Power, sample size and sampling costs for clustered data

The data collected in epidemiological or clinical studies are frequently clustered. In such settings, appropriate variance adjustments must be made in order to estimate the sufficient sample size correctly. This paper works through the sample size calculations for clustered data. Importantly, our explicit variance expressions also enable us to optimize the design with respect to the number of clusters and number of subjects; the objective could be either to maximize the power or to minimize the costs with given costs on the clusters and on the individuals. In our approach, units on different levels and treatment groups can have different costs, but the members of the same cluster are assumed to belong to the same treatment group. Design considerations in the health coaching project TERVA are used as motivating examples. R-functions for carrying out the computations presented are provided. (C) 2011 Elsevier B.V. All rights reserved

Reducing DNA Polymerase in the Absence of Drosophila ATR Leads to P53-Dependent Apoptosis and Developmental Defects

The ability to respond to DNA damage and incomplete replication ensures proper duplication and stability of the genome. Two checkpoint kinases, ATM and ATR, are required for DNA damage and replication checkpoint responses. In Drosophila, the ATR ortholog (MEI-41) is essential for preventing entry into mitosis in the presence of DNA damage. In the absence of MEI-41, heterozygosity for the E(mus304) mutation causes rough eyes. We found that E(mus304) is a mutation in DNApol-α180, which encodes the catalytic subunit of DNA polymerase α. We did not find any defects resulting from reducing Polα by itself. However, reducing Polα in the absence of MEI-41 resulted in elevated P53-dependent apoptosis, rough eyes, and increased genomic instability. Reducing Polα in mutants that lack downstream components of the DNA damage checkpoint (DmChk1 and DmChk2) results in the same defects. Furthermore, reducing levels of mitotic cyclins rescues both phenotypes. We suggest that reducing Polα slows replication, imposing an essential requirement for the MEI-41-dependent checkpoint for maintenance of genome stability, cell survival, and proper development. This work demonstrates a critical contribution of the checkpoint function of MEI-41 in responding to endogenous damage

Precise U-Pb zircon ages and geochemistry of Jurassic granites, Ellsworth-Whitmore terrane, central Antarctica

The Ellsworth-Whitmore Mountain terrane of central Antarctica was part of the early Paleozoic amalgamation of Gondwana, including a 13,000 m section of Cambrian–Permian sediments in the Ellsworth Mountains deposited on Grenville-age crust. The Jurassic breakup of Gondwana involved a regional, bimodal magmatic event during which the Ellsworth-Whitmore terrane was intruded by intraplate granites before translation of the terrane to its present location in central Antarctica. Five widely separated granitic plutons in the Ellsworth-Whitmore terrane were analyzed for their whole-rock geochemistry (X-ray fluorescence), Sr, Nd, and Pb isotopic compositions, and U-Pb zircon ages to investigate the origins of the terrane magmas and their relationships to mafic magmatism of the 183 Ma Karoo-Ferrar large igneous province (LIP). We report high-precision (±0.1 m.y.) isotope dilution–thermal ionization mass spectrometry (ID-TIMS) U-Pb zircon ages from granitic rocks from the Whitmore Mountains (208.0 Ma), Nash Hills (177.4–177.3 Ma), Linck Nunatak (175.3 Ma), Pagano Nunatak (174.8 Ma), and the Pirrit Hills (174.3–173.9 Ma), and U-Pb sensitive high-resolution ion microprobe (SHRIMP) ages from the Whitmore Mountains (200 ± 5 Ma), Linck Nunatak (180 ± 4 Ma), Pagano Nunatak (174 ± 4 Ma), and the Pirrit Hills (168 ± 4 Ma). We then compared these results with existing K-Ar ages and Nd model ages, and used initial Sr, Nd, and Pb isotope ratios, combined with xenocrystic zircon U-Pb inheritance, to infer characteristics of the source(s) of the parent magmas. We conclude that the Jurassic plutons were not derived exclusively from crustal melts, but rather they are hybridized magmas composed of convecting mantle, subcontinental lithospheric mantle, and lower continental crustal contributions. The mantle contributions to the granites share isotopic similarities to the sources of other Jurassic LIP mafic magmas, including radiogenic 87Sr/86Sr (0.706–0.708), unradiogenic 143Nd/144Nd (εNd < –5), and Pb isotopes consistent with a low-µ source (where μ = 238U/204Pb). Isotopes and zircon xenocrysts point toward a crustal end member of predominantly Proterozoic provenance (0.5–1.0 Ga; Grenville crust), extending the trends illustrated by Ferrar mafic intrusive rocks, but contrasting with the inferred Archean crustal and/or lithospheric mantle contributions to some basalts of the Karoo sector of the LIP. The Ellsworth-Whitmore terrane granites are the result of mafic rocks underplating the hydrous crust, causing crustal melting, hybridization, and fractionation to produce granitic magmas that were eventually emplaced as post-Ferrar, within-plate melts at higher crustal levels as the Ellsworth-Whitmore terrane rifted off Gondwana (47°S) before migrating to its current position (82°S) in central Antarctica

Travel Characteristics and Yellow Fever Vaccine Usage Among US Global TravEpiNet Travelers Visiting Countries with Risk of Yellow Fever Virus Transmission, 2009–2011

Yellow fever (YF) vaccine-associated serious adverse events and changing YF epidemiology have challenged healthcare providers to vaccinate only travelers whose risk of YF during travel is greater than their risk of adverse events. We describe the travel characteristics and YF vaccine use among US travelers visiting Global TravEpiNet clinics from January of 2009 to March of 2011. Of 16,660 travelers, 5,588 (34%) had itineraries to areas with risk of YF virus transmission. Of those travelers visiting one country with YF risk (N = 4,517), 71% were vaccinated at the visit, and 20% were presumed to be immune from prior vaccination. However, travelers visiting friends and relatives (odds ratio [OR] = 2.57, 95% confidence interval [95% CI] = 1.27–5.22) or going to Nigeria (OR = 3.01, 95% CI = 1.37–6.62) were significantly more likely to decline vaccination. To optimize YF vaccine use, clinicians should discuss an individual's risk–benefit assessment of vaccination and close knowledge gaps regarding vaccine use among at-risk populations

Lead immobilization in thermally remediated soils and igneous rocks

This is the final report for a three-year, Laboratory-Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). The principal goal of this project was to investigate the speciation of lead in the environment at LANL and to determine the feasibility of using thermal remediation methods to immobilize lead in the environment. Lead occurs as pyromorphite [Pb(PO{sub 4}){sub 3}(Cl, OH)], cerussite (PbCO{sub 3}) and galena (PbS) in vapor-phase-altered Bandelier Tuff samples. LANL soils primarily contain cerussite and PbO. Thermal remediation experiments at high temperatures (up to 400 C) suggest that thermal immobilization of highly-reactive Pb compounds in the environment may be feasible, but that this technique is not optimal for more refractory lead phases such as cerussite and PbO

3-He in the Milky Way Interstellar Medium: Ionization Structure

The cosmic abundance of the 3-He isotope has important implications for many fields of astrophysics. We are using the 8.665 GHz hyperfine transition of 3-He+ to determine the 3-He/H abundance in Milky Way HII regions and planetary nebulae. This is one in a series of papers in which we discuss issues involved in deriving accurate 3-He/H abundance ratios from the available measurements. Here we describe the ionization correction we use to convert the 3-He+/H+ abundance, y3+, to the 3-He/H abundance, y3. In principle the nebular ionization structure can significantly influence the y3 derived for individual sources. We find that in general there is insufficient information available to make a detailed ionization correction. Here we make a simple correction and assess its validity. The correction is based on radio recombination line measurements of H+ and 4-He+, together with simple core-halo source models. We use these models to establish criteria that allow us to identify sources that can be accurately corrected for ionization and those that cannot. We argue that this effect cannot be very large for most of the sources in our observational sample. For a wide range of models of nebular ionization structure we find that the ionization correction factor varies from 1 to 1.8. Although large corrections are possible, there would have to be a conspiracy between the density and ionization structure for us to underestimate the ionization correction by a substantial amount.Comment: 36 pages, 4 figures To appear Astrophysical Journal, 20 August 2007, vol 665, no

Loss of p53 in quaking viable mice leads to Purkinje cell defects and reduced survival

The qkv mutation is a one megabase deletion resulting in abnormal expression of the qkI gene. qkv mice exhibit hypomyelination of the central nervous system and display rapid tremors and seizures as adults. The qkI locus on 6q26-27 has also been implicated as a candidate tumor suppressor gene as the qkI locus maps to a region of genetic instability in Glioblastoma Multiforme (GBM), an aggressive brain tumor of astrocytic lineage. As GBM frequently harbors mutations affecting p53, we crossbred qkv and p53 mutant mice to examine whether qkv mice on a p53−/− background have an increased incidence of GBM. qkv/v; p53−/− mice had a reduced survival rate compared to p53−/− littermates, and the cause of death of the majority of the mice remains unknown. In addition, immunohistochemistry revealed Purkinje cell degeneration in the cerebellum. These results suggest that p53 and qkI are genetically linked for neuronal maintenance and survival

The QKI-6 RNA Binding Protein Regulates Actin-interacting Protein-1 mRNA Stability during Oligodendrocyte Differentiation

We identify new mRNA targets for the QKI-6 RNA binding proteins using an unbiased approach. We show that AIP-1 mRNA is bound by QKI-6 within its 3′-UTR. This regulation is observed in oligodendrocytes and it is essential for oligodendrocyte process outgrowth

Individuals with Le(a+b−) Blood Group Have Increased Susceptibility to Symptomatic Vibrio cholerae O1 Infection

Cholera remains a severe diarrheal disease, capable of causing extensive outbreaks and high mortality. Blood group is one of the genetic factors determining predisposition to disease, including infectious diseases. Expression of different Lewis or ABO blood group types has been shown to be associated with risk of different enteric infections. For example, individuals of blood group O have a higher risk of severe illness due to V. cholerae compared to those with non-blood group O antigens. In this study, we have determined the relationship of the Lewis blood group antigen phenotypes with the risk of symptomatic cholera as well as the severity of disease and immune responses following infection. We show that individuals expressing the Le(a+b−) phenotype were more susceptible to symptomatic cholera, while Le(a–b+) expressing individuals were less susceptible. Individuals with the Le(a–b−) blood group had a longer duration of diarrhea when infected, required more intravenous fluid replacement, and had lower plasma IgA antibody responses to V. cholerae LPS on day 7 following infection. We conclude that there is an association between the Lewis blood group and the risk of cholera, and that this risk may affect the outcome of infection as well as possibly the efficacy of vaccination

Caenorhabditis elegans RSD-2 and RSD-6 promote germ cell immortality by maintaining small interfering RNA populations

Here, we establish a role for small RNAs in promoting transgenerational fertility via an endogenous temperature-sensitive silencing process that is promoted by the RNAi spreading defective (RSD)-2 and RSD-6 proteins, which have been implicated in RNA interference in response to exogenous double-stranded RNA triggers. This process could be broadly relevant to transgenerational maintenance of heterochromatin and is plausibly relevant to regulation of aging of somatic cells as they proliferate