Quasi Likelihood/Moment Method for Generalized and Restricted Generalized Poisson Regression Models and Its Application

This paper reviews the generalized Poisson regression model, the restricted generalized Poisson regression model and the mixed Poisson regression (negative binomial regression and Poisson inverse Gaussian regression) models which can be used for regression analysis of counts. The aim of this study is to demonstrate the quasi likelihood/moment method, which is used for estimation of the parameters of mixed Poisson regression models, also applicable to obtain the estimates of the parameters of the generalized Poisson regression and the restricted generalized Poisson regression models. Besides, at the end of this study an application related to this method for zoological data is given.     

A Monte Carlo Study of Robustness of Pretest and Shrinkage Estimators in Pooling Coefficients of Variation

Pooling data, when justified, is advantageous for estimating the true parameter. In this paper the problem of estimating the coefficient of variation is considered when it is a priori suspected that two coefficients of variation are the same. Various estimators based on pretest and shrinkage rules are considered. A comparison through the Simulated Mean Squared Error (SMSE) criterion is carried out among various proposed estimators of the target coefficient of variation. The relative simulated efficiencies of the restricted, shrinkage restricted and shrinkage pretest estimators are studied. It is found that the proposed estimators are quite robust when the sample sizes are not too large. The result of Monte Carlo study indicates that the proposed shrinkage pretest estimator is efficient than the usual estimator in a wider range.     

Synthesis and NMR Assignment of the Two Diastereomers of 8,6′-Cyclo-2′,6′-Dideoxyadenosine

We herein present the first synthesis and characterization of the two C5′ diastereomers of 8,6′-cyclo-2′,6′-dideoxyadenosine. Starting from commercially available 2′-deoxyadenosine, the target cyclonucleosides were synthesized in 11 linear steps. Following a zinc-mediated cyclization reaction to form the seven-membered ring, the stereochemistry of the newly formed chiral center was established using two-dimensional NOESY NMR experiments.

[Supplemental materials are available for this article. Go to the publisher's online edition of Nucleosides, Nucleotides & Nucleic Acids for the free supplemental resource.]     

Motor and cognitive stereotypies in the BTBR T+tf/J mouse model of autism

The BTBR T+tf/J inbred mouse strain displays a variety of persistent phenotypic alterations similar to those exhibited in autism spectrum disorders (ASDs). The unique genetic background of the BTBR strain is thought to underlie its lack of reciprocal social interactions, elevated repetitive self-directed grooming, and restricted exploratory behaviors. In order to clarify the existence, range, and mechanisms of abnormal repetitive behaviors within BTBR mice, we performed detailed analyses of the microstructure of self-grooming patterns and noted increased overall grooming, higher percentages of interruptions in grooming bouts and a concomitant decrease in the proportion of incorrect sequence transitions compared to C57BL/6J inbred mice. Analyses of active phase home-cage behavior also revealed an increase in stereotypic bar-biting behavior in the BTBR strain relative to B6 mice. Finally, in a novel object investigation task, the BTBR mice exhibited greater baseline preference for specific unfamiliar objects as well as more patterned sequences of sequential investigations of those items. These results suggest that the repetitive, stereotyped behavior patterns of BTBR mice are relatively pervasive and reflect both motor and cognitive mechanisms. Furthermore, other pre-clinical mouse models of ASDs may benefit from these more detailed analyses of stereotypic behavior.     

Synthesis, nucleic acid hybridization properties and molecular modelling studies of conformationally restricted 3'-O,4'-C-methylene-linked alpha-L-ribonucleotides

Nucleotides with conformationally restricted carbohydrate rings such as locked nucleic acid (LNA), alpha-L-LNA or 2',5'-linked 3'-O,4'-C-methyleribonucleotides exhibit significant potential as building blocks for antigene and antisense strategies. 2',5'-Linked alpha-L-ribo configured monomer X (termed alpha-L-ONA) was designed as a potential structural mimic of alpha-L-LNA. The corresponding phosphoramidite building block of monomer X was obtained in five steps (10% overall yield) from the easily obtainable thymine derivative 1. Incorporation of monomer X into oligodeoxyribonucleotides (ONs) results in dramatically decreased thermal stabilities with DNA/RNA complements (DeltaTm/mod=-11.5 to -17.0 degrees C) compared to unmodified reference ONs. Less pronounced decreases (DeltaTm/mod=-4.5 to -8.5 degrees C) are observed when monomer X is incorporated into triplex forming ONs and targeted against double-stranded DNA (parallel orientation, pyrimidine motif). This biophysical data, together with modelling studies, suggest that 2',5'-linked alpha-L-ONA is a poor structural mimic of alpha-L-LNA.     

The efficiency of adaptive search tactics for different prey distribution patterns: a simulation model based on the behaviour of juvenile plaice

Juvenile plaice Pleuronectes platessa are particularly useful for studying forager search behaviour because their search paths are essentially two dimensional, and punctuated by natural stops. Their prey occur in a range of natural distributions from highly aggregated to over‐dispersed. Juvenile plaice use area‐restricted search near aggregated prey and extensive search, consisting of longer moves and fewer turns, between aggregations and when searching for dispersed prey. They search for less conspicuous prey items mainly in the pauses between movements. This saltatory search behaviour contrasts with the continuous search that is usually assumed in search models. A simulation model of saltatory search behaviour showed that a strategy combining extensive and intensive search allows the efficient exploitation of a range of natural prey distribution patterns, and that it is particularly effective when the search behaviour is controlled by perceived prey density. This allows the predator to respond to the localized aggregations which often occur in nature. The selective use of intensive search was more efficient than the continuous use of extensive search even in prey distribution patterns that were statistically over‐dispersed.     

A Nonparametric Test for Ordered Alternatives in Two-Way Layouts with Censored Data

A nonparametric test is presented to test for ordered alternatives of the treatment effects when the data follow a two-way layout. The observations are subject to arbitrary right censorship. The test is similar to the one developed by Hettmansperger and Norton (1987) for uncensored observations.     

Improved Shrinkage Estimation of Relative Potency

This article considers the asymptotic estimation theory for the log relative potency in a symmetric parallel bioassay when uncertain prior information about the true log relative potency is assumed to be a known quantity. Three classes of point estimation, namely, the unrestricted estimator, the shrinkage restricted estimator and shrinkage preliminary test estimator are proposed. Their asymptotic mean squared errors are derived and compared. The relative dominance picture of the estimators is presented. Interestingly, proposed shrinkage preliminary test estimator dominates the unrestricted estimator in a range that is wider than that of the usual preliminary test estimator. Most importantly, the size of the preliminary test is much appropriate than the usual preliminary test estimator.     

Life at the extreme: lessons from the genome

Extremophile plants thrive in places where most plant species cannot survive. Recent developments in high-throughput technologies and comparative genomics are shedding light on the evolutionary mechanisms leading to their adaptation.     

Joint inference for competing risks data using multiple endpoints

Competing risks data are commonly encountered in randomized clinical trials and observational studies. This paper considers the situation where the ending statuses of competing events have different clinical interpretations and/or are of simultaneous interest. In clinical trials, often more than one competing event has meaningful clinical interpretations even though the trial effects of different events could be different or even opposite to each other. In this paper, we develop estimation procedures and inferential properties for the joint use of multiple cumulative incidence functions (CIFs). Additionally, by incorporating longitudinal marker information, we develop estimation and inference procedures for weighted CIFs and related metrics. The proposed methods are applied to a COVID-19 in-patient treatment clinical trial, where the outcomes of COVID-19 hospitalization are either death or discharge from the hospital, two competing events with completely different clinical implications.