Genome-wide association study identifies two loci strongly affecting transferrin glycosylation.

Polysaccharide sidechains attached to proteins play important roles in cell-cell and receptor-ligand interactions. Variation in the carbohydrate component has been extensively studied for the iron transport protein transferrin, because serum levels of the transferrin isoforms asialotransferrin + disialotransferrin (carbohydrate-deficient transferrin, CDT) are used as biomarkers of excessive alcohol intake. We conducted a genome-wide association study to assess whether genetic factors affect CDT concentration in serum. CDT was measured in three population-based studies: one in Switzerland (CoLaus study, n = 5181) and two in Australia (n = 1509, n = 775). The first cohort was used as the discovery panel and the latter ones served as replication. Genome-wide single-nucleotide polymorphism (SNP) typing data were used to identify loci with significant associations with CDT as a percentage of total transferrin (CDT%). The top three SNPs in the discovery panel (rs2749097 near PGM1 on chromosome 1, and missense polymorphisms rs1049296, rs1799899 in TF on chromosome 3) were successfully replicated , yielding genome-wide significant combined association with CDT% (P = 1.9 × 10(-9), 4 × 10(-39), 5.5 × 10(-43), respectively) and explain 5.8% of the variation in CDT%. These allelic effects are postulated to be caused by variation in availability of glucose-1-phosphate as a precursor of the glycan (PGM1), and variation in transferrin (TF) structure.

Secretory IgA in human serum.

Secretory component (SC) was detected by the radioactive single radial diffusion technique in nearly all sera examined. The SC was shown to be associated with polymeric serum IgA. The mean level of secretory IgA (SIgA) in normal sera from India, Africa and Europe was about 0.03 to 0.04 mg/ml. The mean level was elevated in patients with a variety of disorders involving secretory surfaces (e.g., acute bacterial enterocolitis or respiratory tract carcinoma), but also in disorders with no known involvement of secretory surfaces. The highest levels were seen in lactating women, with a mean level five times higher than that in the general population. SIgA was also found at lower levels in cord serum, serum from breast-fed newborns and serum from children 3 to 10 years old.

Bodily perspective taking goes social: the role of personal, interpersonal, and intercultural factors

Mentally placing the self in the physical position of another person might engage social perspective taking because participants have to match their own position with that of another. We investigated the influence of personal (sex), interpersonal (siblings, parental marital status), and cultural (individualistic, collectivistic) factors on individuals' abilities to mentally take the position of front-facing and back-facing figures in an online study (369 participants). Replicating findings from laboratory studies responses were slower for front-facing than back-facing figures. Having siblings, parents' marital status, and cultural background influenced task performance in theoretically predictable ways. The present perspective-taking task is a promising experimental paradigm to assess social perspective taking and one that is free from the response biases inherent in self-report.

No evidence for a causal link between uric acid and type 2 diabetes: a Mendelian randomisation approach.

AIMS/HYPOTHESIS: Epidemiological and experimental evidence suggests that uric acid has a role in the aetiology of type 2 diabetes. Using a Mendelian randomisation approach, we investigated whether there is evidence for a causal role of serum uric acid for development of type 2 diabetes. METHODS: We examined the associations of serum-uric-acid-raising alleles of eight common variants recently identified in genome-wide association studies and summarised this in a genetic score with type 2 diabetes in case-control studies including 7,504 diabetes patients and 8,560 non-diabetic controls. We compared the observed effect size to that expected based on: (1) the association between the genetic score and uric acid levels in non-diabetic controls; and (2) the meta-analysed uric acid level to diabetes association. RESULTS: The genetic score showed a linear association with uric acid levels, with a difference of 12.2 μmol/l (95% CI 9.3, 15.1) by score tertile. No significant associations were observed between the genetic score and potential confounders. No association was observed between the genetic score and type 2 diabetes with an OR of 0.99 (95% CI 0.94, 1.04) per score tertile, significantly different (p = 0.046) from that expected (1.04 [95% CI 1.03, 1.05]) based on the observed uric acid difference by score tertile and the uric acid to diabetes association of 1.21 (95% CI 1.14, 1.29) per 60 μmol/l. CONCLUSIONS/INTERPRETATION: Our results do not support a causal role of serum uric acid for the development of type 2 diabetes and limit the expectation that uric-acid-lowering drugs will be effective in the prevention of type 2 diabetes.

Performance assessment and league tables. Comparing like with like.

We formulate performance assessment as a problem of causal analysis and outline an approach based on the missing data principle for its solution. It is particularly relevant in the context of so-called league tables for educational, health-care and other public-service institutions. The proposed solution avoids comparisons of institutions that have substantially different clientele (intake).

Performance assessment and league tables. Comparing like with like

We formulate performance assessment as a problem of causal analysis and outline an approach based on the missing data principle for its solution. It is particularly relevant in the context of so-called league tables for educational, health-care and other public-service institutions. The proposed solution avoids comparisons of institutions that have substantially different clientele (intake).

A house price index defined in the potential outcomes framework

Current methods for constructing house price indices are based on comparisons of sale prices of residential properties sold two or more times and on regression of the sale prices on the attributes of the properties and of their locations. The two methods have well recognised deficiencies, selection bias and model assumptions, respectively. We introduce a new method based on propensity score matching. The average house prices for two periods are compared by selecting pairs of properties, one sold in each period, that are as similar on a set of available attributes (covariates) as is feasible to arrange. The uncertainty associated with such matching is addressed by multiple imputation, framing the problem as involving missing values. The method is applied to aregister of transactions ofresidential properties in New Zealand and compared with the established alternatives.

An assessment of empirical Bayes and composite estimators for small areas

We compare a set of empirical Bayes and composite estimators of the population means of the districts (small areas) of a country, and show that the natural modelling strategy of searching for a well fitting empirical Bayes model and using it for estimation of the area-level means can be inefficient.

Small-area estimation with spatial similarity

A class of composite estimators of small area quantities that exploit spatial (distancerelated)similarity is derived. It is based on a distribution-free model for the areas, but theestimators are aimed to have optimal design-based properties. Composition is applied alsoto estimate some of the global parameters on which the small area estimators depend.It is shown that the commonly adopted assumption of random effects is not necessaryfor exploiting the similarity of the districts (borrowing strength across the districts). Themethods are applied in the estimation of the mean household sizes and the proportions ofsingle-member households in the counties (comarcas) of Catalonia. The simplest version ofthe estimators is more efficient than the established alternatives, even though the extentof spatial similarity is quite modest.

Inference with the lognormal distribution

Several estimators of the expectation, median and mode of the lognormal distribution are derived. They aim to be approximately unbiased, efficient, or have a minimax property in the class of estimators we introduce. The small-sample properties of these estimators are assessed by simulations and, when possible, analytically. Some of these estimators of the expectation are far more efficient than the maximum likelihood or the minimum-variance unbiased estimator, even for substantial samplesizes.

Monitoring the university admissions process in Spain

The examinations taken by high-school graduates in Spain and the role ofthe examination in the university admissions process are described. Thefollowing issues arising in the assessment of the process are discussed:reliability of grading, comparability of the grades and scores(equating),maintenance of standards, and compilation and use of the grading process,and their integration in the operational grading are proposed. Variousschemes for score adjustment are reviewed and feasibility of theirimplementation discussed. The advantages of pretesting of items and ofempirical checks of experts' judgements are pointed out. The paperconcludes with an outline of a planned reorganisation of the highereducation in Spain, and with a call for a comprehensive programme ofempirical research concurrent with the operation of the examination andscoring system.

Seeking good peer review in geomorphology

This paper provides an extended guide to reviewing for ESPL in particular and geomorphology in general. After a brief consideration of both how we choose reviewers and why we hope that reviewers will accept, I consider what makes a fair and constructive review. I note that we aim to publish papers with the rigour (r) necessary to sustain an original and significant contribution (q). I note that judging q is increasingly difficult because of the ever-growing size of the discipline (the Q). This is the sense in which we rarely have a full appreciation of Q, and our reviews are inevitably going to contain some bias. It is this bias that cannot be avoided (cf. Nicholas and Gordon, 2011) and makes the job of ESPL's Editors of critical importance. With this in mind, I identify six elements of a good review: (1) an introductory statement that explains your assessment of your competences in relation to the manuscript (r and Q); (2) a summative view of the originality and significance of the manuscript (q) in relation to Q: (3) a summative view of the methodological rigour of the manuscript (r); (4) identification and justification of any major concerns; (5) identification of any minor issues to be corrected if you think the manuscript merits eventual publication; and (6) note of any typographical or presentation issues to be addressed although this latter activity is also an editorial responsibility. In addition, I note the importance of a constructive review, grounded in what is written in the manuscript, justified where appropriate and avoiding reference to personal views as far as is possible. I conclude with a discussion of whether or not you should sign your review openly and the importance of reviewer confidentiality. Copyright (C) 2012 John Wiley & Sons, Ltd.