Fitting ACE Structural Equation Models to Case-Control Family Data

Investigators interested in whether a disease aggregates in families often collect case-control family data, which consist of disease status and covariate information for families selected via case or control probands. Here, we focus on the use of case-control family data to investigate the relative contributions to the disease of additive genetic effects (A), shared family environment (C), and unique environment (E). To this end, we describe a ACE model for binary family data and then introduce an approach to fitting the model to case-control family data. The structural equation model, which has been described previously, combines a general-family extension of the classic ACE twin model with a (possibly covariate-specific) liability-threshold model for binary outcomes. Our likelihood-based approach to fitting involves conditioning on the proband’s disease status, as well as setting prevalence equal to a pre-specified value that can be estimated from the data themselves if necessary. Simulation experiments suggest that our approach to fitting yields approximately unbiased estimates of the A, C, and E variance components, provided that certain commonly-made assumptions hold. These assumptions include: the usual assumptions for the classic ACE and liability-threshold models; assumptions about shared family environment for relative pairs; and assumptions about the case-control family sampling, including single ascertainment. When our approach is used to fit the ACE model to Austrian case-control family data on depression, the resulting estimate of heritability is very similar to those from previous analyses of twin data

Galaxy Distances in the Nearby Universe: Corrections For Peculiar Motions

By correcting the redshift--dependent distances for peculiar motions through a number of peculiar velocity field models, we recover the true distances of a wide, all-sky sample of nearby galaxies (~ 6400 galaxies with velocities cz<5500 km/s), which is complete up to the blue magnitude B=14 mag. Relying on catalogs of galaxy groups, we treat ~2700 objects as members of galaxy groups and the remaining objects as field galaxies. We model the peculiar velocity field using: i) a cluster dipole reconstruction scheme; ii) a multi--attractor model fitted to the Mark II and Mark III catalogs of galaxy peculiar velocities. According to Mark III data the Great Attractor has a smaller influence on local dynamics than previously believed, whereas the Perseus-Pisces and Shapley superclusters acquire a specific dynamical role. Remarkably, the Shapley structure, which is found to account for nearly half the peculiar motion of the Local Group, is placed by Mark III data closer to the zone of avoidance with respect to its optical position. Our multi--attractor model based on Mark III data favors a cosmological density parameter Omega ~ 0.5 (irrespective of a biasing factor of order unity). Differences among distance estimates are less pronounced in the ~ 2000 - 4000 km/s distance range than at larger or smaller distances. In the last regions these differences have a serious impact on the 3D maps of the galaxy distribution and on the local galaxy density --- on small scales.Comment: 24 pages including (9 eps figures and 7 tables). Figures 1,2,3,4 are available only upon request. Accepted by Ap

The PREDICTS database: a global database of how local terrestrial biodiversity responds to human impacts

Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species’ threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project – and avert – future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups – including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems – www.predicts.org.uk).We make site-level summary data available alongside this article. The full database will be publicly available in 2015

Estimating the Prevalence of Disease Using Relatives of Case and Control Probands

We introduce a method for estimating the prevalence of disease using data from a case-control family study performed to investigate the aggregation of disease in families. The families are sampled via case and control probands, and the resulting data consist of information on disease status and covariates for the probands and their relatives. We introduce estimators for overall prevalence and for covariate stratum-specific prevalence (e.g., sex-specific prevalence) that yield approximately unbiased estimates of their population counterparts. We also introduce corresponding confidence intervals that have good coverage properties even for small prevalences. The estimators and intervals address the over-representation of diseased individuals in case-control family data by using only the relatives (of the probands) and by taking into account whether each relative was selected via a case or a control proband. Finally, we describe a simulation experiment in which the estimators and intervals were applied to case-control family datasets sampled from a fictional population that resembled the catchment area for an Austrian family study of major depressive disorder. The resulting estimates varied closely and symmetrically around their population counterparts, and the resulting intervals had good coverage properties

Franck-Condon Factors and Radiative Lifetime of the A^{2}\Pi_{1/2} - X^{2}\Sigma^{+} Transition of Ytterbium Monoflouride, YbF

The fluorescence spectrum resulting from laser excitation of the A^{2}\Pi_{1/2} - X^{2}\Sigma^{+} (0,0) band of ytterbium monofluoride, YbF, has been recorded and analyzed to determine the Franck-Condon factors. The measured values are compared with those predicted from Rydberg-Klein-Rees (RKR) potential energy curves. From the fluorescence decay curve the radiative lifetime of the A^{2}\Pi_{1/2} state is measured to be 28\pm2 ns, and the corresponding transition dipole moment is 4.39\pm0.16 D. The implications for laser cooling YbF are discussed.Comment: 5 pages, 5 figure

Redshift-distance Survey of Early-type Galaxies: The D_n-sigma Relation

In this paper R-band photometric and velocity dispersion measurements for a sample of 452 elliptical and S0 galaxies in 28 clusters are used to construct a template D_n-sigma relation. This template relation is constructed by combining the data from the 28 clusters, under the assumption that galaxies in different clusters have similar properties. The photometric and spectroscopic data used consist of new as well as published measurements, converted to a common system, as presented in a accompanying paper. The resulting direct relation, corrected for incompleteness bias, is log{D_n} =1.203 log{sigma} + 1.406; the zero-point has been defined by requiring distant clusters to be at rest relative to the CMB. This zero-point is consistent with the value obtained by using the distance to Virgo as determined by the Cepheid period-luminosity relation. This new D_n-sigma relation leads to a peculiar velocity of -72 (\pm 189) km/s for the Coma cluster. The scatter in the distance relation corresponds to a distance error of about 20%, comparable to the values obtained for the Fundamental Plane relation. Correlations between the scatter and residuals of the D_n-sigma relation with other parameters that characterize the cluster and/or the galaxy stellar population are also analyzed. The direct and inverse relations presented here have been used in recent studies of the peculiar velocity field mapped by the ENEAR all-sky sample.Comment: 46 pages, 20 figures, and 7 tables. To appear in AJ, vol. 123, no. 5, May 200

Can oral infection be a risk factor for Alzheimer’s disease?

Alzheimer’s disease (AD) is a scourge of longevity that will drain enormous resources from public health budgets in the future. Currently, there is no diagnostic biomarker and/or treatment for this most common form of dementia in humans. AD can be of early familial-onset or sporadic with a late-onset. Apart from the two main hallmarks, amyloid-beta and neurofibrillary tangles, inflammation is a characteristic feature of AD neuropathology. Inflammation may be caused by a local central nervous system insult and/or by peripheral infections. Numerous microorganisms are suspected in AD brains ranging from bacteria (mainly oral and non-oral Treponema species), viruses (Herpes simplex type I) and yeasts (Candida species). A causal relationship between periodontal pathogens/non-oral Treponema species of bacteria has been proposed via the amyloid-beta and inflammatory links. Periodontitis constitutes a peripheral oral infection that can provide the brain with intact bacteria and virulence factors and inflammatory mediators due to daily, transient bacteraemias. If and when genetic risk factors meet environmental risk factors in the brain, disease is expressed, in which neurocognition may be impacted, leading to the development of dementia. To achieve the goal of finding a diagnostic biomarker and possible prophylactic treatment for AD, there is an initial need to solve the etiological puzzle contributing to its pathogenesis. This review therefore addresses oral infection as the plausible aetiology of late onset AD (LOAD)

Controlled single electron transfer between Si:P dots

We demonstrate electrical control of Si:P double dots in which the potential is defined by nanoscale phosphorus doped regions. Each dot contains approximately 600 phosphorus atoms and has a diameter close to 30 nm. On application of a differential bias across the dots, electron transfer is observed, using single electron transistors in both dc- and rf-mode as charge detectors. With the possibility to scale the dots down to few and even single atoms these results open the way to a new class of precision-doped quantum dots in silicon.Comment: 3 figures, 3 page

Measurement of the electron's electric dipole moment using YbF molecules: methods and data analysis

We recently reported a new measurement of the electron's electric dipole moment using YbF molecules [Nature 473, 493 (2011)]. Here, we give a more detailed description of the methods used to make this measurement, along with a fuller analysis of the data. We show how our methods isolate the electric dipole moment from imperfections in the experiment that might mimic it. We describe the systematic errors that we discovered, and the small corrections that we made to account for these. By making a set of additional measurements with greatly exaggerated experimental imperfections, we find upper bounds on possible uncorrected systematic errors which we use to determine the systematic uncertainty in the measurement. We also calculate the size of some systematic effects that have been important in previous electric dipole moment measurements, such as the motional magnetic field effect and the geometric phase, and show them to be negligibly small in the present experiment. Our result is consistent with an electric dipole moment of zero, so we provide upper bounds to its size at various confidence levels. Finally, we review the prospects for future improvements in the precision of the experiment.Comment: 35 pages, 15 figure