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Registry-based trials have emerged as a potentially cost-saving study methodology. Early estimates of cost savings, however, conflated the benefits associated with registry utilisation and those associated with other aspects of pragmatic trial designs, which might not all be as broadly applicable. In this study, we sought to build a practical tool that investigators could use across disciplines to estimate the ranges of potential cost differences associated with implementing registry-based trials versus standard clinical trials.
We built simulation Markov models to compare unique costs associated with data acquisition, cleaning, and linkage under a registry-based trial design versus a standard clinical trial. We conducted one-way, two-way, and probabilistic sensitivity analyses, varying study characteristics over broad ranges, to determine thresholds at which investigators might optimally select each trial design.
Registry-based trials were more cost effective than standard clinical trials 98.6% of the time. Data-related cost savings ranged from $4300 to $600,000 with variation in study characteristics. Cost differences were most reactive to the number of patients in a study, the number of data elements per patient available in a registry, and the speed with which research coordinators could manually abstract data. Registry incorporation resulted in cost savings when as few as 3768 independent data elements were available and when manual data abstraction took as little as 3.4 seconds per data field.
Registries offer important resources for investigators. When available, their broad incorporation may help the scientific community reduce the costs of clinical investigation. We offer here a practical tool for investigators to assess potential costs savings.
Terrestrial gastropods are problematical for radiocarbon (14C) measurement because they tend to incorporate carbon from ancient sources as a result of their dietary behavior. The 14C ecology of the pulmonate land snail, Helix melanostoma in Cyrenaica, northeastern Libya, was investigated as part of a wider study on the potential of using terrestrial mollusk shell for 14C dating of archaeological deposits. H. melanostoma was selected out of the species available in the region as it has the most predictable 14C ecology and also had a ubiquitous presence within the local archaeology. The ecological observations indicate that H. melanostoma has a very homogenous 14C ecology with consistent variations in F14C across sample sites controlled by availability of dietary vegetation. The majority of dated specimens from non-urbanized sample locations have only a small old-carbon effect, weighted mean of 476±48 14C yr, with between ~1% and 9% of dietary F14C from non-organic carbonate sources. Observed instabilities in the 14C ecology can all be attributed to the results of intense human activity not present before the Roman Period. Therefore, H. melanostoma and species with similar ecological behavior are suitable for 14C dating of archaeological and geological deposits with the use of a suitable offset.
A survey of the Milky Way disk and the Magellanic System at the wavelengths of the 21-cm atomic hydrogen (H i) line and three 18-cm lines of the OH molecule will be carried out with the Australian Square Kilometre Array Pathfinder telescope. The survey will study the distribution of H i emission and absorption with unprecedented angular and velocity resolution, as well as molecular line thermal emission, absorption, and maser lines. The area to be covered includes the Galactic plane (|b| < 10°) at all declinations south of δ = +40°, spanning longitudes 167° through 360°to 79° at b = 0°, plus the entire area of the Magellanic Stream and Clouds, a total of 13 020 deg2. The brightness temperature sensitivity will be very good, typically σT≃ 1 K at resolution 30 arcsec and 1 km s−1. The survey has a wide spectrum of scientific goals, from studies of galaxy evolution to star formation, with particular contributions to understanding stellar wind kinematics, the thermal phases of the interstellar medium, the interaction between gas in the disk and halo, and the dynamical and thermal states of gas at various positions along the Magellanic Stream.
In previous analyses, the variation in actual, or realized, relationship has been derived as a function of map length of chromosomes and type of relationship, the variation being greater the shorter the total chromosome length and the coefficient of variation being greater the more distant the relationship. Here, the results are extended to allow for the relatives’ ancestor being inbred. Inbreeding of a parent reduces variation in actual relationship among its offspring, by an amount that depends on the inbreeding level and the type of mating that led to that level. For descendants of full-sibs, the variation is reduced in later generations, but for descendants of half-sibs, it is increased.
A heuristic greedy algorithm is developed for efficiently tiling spatially dense redshift surveys. In its first application to the Galaxy and MassAssembly (GAMA) redshift survey we find it rapidly improves the spatial uniformity of our data, and naturally corrects for any spatial bias introduced by the 2dF multi-object spectrograph. We make conservative predictions for the final state of the GAMA redshift survey after our final allocation of time, and can be confident that even if worse than typical weather affects our observations, all of our main survey requirements will be met.
Paleoindian archaeology on the Great Plains is often characterized by the investigation of large mammal kill/butchery bonebeds with relatively high archaeological visibility. Extensively documented aspects of Paleoindian behavioral variability include the form and composition of weaponry systems, hunting strategies, carcass exploitation, and hunter mobility. Non-hunting oriented aspects of settlement and subsistence behavior are less documented. Information from Component 2 at the O.V. Clary site, in Ash Hollow, western Nebraska, lessens this imbalance of knowledge. It provides a fine-grained, spatially extensive record of Late Paleoindian (Allen Complex) activities at a winter base camp occupied for 5-7 months. This paper highlights elements of site structure and activity organization, emphasizing domestic behaviors including hearth use, site maintenance, and hide working. ArcGIS 9.3.1 (ESRI) and GeoDa 0.9.5-1 (Anselin 2003; Anselin et al. 2006) are employed in conjunction with middle-range observations and expectations to document and interpret spatial patterning in the distribution of over 57,000 artifacts, ecofacts, and red ochre nodules. More broadly, results are related to two models of Paleoindian residential mobility: the place-oriented model and the high-tech forager model. Rather than mutually exclusive scenarios, Component 2 indicates that these models reflect complementary structural poses within the overall behavioral system.
In breeding programs, robustness of animals and uniformity of end product can be improved by exploiting genetic variation in residual variance. Residual variance can be defined as environmental variance after accounting for all identifiable effects. The aims of this study were to estimate genetic variance in residual variance of body weight, and to estimate genetic correlations between body weight itself and its residual variance and between female and male residual variance for broilers. The data sets comprised 26 972 female and 24 407 male body weight records. Variance components were estimated with ASREML. Estimates of the heritability of residual variance were in the range 0.029 (s.e. = 0.003) to 0.047 (s.e. = 0.004). The genetic coefficients of variation were high, between 0.35 and 0.57. Heritabilities were higher in females than in males. Accounting for heterogeneous residual variance increased the heritabilities for body weight as well. Genetic correlations between body weight and its residual variance were −0.41 (s.e. = 0.032) and −0.45 (s.e. = 0.040), respectively, in females and males. The genetic correlation between female and male residual variance was 0.11 (s.e. = 0.089), indicating that female and male residual variance are different traits. Results indicate good opportunities to simultaneously increase the mean and improve uniformity of body weight of broilers by selection.
Re-evaluation of recently published figures comparing the tuberculin Tine Test+ and the Mantoux showed that, contrary to original opinion, the Tine Test+ did perform satisfactorily, the reason for the apparent ineffectiveness lying in the original interpretation of the results.
The pattern of changes of the genetic covariance between two characters on selection was examined in an effort to explain the asymmetry of correlated responses in two traits, or of the same trait in two environments, frequently observed in experimental results.
The algebraic conclusions were further examined by model selection experiments using a computer. The computer was programmed to calculate the change in gene frequency from generation to generation and to calculate from it the expected changes in genetic variances and covariance as selection proceeded. This procedure was carried out with several models of gene effects and gene frequencies.
Asymmetry of the genetic covariance, and consequently of the correlated responses, resulted when the relative change in gene frequency at the loci contributing positively and negatively to the covariance depended on the trait selected. The conditions necessary for the development of asymmetry were examined and the results suggest that any symmetry found in an experiment is perhaps more surprising than asymmetry. Probably the most frequent contribution to asymmetry in practice will be from loci contributing negatively to the covariance and having frequencies other than 0·5.
Accurate prediction of correlated response over many generations is therefore not possible without prior knowledge of the composition of the genetic covariance, as well as its magnitude. The validity of existing theory for the prediction of correlated responses is likely to be much poorer than for the prediction of direct responses. Predictions would then have to be based on the genetic parameters estimated in each generation.
The influence of linkage on the rates of response to continued directional selection of quantitative traits deriving from variation contributed by new mutations in finite populations is investigated. Mutant genes are assumed to have additive effects which are randomly sampled from a symmetric distribution, and to be randomly located on the chromosome. Results were obtained by Monte Carlo simulation.
The expected steady rate of response, when variability from new mutations is balanced by that lost by drift and selection, is reduced the tighter the linkage, but the reduction is small unless there are few, short chromosomes. For a given rate of new mutational variance per haploid chromosome set per generation, greater effects of linkage are obtained in large than in small populations, because more mutants segregate. The response and influence of linkage are essentially the same whether the new variance is due to many genes of small effect or few of large effect.
The variability of response between replicates and generations was investigated, and the contribution to this of new mutants or recombination of existing mutants compared. Usually most genetic variability was due to the occurrence of a new favourable mutant of large effect.
Fixation probabilities and mean times to fixation of new mutant alleles in an isogenic population having an effect on a quantitative trait under truncation selection were computed using stochastic simulation. A variety of population structures and breeding systems were studied in order to find an optimal design for maximizing the fixation probability for recessive genes without impairing that for non-recessives or delaying times to fixation. Circular mating or cycles with repeated generations of close inbreeding alternating with combination of the families proved to be very inefficient. The most successful scheme found, considering fixation probabilities and times to fixation jointly, was to practise individual selection and mate full sibs whenever possible, otherwise mate at random. The benefit was directly proportional to the number of full-sib matings performed, which, in turn, almost exclusively depended on the number of selected individuals with very little effect of selection intensity or magnitude of gene effects. Fixation rates could be well approximated by diffusion methods. When selection was practised in only one sex and, therefore, the proportion of full-sib matings could be varied from zero to one, maximizing the amount of full-sib mating was found to maximize fixation probability, at least for single mutants.