Resource stability and geographic isolation are associated with genome divergence in western Palearctic crossbills.

While many conifers produce annually variable seed crops, serotinous species (which hold seeds in cones for multiple years) represent unusually stable food resources for seed predators. Such stability is conducive to residency and potentially population divergence of consumers as exemplified by the Cassia crossbill (Loxia sinesciuris) in North America. We used genotyping by sequencing (GBS) to test whether three Mediterranean subspecies of common crossbills (L. curvirostra) associated with the serotinous Aleppo pine (Pinus halepensis) were more genetically distinct than European crossbills associated with nonserotinous conifers. We assembled a Cassia crossbill draft genome as a reference for mapping GBS reads and as a first step towards a more contiguous genome assembly. We found clear patterns of genetic divergence for each of the P. halepensis-associated subspecies. Geographic isolation, as promoted by resource stability and residency, is associated with genetic divergence of two of these subspecies. However, geographic isolation cannot account for divergence of L. c. hispana. Instead, resource stability likely contributed to divergence by reducing dispersal and increasing resource competition that may limit breeding by immigrants. In contrast, we found no differentiation among common crossbills associated with less stable resources, and only slight differentiation between common crossbills and parrot crossbills (L. pytyopsittacus). The substantial morphological divergence between common and parrot crossbills has likely originated or been maintained by selection despite gene flow generated by spatiotemporal resource fluctuation. Our results indicate that phenological as well as morphological characteristics of conifers have influenced crossbill diversification, and suggest a possible link between resource stability and population divergence.

A national survey of computerized decision support systems available to nurses in England.

AIM: To examine the characteristics of computerized decision support systems (CDSS) currently available to nurses working in the National Health Service (NHS) in England. METHOD: A questionnaire survey sent to a stratified random sample of 50% of all NHS care providers (Trusts) in England, asking respondents to provide information on CDSS currently used by nurses. RESULTS: Responses were received from 108 of the 277 Trusts included in the sample. Electronic patient record systems were the most common type of CDSS reported by Trusts (n = 61) but they were least likely to have features that have been associated with improved clinical outcomes. CONCLUSIONS: The availability of CDSS with features that have been associated with improved patient outcomes for nurses in the NHS in England is limited. There is some evidence that the nature of the Trust affects whether or not nurses have access to CDSS to assist their decision making. IMPLICATIONS FOR NURSING MANAGEMENT: The implementation of CDSS is increasing throughout the NHS. Many CDSS are introduced without adequate evidence to support its introduction and there is little evaluation of the benefits once they are implemented. Policy makers and nursing management should consider whether the introduction of CDSS aids nurse decision making and benefits patient outcomes.

Population structure of Purple Sandpipers (Calidris maritima) as revealed by mitochondrial DNA and microsatellites.

The Purple Sandpiper (Calidris maritima) is a medium-sized shorebird that breeds in the Arctic and winters along northern Atlantic coastlines. Migration routes and affiliations between breeding grounds and wintering grounds are incompletely understood. Some populations appear to be declining, and future management policies for this species will benefit from understanding their migration patterns. This study used two mitochondrial DNA markers and 10 microsatellite loci to analyze current population structure and historical demographic trends. Samples were obtained from breeding locations in Nunavut (Canada), Iceland, and Svalbard (Norway) and from wintering locations along the coast of Maine (USA), Nova Scotia, New Brunswick, and Newfoundland (Canada), and Scotland (UK). Mitochondrial haplotypes displayed low genetic diversity, and a shallow phylogeny indicating recent divergence. With the exception of the two Canadian breeding populations from Nunavut, there was significant genetic differentiation among samples from all breeding locations; however, none of the breeding populations was a monophyletic group. We also found differentiation between both Iceland and Svalbard breeding populations and North American wintering populations. This pattern of divergence is consistent with a previously proposed migratory pathway between Canadian breeding locations and wintering grounds in the United Kingdom, but argues against migration between breeding grounds in Iceland and Svalbard and wintering grounds in North America. Breeding birds from Svalbard also showed a genetic signature intermediate between Canadian breeders and Icelandic breeders. Our results extend current knowledge of Purple Sandpiper population genetic structure and present new information regarding migration routes to wintering grounds in North America.

An information-driven approach to pharmacogenomics.

Effective information management of the pharmacogenomics discipline presents many unique challenges. Genetic and genomic data generated via high-throughput methods need to be integrated with phenotypic data which are defined at multiscale levels, ranging from the molecular to the clinical level. Repositories storing these data are distributed and vary in terms of syntax and semantics which result in issues concerning data exchange and integration. The application of the emerging semantic web offers a promising solution to these interoperability issues.

An overview of cardiac morphogenesis.

Accurate knowledge of normal cardiac development is essential for properly understanding the morphogenesis of congenital cardiac malformations that represent the most common congenital anomaly in newborns. The heart is the first organ to function during embryonic development and is fully formed at 8 weeks of gestation. Recent studies stemming from molecular genetics have allowed specification of the role of cellular precursors in the field of heart development. In this article we review the different steps of heart development, focusing on the processes of alignment and septation. We also show, as often as possible, the links between abnormalities of cardiac development and the main congenital heart defects. The development of animal models has permitted the unraveling of many mechanisms that potentially lead to cardiac malformations. A next step towards a better knowledge of cardiac development could be multiscale cardiac modelling.

Epithelial to mesenchymal transition-the roles of cell morphology, labile adhesion and junctional coupling.

Epithelial to mesenchymal transition (EMT) is a fundamental process during development and disease, including development of the heart valves and tumour metastases. An extended cellular Potts model was implemented to represent the behaviour emerging from autonomous cell morphology, labile adhesion, junctional coupling and cell motility. Computer simulations normally focus on these functional changes independently whereas this model facilitates exploration of the interplay between cell shape changes, adhesion and migration. The simulation model is fitted to an in vitro model of endocardial EMT, and agrees with the finding that Notch signalling increases cell-matrix adhesion in addition to modulating cell-cell adhesion.

Towards multiscale systems modeling of endocardial to mesenchymal transition.

Cell behavior during endocardial to mesenchymal transition (EMT) was simulated using the cellular Potts formalism in Compucell 3D. The processes of loss of endocardial cohesion and invasion into the extracellular matrix (ECM) were stimulated by changing surface energy parameters. The simulations match in vitro results which suggest that endocardial motility on the surface of collagen gel can be induced separately from 3D invasion of the gel, via Notch signaling in the absence of BMP2. A principle by which the rate of mitosis would regulate the monolayer was demonstrated; suggesting a route for Vascular Endothelial Growth Factor (VEGF) control of EMT. A conceptual model of the system of protein interactions during EMT was assembled from multiple studies. A route for subcellular models to be formalized as Systems Biology Markup Language (SBML) differential equations is indicated. Scale linking would be achieved through Compucell 3D periodically integrating the SBML models for each cell during a simulation run, and updating parameters for protein concentrations assigned to individual cells. The surface energy parameters for the cells would be recalculated at each step from their simulated protein concentrations. Such scale linking opens up the potential for complexity to be gradually introduced, while maintaining experimental validation.

Do multiple herbivores maintain chemical diversity of Scots pine monoterpenes?

A central issue in our understanding of the evolution of the diversity of plant secondary metabolites (PSMs) is whether or not compounds are functional, conferring an advantage to the plant, or non-functional. We examine the hypothesis that the diversity of monoterpene PSMs within a plant species (Scots pine Pinus sylvestris) may be explained by different compounds acting as defences against high-impact herbivores operating at different life stages. We also hypothesize that pairwise coevolution, with uncorrelated interactions, is more likely to result in greater PSM diversity, than diffuse coevolution. We tested whether up to 13 different monoterpenes in Scots pine were inhibitory to herbivory by slugs (Arion ater), bank voles (Clethrionomys glareolus), red deer (Cervus elaphus) and capercaillie (Tetrao urogallus), each of which attack trees at a different life stage. Plants containing more α-pinene were avoided by both slugs and capercaillie, which may act as reinforcing selective agents for this dominant defensive compound. Herbivory by red deer and capercaillie were, respectively, weakly negatively associated with δ(3)-carene, and strongly negatively correlated with the minor compound ß-ocimene. Three of the four herbivores are probably contributory selective agents on some of the terpenes, and thus maintain some, but by no means all, of the phytochemical diversity in the species. The correlated defensive function of α-pinene against slugs and capercaillie is consistent with diffuse coevolutionary processes.

Simultaneous screening for osteoporosis at CT colonography: bone mineral density assessment using MDCT attenuation techniques compared with the DXA reference standard.

The purpose of this study was to evaluate the utility of lumbar spine attenuation measurement for bone mineral density (BMD) assessment at screening computed tomographic colonography (CTC) using central dual-energy X-ray absorptiometry (DXA) as the reference standard. Two-hundred and fifty-two adults (240 women and 12 men; mean age 58.9 years) underwent CTC screening and central DXA BMD measurement within 2 months (mean interval 25.0 days). The lowest DXA T-score between the spine and hip served as the reference standard, with low BMD defined per World Health Organization as osteoporosis (DXA T-score ≤ -2.5) or osteopenia (DXA T-score between -1.0 and -2.4). Both phantomless quantitative computed tomography (QCT) and simple nonangled region-of-interest (ROI) multi-detector CT (MDCT) attenuation measurements were applied to the T(12) -L(5) levels. The ability to predict osteoporosis and low BMD (osteoporosis or osteopenia) by DXA was assessed. A BMD cut-off of 90 mg/mL at phantomless QCT yielded 100% sensitivity for osteoporosis (29 of 29) and a specificity of 63.8% (143 of 224); 87.2% (96 of 110) below this threshold had low BMD and 49.6% (69 of 139) above this threshold had normal BMD at DXA. At L(1) , a trabecular ROI attenuation cut-off of 160 HU was 100% sensitive for osteoporosis (29 of 29), with a specificity of 46.4% (104 of 224); 83.9% (125 of 149) below this threshold had low BMD and 57.5% (59/103) above had normal BMD at DXA. ROI performance was similar at all individual T(12) -L(5) levels. At ROC analysis, AUC for osteoporosis was 0.888 for phantomless QCT [95% confidence interval (CI) 0.780-0.946] and ranged from 0.825 to 0.853 using trabecular ROIs at single lumbar levels (0.864; 95% CI 0.752-0.930 at multivariate analysis). Supine-prone reproducibility was better with the simple ROI method compared with QCT. It is concluded that both phantomless QCT and simple ROI attenuation measurements of the lumbar spine are effective for BMD screening at CTC with high sensitivity for osteoporosis, as defined by the DXA T-score.

Multiscale systems modeling of the tetralogy of Fallot.

This paper provides a first description of a multiscale systems modeling approach applied to the congenital birth defect known as the tetralogy of Fallot. The multiscale approach adopted owes a lot to the effort of the world-wide physiome consortium and the work of research groups within the European Union on the Virtual Physiological Human. Both a spatial scale and time scale are used to establish the systems boundaries of the application. The tetralogy of Fallot includes up to four simultaneously occurring anatomic abnormalities that underpin the defect. The use of finite state machines and cellular automata pave the way to understand the processes in time and space that contribute to the defect.

Innovation for personalization: a healthcare case study.

This paper describes a research and innovation platform for the development of ideas relating to the investigation of blood perfusion in peripheral tissue. The Loughborough Innovation Platform for Health Technologies (LIPHT) can be used to demonstrate the use of the research and innovation pipe-line in more than one dimension. For this paper the first dimension considered is that of 'blue sky' idea through to their exploitation for the benefit of users and at the same time creating a wealth stream; the second dimension is the changing market as the ideas develop--from a hospital-based instrument operated by clinicians through to a point and click device for the use by the knowledgeable layman in the community. The starting point for these developments is a medical device known to many people as the 'finger clip' that measures arterial blood oxygen saturation; the end point is an optical device capable of imaging blood perfusion.

Innovations in clinical trials informatics.

This paper will investigate innovations in information management for use in clinical trials. The application typifies a complex, adaptive, distributed and information-rich environment for which continuous innovation is necessary. Organisational innovation is highlighted as well as the technical innovations in workflow processes and their representation as an integrated set of web services. Benefits realization uncovers further innovations in the business strand of the work undertaken. Following the description of the development of this information management system, the semantic web is postulated as a possible solution to tame the complexity related to information management issues found within clinical trials support systems.

Mobile healthcare in the home environment.

Mobile healthcare provision in the home environment presents many challenges. Patients are becoming more informed about the management of chronic conditions and the use of technology to support the process is rising. Issues such as system interoperability, cost, security and training all have to be addressed to ensure effective use of mobile devices within the home healthcare arena. An aging population will impact upon traditional healthcare delivery methods.