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.

Devolution in Northern Ireland/Ulster/the North/Six counties: Delete as appropriate

The aim of the Agreement and devolution in Northern Ireland is to draw together atavistic political groups in order to promote a consociational accord which upholds minority rights and cultural demands. However, it is important to understand that disagreements between the pro-British and pro-Irish populations remain and that devolution has a multiplicity of political and cultural meanings. Indeed, determining the incapacity of Northern Irish society to shift towards pluralist and less culturally subjective categorizations of belonging and political devotion remains crucially importance. This article argues that devolution is a first, although as yet unclear, step toward a range of future constitutional changes.

Absorbing new knowledge in small and medium-sized enterprises: A multiple case analysis of Six Sigma

The primary aim of this article is to critically analyse the development of Six Sigma theory and practice within small and medium-sized enterprises (SMEs) using a multiple case study approach. The article also explores the subsequent development of Lean Six Sigma as a means of addressing the perceived limitations of the efficacy of Six Sigma in this context. The overarching theoretical framework is that of absorptive capacity, where Six Sigma is conceptualized as new knowledge to be absorbed by smaller firms. The findings from a multiple case study involving repeat interviews and focus groups informed the development of an analytical model demonstrating the dynamic underlying routines for the absorptive capacity process and the development of a number of summative propositions relating the characteristics of SMEs to Six Sigma and Lean Six Sigma implementation.

Hubble Space Telescope imaging of the progenitor sites of six nearby core-collapse supernovae

The search for the progenitors of six core-collapse supernovae (CCSNe) in archival Hubble Space Telescope (HST) WFPC2 pre-explosion imaging is presented. These SNe are 1999an, 1999br, 1999ev, 2000ds, 2000ew and 2001B. Post-explosion imaging of the SNe, with the HST ACS/WFC, has been utilized with the technique of differential astrometry to identify the progenitor locations on the pre-explosion imaging. SNe 1999br, 1999ev, 2000ew and 2001B are recovered in late-time imaging, and estimates of the progenitor locations on the pre-explosion imaging, with subpixel accuracy, have been made. Only the progenitor of the Type II-P SN 1999ev has been recovered, on pre-explosion F555W imaging, at a 4.8 sigma significance level. Assuming a red supergiant progenitor, the pre-explosion observation is consistent with M-ZAMS = 15-18 M-circle dot. The progenitors of the other five SNe were below the 3 sigma detection threshold of the pre-explosion observations. The detection thresholds were translated to mass limits for the progenitors by comparison with stellar evolution models. Pre-explosion observations of the peculiarly faint SN 1999br limit the mass of a red supergiant progenitor to M-ZAMS

Time-averaged velocity and turbulence intensity at the initial downstream flow from a six-bladed propeller

The current study investigated the time-averaged velocity and turbulence intensity at the initial downstream flow from a six-bladed ship propeller. The six-bladed propeller provided the rapid periodical pulses of thrust in one revolution due to the blades leading to a complex downstream jet. The six-bladed propeller is popular as a boat racing propeller, but the presentation of its flow structure was rarely found in the previous studies. In this study, the experiments were carried out in a water tank to measure the time-averaged velocity and turbulence intensity by using a Laser Doppler Anemometry (LDA) system. The jet was produced by rotating the propeller at a constant speed powered by an electric motor. The maximum tangential and radial velocities of the six-bladed propeller were of 76% and 17% of the maximum axial velocity respectively. The study found that the six-bladed propeller has a lower tangential velocity, but a higher radial velocity with its own diffusing mechanism when comparing to the three-bladed propeller.

"The End" for piano and computer. Performed by Shiau-uen Ding. Composer's Voice Concert Series: 15 Minutes of Fame. Jan Hus Church, NYC. General information State: Published Organisations: School of Creative Arts, Sonic Arts, UOA35 - Music, Drama, Dance and Performing Arts Authors: Lyon, E.

Performed by Shiau-uen Ding. Composer's Voice Concert Series: 15 Minutes of Fame. Jan Hus Church, NYC.

Development of a five-plex flow cytometric immunoassay for the simultaneous detection of six coccidiostats in feed and eggs

Coccidiostats are the only veterinary drugs still permitted to be used as feed additives to treat poultry for coccidiosis. To protect consumers, maximum levels for their presence in food and feed have been set by the European Union (EU). To monitor these coccidiostats, a rapid and inexpensive screening method would be a useful tool. The development of such a screening method, using a flow cytometry-based immunoassay, is described. The assay uses five sets of colour-coded paramagnetic microspheres for the detection of six selected priority coccidiostats. Different coccidiostats, with and without carrier proteins, were covalently coupled onto different bead sets and tested in combination with polyclonal antisera and with a fluorescent-labelled secondary antibody. The five optimal combinations were selected for this multiplex and a simple-to-use sample extraction method was applied for screening blank and spiked eggs and feed samples. A very good correlation (r ranging from 0.995 to 0.999) was obtained with the responses obtained in two different flow cytometers (Luminex 100 and FLEXMAP 3D). The sensitivities obtained were in accordance with the levels set by the EU as the measured limits of detection for narasin/salinomycin, lasalocid, diclazuril, nicarbazin (4,4'-dinitrocarbanilide) and monensin in eggs were 0.01, 0.1, 0.5, 53 and 0.1 µg/kg and in feed 0.1, 0.2, 0.3, 9 and 1.5 µg/kg, respectively.

Estimates of peer effects in adolescent smoking across twenty six European countries

Although it is widely believed that one of the key factors influencing whether an adolescent smokes or not is the smoking behaviour of his or her peers, empirical evidence on the magnitude of such peer effects, and even on their existence, is mixed. This existing evidence comes from a range of studies using a variety of country-specific data sources and a variety of identification strategies. This paper exploits a rich source of individual level, school-based, survey data on adolescent substance use across countries - the 2007 European Schools Survey Project on Alcohol and Other Drugs - to provide estimates of peer effects between classmates in adolescent smoking for 75,000 individuals across 26 European countries, using the same methods in each case. The results suggest statistically significant peer effects in almost all cases. These peer effects estimates are large: on average across countries, the probability that a 'typical' adolescent smokes increases by between.31 and.38 percentage points for a one percentage point increase in the proportion of classmates that smoke. Further, estimated peer effects in adolescent smoking are stronger intra-gender than inter-gender. They also vary across countries: in Belgium, for example, a one percentage point increase in reference group smoking is associated with a.16 to.27 percentage point increase in own smoking probability; in the Netherlands the corresponding increase is between.42 and.59 percentage points. © 2011 Elsevier Ltd.

Characterization of the six glycosyltransferases involved in the biosynthesis of Yersinia enterocolitica serotype O:3 lipopolysaccharide outer core

Yersinia enterocolitica (Ye) is a gram-negative bacterium; Ye serotype O:3 expresses lipopolysaccharide (LPS) with a hexasaccharide branch known as the outer core (OC). The OC is important for the resistance of the bacterium to cationic antimicrobial peptides and also functions as a receptor for bacteriophage phiR1-37 and enterocoliticin. The biosynthesis of the OC hexasaccharide is directed by the OC gene cluster that contains nine genes (wzx, wbcKLMNOPQ, and gne). In this study, we inactivated the six OC genes predicted to encode glycosyltransferases (GTase) one by one by nonpolar mutations to assign functions to their gene products. The mutants expressed no OC or truncated OC oligosaccharides of different lengths. The truncated OC oligosaccharides revealed that the minimum structural requirements for the interactions of OC with bacteriophage phiR1-37, enterocoliticin, and OC-specific monoclonal antibody 2B5 were different. Furthermore, using chemical and structural analyses of the mutant LPSs, we could assign specific functions to all six GTases and also revealed the exact order in which the transferases build the hexasaccharide. Comparative modeling of the catalytic sites of glucosyltransferases WbcK and WbcL followed by site-directed mutagenesis allowed us to identify Asp-182 and Glu-181, respectively, as catalytic base residues of these two GTases. In general, conclusive evidence for specific GTase functions have been rare due to difficulties in accessibility of the appropriate donors and acceptors; however, in this work we were able to utilize the structural analysis of LPS to get direct experimental evidence for five different GTase specificities.

Stage at diagnosis and colorectal cancer survival in six high-income countries:A population-based study of patients diagnosed during 2000-2007

Background. Large international differences in colorectal cancer survival exist, even between countries with similar healthcare. We investigate the extent to which stage at diagnosis explains these differences. Methods. Data from population-based cancer registries in Australia, Canada, Denmark, Norway, Sweden and the UK were analysed for 313 852 patients diagnosed with colon or rectal cancer during 2000-2007. We compared the distributions of stage at diagnosis. We estimated both stage-specific net survival and the excess hazard of death up to three years after diagnosis, using flexible parametric models on the log-cumulative excess hazard scale. Results. International differences in colon and rectal cancer stage distributions were wide: Denmark showed a distribution skewed towards later-stage disease, while Australia, Norway and the UK showed high proportions of 'regional' disease. One-year colon cancer survival was 67% in the UK and ranged between 71% (Denmark) and 80% (Australia and Sweden) elsewhere. For rectal cancer, one-year survival was also low in the UK (75%), compared to 79% in Denmark and 82-84% elsewhere. International survival differences were also evident for each stage of disease, with the UK showing consistently lowest survival at one and three years. Conclusion. Differences in stage at diagnosis partly explain international differences in colorectal cancer survival, with a more adverse stage distribution contributing to comparatively low survival in Denmark. Differences in stage distribution could arise because of differences in diagnostic delay and awareness of symptoms, or in the thoroughness of staging procedures. Nevertheless, survival differences also exist for each stage of disease, suggesting unequal access to optimal treatment, particularly in the UK. © 2013 Informa Healthcare.

Encouraging children to think counterfactually enhances blocking in a causal learning task

According to a higher order reasoning account, inferential reasoning processes underpin the widely observed cue competition effect of blocking in causal learning. The inference required for blocking has been described as modus tollens (if p then q, not q therefore not p). Young children are known to have difficulties with this type of inference, but research with adults suggests that this inference is easier if participants think counterfactually. In this study, 100 children (51 five-year-olds and 49 six- to seven-year-olds) were assigned to two types of pretraining groups. The counterfactual group observed demonstrations of cues paired with outcomes and answered questions about what the outcome would have been if the causal status of cues had been different, whereas the factual group answered factual questions about the same demonstrations. Children then completed a causal learning task. Counterfactual pretraining enhanced levels of blocking as well as modus tollens reasoning but only for the younger children. These findings provide new evidence for an important role for inferential reasoning in causal learning.