On the numerical integration of a class of singular perturbation problems

A three-point difference scheme recently proposed in Ref. 1 for the numerical solution of a class of linear, singularly perturbed, two-point boundary-value problems is investigated. The scheme is derived from a first-order approximation to the original problem with a small deviating argument. It is shown here that, in the limit, as the deviating argument tends to zero, the difference scheme converges to a one-sided approximation to the original singularly perturbed equation in conservation form. The limiting scheme is shown to be stable on any uniform grid. Therefore, no advantage arises from using the deviating argument, and the most accurate and efficient results are obtained with the deviation at its zero limit.

Integration of a 3D Variational data assimilation scheme with a coastal area morphodynamic model of Morecambe Bay

This paper describes the implementation of a 3D variational (3D-Var) data assimilation scheme for a morphodynamic model applied to Morecambe Bay, UK. A simple decoupled hydrodynamic and sediment transport model is combined with a data assimilation scheme to investigate the ability of such methods to improve the accuracy of the predicted bathymetry. The inverse forecast error covariance matrix is modelled using a Laplacian approximation which is calibrated for the length scale parameter required. Calibration is also performed for the Soulsby-van Rijn sediment transport equations. The data used for assimilation purposes comprises waterlines derived from SAR imagery covering the entire period of the model run, and swath bathymetry data collected by a ship-borne survey for one date towards the end of the model run. A LiDAR survey of the entire bay carried out in November 2005 is used for validation purposes. The comparison of the predictive ability of the model alone with the model-forecast-assimilation system demonstrates that using data assimilation significantly improves the forecast skill. An investigation of the assimilation of the swath bathymetry as well as the waterlines demonstrates that the overall improvement is initially large, but decreases over time as the bathymetry evolves away from that observed by the survey. The result of combining the calibration runs into a pseudo-ensemble provides a higher skill score than for a single optimized model run. A brief comparison of the Optimal Interpolation assimilation method with the 3D-Var method shows that the two schemes give similar results.

Structural spoilers or structural supports? Unionism and the strategic integration of HR functions

The strategic integration of the human resource (HR) function is regarded as crucial in the literature on (strategic) human resource management ((S)HRM). Evidence on the contextual or structural influences on this integration is, however, limited. The structural implications of unionism are particularly intriguing given the evolution of study of the employment relationship. Pluralism is typically seen as antithetical to SHRM, and unions as an impediment to the strategic integration of HR functions, but there are also suggestions in the literature that unionism might facilitate the strategic integration of HR. This paper deploys large-scale international survey evidence to examine the organization-level influence of unionism on this strategic integration, allowing for other established and plausible influences. The analysis reveals that exceptionally, where the organization-level role of unions is particularly contested, unionism does impede the strategic integration of HR. However, it is the predominance of the facilitation of the strategic integration of HR by unionism which is most remarkable.

The integration of proteomics and systems approaches to map regulatory mechanisms underpinning platelet function.

Platelets in the circulation are triggered by vascular damage to activate, aggregate and form a thrombus that prevents excessive blood loss. Platelet activation is stringently regulated by intracellular signalling cascades, which when activated inappropriately lead to myocardial infarction and stroke. Strategies to address platelet dysfunction have included proteomics approaches which have lead to the discovery of a number of novel regulatory proteins of potential therapeutic value. Global analysis of platelet proteomes may enhance the outcome of these studies by arranging this information in a contextual manner that recapitulates established signalling complexes and predicts novel regulatory processes. Platelet signalling networks have already begun to be exploited with interrogation of protein datasets using in silico methodologies that locate functionally feasible protein clusters for subsequent biochemical validation. Characterization of these biological systems through analysis of spatial and temporal organization of component proteins is developing alongside advances in the proteomics field. This focused review highlights advances in platelet proteomics data mining approaches that complement the emerging systems biology field. We have also highlighted nucleated cell types as key examples that can inform platelet research. Therapeutic translation of these modern approaches to understanding platelet regulatory mechanisms will enable the development of novel anti-thrombotic strategies.

Continuity of care for people with psychotic illness: its relationship to clinical and social functioning.

Background: The relationship between continuity of care and user characteristics or outcomes has rarely been explored. The ECHO study operationalized and tested a multi-axial definition of continuity of care, producing a seven-factor model used here. Aims: To assess the relationship between user characteristics and established components of continuity of care, and the impact of continuity on clinical and social functioning. Methods: The sample comprised 180 community mental health team users with psychotic disorders who were interviewed at three annual time-points, to assess their experiences of continuity of care and clinical and social functioning. Scores on seven continuity factors were tested for association with user-level variables. Results: Improvement in quality of life was associated with better Experience & Relationship continuity scores (better user-rated continuity and therapeutic relationship) and with lower Meeting Needs continuity factor scores. Higher Meeting Needs scores were associated with a decrease in symptoms. Conclusion: Continuity is a dynamic process, influenced significantly by care structures and organizational change.

Continuity of care for carers of people with severe mental illness: results of a longitudinal study

Introduction: Continuity of care has been demonstrated to be important for service users and carer groups have voiced major concerns over disruptions of care. We aimed to assess the experienced continuity of care in carers of patients with both psychotic and non-psychotic disorders and explore its association with carer characteristics and psychological well-being. Methods: Friends and relatives caring for two groups of service users in the care of community mental health teams (CMHTs), 69 with psychotic and 38 with non-psychotic disorders, were assessed annually at three and two time points, respectively. CONTINUES, a measure specifically designed to assess continuity of care for carers themselves, was utilized along with assessments of psychological well-being and caregiving. Results: One hundred and seven carers participated. They reported moderately low continuity of care. Only 22 had had a carer’s assessment and just under a third recorded psychological distress on the GHQ. For those caring for people with psychotic disorders, reported continuity was higher if the carer was male, employed, lived with the user and had had a carer’s assessment; for those caring for people with non-psychotic disorders, it was higher if the carer was from the service user’s immediate family, lived with them and had had a carer’s assessment. Conclusion: The vast majority of the carers had not had a carer’s assessment provided by the CMHT despite this being a clear national priority and being an intervention with obvious potential to increase carers’ reported low levels of continuity of care. Improving continuity of contact with carers may have an important part to play in the overall improvement of care in this patient group and deserves greater attention.

Integration of Space and In Situ Observations to Study Global Climate Change

The currently available model-based global data sets of atmospheric circulation are a by-product of the daily requirement of producing initial conditions for numerical weather prediction (NWP) models. These data sets have been quite useful for studying fundamental dynamical and physical processes, and for describing the nature of the general circulation of the atmosphere. However, due to limitations in the early data assimilation systems and inconsistencies caused by numerous model changes, the available model-based global data sets may not be suitable for studying global climate change. A comprehensive analysis of global observations based on a four-dimensional data assimilation system with a realistic physical model should be undertaken to integrate space and in situ observations to produce internally consistent, homogeneous, multivariate data sets for the earth's climate system. The concept is equally applicable for producing data sets for the atmosphere, the oceans, and the biosphere, and such data sets will be quite useful for studying global climate change.

Integration of retrotransposons-based markers in a linkage map of barley

A deeper understanding of random markers is important if they are to be employed for a range of objectives. The sequence specific amplified polymorphism (S-SAP) technique is a powerful genetic analysis tool which exploits the high copy number of retrotransposon long terminal repeats (LTRs) in the plant genome. The distribution and inheritance of S-SAP bands in the barley genome was studied using the Steptoe × Morex (S × M) double haploid (DH) population. Six S-SAP primer combinations generated 98 polymorphic bands, and map positions were assigned to all but one band. Eight putative co-dominant loci were detected, representing 16 of the mapped markers. Thus at least 81 of the mapped S-SAP loci were dominant. The markers were distributed along all of the seven chromosomes and a tendency to cluster was observed. The distribution of S-SAP markers over the barley genome concurred with the knowledge of the high copy number of retrotransposons in plants. This experiment has demonstrated the potential for the S-SAP technique to be applied in a range of analyses such as genetic fingerprinting, marker assisted breeding, biodiversity assessment and phylogenetic analyses.

Towards a model-based integration of co-registered electroencephalography/functional magnetic resonance imaging data with realistic neural population meshes

Brain activity can be measured with several non-invasive neuroimaging modalities, but each modality has inherent limitations with respect to resolution, contrast and interpretability. It is hoped that multimodal integration will address these limitations by using the complementary features of already available data. However, purely statistical integration can prove problematic owing to the disparate signal sources. As an alternative, we propose here an advanced neural population model implemented on an anatomically sound cortical mesh with freely adjustable connectivity, which features proper signal expression through a realistic head model for the electroencephalogram (EEG), as well as a haemodynamic model for functional magnetic resonance imaging based on blood oxygen level dependent contrast (fMRI BOLD). It hence allows simultaneous and realistic predictions of EEG and fMRI BOLD from the same underlying model of neural activity. As proof of principle, we investigate here the influence on simulated brain activity of strengthening visual connectivity. In the future we plan to fit multimodal data with this neural population model. This promises novel, model-based insights into the brain's activity in sleep, rest and task conditions.

Realistic mean field forward predictions for the integration of co-registered EEG/fMRI

Brain activity can be measured non-invasively with functional imaging techniques. Each pixel in such an image represents a neural mass of about 105 to 107 neurons. Mean field models (MFMs) approximate their activity by averaging out neural variability while retaining salient underlying features, like neurotransmitter kinetics. However, MFMs incorporating the regional variability, realistic geometry and connectivity of cortex have so far appeared intractable. This lack of biological realism has led to a focus on gross temporal features of the EEG. We address these impediments and showcase a "proof of principle" forward prediction of co-registered EEG/fMRI for a full-size human cortex in a realistic head model with anatomical connectivity, see figure 1. MFMs usually assume homogeneous neural masses, isotropic long-range connectivity and simplistic signal expression to allow rapid computation with partial differential equations. But these approximations are insufficient in particular for the high spatial resolution obtained with fMRI, since different cortical areas vary in their architectonic and dynamical properties, have complex connectivity, and can contribute non-trivially to the measured signal. Our code instead supports the local variation of model parameters and freely chosen connectivity for many thousand triangulation nodes spanning a cortical surface extracted from structural MRI. This allows the introduction of realistic anatomical and physiological parameters for cortical areas and their connectivity, including both intra- and inter-area connections. Proper cortical folding and conduction through a realistic head model is then added to obtain accurate signal expression for a comparison to experimental data. To showcase the synergy of these computational developments, we predict simultaneously EEG and fMRI BOLD responses by adding an established model for neurovascular coupling and convolving "Balloon-Windkessel" hemodynamics. We also incorporate regional connectivity extracted from the CoCoMac database [1]. Importantly, these extensions can be easily adapted according to future insights and data. Furthermore, while our own simulation is based on one specific MFM [2], the computational framework is general and can be applied to models favored by the user. Finally, we provide a brief outlook on improving the integration of multi-modal imaging data through iterative fits of a single underlying MFM in this realistic simulation framework.

Structural spoilers or structural supports? Unions and the strategic integration of HR functions

The strategic integration of the human resource (HR) function is regarded as crucial in the literature on (strategic) human resource management ((S)HRM). Evidence on the contextual or structural influences on this integration is, however, limited. The structural implications of unionism are particularly intriguing given the evolution of study of the employment relationship. Pluralism is typically seen as antithetical to SHRM, and unions as an impediment to the strategic integration of HR functions, but there are also suggestions in the literature that unionism might facilitate the strategic integration of HR. This paper deploys large-scale international survey evidence to examine the organization-level influence of unionism on this strategic integration, allowing for other established and plausible influences. The analysis reveals that exceptionally, where the organization-level role of unions is particularly contested, unionism does impede the strategic integration of HR. However, it is the predominance of the facilitation of the strategic integration of HR by unionism which is most remarkable.

The integration of lipid-sensing and anti-inflammatory effects: how the PPARs play a role in metabolic balance

The peroxisomal proliferating-activated receptors (PPARs) are lipid-sensing transcription factors that have a role in embryonic development, but are primarily known for modulating energy metabolism, lipid storage, and transport, as well as inflammation and wound healing. Currently, there is no consensus as to the overall combined function of PPARs and why they evolved. We hypothesize that the PPARs had to evolve to integrate lipid storage and burning with the ability to reduce oxidative stress, as energy storage is essential for survival and resistance to injury/infection, but the latter increases oxidative stress and may reduce median survival (functional longevity). In a sense, PPARs may be an evolutionary solution to something we call the 'hypoxia-lipid' conundrum, where the ability to store and burn fat is essential for survival, but is a 'double-edged sword', as fats are potentially highly toxic. Ways in which PPARs may reduce oxidative stress involve modulation of mitochondrial uncoupling protein (UCP) expression (thus reducing reactive oxygen species, ROS), optimising forkhead box class O factor (FOXO) activity (by improving whole body insulin sensitivity) and suppressing NFkB (at the transcriptional level). In light of this, we therefore postulate that inflammation-induced PPAR downregulation engenders many of the signs and symptoms of the metabolic syndrome, which shares many features with the acute phase response (APR) and is the opposite of the phenotype associated with calorie restriction and high FOXO activity. In genetically susceptible individuals (displaying the naturally mildly insulin resistant 'thrifty genotype'), suboptimal PPAR activity may follow an exaggerated but natural adipose tissue-related inflammatory signal induced by excessive calories and reduced physical activity, which normally couples energy storage with the ability to mount an immune response. This is further worsened when pancreatic decompensation occurs, resulting in gluco-oxidative stress and lipotoxicity, increased inflammatory insulin resistance and oxidative stress. Reactivating PPARs may restore a metabolic balance and help to adapt the phenotype to a modern lifestyle.

Ethics of care in supporting disabled forced migrants: interactions with professionals and ethical dilemmas in health and social care in the South-East of England

This article explores the interactions between disabled forced migrants with care needs and professionals and the restrictive legal, policy and practice context that health and social care professionals have to confront, based on the findings of a qualitative study with 45 participants in the South-East of England. In-depth interviews were conducted with 15 forced migrants who had diverse impairments and chronic illnesses (8 women and 7 men), 13 family caregivers and 17 support workers and strategic professionals working in social care and the third sector in Slough, Reading and London. The legal status of forced migrants significantly affects their entitlements to health and social care provision, resulting in prolonged periods of destitution for many families. National asylum support policies, difficult working relationships with UK Border Agency, higher eligibility thresholds and reduced social care budgets of local authorities were identified as significant barriers in responding to the support needs of disabled forced migrants and family caregivers. In this context, social workers experienced considerable ethical dilemmas. The research raises profound questions about the potential and limitations of health and social care policies, provision, and practice as means of protection and support in fulfilling the human rights of forced migrants with care needs.