Classification of perinatal deaths: Development of the Australian and New Zealand classifications

Classifications of perinatal deaths have been undertaken for surveillance of causes of death, but also for auditing individual deaths to identify suboptimal care at any level, so that preventive strategies may be implemented. This paper describes the history and development of the paired obstetric and neonatal Perinatal Society of Australia and New Zealand (PSANZ) classifications in the context of other classifications. The PSANZ Perinatal Death Classification is based on obstetric antecedent factors that initiated the sequence of events leading to the death, and was developed largely from the Aberdeen and Whitfield classifications. The PSANZ Neonatal Death Classification is based on fetal and neonatal factors associated with the death. The classifications, accessible on the PSANZ website (http://www.psanz.org), have definitions and guidelines for use, a high level of agreement between classifiers, and are now being used in nearly all Australian states and New Zealand.

Topological side-chain classification of beta-turns: Ideal motifs for peptidomimetic development

beta-turns are important topological motifs for biological recognition of proteins and peptides. Organic molecules that sample the side chain positions of beta-turns have shown broad binding capacity to multiple different receptors, for example benzodiazepines. beta-turns have traditionally been classified into various types based on the backbone dihedral angles (phi 2, psi 2, phi 3 and psi 3). Indeed, 57-68% of beta-turns are currently classified into 8 different backbone families (Type I, Type II, Type I', Type II', Type VIII, Type VIa1, Type VIa2 and Type VIb and Type IV which represents unclassified beta-turns). Although this classification of beta-turns has been useful, the resulting beta-turn types are not ideal for the design of beta-turn mimetics as they do not reflect topological features of the recognition elements, the side chains. To overcome this, we have extracted beta-turns from a data set of non-homologous and high-resolution protein crystal structures. The side chain positions, as defined by C-alpha-C-beta vectors, of these turns have been clustered using the kth nearest neighbor clustering and filtered nearest centroid sorting algorithms. Nine clusters were obtained that cluster 90% of the data, and the average intra-cluster RMSD of the four C-alpha-C-beta vectors is 0.36. The nine clusters therefore represent the topology of the side chain scaffold architecture of the vast majority of beta-turns. The mean structures of the nine clusters are useful for the development of beta-turn mimetics and as biological descriptors for focusing combinatorial chemistry towards biologically relevant topological space.

The properties of the International Classification of the External Cause of Injury when used as an instrument for injury prevention research

Objective: To demonstrate properties of the International Classification of the External Cause of Injury (ICECI) as a tool for use in injury prevention research. Methods: The Childhood Injury Prevention Study (CHIPS) is a prospective longitudinal follow up study of a cohort of 871 children 5 - 12 years of age, with a nested case crossover component. The ICECI is the latest tool in the International Classification of Diseases (ICD) family and has been designed to improve the precision of coding injury events. The details of all injury events recorded in the study, as well as all measured injury related exposures, were coded using the ICECI. This paper reports a substudy on the utility and practicability of using the ICECI in the CHIPS to record exposures. Interrater reliability was quantified for a sample of injured participants using the Kappa statistic to measure concordance between codes independently coded by two research staff. Results: There were 767 diaries collected at baseline and event details from 563 injuries and exposure details from injury crossover periods. There were no event, location, or activity details which could not be coded using the ICECI. Kappa statistics for concordance between raters within each of the dimensions ranged from 0.31 to 0.93 for the injury events and 0.94 and 0.97 for activity and location in the control periods. Discussion: This study represents the first detailed account of the properties of the ICECI revealed by its use in a primary analytic epidemiological study of injury prevention. The results of this study provide considerable support for the ICECI and its further use.

Molecular classification of cutaneous malignant melanoma by gene expression profiling

The most common human cancers are malignant neoplasms of the skin(1,2). Incidence of cutaneous melanoma is rising especially steeply, with minimal progress in non-surgical treatment of advanced disease(3,4). Despite significant effort to identify independent predictors of melanoma outcome, no accepted histopathological, molecular or immunohistochemical marker defines subsets of this neoplasm(2,3). Accordingly, though melanoma is thought to present with different 'taxonomic' forms, these are considered part of a continuous spectrum rather than discrete entities(2). Here we report the discovery of a subset of melanomas identified by mathematical analysis of gene expression in a series of samples. Remarkably, many genes underlying the classification of this subset are differentially regulated in invasive melanomas that form primitive tubular networks in vitro, a feature of some highly aggressive metastatic melanomas(5). Global transcript analysis can identify unrecognized subtypes of cutaneous melanoma and predict experimentally verifiable phenotypic characteristics that may be of importance to disease progression.