A road map for efficient and reliable human genome epidemiology

Networks of investigators have begun sharing best practices, tools and methods for analysis of associations between genetic variation and common diseases. A Network of Investigator Networks has been set up to drive the process, sponsored by the Human Genome Epidemiology Network. A workshop is planned to develop consensus guidelines for reporting results of genetic association studies. Published literature databases will be integrated, and unpublished data, including 'negative' studies, will be captured by online journals and through investigator networks. Systematic reviews will be expanded to include more meta-analyses of individual-level data and prospective meta-analyses. Field synopses will offer regularly updated overviews.     

Assessing time series models for forecasting international migration: Lessons from the United Kingdom

Migration is one of the most unpredictable demographic processes. The aim of this article is to provide a blueprint for assessing various possible forecasting approaches in order to help safeguard producers and users of official migration statistics against misguided forecasts. To achieve that, we first evaluate the various existing approaches to modelling and forecasting of international migration flows. Subsequently, we present an empirical comparison of ex post performance of various forecasting methods, applied to international migration to and from the United Kingdom. The overarching goal is to assess the uncertainty of forecasts produced by using different forecasting methods, both in terms of their errors (biases) and calibration of uncertainty. The empirical assessment, comparing the results of various forecasting models against past migration estimates, confirms the intuition about weak predictability of migration, but also highlights varying levels of forecast errors for different migration streams. There is no single forecasting approach that would be well suited for different flows. We therefore recommend adopting a tailored approach to forecasts, and applying a risk management framework to their results, taking into account the levels of uncertainty of the individual flows, as well as the differences in their potential societal impact.     

Zoogeography of Great Basin butterflies: patterns of distribution and differentiation

The butterflies of the Great Basin exhibit general patterns of distribution and speciation similar to those found for other taxa, particularly birds. Two major centers of infraspecific differentiation and coinciding distribution limits of taxa are identified, each with three subregions. Great Basin butterflies are characterized by pallidity and substantial endemism below the species level.     

Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease

We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis identified 13 loci newly associated with CAD at P < 5 × 10?? and confirmed the association of 10 of 12 previously reported CAD loci. The 13 new loci showed risk allele frequencies ranging from 0.13 to 0.91 and were associated with a 6% to 17% increase in the risk of CAD per allele. Notably, only three of the new loci showed significant association with traditional CAD risk factors and the majority lie in gene regions not previously implicated in the pathogenesis of CAD. Finally, five of the new CAD risk loci appear to have pleiotropic effects, showing strong association with various other human diseases or traits.     

On “the application of science to science itself:” chemistry,instruments, and the scientific labor process

The “Instrumental Revolution” in chemistry refers to a transitional period in the mid-20th century during which sophisticated instrumentation based on physical principles was introduced to solve chemical problems. Historical and philosophical reflection on whether the revolution was a scientific one has been dominated by general models of scientific revolution, in particular, those proposed by Thomas Kuhn, I. B. Cohen and Ian Hacking. In this article I propose that the Industrial Revolution is a useful model for understanding the transformation wrought by the increasingly important role of machines in chemical research. Drawing on Marx's analysis of that event, I argue that that the Instrumental Revolution bears a striking resemblance to the industrial one. I offer grounds for thinking that the resemblance is not fortuitous, but rather reflects a general pattern of development involving the mechanization of the labor process. It is suggested that the cognitive consequences of radical changes in the means of production, as exemplified in the Instrumental Revolution, warrant the consideration of whether the latter is an instance of a kind of revolution in science rather than a singular episode.     

Lung cancer susceptibility locus at 5p15.33

We carried out a genome-wide association study of lung cancer (3,259 cases and 4,159 controls), followed by replication in 2,899 cases and 5,573 controls. Two uncorrelated disease markers at 5p15.33, rs402710 and rs2736100 were detected by the genome-wide data (P = 2 x 10(-7) and P = 4 x 10(-6)) and replicated by the independent study series (P = 7 x 10(-5) and P = 0.016). The susceptibility region contains two genes, TERT and CLPTM1L, suggesting that one or both may have a role in lung cancer etiology.     

Anomalous properties in ferroelectrics induced by atomic ordering.

Complex insulating perovskite alloys are of considerable technological interest because of their large dielectric and piezoelectric responses. Examples of such alloys include (Ba1-xSrx)TiO3, which has emerged as a leading candidate dielectric material for the memory-cell capacitors in dynamic random access memories; and Pb(Zr1-xTix)O3 (PZT), which is widely used in transducers and actuators. The rich variety of structural phases that these alloys can exhibit, and the challenge of relating their anomalous properties to the microscopic structure, make them attractive from a fundamental point of view. Theoretical investigations of modifications to the atomic ordering of these alloys suggest the existence of further unexpected structural properties and hold promise for the development of new functional materials with improved electromechanical properties. Here we report ab initio calculations that show that a certain class of atomic rearrangement should lead simultaneously to large electromechanical responses and to unusual structural phases in a given class of perovskite alloys. Our simulations also reveal the microscopic mechanism responsible for these anomalies.     

An experiment to evaluate methods for estimating fossil fuel resources

Estimates of petroleum and natural gas resources vary substantially, both over time and across estimation methods. This paper develops a simulation model of global oil resources to evaluate different resource estimation techniques. Protocols for the Hubbert life cycle and USGS geological analogy methods are developed and applied to synthetic data generated by the model. It is shown that the Hubbert method can generate an accurate estimate as early as twenty years before the peak of global production, but the geological analogy approach overestimates the true resource base over the life cycle of the resource. The results show the applicability of simulation and the synthetic data approach to the problem of evaluating forecasting methods.     

Length of the year in pre-epicyclic planetary theory

An estimate is made of the length of the year implied in the pre-epicyclic planetary theory of the Pañcasiddhntik. It is shown that this could be the same as the year-length of the corresponding Babylonian theory.