Spatial multistate transitional models for longitudinal event data

Summary .   Follow-up medical studies often collect longitudinal data on patients. Multistate transitional models are useful for analysis in such studies where at any point in time, individuals may be said to occupy one of a discrete set of states and interest centers on the transition process between states. For example, states may refer to the number of recurrences of an event, or the stage of a disease. We develop a hierarchical modeling framework for the analysis of such longitudinal data when the processes corresponding to different subjects may be correlated spatially over a region. Continuous-time Markov chains incorporating spatially correlated random effects are introduced. Here, joint modeling of both spatial dependence as well as dependence between different transition rates is required and a multivariate spatial approach is employed. A proportional intensities frailty model is developed where baseline intensity functions are modeled using parametric Weibull forms, piecewise-exponential formulations, and flexible representations based on cubic B-splines. The methodology is developed within the context of a study examining invasive cardiac procedures in Quebec. We consider patients admitted for acute coronary syndrome throughout the 139 local health units of the province and examine readmission and mortality rates over a 4-year period.     

Latent Class Modeling Approaches for Assessing Diagnostic Error without a Gold Standard: With Applications to p53 Immunohistochemical Assays in Bladder Tumors

Improved characterization of tumors for purposes of guiding treatment decisions for cancer patients will require that accurate and reproducible assays be developed for a variety of tumor markers. No gold standards exist for most tumor marker assays. Therefore, estimates of assay sensitivity and specificity cannot be obtained unless a latent class model-based approach is used. Our goal in this article is to estimate sensitivity and specificity for p53 immunohistochemical assays of bladder tumors using data from a reproducibility study conducted by the National Cancer Institute Bladder Tumor Marker Network. We review latent class modeling approaches proposed by previous authors, and we find that many of these approaches impose assumptions about specimen heterogeneity that are not consistent with the biology of bladder tumors. We present flexible mixture model alternatives that are biologically plausible for our example, and we use them to estimate sensitivity and specificity for our p53 assay example. These mixture models are shown to offer an improvement over other methods in a variety of settings, but we caution that, in general, care must be taken in applying latent class models.     

长尾姬鼠分类地位的探讨

长期以来长尾姬鼠（Ａｐｏｄｅｍｕｓ ｏｒｅｓｔｅｓ）的分类地位一直不确定。基于在云南中部无量山区采集的大量姬鼠类标本,经单变量和多变量分析,长尾姬鼠明显区别于中华姬鼠（Ａ．ｄｒａｃｏ）。主要鉴别特征在于体长、尾长及尾长与本长的比例,且相关分析表明,该两种的尾长与体长具显著的相关性。而对无量山姬鼠的生态地理分布研究显示,长尾姬鼠与中华姬鼠具完全同域分布,因此认为长尾姬鼠是一有效种。无量山区现有姬鼠３     

Molecular characterization of lactic acid bacteria from sourdough breads produced in Sardinia (Italy) and multivariate statistical analyses of results

The objective of this work was to investigate the structure and diversity of lactic acid bacteria (LAB) communities in sourdough used for the production of traditional breads (Carasau, Moddizzosu, Spianata, Zichi) in Sardinia. 16S rDNA sequencing and Randomly Amplified Polymorphic DNA (RAPD-PCR) was applied for the identification and typing of the LAB isolated from 25 samples of sourdoughs. Multivariate statistical techniques were applied to RAPD-PCR pattern to study the biological diversity of sourdough samples. Twelve different species of LAB were identified, and most isolates were classified as facultative heterofermentative lactobacilli. Lactobacillus pentosus dominated the lactic microflora of many samples while Lactobacillus sanfranciscensis was isolated only from a limited number of samples. Although heterofermentative species represented between between 30% and 60% of the isolates in Carasau, Spianata and Zichi sourdoughs, only 2% of the isolates from Moddizzosu sourdoughs were identified as heterofermentative LAB. RAPD-PCR with a single primer followed by cluster analysis did not allow the identification of the isolates at the species level. However, a multidimensional scaling/bootstrapping approach on the RAPD-PCR patterns uncovered the diversity of the LAB communities of LAB showing differences both within and between bread types.     

A sterol biosynthetic geneAtCYP51A2 promoter for constitutive and ectopic expression of a transgene in plants

Arabidopsis CYP51A2 (AtCYP51A2) mediates the sterol 14α-demethylation step inde novo sterol biosynthesis, and is constitutively and highly expressed in all plant tissues (Kim et al., 2005). We exploited the molecular features of its expression and the fundamental role of sterol biosynthesis in cells to develop a plant-derived promoter. Our GUS expression analysis between transgenicArabidopsis lines forAtCYP51A2::GUS and35S::GUS revealed that activity of theAtCYP51A2 promoter was comparable to that of the35S promoter, based on enzymatic activities and protein levels. TheAtCYP51A2 promoter was also constitutively active in transgenic tobacco, indicating that 5′ regulatory elements could be conserved amongCYP51 promoters in dicot plants. A homologue ofAtCYP51A2 was identified from rape seed, a crop species closely related toArabidopsis. Its constitutive tissue expression pattern implies that the application of thisAtCYP51A2 promoter is possible for that species. Based on these results, we present a new binary vector system with the plant-derivedAtCYP51A2 promoter, which is able to constitutively and ectopically drive a transgene in various dicotyledonous plants. These two authors are equally contributed to this work.     

Multivariate chromatographic fingerprint preparation and authentication of plant material from the genus Bauhinia

Multivariate analysis and statistical mixture designs were used for chromatographic fingerprint preparation and authentication of the plant material of three species of the genus Bauhinia. The extracts were analysed by reversed-phase high-performance liquid chromatography. Mixture design gave an optimum solvent composition for extracting components from the plants of 36% dichloromethane, 17% ethanol and 47% ethyl acetate (by volume), while an optimum mobile phase for chromatographic analyses was found to be 27% methanol, 27% acetonitrile and 46% of water (by volume). Results from principal component analysis, hierarchical analysis and soft independent modelling by class analogy showed that Bauhinia candicans cannot be synonymous with B. forficata Link. It was also possible to trace the metabolic profile without identifying its chemical constituents and to determine a chromatographic discriminating region. The characteristics responsible for discrimination between B. candicans and B. forficata were more polar substances that presented peaks with retention times around 1.65 and 1.81 min.     

Human activity facilitates altitudinal expansion of exotic plants along a road in montane grassland,South Africa

Question: Do anthropogenic activities facilitate the distribution of exotic plants along steep altitudinal gradients? Location: Sani Pass road, Grassland biome, South Africa. Methods: On both sides of this road, presence and abundance of exotic plants was recorded in four 25‐m long road‐verge plots and in parallel 25 m x 2 m adjacent land plots, nested at five altitudinal levels: 1500, 1800, 2100, 2400 and 2700 m a.s.l. Exotic community structure was analyzed using Canonical Correspondence Analysis while a two‐level nested Generalized Linear Model was fitted for richness and cover of exotics. We tested the upper altitudinal limits for all exotics along this road for spatial clustering around four potential propagule sources using a t‐test. Results: Community structure, richness and abundance of exotics were negatively correlated with altitude. Greatest invasion by exotics was recorded for adjacent land at the 1500 m level. Of the 45 exotics, 16 were found at higher altitudes than expected and observations were spatially clustered around potential propagule sources. Conclusions: Spatial clustering of upper altitudinal limits around human inhabited areas suggests that exotics originate from these areas, while exceeding expected altitudinal limits suggests that distribution ranges of exotics are presently underestimated. Exotics are generally characterised by a high propagule pressure and/or persistent seedbanks, thus future tarring of the Sani Pass may result in an increase of exotic species richness and abundance. This would initially result from construction‐related soil disturbance and subsequently from increased traffic, water run‐off, and altered fire frequency. We suggest examples of management actions to prevent this.     

Worms by number

This paper investigates alternation patterns in length, shape and orientation of dorsal cirri (fleshy segmental appendages) of phyllodocidans, a large group of polychaete worms (Annelida). We document the alternation patterns in several families of Phyllodocida (Syllidae, Hesionidae, Sigalionidae, Polynoidae, Aphroditidae and Acoetidae) and identify the simple mathematical rule bases that describe the progression of these sequences. Two fundamentally different binary alternation patterns were found on the first four segments: 1011 for nereidiform families and 1010 for aphroditiform families. The alternation pattern in all aphroditiform families matches a simple one-dimensional cellular automaton and that for Syllidae (nereidiform) matches the Fibonacci string sequence. Hesionidae (nereidiform) showed the greatest variation in alternation patterns, but all corresponded to various known substitution rules. Comparison of binary patterns of the first 22 segments using a distance measure supports the current ideas on phylogeny within Phyllodocida. These results suggest that gene(s) involved in post-larval segmental growth employ a switching sequence that corresponds to simple mathematical substitution rules.     

A mini binary vector series for plant transformation

A streamlined mini binary vector was constructed that is less than 1/2 the size of the pBIN19 backbone (3.5 kb). This was accomplished by eliminating over 5 kb of non-T-DNA sequences from the pBIN19 vector. The vector still retains all the essential elements required for a binary vector. These include a RK2 replication origin, the nptIII gene conferring kanamycin resistance in bacteria, both the right and left T-DNA borders, and a multiple cloning site (MCS) in between the T-DNA borders to facilitate cloning. Due to the reduced size, more unique restriction sites are available in the MCS, thus allowing more versatile cloning. Since the traF region was not included, it is not possible to mobilize this binary vector into Agrobacterium by triparental mating. This problem can be easily resolved by direct transformation. The mini binary vector has been demonstrated to successfully transform Arabidopsis plants. Based on this mini binary vector, a series of binary vectors were constructed for plant transformation.     

Discrimination of Francisella tularensis subspecies using surface enhanced laser desorption ionization mass spectrometry and multivariate data analysis

Francisella tularensis causes the zoonotic disease tularemia, and is considered a potential bioterrorist agent due to its extremely low infection dose and potential for airborne transmission. Presently, F. tularensis is divided into four subspecies; tularensis, holarctica, mediasiatica and novicida. Phenotypic discrimination of the closely related subspecies with traditional methods is difficult and tedious. Furthermore, the results may be vague and they often need to be complemented with virulence tests in animals. Here, we have used surface enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF-MS) to discriminate between the four subspecies of F. tularensis. The method is based on the differential binding of protein subsets to chemically modified surfaces. Bacterial thermolysates were added to anionic, cationic, and copper ion-loaded immobilized metal affinity SELDI chip surfaces. After binding, washing, and SELDI-TOF-MS different protein profiles were obtained. The spectra generated from the different surfaces were then used to characterize each bacterial strain. The results showed that the method was reproducible, with an average intensity variation of 21%, and that the mass precision was good (300-450 ppm). Moreover, in subsequent cluster analysis and principal component analysis (PCA) data for the analyzed Francisella strains grouped according to the recognized subspecies. Partial least squares-discriminant analysis (PLS-DA) of the protein profiles also identified proteins that differed between the strains. Thus, the protein profiling approach based on SELDI-TOF-MS holds great promise for rapid high-resolution phenotypic identification of bacteria.