Sample size reestimation by Bayesian prediction

We review a Bayesian predictive approach for interim data monitoring and propose its application to interim sample size reestimation for clinical trials. Based on interim data, this approach predicts how the sample size of a clinical trial needs to be adjusted so as to claim a success at the conclusion of the trial with an expected probability. The method is compared with predictive power and conditional power approaches using clinical trial data. Advantages of this approach over the others are discussed.     

Quantifying Littoral Vertical Habitat Structure and Fish Community Associations using Underwater Visual Census

Synopsis We developed and tested a new visual census technique to quantify the importance of vertical habitat structure on the associated fish assemblages in the littoral zone of a freshwater lake. We demonstrated that the primary environmental gradient, accounting for the most variation in the species data, represented a temporal gradient of seasonal characteristics. The secondary environmental gradient was related to the vertical structure at the sampling locations, showing the importance of the vertical component of the environment on fish community structure. Characterizing the vertical component at different resolutions provided different interpretations. The primary difference was the strength of influence of woody material on community structure. Woody material had a stronger influence on community structure throughout the water column when a single vertical unit defined the fish data. The appropriateness of defining the data by either multiple vertical strata or by a single vertical one would be dependent on the objectives of the study, as neither approach was found to explain substantially more variation in the species data. The current study demonstrates that fish are closely associated with particular elements of habitat structure in the littoral zone, even in the absence of major piscivorous predators. We provide a novel study quantifying the vertical multiple habitat structures and habitat use by fish in the water column of a freshwater lake. The new vertical visual census technique can be used to more comprehensively sample the three-dimensional environment of lake littoral zones, and quantify the fish–habitat spatial relationships across a range of abiotic and biotic habitat features.     

Morphological analysis of three equivocal sibling species of Deprea (Solanaceae)

Taxonomic confusion among closely related and morphologically similar Deprea species has persisted in the literature and in the identification of species. Morphological variation among three closely related, monophyletic Deprea species was studied to determine if and how they can be distinguished. Their sympatric occurrence in Venezuela afforded an opportunity to couple field study with analysis of herbarium specimens representing their entire geographic range. An analysis of 94 morphological characters resulted in five vegetative and 13 reproductive taxonomically informative traits. Canonical variates analysis clearly separated the three species using six quantitative traits. We conclude that these taxa, although quite variable and similar morphologically, are taxonomically distinct. Results of character analysis indicated that D. orinocensis is morphologically more similar to D. bitteriana than either are to D. paneroi. In D. paneroi, small, sterile anthers on fruit-bearing plants and the absence of fruits on plants possessing large, plllen-bearing anthers, suggest cryptic dioecy. Based on these data, D. granulosa is considered to be a synonym of D. orinocensis: Athenaea bitteriana, a misapplied synonym, is the correct basionym and is applicable to many specimens identified as D. granulosa. We submit a new combination, D. bitteriana (Werderm.) Sawyer & Benítez, and designate a lectotype to accommodate these findings.     

The Predictive Power of R 0 in an Epidemic Probabilistic System

An important issue in theoretical epidemiology is the epidemic thresholdphenomenon, which specify the conditions for an epidemic to grow or die out.In standard (mean-field-like) compartmental models the concept of the basic reproductive number, R ₀, has been systematically employed as apredictor for epidemic spread and as an analytical tool to study thethreshold conditions. Despite the importance of this quantity, there are nogeneral formulation of R ₀ when one considers the spread of a disease ina generic finite population, involving, for instance, arbitrary topology ofinter-individual interactions and heterogeneous mixing of susceptible andimmune individuals. The goal of this work is to study this concept in ageneralized stochastic system described in terms of global and localvariables. In particular, the dependence of R ₀ on the space ofparameters that define the model is investigated; it is found that near ofthe `classical' epidemic threshold transition the uncertainty about thestrength of the epidemic process still is significantly large. Theforecasting attributes of R ₀ for a discrete finite system is discussedand generalized; in particular, it is shown that, for a discrete finitesystem, the pretentious predictive power of R ₀ is significantlyreduced.     

Generation of clinical 177Lu SPECT/CT images based on Monte Carlo simulation with GATE

PurposePatient-specific dosimetry in MRT relies on quantitative imaging, pharmacokinetic assessment and absorbed dose calculation. The DosiTest project was initiated to evaluate the uncertainties associated with each step of the clinical dosimetry workflow through a virtual multicentric clinical trial. This work presents the generation of simulated clinical SPECT datasets based on GATE Monte Carlo modelling with its corresponding experimental CT image, which can subsequently be processed by commercial image workstations.MethodsThis study considers a therapy cycle of 6.85 GBq ¹⁷⁷Lu-labelled DOTATATE derived from an IAEA-Coordinated Research Project (E23005) on “Dosimetry in Radiopharmaceutical therapy for personalised patient treatment”. Patient images were acquired on a GE Infinia-Hawkeye 4 gamma camera using a medium energy (ME) collimator. Simulated SPECT projections were generated based on experimental time points and validated against experimental SPECT projections using flattened profiles and gamma index. The simulated projections were then incorporated into the patient SPECT/CT DICOM envelopes for processing and their reconstruction within a commercial image workstation.ResultsGamma index passing rate (2% − 1 pixel criteria) between 95 and 98% and average gamma between 0.28 and 0.35 among different time points revealed high similarity between simulated and experimental images. Image reconstruction of the simulated projections was successful on HERMES and Xeleris workstations, a major step forward for the initiation of a multicentric virtual clinical dosimetry trial based on simulated SPECT/CT images.ConclusionsRealistic ¹⁷⁷Lu patient SPECT projections were generated in GATE. These modelled datasets will be circulated to different clinical departments to perform dosimetry in order to assess the uncertainties in the entire dosimetric chain.     

Seamounts: centres of endemism or species richness for ophiuroids?

Aim To test the hypotheses that seamounts exhibit high rates of endemism and/or species richness compared to surrounding areas of the continental slope and oceanic ridges. Location The south‐west Pacific Ocean from 19–57° S to 143–171° E. Methods Presence/absence museum data were compiled for seamount and non‐seamount areas at depths between 100 and 1500 m for the Ophiuroidea (brittle‐stars), an abundant and speciose group of benthic invertebrates. Large‐scale biogeographical gradients were examined through multivariate analyses at two spatial scales, at the scale of seamounts (< 1° of latitude/longitude) and regions (5–9°). The robustness of these patterns to spatially inconsistent sampling effort was tested using Monte Carlo‐style simulations. Levels of local endemism and species richness over numbers of samples were compared for seamount and non‐seamount areas using linear regressions. Non‐seamount populations were randomly generated from areas and depth ranges that reflected the typical sampling profile of seamounts. Results Seamount ophiuroid assemblages did not exhibit elevated levels of species richness or narrow‐range endemism compared with non‐seamount areas. Seamounts can exhibit high overall species richness for low numbers of samples, particularly on seamounts supporting a dense coral matrix, but this does not increase with additional sampling at the rates found in non‐seamount areas. There were relatively few identifiable seamount specialists. In general, seamount faunas reflected those found at similar depths in surrounding areas, including the continental slope. Seamount and non‐seamount faunas within the study area exhibited congruent latitudinal and bathymetric species turnover. Main conclusions Seamount faunas were variable for ophiuroid faunal composition, species richness and narrow‐range endemism, reflecting their environmental diversity and complex history. The continental slope was also variable, with some areas being particularly species rich. Broad geomorphological habitat categories such as ‘seamounts’ or ‘continental slope’ may be at the wrong scale to be useful for conservation planning.     

肌球蛋白Ⅵ定向运动的蒙特卡罗模拟

根据myosin Ⅵ分子马达头部核苷的变化建立一个四态循环,然后利用蒙特卡罗方法模拟分子马达的动力学性质,讨论了myosin Ⅵ速度、滞留时间与溶液中ATP浓度、ADP浓度和负载力F的关系。模拟得到：myosin Ⅵ会在轨道微丝上进行梯跳运动并且每次在微丝上的滞留时间并不相同;另外,myosin Ⅵ的速度会随着ATP浓度的增加而增大,随着ADP浓度和负载力的增加而减小;负载力对myosin Ⅵ在胞内执行输运还是连接功能起一定的调节作用。     

Role of histidine for charge regulation of unstructured peptides at interfaces and in bulk

Histidine‐rich, unstructured peptides adsorb to charged interfaces such as mineral surfaces and microbial cell membranes. At a molecular level, we investigate the adsorption mechanism as a function of pH, salt, and multivalent ions showing that (1) proton charge fluctuations are—in contrast to the majority of proteins—optimal at neutral pH, promoting electrostatic interactions with anionic surfaces through charge regulation and (2) specific zinc(II)‐histidine binding competes with protons and ensures an unusually constant charge distribution over a broad pH interval. In turn, this further enhances surface adsorption. Our analysis is based on atomistic molecular dynamics simulations, coarse grained Metropolis Monte Carlo, and classical polymer density functional theory. This multiscale modeling provides a consistent picture in good agreement with experimental data on Histatin 5, an antimicrobial salivary peptide. Biological function is discussed and we suggest that charge regulation is a significant driving force for the remarkably robust activity of histidine‐rich antimicrobial peptides. Proteins 2014; 82:657–667. © 2013 Wiley Periodicals, Inc.     

A Modified Valley Restrained Monte Carlo Method to Efficiently Search the Low Energy Structures of Peptides

Abstract

A new Monte Carlo sampling scheme, namely the Modified Valley Restrained Monte Carlo procedure, is used to obtain the global energy minimum conformations for polypeptides, such as Met-enkephalin and Melittin. For each peptide, we found close agreement with previous results from both theoretical and experimental studies. The simple idea for controlling the step size according to the Valley Function, provides useful suggestions in searching the global energy minimum structures, and furthermore helps solve the multiple minima problem.