Discrete Conditional Phase-type models utilising classification trees: Application to modelling health service capacities

Discrete Conditional Phase-type (DC-Ph) models consist of a process component (survival distribution) preceded by a set of related conditional discrete variables. This paper introduces a DC-Ph model where the conditional component is a classification tree. The approach is utilised for modelling health service capacities by better predicting service times, as captured by Coxian Phase-type distributions, interfaced with results from a classification tree algorithm. To illustrate the approach, a case-study within the healthcare delivery domain is given, namely that of maternity services. The classification analysis is shown to give good predictors for complications during childbirth. Based on the classification tree predictions, the duration of childbirth on the labour ward is then modelled as either a two or three-phase Coxian distribution. The resulting DC-Ph model is used to calculate the number of patients and associated bed occupancies, patient turnover, and to model the consequences of changes to risk status.

RhoA protein expression correlates positively with degree of malignancy in astrocytomas

Astrocytic tumors are the most common intracranial neoplasms. Their prognoses correlate with a conventional morphological grading system that suffers from diagnostic subjectivity and hence, inter-observer inconsistency. A molecular marker that provides an objective reference for classification and prognostication of astrocytic tumors would be useful in diagnostic pathology. RhoA, a GTPase protein involved in cell migration and adhesion has been shown to be upregulated in a variety of human cancers. Based on direct analysis of clinical materials, our study demonstrates increased expression of RhoA in high-grade astrocytomas. This observation may be relevant to astrocytoma biology and the development of potential therapeutics against high-grade astrocytomas. Of more immediate consequence, utilization of this marker may aid in the routine pathological grading (and hence prognostication) of astrocytomas. (c) 2006 Elsevier Ireland Ltd. All rights reserved.

Tissue microarray study for classification of breast tumors

Clinical and pathological heterogeneity of breast cancer hinders selection of appropriate treatment for individual cases. Molecular profiling at gene or protein levels may elucidate the biological variance of tumors and provide a new classification system that correlates better with biological, clinical and prognostic parameters. We studied the immunohistochemical profile of a panel of seven important biomarkers using tumor tissue arrays. The tumor samples were then classified with a monothetic (binary variables) clustering algorithm. Two distinct groups of tumors are characterized by the estrogen receptor (ER) status and tumor grade (p = 0.0026). Four biomarkers, c-erbB2, Cox-2, p53 and VEGF, were significantly overexpressed in tumors with the ER-negative (ER-) phenotype. Eight subsets of tumors were further identified according to the expression status of VEGF, c-erbB2 and p53. The malignant potential of the ER-/VEGF+ subgroup was associated with the strong correlations of Cox-2 and c-erb132 with VEGF. Our results indicate that this molecular classification system, based on the statistical analysis of immunohistochemical profiling, is a useful approach for tumor grouping. Some of these subgroups have a relative genetic homogeneity that may allow further study of specific genetically-controlled metabolic pathways. This approach may hold great promise in rationalizing the application of different therapeutic strategies for different subgroups of breast tumors. (C) 2003 Elsevier Inc. All rights reserved.

Evolution in the deep sea: a combined analysis of the earliest diverging living chitons (Mollusca : Polyplacophora : Lepidopleurida)

Lepidopleurida is the earliest diverged group of living polyplacophoran molluscs. They are found predominantly in the deep sea, including sunken wood, cold seeps, other abyssal habitats, and a few species are found in shallow water. The group is morphologically identified by anatomical features of their gills, sensory aesthetes, and gametes. Their shell features closely resemble the oldest fossils that can be identified as modern polyplacophorans. We present the first molecular phylogenetic study of this group, and also the first combined phylogenetic analysis for any chiton, including three gene regions and 69 morphological characters. The results show that Lepidopleurida is unambiguously monophyletic, and the nine genera fall into five distinct clades, which partly support the current view of polyplacophoran taxonomy. The genus Hanleyella Sirenko, 1973 is included in the family Protochitonidae, and Ferreiraellidae constitutes another distinct clade. The large cosmopolitan genus Leptochiton Gray, 1847 is not monophyletic; Leptochiton and Leptochitonidae sensu stricto are restricted to North Atlantic and Mediterranean taxa. Leptochitonidae s. str. is sister to Protochitonidae. The results also suggest two separate clades independently inhabiting sunken wood substrates in the south-west Pacific. Antarctic and other chemosynthetic-dwelling species may be derived from wood-living species. Substantial taxonomic revision remains to be done to resolve lepidopleuran classification, but the phylogeny presented here is a dramatic step forward in clarifying the relationships within this interesting group.