Training Module for ALS Moderators: Report on conceptual and methodological aspects of the first workshop in Pemba Metuge, Cabo Delgado, Mozambique, April 2005

Report on conceptual and methodological aspects of the first workshop for training moderators and trainers in ALS and sustainable management of natural resources, in Pemba Metuge, Cabo Delgado, Mozambique, April 2005.

Inference of evolutionary forces acting on human biological pathways

Because natural selection is likely to act on multiple genes underlying a given phenotypic trait, we study here the potential effect of ongoing and past selection on the genetic diversity of human biological pathways. We first show that genes included in gene sets are generally under stronger selective constraints than other genes and that their evolutionary response is correlated. We then introduce a new procedure to detect selection at the pathway level based on a decomposition of the classical McDonald–Kreitman test extended to multiple genes. This new test, called 2DNS, detects outlier gene sets and takes into account past demographic effects and evolutionary constraints specific to gene sets. Selective forces acting on gene sets can be easily identified by a mere visual inspection of the position of the gene sets relative to their two-dimensional null distribution. We thus find several outlier gene sets that show signals of positive, balancing, or purifying selection but also others showing an ancient relaxation of selective constraints. The principle of the 2DNS test can also be applied to other genomic contrasts. For instance, the comparison of patterns of polymorphisms private to African and non-African populations reveals that most pathways show a higher proportion of nonsynonymous mutations in non-Africans than in Africans, potentially due to different demographic histories and selective pressures.

PSHARE: Stata module to compute and graph percentile shares

-pshare- computes and graphs percentile shares from individual level data. Percentile shares are often used in inequality research to study the distribution of income or wealth. They are defined as differences between Lorenz ordinates of the outcome variable. Technically, the observations are sorted in increasing order of the outcome variable and the specified percentiles are computed from the running sum of the outcomes. Percentile shares are then computed as differences between percentiles, divided by total outcome. pshare requires moremata to be installed on the system; see ssc describe moremata.

A growth factor-induced, spatially organizing cytoskeletal module enables rapid and persistent fibroblast migration

Directional migration requires robust front/back polarity. We find that fibroblasts treated with platelet-derived growth factor (PDGF) and prepolarized by plating on a fibronectin line substrate exhibit persistent migration for hours. This does not occur in the absence of PDGF or on uniformly coated fibronectin substrates. Persistent migration arises from establishment of two functional modules at cell front and back. At the front, formation of a zone containing podosome-like structures (PLS) dynamically correlates with low RhoA and myosin activity and absence of a contractile lamella. At the back, myosin contractility specifically controls tail retraction with minimal crosstalk to the front module. The PLS zone is maintained in a dynamic steady state that preserves size and position relative to the cell front, allowing for long-term coordination of front and back modules. We propose that front/back uncoupling achieved by the PLS zone is crucial for persistent migration in the absence of directional cues.

An intercontinental comparison of chironomid palaeotemperature inference models: Europe vs North America

Chironomid-temperature inference models based on North American, European and combined surface sediment training sets were compared to assess the overall reliability of their predictions. Between 67 and 76 of the major chironomid taxa in each data set showed a unimodal response to July temperature, whereas between 5 and 22 of the common taxa showed a sigmoidal response. July temperature optima were highly correlated among the training sets, but the correlations for other taxon parameters such as tolerances and weighted averaging partial least squares (WA-PLS) and partial least squares (PLS) regression coefficients were much weaker. PLS, weighted averaging, WA-PLS, and the Modern Analogue Technique, all provided useful and reliable temperature inferences. Although jack-knifed error statistics suggested that two-component WA-PLS models had the highest predictive power, intercontinental tests suggested that other inference models performed better. The various models were able to provide good July temperature inferences, even where neither good nor close modern analogues for the fossil chironomid assemblages existed. When the models were applied to fossil Lateglacial assemblages from North America and Europe, the inferred rates and magnitude of July temperature changes varied among models. All models, however, revealed similar patterns of Lateglacial temperature change. Depending on the model used, the inferred Younger Dryas July temperature decrease ranged between 2.5 and 6°C.

GMM Based Inference with Standard Stratified Samples when the Aggregate Shares are Known

We show how to do efficient moment based inference using the generalized method of moments (GMM) when data is collected by standard stratified sampling and the maintained assumption is that the aggregate shares are known.

Polytomies and bayesian phylogenetic inference

Bayesian phylogenetic analyses are now very popular in systematics and molecular evolution because they allow the use of much more realistic models than currently possible with maximum likelihood methods. There are, however, a growing number of examples in which large Bayesian posterior clade probabilities are associated with very short edge lengths and low values for non-Bayesian measures of support such as nonparametric bootstrapping. For the four-taxon case when the true tree is the star phylogeny, Bayesian analyses become increasingly unpredictable in their preference for one of the three possible resolved tree topologies as data set size increases. This leads to the prediction that hard (or near-hard) polytomies in nature will cause unpredictable behavior in Bayesian analyses, with arbitrary resolutions of the polytomy receiving very high posterior probabilities in some cases. We present a simple solution to this problem involving a reversible-jump Markov chain Monte Carlo (MCMC) algorithm that allows exploration of all of tree space, including unresolved tree topologies with one or more polytomies. The reversible-jump MCMC approach allows prior distributions to place some weight on less-resolved tree topologies, which eliminates misleadingly high posteriors associated with arbitrary resolutions of hard polytomies. Fortunately, assigning some prior probability to polytomous tree topologies does not appear to come with a significant cost in terms of the ability to assess the level of support for edges that do exist in the true tree. Methods are discussed for applying arbitrary prior distributions to tree topologies of varying resolution, and an empirical example showing evidence of polytomies is analyzed and discussed.

Moment Based Inference with Stratified Data

Many datasets used by economists and other social scientists are collected by stratified sampling. The sampling scheme used to collect the data induces a probability distribution on the observed sample that differs from the target or underlying distribution for which inference is to be made. If this effect is not taken into account, subsequent statistical inference can be seriously biased. This paper shows how to do efficient semiparametric inference in moment restriction models when data from the target population is collected by three widely used sampling schemes: variable probability sampling, multinomial sampling, and standard stratified sampling.

Polytomies and bayesian phylogenetic inference

Bayesian phylogenetic analyses are now very popular in systematics and molecular evolution because they allow the use of much more realistic models than currently possible with maximum likelihood methods. There are, however, a growing number of examples in which large Bayesian posterior clade probabilities are associated with very short edge lengths and low values for non-Bayesian measures of support such as nonparametric bootstrapping. For the four-taxon case when the true tree is the star phylogeny, Bayesian analyses become increasingly unpredictable in their preference for one of the three possible resolved tree topologies as data set size increases. This leads to the prediction that hard (or near-hard) polytomies in nature will cause unpredictable behavior in Bayesian analyses, with arbitrary resolutions of the polytomy receiving very high posterior probabilities in some cases. We present a simple solution to this problem involving a reversible-jump Markov chain Monte Carlo (MCMC) algorithm that allows exploration of all of tree space, including unresolved tree topologies with one or more polytomies. The reversible-jump MCMC approach allows prior distributions to place some weight on less-resolved tree topologies, which eliminates misleadingly high posteriors associated with arbitrary resolutions of hard polytomies. Fortunately, assigning some prior probability to polytomous tree topologies does not appear to come with a significant cost in terms of the ability to assess the level of support for edges that do exist in the true tree. Methods are discussed for applying arbitrary prior distributions to tree topologies of varying resolution, and an empirical example showing evidence of polytomies is analyzed and discussed.

Bayesian inference and its application to meta-analysis of epidemiologic data

In Part One, the foundations of Bayesian inference are reviewed, and the technicalities of the Bayesian method are illustrated. Part Two applies the Bayesian meta-analysis program, the Confidence Profile Method (CPM), to clinical trial data and evaluates the merits of using Bayesian meta-analysis for overviews of clinical trials.^ The Bayesian method of meta-analysis produced similar results to the classical results because of the large sample size, along with the input of a non-preferential prior probability distribution. These results were anticipated through explanations in Part One of the mechanics of the Bayesian approach. ^

LORENZ: Stata module to estimate and display Lorenz curves and concentration curves

Lorenz estimates Lorenz and concentration curves from individual-level data and, optionally, displays the results in a graph. Relative as well as generalized, absolute, unnormalized, or custom-normalized Lorenz or concentration curves are supported, and tools for computing contrasts between different subpopulations or outcome variables are provided. Variance estimation for complex samples is fully supported.