts in Alzheimer's disease cases compared to controls and no individual run of homozygosity showed association to Alzheimer's disease.

The journey of a ‘green’ micro-enterprise – The Green Planet

This teaching case explores the longitudinal evolution of a small environmental micro-enterprise, The Green Planet retail store. Exploring two decades of business history it analyses the development of this business as sustainability issues and greener consumer goods mainstreamed in society. The case presents one of the first explorations of the individual trade-offs that owners make between economic, environmental and social criteria, alongside an exploration of the role that the personal values of the owner played in the evolution of this business. Also presented is a sample of other environmental enterprises profiled alongside The Green Planet in the early 1990s. This additional dataset provides a rich resource for readers, and a number of indicative discussion themes are identified. Readers interested in topics such as marketing, business strategy, innovation, entrepreneurship, corporate social responsibility and environmental management will find this case a valuable addition to their teaching resources.

Population dynamics of the liver fluke, Fasciola hepatica: the effect of time and spatial separation on the genetic diversity of fluke populations in the Netherlands

An evaluation of the genetic diversity within Fasciola hepatica (liver fluke) may provide an insight into its potential to respond to environmental changes, such as anthelmintic use or climate change. In this study, we determined the mitochondrial DNA haplotypes of >400 flukes from 29 individual cattle, from 2 farms in the Netherlands, as an exemplar of fasciolosis in a European context. Analysis of this dataset has provided us with a measure of the genetic variation within infrapopulations (individual hosts) and the diversity between infrapopulations within a herd of cattle. Temporal sampling from one farm allowed for the measurement of the stability of genetic variation at a single location, whilst the comparison between the two farms provided information on the variation in relation to distance and previous anthelmintic regimes. We showed that the liver fluke population in this region is predominantly linked to 2 distinct clades. Individual infrapopulations contain a leptokurtic distribution of genetically diverse flukes. The haplotypes present on a farm have been shown to change significantly over a relatively short time-period.

Technical Note: Assessing a 24/7 solution for monitoring water quality loads in small river catchments

Quantifying nutrient and sediment loads in catchments is dif?cult owing to diffuse controls related to storm hydrology. Coarse sampling and interpolation methods are prone to very high uncertainties due to under-representation of high discharge, short duration events. Additionally, important low-?ow processes such as diurnal signals linked to point source impacts are missed. Here we demonstrate a solution based on a time-integrated approach to sampling with a standard 24 bottle autosampler con?gured to take a sample every 7 h over a week according to a Plynlimon design. This is evaluated with a number of other sampling strategies using a two-year dataset of sub-hourly discharge and phosphorus concentration data. The 24/7 solution is shown to be among the least uncertain in estimating load (inter-quartile range: 96% to 110% of actual load in year 1 and 97% to 104% in year 2) due to the increased frequency raising the probability of sampling storm events and point source signals. The 24/7 solution would appear to be most parsimonious in terms of data coverage and certainty, process signal representation, potential laboratory commitment, technology requirements and the ability to be widely deployed in complex catchments.

Bioaccessibility of trace elements in soils in Northern Ireland

Assessment of elevated concentrations of potentially toxic elements (PTE) in soils and the association with specific soil parent material have been the focus of research for a number of years. Risk-based assessment of potential exposure scenarios to identified elevated PTE concentrations has led to the derivation of site- and contaminant-specific soil guideline values (SGVs), which represent generic assessment criteria (GACs) to identify exceeded levels that may reflect an unacceptable risk to human health. A better understanding of the ‘bioavailable’ or ‘bioaccessible’ contaminant concentrations offers an opportunity to better refine contaminant exposure assessments. Utilizing a comprehensive soil geochemical dataset for Northern Ireland provided by the Tellus Survey (GSNI) in conjunction with supplementary bioaccessibility testing of selected soil samples following the Unified BARGE Method, this paper uses exploratory data analysis and geostatistical analysis to investigate the spatial variability of pseudo-total and bioaccessible concentrations of As, Cd, Co, Cr. Cu, Ni, Pb, U, V and Zn. The paper investigates variations in individual element concentrations as well as cross-element correlations and observed lithological/pedological associations. The analysis of PTE concentrations highlighted exceeded levels of GAC values for V and Cr and exceeded SGV/GAC values for Cd, Cu, Ni, Pb, and Zn. UBM testing showed that for some soil parent materials associated with elevated PTE concentrations e.g. the Antrim Lava Group with high Ni concentrations, the measured oral bioaccessible fraction was relatively low. For other soil parent materials with relatively moderate PTE concentrations, measured oral bioaccessible fraction was relatively high (e.g. the Gala Sandstone Group of the Southern Uplands-Down Longford Terrain). These findings have implications for regional human health risk assessments for specific PTEs.

Novel Analysis of Oceanic Surface Water Metagenomes Suggests Importance of Polyphosphate Metabolism in Oligotrophic Environments

Polyphosphate is a ubiquitous linear homopolymer of phosphate residues linked by high-energy bonds similar to those found in ATP. It has been associated with many processes including pathogenicity, DNA uptake and multiple stress responses across all domains. Bacteria have also been shown to use polyphosphate as a way to store phosphate when transferred from phosphate-limited to phosphate-rich media - a process exploited in wastewater treatment and other environmental contaminant remediation. Despite this, there has, to date, been little research into the role of polyphosphate in the survival of marine bacterioplankton in oligotrophic environments. The three main proteins involved in polyphosphate metabolism, Ppk1, Ppk2 and Ppx are multi-domain and have differential inter-domain and inter-gene conservation, making unbiased analysis of relative abundance in metagenomic datasets difficult. This paper describes the development of a novel Isofunctional Homolog Annotation Tool (IHAT) to detect homologs of genes with a broad range of conservation without bias of traditional expect-value cutoffs. IHAT analysis of the Global Ocean Sampling (GOS) dataset revealed that genes associated with polyphosphate metabolism are more abundant in environments where available phosphate is limited, suggesting an important role for polyphosphate metabolism in marine oligotrophs.

RNAi Effector Diversity in Nematodes

While RNA interference (RNAi) has been deployed to facilitate gene function studies in diverse helminths, parasitic nematodes appear variably susceptible. To test if this is due to inter-species differences in RNAi effector complements, we performed a primary sequence similarity survey for orthologs of 77 Caenorhabditis elegans RNAi pathway proteins in 13 nematode species for which genomic or transcriptomic datasets were available, with all outputs subjected to domain-structure verification. Our dataset spanned transcriptomes of Ancylostoma caninum and Oesophagostomum dentatum, and genomes of Trichinella spiralis, Ascaris suum, Brugia malayi, Haemonchus contortus, Meloidogyne hapla, Meloidogyne incognita and Pristionchus pacificus, as well as the Caenorhabditis species C. brenneri, C. briggsae, C. japonica and C. remanei, and revealed that: (i) Most of the C. elegans proteins responsible for uptake and spread of exogenously applied double stranded (ds)RNA are absent from parasitic species, including RNAi-competent plant-nematodes; (ii) The Argonautes (AGOs) responsible for gene expression regulation in C. elegans are broadly conserved, unlike those recruited during the induction of RNAi by exogenous dsRNA; (iii) Secondary Argonautes (SAGOs) are poorly conserved, and the nuclear AGO NRDE-3 was not identified in any parasite; (iv) All five Caenorhabditis spp. possess an expanded RNAi effector repertoire relative to the parasitic nematodes, consistent with the propensity for gene loss in nematode parasites; (v) In spite of the quantitative differences in RNAi effector complements across nematode species, all displayed qualitatively similar coverage of functional protein groups. In summary, we could not identify RNAi effector deficiencies that associate with reduced susceptibility in parasitic nematodes. Indeed, similarities in the RNAi effector complements of RNAi refractory and competent nematode parasites support the broad applicability of this research genetic tool in nematodes.

How different are the correlates of onset and continuation of civil wars?

It is very common to analyse the factors associated with the onset and continuation of civil wars entirely separately, as if there were likely to be no similarity between them. This is an overstatement of the theoretical position, which has established only that they may be different (i.e. less than perfectly correlated). The hypothesis that the explanatory variables are the same is not theoretically excludable and is empirically testable, both for individual variables and for combinations of them. Starting from this approach yields a rather different picture of the factors associated with the continuation of civil wars, because the relatively small sample size means that confidence intervals on individual coefficients are wide in this case. It is shown here that country size, mountainous terrain and (in most datasets) ethnic diversity seem significant for the continuation of civil wars, starting from the null hypothesis that variables affect onset and continuation probabilities identically, rather than entirely independently. One variable that affects onset and continuation significantly differently is anocracy, which we find to matter only for onset. Civil war is more likely if it occurred two years previously, as well as one year previously, which indicates that wars are more likely to restart after only one year of peace, and also more likely to stop in their first year. The combined model strengthens the result that ethnic diversity matters (it is consistently significant across datasets, whereas it is not when onset is analysed separately), although in the UCD/PRIO dataset it is significant only for onset. By contrast, if continuation is analysed independently, virtually nothing is significant except a pre-1991 dummy and a dummy for civil war two years previously.

Qualifications, examinations and assessment: views and perspectives of students in the 14–19 phase on policy and practice

This paper brings to the forefront students’ views on one of the most significant aspects of education in the 14-19 phase, specifically the qualifications, examinations and assessment they experience. In this respect the paper foregrounds students as ‘policy actors’, they are significant players in the mediation of national qualification systems rather than just subjects in their implementation. Data from a national dataset of focus groups with 243 students from the 14-19 phase is presented. Key themes are highlighted relating to young people’s experiences of qualifications, examinations and assessment at this stage of education in a context of continuous initiatives and change as well as the impact of students being on the receiving end of qualification reform in situ which can be confusing, unsettling and ultimately detrimental to future success.

Residential consumption of gas and electricity in the U.S.: The role of prices and income

We study the residential demand for electricity and gas, working with nationwide household-level data that cover recent years, namely 1997-2007. Our dataset is a mixed panel/multi-year cross-sections of dwellings/households in the 50 largest metropolitan areas in the United States as of 2008. We estimate static and dynamic models of electricity and gas demand. We find strong household response to energy prices, both in the short and long term. From the static models, we get estimates of the own price elasticity of electricity demand in the -0.860 to -0.667 range, while the own price elasticity of gas demand is -0.693 to -0.566. These results are robust to a variety of checks. Contrary to earlier literature (Metcalf and Hassett, 1999; Reiss and White, 2005), we find no evidence of significantly different elasticities across households with electric and gas heat. The price elasticity of electricity demand declines with income, but the magnitude of this effect is small. These results are in sharp contrast to much of the literature on residential energy consumption in the United States, and with the figures used in current government agency practice. Our results suggest that there might be greater potential for policies which affect energy price than may have been previously appreciated. (C) 2011 Elsevier B.V. All rights reserved.

Small-scale Hα jets in the solar chromosphere

Aims. High temporal and spatial resolution observations from the Rapid Oscillations in the Solar Atmosphere (ROSA) multiwavelength imager on the Dunn Solar Telescope are used to study the velocities of small-scale Hα jets in an emerging solar active region.
Methods. The dataset comprises simultaneous imaging in the Hα core, Ca ii K, and G band, together with photospheric line-of-sight magnetograms. Time-distance techniques are employed to determine projected plane-of-sky velocities.
Results. The Hα images are highly dynamic in nature, with estimated jet velocities as high as 45 km s-1. These jets are one-directional, with their origin seemingly linked to underlying Ca ii K brightenings and G-band magnetic bright points.
Conclusions. It is suggested that the siphon flow model of cool coronal loops is suitable for interpreting our observations. The jets are associated with small-scale explosive events, and may provide a mass outflow from the photosphere to the corona.

How Porosity and Permeability Vary Spatially With Grain Size, Sorting, Cement Volume, and Mineral Dissolution In Fluvial Triassic Sandstones: The Value of Geostatistics and Local Regression

Although it is well known that sandstone porosity and permeability are controlled by a range of parameters such as grain size and sorting, amount, type, and location of diagenetic cements, extent and type of compaction, and the generation of intergranular and intragranular secondary porosity, it is less constrained how these controlling parameters link up in rock volumes (within and between beds) and how they spatially interact to determine porosity and permeability. To address these unknowns, this study examined Triassic fluvial sandstone outcrops from the UK using field logging, probe permeametry of 200 points, and sampling at 100 points on a gridded rock surface. These field observations were supplemented by laser particle-size analysis, thin-section point-count analysis of primary and diagenetic mineralogy, quantitiative XRD mineral analysis, and SEM/EDAX analysis of all 100 samples. These data were analyzed using global regression, variography, kriging, conditional simulation, and geographically weighted regression to examine the spatial relationships between porosity and permeability and their potential controls. The results of bivariate analysis (global regression) of the entire outcrop dataset indicate only a weak correlation between both permeability porosity and their diagenetic and depositional controls and provide very limited information on the role of primary textural structures such as grain size and sorting. Subdividing the dataset further by bedding unit revealed details of more local controls on porosity and permeability. An alternative geostatistical approach combined with a local modelling technique (geographically weighted regression; GWR) subsequently was used to examine the spatial variability of porosity and permeability and their controls. The use of GWR does not require prior knowledge of divisions between bedding units, but the results from GWR broadly concur with results of regression analysis by bedding unit and provide much greater clarity of how porosity and permeability and their controls vary laterally and vertically. The close relationship between depositional lithofacies in each bed, diagenesis, and permeability, porosity demonstrates that each influences the other, and in turn how understanding of reservoir properties is enhanced by integration of paleoenvironmental reconstruction, stratigraphy, mineralogy, and geostatistics.