On meta-analytic assessment of surrogate outcomes

We discuss the strengths and weaknesses of the meta-analytic approach to estimating the effect of a new treatment on a true clinical outcome measure, T, from the effect of treatment on a surrogate response, S. The meta-analytic approach (see Daniels and Hughes (1997) 16, 1965-1982) uses data from a series of previous studies of interventions similar to the new treatment. The data are used to estimate relationships between summary measures of treatment effects on T and S that can be used to infer the magnitude of the effect of the new treatment on T from its effects on S. We extend the class of models to cover a broad range of applications in which the parameters define features of the marginal distribution of (T, S). We present a new bootstrap procedure to allow for the variability in estimating the distribution that governs the between-study variation. Ignoring this variability can lead to confidence intervals that are much too narrow. The meta-analytic approach relies on quite different data and assumptions than procedures that depend, for example, on the conditional independence, at the individual level, of treatment and T, given S (see Prentice (1989) 8, 431-440). Meta-analytic calculations in this paper can be used to determine whether a new study, based only on S, will yield estimates of the treatment effect on T that are precise enough to be useful. Compared to direct measurement on T, the meta-analytic approach has a number of limitations, including likely serious loss of precision and difficulties in defining the class of previous studies to be used to predict the effects on T for a new intervention.     

北京东灵山地区植物群落多样性研究 Ⅵ.几种类型植物群落物种数目的估计

采用经验贝叶斯方法、非参数方法（刀切法和自助法）和种－面积曲线外推方法对北京东灵山地区５种类型植物群落的物种数目进行了估计,考察了这些方法的估计行为,从中得出如下结论：（１）只要抽样强度不是很小,经验贝叶斯方法就能给出群落物种数目很好的估计,但与非参数方法相比,其估计的标准差较大;（２）在适当的抽样强度下,非参数方法也能给出群落物种数目很好的估计。如果抽样强度过低,则估计值也偏低;相反,如果抽样强度过高,则估计值也偏高。但在各种抽样强度下,非参数方法估计的标准差都比经验贝叶斯方法的小;（３）种－面积曲线２、３、４、５、６可以给出群落物种数目较好的估计,曲线１的估计值偏高,而曲线７、８、９、１０的估计值则偏低;（４）经过几种方法的综合比较,可以对群落１、２、３、４、５的各层及整个群落的物种数目分别做出如下估计;乔木层１６、１９、２１、１２、１６,灌木层１３、１５、２１、１４、２１,草本层４９、４６、５４、８２、５５,整个群落７９、８０、９６、１０７、９２。     

From Africa via Europe to South America: migrational route of a species‐rich genus of Neotropical lowland rain forest trees (Guatteria,Annonaceae)

Aim Several recent studies have suggested that a substantial portion of today’s plant diversity in the Neotropics has resulted from the dispersal of taxa into that region rather than by vicariance. In general, three routes have been documented for the dispersal of taxa onto the South American continent: (1) via the North Atlantic Land Bridge, (2) via the Bering Land Bridge, or (3) from Africa directly onto the continent. Here a species‐rich genus of Neotropical lowland rain forest trees (Guatteria, Annonaceae) is used as a model to investigate these three hypotheses. Location The Neotropics. Methods The phylogenetic relationships within the long‐branch clade of Annonaceae were reconstructed (using maximum parsimony, maximum likelihood and Bayesian inference) in order to gain insight in the phylogenetic position of Guatteria. Furthermore, Bayesian molecular dating and Bayesian dispersal–vicariance (Bayes‐DIVA) analyses were undertaken. Results Most of the relationships within the long‐branch clade of Annonaceae were reconstructed and had high support. However, the relationship between the Duguetia clade, the Xylopia–Artabotrys clade and Guatteria remained unclear. The stem node age estimate of Guatteria ranged between 49.2 and 51.3 Ma, whereas the crown node age estimate ranged between 11.4 and 17.8 Ma. For the ancestral area of Guatteria and its sister group, the area North America–Africa was reconstructed in 99% of 10,000 DIVA analyses, while South America–North America was found just 1% of the time. Main conclusions The estimated stem to crown node ages of Guatteria in combination with the Bayes‐DIVA analyses imply a scenario congruent with an African origin followed by dispersal across the North Atlantic Land Bridge in the early to middle Eocene and further dispersal into North and Central America (and ultimately South America) in the Miocene. The phylogenetically and morphologically isolated position of the genus is probably due to extinction of the North American and European stem lineages in the Tertiary.     

Bayesian Hierarchical Functional Data Analysis Via Contaminated Informative Priors

Summary .  A variety of flexible approaches have been proposed for functional data analysis, allowing both the mean curve and the distribution about the mean to be unknown. Such methods are most useful when there is limited prior information. Motivated by applications to modeling of temperature curves in the menstrual cycle, this article proposes a flexible approach for incorporating prior information in semiparametric Bayesian analyses of hierarchical functional data. The proposed approach is based on specifying the distribution of functions as a mixture of a parametric hierarchical model and a nonparametric contamination. The parametric component is chosen based on prior knowledge, while the contamination is characterized as a functional Dirichlet process. In the motivating application, the contamination component allows unanticipated curve shapes in unhealthy menstrual cycles. Methods are developed for posterior computation, and the approach is applied to data from a European fecundability study.     

Use of genotyping by sequencing data to develop a high‐throughput and multifunctional SNP panel for conservation applications in Pacific lamprey

Next‐generation sequencing data can be mined for highly informative single nucleotide polymorphisms (SNPs) to develop high‐throughput genomic assays for nonmodel organisms. However, choosing a set of SNPs to address a variety of objectives can be difficult because SNPs are often not equally informative. We developed an optimal combination of 96 high‐throughput SNP assays from a total of 4439 SNPs identified in a previous study of Pacific lamprey (Entosphenus tridentatus) and used them to address four disparate objectives: parentage analysis, species identification and characterization of neutral and adaptive variation. Nine of these SNPs are F_ST outliers, and five of these outliers are localized within genes and significantly associated with geography, run‐timing and dwarf life history. Two of the 96 SNPs were diagnostic for two other lamprey species that were morphologically indistinguishable at early larval stages and were sympatric in the Pacific Northwest. The majority (85) of SNPs in the panel were highly informative for parentage analysis, that is, putatively neutral with high minor allele frequency across the species’ range. Results from three case studies are presented to demonstrate the broad utility of this panel of SNP markers in this species. As Pacific lamprey populations are undergoing rapid decline, these SNPs provide an important resource to address critical uncertainties associated with the conservation and recovery of this imperiled species.     

A new method to measure and calculate light intensity and light quality simultaneously by using portable spectrometer

The influence of light intensity and light quality on plants is highly concerned in the field of plant physiology and ecology. However, the calibrated quantum meter for measurement of light intensity cannot measure light quality, and vice versa. Here we developed an empirical formula to convert light energy to photon flux density, based on the measurement conditions of spectrometer. Under the guide of the formula, a portable spectrometer (AvaSpec-ULS2048×64) was calibrated by using four narrowband light emitting diode (LEDs) in combination with a calibrated quantum meter (LI-190SB). After calibration of the spectrometer, we can calculate photosynthetic photon flux density (PPFD or PAR) and measure spectrum of radiation flux simultaneously. Under natural light conditions, the errors between measured and calculated PPFDs are in the range from -2% to 5%, indicating the reliability of the method. With this new approach, the application of portable spectrometer can be greatly broadened: 1) the light intensity and quality of light source and plant growth light environment can be obtained simultaneously, 2) PPFD can be obtained within any specified wavelength range, and 3) there is no need to use standard light source to obtain the absolute light/radiation flux of a spectrum measured by spectrometer. In conclusion, this method has potential applications for the study of plant physiology and ecology.     

Information‐theoretic analysis of the reference state in contact potentials used for protein structure prediction

Using information‐theoretic concepts, we examine the role of the reference state, a crucial component of empirical potential functions, in protein fold recognition. We derive an information‐based connection between the probability distribution functions of the reference state and those that characterize the decoy set used in threading. In examining commonly used contact reference states, we find that the quasi‐chemical approximation is informatically superior to other variant models designed to include characteristics of real protein chains, such as finite length and variable amino acid composition from protein to protein. We observe that in these variant models, the total divergence, the operative function that quantifies discrimination, decreases along with threading performance. We find that any amount of nativeness encoded in the reference state model does not significantly improve threading performance. A promising avenue for the development of better potentials is suggested by our information‐theoretic analysis of the action of contact potentials on individual protein sequences. Our results show that contact potentials perform better when the compositional properties of the data set used to derive the score function probabilities are similar to the properties of the sequence of interest. Results also suggest to use only sequences of similar composition in deriving contact potentials, to tailor the contact potential specifically for a test sequence. Proteins 2010. © 2009 Wiley‐Liss, Inc.     

Origins and colonization history of pandemic Vibrio parahaemolyticus in South America

The dynamics of dissemination of the environmental human pathogen Vibrio parahaemolyticus are uncertain. The O3:K6 clone was restricted to Asia until its detection along the Peruvian coasts and in northern Chile in 1997 in phase with the arrival of El Niño waters. A subsequent emergence of O3:K6 strains was detected in austral Chile in 2004. The origin of these 1997 and 2004 population radiations has not yet been conclusively determined. Multiple loci VNTR analysis using seven polymorphic loci was carried out with a number of representative strains from Asia, Peru and Chile to determine their genetic characteristics and population structure. Asian and Chilean subpopulations were the most genetically distant groups with an intermediate subpopulation in Peru. Population structure inferred from a minimum‐spanning tree and Bayesian analysis divided the populations into two genetically distinct groups, consistent with the epidemic dynamics of the O3:K6 clone in South America. One group comprised strains from the original Asiatic population and strains arriving in Peru and Chile in 1997. The second group included the remaining Peruvian Strains and Chilean strains obtained from Puerto Montt in 2004. The analysis of the arrival of the O3:K6 clone at the Pacific coasts of South America has provided novel insights linking the origin of the invasion in 1997 to Asian populations and describing the successful establishment of the O3:K6 populations, first in Peru and subsequently in the South of Chile owing to a possible radiation of Peruvian populations.