Many late-phase clinical trials recruit subjects at multiple study sites. This introduces a hierarchical structure into the data that can result in a power-loss compared to a more homogeneous single-center trial. Building on a recently proposed approach to sample size determination, we suggest a sample size recalculation procedure for multicenter trials with continuous endpoints. The procedure estimates nuisance parameters at interim from noncomparative data and recalculates the sample size required based on these estimates. In contrast to other sample size calculation methods for multicenter trials, our approach assumes a mixed effects model and does not rely on balanced data within centers. It is therefore advantageous, especially for sample size recalculation at interim. We illustrate the proposed methodology by a study evaluating a diabetes management system. Monte Carlo simulations are carried out to evaluate operation characteristics of the sample size recalculation procedure using comparative as well as noncomparative data, assessing their dependence on parameters such as between-center heterogeneity, residual variance of observations, treatment effect size and number of centers. We compare two different estimators for between-center heterogeneity, an unadjusted and a bias-adjusted estimator, both based on quadratic forms. The type 1 error probability as well as statistical power are close to their nominal levels for all parameter combinations considered in our simulation study for the proposed unadjusted estimator, whereas the adjusted estimator exhibits some type 1 error rate inflation. Overall, the sample size recalculation procedure can be recommended to mitigate risks arising from misspecified nuisance parameters at the planning stage. 相似文献
Protecting and restoring shallow tropical lakes and wetlands requires a knowledge of what shapes and controls algal dynamics and primary productivity in these systems. Algal community structure and composition can be regulated either through biotic or abiotic controls. Large-scale changes in fish populations can affect algal communities by altering food web dynamics and the physical and chemical properties of the aquatic environment. A reduction in fish biomass can lead to a reduction in algal biomass because of increased grazing by zooplankton and reduced availablity of nutrients. However, the omnivorous fish common in tropical systems often consume algae, and their reduction can increase algal biomass. There is a need for more information on the effect of fish removals/reductions in tropical systems. In a five-year study of a shallow, tropical pond in Hawaii, I investigated the water quality effects of tilapia removal following the occurrence of two natural fish die-offs. I describe the concurrent impacts of water-level fluctuations and the fish die-offs on the physical and chemical conditions of the pond and the subsequent changes in the algal community. Overall, nutrients, suspended sediment, organic matter, and algal biomass were significantly reduced and light availability significantly increased in the absence of tilapia.
We compared the shape and eggshell thickness of Great Auk Pinguinus impennis eggs with those of its closest relatives, the Razorbill Alca torda, Common Guillemot Uria aalge and Brünnich's Guillemot Uria lomvia, in order to gain additional insights into the breeding biology of the extinct Great Auk. The egg of the Great Auk was most similar in shape to that of Brünnich's Guillemot. The absolute thickness of the Great Auk eggshell was greater than that of the Common Guillemot and Razorbill egg, which is as expected given its greater size, but the relative shell thickness at the equator and pointed end (compared with the blunt end) was more similar to that of the Common Guillemot. On the basis of these and other results we suggest that Great Auk incubated in an upright posture in open habitat with little or no nest, where its pyriform egg shape provided stability and allowed safe manoeuvrability during incubation. On the basis of a recent phylogeny of the Alcidae, we speculate that a single brood patch, a pyriform egg and upright incubation posture, as in the Great Auk and the two Uria guillemots, is the ancestral state, and that the Razorbill – the Great Auk's closest relative – secondarily evolved two brood patches and an elliptical egg as adaptations for horizontal incubation, which provides flexibility in incubation site selection, allowing breeding in enclosed spaces such as crevices, burrows or under boulders, as well as on open ledges. 相似文献
Microorganisms play fundamental roles in the ecosystem of the Gulf of Mexico (GOM), yet their vertical distributions along the depth continuum of water column are not well known. In this study, we presented the 16S rDNA sequences and lipid profiles in the context of water chemistry to characterize the archaeal community structure above a gas hydrate mound (MC 118) in GOM. Our results showed that all archaeal sequences were related to unknown species of Crenarchaeota or Euryarchaeota. Phylogenetically, group II –β Euryarchaeota dominated the surface water and mid-depth (400-m) water (74% and 58% of total archaeal species, respectively) whereas the marine group I-γ Crenarchaeota dominated the bottom (869 m) water (61% of total archaeal species). Estimates of the Shannon index showed the highest diversity of planktonic Archaea at the 400 m depth. Glycerol dialkyl glycerol tetraether (GDGT) lipids were detected from the 400- and 869-m depths only and characterized by relatively high abundances of GDGT-5 (crenarchaeol) and GDGT-0. Our studies suggested a possible zonation of archaeal community in the water column, which did not seem to be affected by the possible venting of hydrocarbons from the hydrate location in GOM. 相似文献
Iron deposits (Fe plaque) on wetland plant roots contain abundant microbial populations, including Fe(II)-oxidizing bacteria (FeOB) that have not been cultured previously. In this study, 4 strains of Fe plaque-associated FeOB were isolated from 4 species of wetland plants. All 4 isolates grew in tight association with Fe-oxides, but did not form any identifiable Fe-oxide structures. All strains were obligate lithotrophic Fe(II)-oxidizers that were microaerobic, and were unable to use other inorganic or organic energy sources. One strain, BrT, was shown to fix 14CO2 at a rate consistent with its requirement for total cell carbon. The doubling times for the strains varied between 9.5 and 15.8 hours. The fatty acid methyl ester (FAME) profiles of 2 strains, BrT and CCJ, revealed that 16:0, 15:1 isoG, and 14:0 were dominant fatty acids. Phylogenetic analysis of the 16S rRNA gene indicated that all the strains were Betaproteobacteria. Two of the strains, BrT and Br-1 belong to a new species, Sideroxydans paludicola; a third strain, LD-1, is related to Sideroxydans lithotrophicus, a recently described species of FeOB. The fourth isolate, Ferritrophicum radicicola, represented a new genus in a new order of Betaproteobacteria, the Ferritrophicales. There are no other cultured isolates in this order. A small subunit rRNA gene-based, cultivation-independent analysis of Typha latifolia collected from a wetland revealed terminal restriction fragment profiles (tRFLP) consistent with the presence of these bacteria in the rhizosphere. These novel organisms likely play an important role in Fe(II) oxidation kinetics and Fe cycling within many terrestrial and freshwater environments. 相似文献
Recruitment of the growth factor receptor-bound protein 2 (Grb2) by the plasma membrane-associated adapter protein downstream of kinase 3 (Dok-3) attenuates signals transduced by the B cell antigen receptor (BCR). Here we describe molecular details of Dok-3/Grb2 signal integration and function, showing that the Lyn-dependent activation of the BCR transducer kinase Syk is attenuated by Dok-3/Grb2 in a site-specific manner. This process is associated with the SH3 domain-dependent translocation of Dok-3/Grb2 complexes into BCR microsignalosomes and augmented phosphorylation of the inhibitory Lyn target SH2 domain-containing inositol 5′ phosphatase. Hence, our findings imply that Dok-3/Grb2 modulates the balance between activatory and inhibitory Lyn functions with the aim to adjust BCR signaling efficiency. 相似文献