Resource Modelling: The Missing Piece of the HTA Jigsaw?

Within health technology assessment (HTA), cost-effectiveness analysis and budget impact analyses have been broadly accepted as important components of decision making. However, whilst they address efficiency and affordability, the issue of implementation and feasibility has been largely ignored. HTA commonly takes place within a deliberative framework that captures issues of implementation and feasibility in a qualitative manner. We argue that only through a formal quantitative assessment of resource constraints can these issues be fully addressed. This paper argues the need for resource modelling to be considered explicitly in HTA. First, economic evaluation and budget impact models are described along with their limitations in evaluating feasibility. Next, resource modelling is defined and its usefulness is described along with examples of resource modelling from the literature. Then, the important issues that need to be considered when undertaking resource modelling are described before setting out recommendations for the use of resource modelling in HTA

Proteotypic classification of spontaneous and transgenic mammary neoplasms

INTRODUCTION: Mammary tumors in mice are categorized by using morphologic and architectural criteria. Immunolabeling for terminal differentiation markers was compared among a variety of mouse mammary neoplasms because expression of terminal differentiation markers, and especially of keratins, provides important information on the origin of neoplastic cells and their degree of differentiation. METHODS: Expression patterns for terminal differentiation markers were used to characterize tumor types and to study tumor progression in transgenic mouse models of mammary neoplasia (mice overexpressing Neu (Erbb2), Hras, Myc, Notch4, SV40-TAg, Tgfa, and Wnt1), in spontaneous mammary carcinomas, and in mammary neoplasms associated with infection by the mouse mammary tumor virus (MMTV). RESULTS: On the basis of the expression of terminal differentiation markers, three types of neoplasm were identified: first, simple carcinomas composed exclusively of cells with a luminal phenotype are characteristic of neoplasms arising in mice transgenic for Neu, Hras, Myc, Notch4, and SV40-TAg; second, 'complex carcinomas' displaying luminal and myoepithelial differentiation are characteristic of type P tumors arising in mice transgenic for Wnt1, neoplasms arising in mice infected by the MMTV, and spontaneous adenosquamous carcinomas; and third, 'carcinomas with epithelial to mesenchymal transition (EMT)' are a characteristic feature of tumor progression in Hras-, Myc-, and SV40-TAg-induced mammary neoplasms and PL/J and SJL/J mouse strains, and display de novo expression of myoepithelial and mesenchymal cell markers. In sharp contrast, EMT was not detected in papillary adenocarcinomas arising in BALB/cJ mice, spontaneous adenoacanthomas, neoplasms associated with MMTV-infection, or in neoplasms arising in mice transgenic for Neu and Wnt1. CONCLUSIONS: Immunohistochemical profiles of complex neoplasms are consistent with a stem cell origin, whereas simple carcinomas might originate from a cell committed to the luminal lineage. In addition, these results suggest that the initiating oncogenic events determine the morphologic features associated with cancer progression because EMT is observed only in certain types of neoplasm

Novel Genotypes of H9N2 Influenza A Viruses Isolated from Poultry in Pakistan Containing NS Genes Similar to Highly Pathogenic H7N3 and H5N1 Viruses

The impact of avian influenza caused by H9N2 viruses in Pakistan is now significantly more severe than in previous years. Since all gene segments contribute towards the virulence of avian influenza virus, it was imperative to investigate the molecular features and genetic relationships of H9N2 viruses prevalent in this region. Analysis of the gene sequences of all eight RNA segments from 12 viruses isolated between 2005 and 2008 was undertaken. The hemagglutinin (HA) sequences of all isolates were closely related to H9N2 viruses isolated from Iran between 2004 and 2007 and contained leucine instead of glutamine at position 226 in the receptor binding pocket, a recognised marker for the recognition of sialic acids linked α2–6 to galactose. The neuraminidase (NA) of two isolates contained a unique five residue deletion in the stalk (from residues 80 to 84), a possible indication of greater adaptation of these viruses to the chicken host. The HA, NA, nucleoprotein (NP), and matrix (M) genes showed close identity with H9N2 viruses isolated during 1999 in Pakistan and clustered in the A/Quail/Hong Kong/G1/97 virus lineage. In contrast, the polymerase genes clustered with H9N2 viruses from India, Iran and Dubai. The NS gene segment showed greater genetic diversity and shared a high level of similarity with NS genes from either H5 or H7 subtypes rather than with established H9N2 Eurasian lineages. These results indicate that during recent years the H9N2 viruses have undergone extensive genetic reassortment which has led to the generation of H9N2 viruses of novel genotypes in the Indian sub-continent. The novel genotypes of H9N2 viruses may play a role in the increased problems observed by H9N2 to poultry and reinforce the continued need to monitor H9N2 infections for their zoonotic potential

A Genome Wide Association Study of arabinoxylan content in 2-row spring barley grain

In barley endosperm arabinoxylan (AX) is the second most abundant cell wall polysaccharide and in wheat it is the most abundant polysaccharide in the starchy endosperm walls of the grain. AX is one of the main contributors to grain dietary fibre content providing several health benefits including cholesterol and glucose lowering effects, and antioxidant activities. Due to its complex structural features, AX might also affect the downstream applications of barley grain in malting and brewing. Using a high pressure liquid chromatography (HPLC) method we quantified AX amounts in mature grain in 128 spring 2-row barley accessions. Amounts ranged from ~ 5.2 μg/g to ~ 9 μg/g. We used this data for a Genome Wide Association Study (GWAS) that revealed three significant quantitative trait loci (QTL) associated with grain AX levels which passed a false discovery threshold (FDR) and are located on two of the seven barley chromosomes. Regions underlying the QTLs were scanned for genes likely to be involved in AX biosynthesis or turnover, and strong candidates, including glycosyltransferases from the GT43 and GT61 families and glycoside hydrolases from the GH10 family, were identified. Phylogenetic trees of selected gene families were built based on protein translations and were used to examine the relationship of the barley candidate genes to those in other species. Our data reaffirms the roles of existing genes thought to contribute to AX content, and identifies novel QTL (and candidate genes associated with them) potentially influencing the AX content of barley grain. One potential outcome of this work is the deployment of highly associated single nucleotide polymorphisms markers in breeding programs to guide the modification of AX abundance in barley grain

Inter-population differences in diving behaviour of adult male southern elephant seals (Mirounga leonina)

Access to different environments may lead to inter-population behavioural changes within a species that allow populations to exploit their immediate environments. Elephant seals from Marion Island (MI) and King George Island (KGI) (Isla 25 de Mayo) forage in different oceanic environments and evidently employ different foraging strategies. This study elucidates some of the factors influencing the diving behaviour of male southern elephant seals from these populations tracked between 1999 and 2002. Mixed-effects models were used to determine the influence of bathymetry, population of origin, body length (as a proxy for size) and individual variation on the diving behaviour of adult male elephant seals from the two populations. Males from KGI and MI showed differences in all dive parameters. MI males dived deeper and longer (median: 652.0 m and 34.00 min) than KGI males (median: 359.1 m and 25.50 min). KGI males appeared to forage both benthically and pelagically while MI males in this study rarely reached depths close to the seafloor and appeared to forage pelagically. Model outputs indicate that males from the two populations showed substantial differences in their dive depths, even when foraging in areas of similar water depth. Whereas dive depths were not significantly influenced by the size of the animals, size played a significant role in dive durations, though this was also influenced by the population that elephant seals originated from. This study provides some support for inter-population differences in dive behaviour of male southern elephant seals