Reliable confidence intervals in quantitative genetics: narrow-sense heritability

Many quantitative genetic statistics are functions of variance components, for which a large number of replicates is needed for precise estimates and reliable measures of uncertainty, on which sound interpretation depends. Moreover, in large experiments the deaths of some individuals can occur, so methods for analysing such data need to be robust to missing values. We show how confidence intervals for narrow-sense heritability can be calculated in a nested full-sib/half-sib breeding design (males crossed with several females) in the presence of missing values. Simulations indicate that the method provides accurate results, and that estimator uncertainty is lowest for sampling designs with many males relative to the number of females per male, and with more females per male than progenies per female. Missing data generally had little influence on estimator accuracy, thus suggesting that the overall number of observations should be increased even if this results in unbalanced data. We also suggest the use of parametrically simulated data for prior investigation of the accuracy of planned experiments. Together with the proposed confidence intervals an informed decision on the optimal sampling design is possible, which allows efficient allocation of resource

Converging seasonal prevalence dynamics in experimental epidemics

Background Regular seasonal changes in prevalence of infectious diseases are often observed in nature, but the mechanisms are rarely understood. Empirical tests aiming at a better understanding of seasonal prevalence patterns are not feasible for most diseases and thus are widely lacking. Here, we set out to study experimentally the seasonal prevalence in an aquatic host-parasite system. The microsporidian parasite Hamiltosporidium tvärminnensis exhibits pronounced seasonality in natural rock pool populations of its host, Daphnia magna with a regular increase of prevalence during summer and a decrease during winter. An earlier study was, however, unable to test if different starting conditions (initial prevalence) influence the dynamics of the disease in the long term. Here, we aim at testing how the starting prevalence affects the regular prevalence changes over a 4-year period in experimental populations.Results In an outdoor experiment, populations were set up to include the extremes of the prevalence spectrum observed in natural populations: 5% initial prevalence mimicking a newly invading parasite, 100% mimicking a rock pool population founded by infected hosts only, and 50% prevalence which is commonly observed in natural populations in spring. The parasite exhibited similar prevalence changes in all treatments, but seasonal patterns in the 100% treatment differed significantly from those in the 5% and 50% treatments. Populations started with 5% and 50% prevalence exhibited strong and regular seasonality already in the first year. In contrast, the amplitude of changes in the 100% treatment was low throughout the experiment demonstrating the long-lasting effect of initial conditions on prevalence dynamics.Conclusions Our study shows that the time needed to approach the seasonal changes in prevalence depends strongly on the initial prevalence. Because individual D. magna populations in this rock pool metapopulation are mostly short lived, only few populations might ever reach a point where the initial conditions are not visible anymore

Quality assessment of a randomly selected sample of Swiss medical expertises : a pilot study

Background: Considerable criticism has lately been raised by the media regarding the quality of Swiss medical expertises. The present investigation was therefore undertaken to assess the professional quality of Swiss medical expertises. The study was part of a market analysis of medical expertises (MGS study). Methods: A sample of 97 anonymised expertises randomly chosen from a total of 3165, collected in the MGS study over a period of 3 months, were evaluated by an international board of medical experts and reviewers, using a stepwise developed questionnaire. Each expertise was independently evaluated by two experts. Data were then tested for plausibility (obvious errors and misunderstandings). The main outcome was the overall quality rating of the expertise that was graded from 1 (very poor) to 6 (excellent) in analogy to the Swiss school grading system. For analysis and interpretation the grades were divided into sufficient (grades >= 4) and insufficient (grades <4). Results: Overall 19.6% (95% confidence interval: 13.1%; 28.3%) of the expertises were rated to be of insufficient quality. The quality was inversely related to the number of involved medical disciplines, the time relapsed since injury and positively related to the difficulty of the expertise. In addition, expertises in the French and Italian languages were rated superior to those in German. Conclusions: Our results confirm recent criticisms that the professional quality of expertises does not suffice. This is hardly acceptable in face of the financial and personal consequences. There is an obvious need for further research using larger samples and for educational programmes on all levels

The Dscam homologue of the crustacean Daphnia is diversified by alternative splicing like in insects

In insects, the homologue of the Down syndrome cell adhesion molecule (Dscam) is a unique case of a single-locus gene whose expression has extensive somatic diversification in both the nervous and immune systems. How this situation evolved is best understood through comparative studies. We describe structural, expression, and evolutionary aspects of a Dscam homolog in 2 species of the crustacean Daphnia. The Dscam of Daphnia generates up to 13,000 different transcripts by the alternative splicing of variable exons. This extends the taxonomic range of a highly diversified Dscam beyond the insects. Additionally, we have identified 4 alternative forms of the cytoplasmic tail that generate isoforms with or without inhibitory or activating immunoreceptor tyrosine-based motifs (ITIM and ITAM respectively), something not previously reported in insect's Dscam. In Daphnia, we detected exon usage variability in both the brain and hemocytes ( the effector cells of immunity), suggesting that Dscam plays a role in the nervous and immune systems of crustaceans, as it does in insects. Phylogenetic analysis shows a high degree of amino acid conservation between Daphnia and insects except in the alternative exons, which diverge greatly between these taxa. Our analysis shows that the variable exons diverged before the split of the 2 Daphnia species and is in agreement with the nearest-neighbor model for the evolution of the alternative exons. The genealogy of the Dscam gene family from vertebrates and invertebrates confirmed that the highly diversified form of the gene evolved from a nondiversified form before the split of insects and crustaceans

Creative Use of Mountain Biodiversity Databases: The Kazbegi Research Agenda of GMBA-DIVERSITAS

Geo-referenced archive databases on mountain organisms are very promising tools for achieving a better understanding of mountain biodiversity and predicting its changes. The Global Mountain Biodiversity Assessment (GMBA) of DIVERSITAS, in cooperation with the Global Biodiversity Information Facility, encourages a global effort to mine biodiversity databases on mountain organisms. The wide range of climatic conditions and topographies across the world's mountains offers an unparalleled opportunity for developing and testing biodiversity theory. The power of openly accessible, interconnected electronic databases for scientific biodiversity research, which by far exceeds the original intent of archiving for mainly taxonomic purposes, has been illustrated. There is an urgent need to increase the amount and quality of geo-referenced data on mountain biodiversity provided online, in order to meet the challenges of global change in mountains

The shape of dark matter haloes: results from weak lensing in the Ultraviolet Near-Infrared Optical Northern Survey (UNIONS)

Cold dark matter haloes are expected to be triaxial, and so appear elliptical in projection. We use weak gravitational lensing from the Canada-France Imaging Survey (CFIS) component of the Ultraviolet-Near Infrared Optical Northern Survey (UNIONS) to measure the ellipticity of the dark matter haloes around Luminous Red Galaxies (LRGs) from the Sloan Digital Sky Survey Data Release 7 (DR7) and from the CMASS and LOWZ samples of the Baryon Oscillation Spectroscopic Survey (BOSS), assuming their major axes are aligned with the stellar light. We find that DR7 LRGs with masses $M \sim 2.5\times10^{13} \textrm{M}_{\odot}/h$ have halo ellipticities $e=0.35\pm0.09$. Expressed as a fraction of the galaxy ellipticity, we find $f_h = 1.4\pm0.4$. For BOSS LRGs, the detection is of marginal significance: $e = 0.17\pm0.10$ and $f_h=0.1\pm0.4$. These results are in agreement with other measurements of halo ellipticity from weak lensing and, taken together with previous results, suggest an increase of halo ellipticity of $0.10\pm0.05$ per decade in halo mass. This trend agrees with the predictions from hydrodynamical simulations, which find that at higher halo masses, not only do dark matter haloes become more elliptical, but that the misalignment between major axis of the stellar light in the central galaxy and that of the dark matter decreases

Clinical and histologic comparison of two different composite grafts for sinus augmentation: a pilot clinical trial

Background and objectives : Sinus augmentation is a procedure used for augmenting insufficient bone height that is often observed in the maxillary posterior areas. Many different techniques as well as bone graft regimens have been suggested for performing this procedure. It was the goal of this study to compare, clinically and histologically, two different composite grafting regimens used for sinus augmentation. Material and methods : Five patients, needing a bilateral sinus augmentation to allow implant placement, were recruited for this study. Right sinuses were grafted with cortical bone (collected from overlying the sinus membrane) and bovine hydroxyapatite (HA), while the left side sinuses were grafted with overlying autologous bone plus a bioglass (BG) material. Bone core biopsies were taken at 6 months after sinus graft or at the time of implant insertion. A waiting period of 6 additional months was granted to allow healing, before prosthetic restoration and functional loading. The level of peri-implant bone was evaluated 12 months after loading. A comparative histomorphometric analysis was conducted and a statistical analysis was performed. Results : All implants in both groups were functional after a 12-month loading period. No bone loss was observed radiographically or clinically in both groups. Histologic analysis revealed that both composite grafts had a high biocompatibility. In the bovine HA-containing group, minimal xenogenic graft absorption was noted. In contrast, BG group samples presented a high absorption rate with some remaining particles imbedded in new normal bone. Conclusions : Sinus augmentation using a combination of autogenous bone plus either bovine HA or BG is a predictable technique. To cite this article: Galindo-Moreno P, Ávila G, FernÁndez-Barbero JE, Mesa F, O'Valle-Ravassa F, Wang H-L. Clinical and histologic comparison of two different composite grafts for sinus augmentation: a pilot clinical trial. Clin. Oral Impl. Res . 19 , 2008; 755–759 doi: 10.1111/j.1600-0501.2008.01536.xPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73800/1/j.1600-0501.2008.01536.x.pd

Spectra of High-Redshift Type Ia Supernovae and a Comparison with their Low-Redshift Counterparts

We present spectra for 14 high-redshift (0.17 < z < 0.83) supernovae, which were discovered by the Supernova Cosmology Project as part of a campaign to measure cosmological parameters. The spectra are used to determine the redshift and classify the supernova type, essential information if the supernovae are to be used for cosmological studies. Redshifts were derived either from the spectrum of the host galaxy or from the spectrum of the supernova itself. We present evidence that these supernovae are of Type Ia by matching to spectra of nearby supernovae. We find that the dates of the spectra relative to maximum light determined from this fitting process are consistent with the dates determined from the photometric light curves, and moreover the spectral time-sequence for SNe Type Ia at low and high redshift is indistinguishable. We also show that the expansion velocities measured from blueshifted CaHK are consistent with those measured for low-redshift Type Ia supernovae. From these first-level quantitative comparisons we find no evidence for evolution in SNIa properties between these low- and high-redshift samples. Thus even though our samples may not be complete, we conclude that there is a population of SNe Ia at high redshift whose spectral properties match those at low redshift.Comment: Accepted for publication in AJ. Also available at http://supernova.lbl.gov

Second Generation of Antisense Oligonucleotides: From Nuclease Resistance to Biological Efficacy in Animals

From efforts to improve the biophysical properties of antisense oligonucleotides by incorporating backbone- or sugar-modified nucleoside analogs, 2'-O-methoxyethyl ribonucleosides 8b were identified as building blocks for a second generation of antisense oligonucleotides. Compounds containing these modifications were demonstrated to combine the benefit of a high binding affinity to the RNA complement with a large increase in nuclease resistance, allowing the use of regular phosphodiester linkages. Chimeric oligonucleotides with 2'-O-methoxyethyl ribonucleosides, 8b, in the wings and a central DNA-phosphorothioate window were shown to efficiently downregulate C-'raf' kinase and PKC-α messenger-RNA in tumor cell lines resulting in a profound inhibition of cell proliferation. The same compounds were able to effectively reduce the growth of tumors in animal models at low concentrations indicating the potential utility of these second generation antisense oligonucleotides for therapeutic applications