4-dimensional local radial basis function interpolation of large, uniformly spaced datasets.

BACKGROUND AND OBJECTIVE: Large, uniformly spaced, complex and time varying datasets derived from high resolution medical image velocimetry can provide a wealth of information regarding small-scale transient physiological flow phenomena and pulsation of anatomical boundaries. However, there remains a need for interpolation techniques to effectively reconstruct a fully 4-dimensional functional relationship from this data. This paper presents a preliminary evaluation of a 4-dimensional local radial basis function (RBF) algorithm as a means of addressing this problem for laminar flows. METHODS: A 4D interpolation algorithm is proposed based on a Local Hermitian Interpolation (LHI) using a combination of multi-quadric RBF with a partition of unity scheme. The domain is divided into uniform sub-systems with size restricted to immediately neighbouring points. The validity of the algorithm is first established on a known 4D analytical dataset and a CFD based laminar flow phantom. Application is then demonstrated through characterisation of a large 4D laminar flow dataset obtained from magnetic resonance imaging (MRI) measurements of cerebrospinal fluid velocities in the brain. RESULTS: Performance of the algorithm is compared to that of a quad-linear interpolation, demonstrating favourable improvement in accuracy. The technique is shown to be robust, computationally efficient and capable of refined interpolation in Euclidean space and time. Application to MR velocimetry data is shown to produce promising results for the 4D reconstruction of the transient flow field and movement of the fluid boundaries at spatial and temporal locations intermediate to the original data. CONCLUSION: This study has demonstrated feasibility of an accurate, stable and efficient 4-dimensional local RBF interpolation method for large, transient laminar flow velocimetry datasets. The proposed approach does not suffer from ill-conditioning or high computational cost due to domain decomposition into local stencils where the RBF is only ever applied to a limited number of points. This work offers a potential tool to assist medical diagnoses and drug delivery through better understanding of physiological flow fields such as cerebrospinal fluid. Further work will evaluate the technique on a wider range of flow fields and against CFD simulation.

Folic acid supplementation does not decrease stillbirths and congenital malformations in a guide dog colony.

OBJECTIVES: To investigate if maternal folic acid supplementation (5 mg) is associated with a reduction of cleft palates, umbilical hernias, stillbirths and caesarean sections in a guide dog breeding colony. MATERIALS AND METHODS: Labrador retrievers, golden retrievers and Labrador/golden Crosses from the breeding colony of a professional guide dog training organisation were eligible for inclusion. Dams in the treatment group (n = 137) received 5 mg oral folic acid supplementation daily from the start of pro-oestrous through day 40 of gestation. A historical control group (n = 134) was selected from the previous calendar year for comparison. A logistic regression model identified the relative risk of disease (cleft palates, umbilical hernias, stillbirths and caesarean sections) for puppies whose dams did or did not receive folic acid supplementation. RESULTS: A total of 1917 puppies (890 control, 1027 treatment; from 294 litters) were produced during the entire study period, with 994 puppies (494 control, 500 treatment; from 144 litters) born to the subset of dams (n = 72) who produced litters during both the control and treatment periods. All 95% highest posterior densities of relative risk included 1.0, failing to detect differences between the treatment and control groups on incidence rate of cleft palate (control: 2.25%; treatment: 2.34%), umbilical hernias (control: 1.91%; treatment: 3.12%), stillbirths (control: 3.26%; treatment: 2.92%) and caesarean sections (control: 1.45%; treatment: 1.28%). CLINICAL SIGNIFICANCE: There was no observable reduction of cleft palate, umbilical hernia, stillbirth or caesarean section associated with folic acid supplementation during pregnancy in the study colony. For a domestic dog cohort with a low tendency of hereditary malformations, such as this study colony, 5 mg dietary folic acid supplementation should not be expected to drastically improve or eradicate these diseases.

Cost Consequences for the NHS of Using a Two-Step Testing Method for the Detection of Clostridium difficile with a Point of Care, Polymerase Chain Reaction Test as the First Step.

Clostridium difficile infection (CDI) is a common healthcare-associated infection. Current practice for diagnosing CDI in the Newcastle upon Tyne Hospitals NHS Foundation Trust involves a three-step, laboratory testing strategy using glutamate dehydrogenase (GDH) enzyme immunoassay (EIA), followed by a polymerase chain reaction (PCR) test then a toxin EIA. However, a PCR point of care test (POCT) for the C. difficile tcdB gene for screening suspected CDI cases, may provide a more efficient way of facilitating an equally effective, two-step, testing strategy with a toxin EIA. This study evaluated the cost consequences of changing from the three-step to a two-step testing strategy. A cost-consequences model was developed to compare the costs and consequences of the two strategies. Uncertainties in the model inputs were investigated with one- and two-way sensitivity analysis. The two-step, POCT strategy was estimated to save £283,282 per 1000 hospitalized NHS patients with suspected infectious diarrhea. Sensitivity analysis indicated that the turnaround time for the POCT was the largest driver for cost savings. Providing the POCT has sufficiently high diagnostic accuracy for detecting C. difficile, the two-step, POCT strategy for CDI identification is likely to be cost saving for NHS hospitals with an offsite laboratory.

How to Ease the Pain of Taking a Diagnostic Point of Care Test to the Market: A Framework for Evidence Development.

Bringing a diagnostic point of care test (POCT) to a healthcare market can be a painful experience as it requires the manufacturer to meet considerable technical, financial, managerial, and regulatory challenges. In this opinion article we propose a framework for developing the evidence needed to support product development, marketing, and adoption. We discuss each step in the evidence development pathway from the invention phase to the implementation of a new POCT in the healthcare system. We highlight the importance of articulating the value propositions and documenting the care pathway. We provide guidance on how to conduct care pathway analysis as little has been published on this. We summarize the clinical, economic and qualitative studies to be considered for developing evidence, and provide useful links to relevant software, on-line applications, websites, and give practical advice. We also provide advice on patient and public involvement and engagement (PPIE), and on product management. Our aim is to help device manufacturers to understand the concepts and terminology used in evaluation of in vitro diagnostics (IVDs) so that they can communicate effectively with evaluation methodologists, statisticians, and health economists. Manufacturers of medical tests and devices can use the proposed framework to plan their evidence development strategy in alignment with device development, applications for regulatory approval, and publication.

Multilevel and quasi-Monte Carlo methods for uncertainty quantification in particle travel times through random heterogeneous porous media.

In this study, we apply four Monte Carlo simulation methods, namely, Monte Carlo, quasi-Monte Carlo, multilevel Monte Carlo and multilevel quasi-Monte Carlo to the problem of uncertainty quantification in the estimation of the average travel time during the transport of particles through random heterogeneous porous media. We apply the four methodologies to a model problem where the only input parameter, the hydraulic conductivity, is modelled as a log-Gaussian random field by using direct Karhunen-Loéve decompositions. The random terms in such expansions represent the coefficients in the equations. Numerical calculations demonstrating the effectiveness of each of the methods are presented. A comparison of the computational cost incurred by each of the methods for three different tolerances is provided. The accuracy of the approaches is quantified via the mean square error.

Dynamic-wetting effects in finite-mobility-ratio Hele-Shaw flow.

In this paper we study the effects of dynamic wetting on the immiscible displacement of a high viscosity fluid subject to the radial injection of a less viscous fluid in a Hele-Shaw cell. The displaced fluid can leave behind a trailing film that coats the cell walls, dynamically affecting the pressure drop at the fluid interface. By considering the nonlinear pressure drop in a boundary element formulation, we construct a Picard scheme to iteratively predict the interfacial velocity and subsequent displacement in finite-mobility-ratio flow regimes. Dynamic wetting delays the onset of finger bifurcation in the late stages of interfacial growth and at high local capillary numbers can alter the fundamental mode of bifurcation, producing vastly different finger morphologies. In low mobility ratio regimes, we see that finger interaction is reduced and characteristic finger breaking mechanisms are delayed but never fully inhibited. In high mobility ratio regimes, finger shielding is reduced when dynamic wetting is present. Finger bifurcation is delayed, which allows the primary fingers to advance further into the domain before secondary fingers are generated, reducing the level of competition.

Breed and site predispositions of dogs with atopic dermatitis: a comparison of five locations in three continents.

The objectives of this multicentre study were to analyse and compare breed predispositions and lesion distributions of 552 dogs diagnosed with atopic dermatitis from five different dermatologic referral centres located in Australia, Germany (2) and the United States (2). Breeds were compared with the canine population in the respective locations. Breed predispositions varied from geographical site, although golden retrievers and German shepherd dogs were predisposed in three of five practices. Lesions were present most commonly on the paws (62%), ventrum (51%), ears (48%) and face (39%). Various breeds had specific site predilections. Based on this study, breed predispositions can vary greatly both between continents and also between different locations on the same continent. In addition, some breeds showed predispositions for certain body sites which also varied in some instances with the geographical location.

Three-dimensional cerebrospinal fluid flow within the human ventricular system.

Cerebrospinal fluid (CSF) is a Newtonian fluid and can, therefore, be modelled using computational fluid dynamics (CFD). Previous modelling of the CSF has been limited to simplified geometric models. This work describes a geometrically accurate three dimensional (3D) computational model of the human ventricular system (HVS) constructed from magnetic resonance images (MRI) of the human brain. It is an accurate and full representation of the HVS and includes appropriately positioned CSF production and drainage locations. It was used to investigate the pulsatile motion of CSF within the human brain. During this investigation CSF flow rate was set at a constant 500 ml/day, to mimic real life secretion of CSF into the system, and a pulsing velocity profile was added to the inlets to incorporate the effect of cardiac pulsations on the choroid plexus and their subsequent influence on CSF motion in the HVS. Boundary conditions for the CSF exits from the ventricles (foramina of Magendie and Lushka) were found using a "nesting" approach, in which a simplified model of the entire central nervous system (CNS) was used to examine the effects of the CSF surrounding the ventricular system (VS). This model provided time varying pressure data for the exits from the VS nested within it. The fastest flow was found in the cerebral aqueduct, where a maximum velocity of 11.38 mm/s was observed over five cycles. The maximum Reynolds number recorded during the simulation was 15 with an average Reynolds number of the order of 0.39, indicating that CSF motion is creeping flow in most of the computational domain and consequently will follow the geometry of the model. CSF pressure also varies with geometry with a maximum pressure drop of 1.14 Pa occurring through the cerebral aqueduct. CSF flow velocity is substantially slower in the areas that are furthest away from the inlets; in some areas flow is nearly stagnant.

Morphine Use in the Last Six Days of Life of Patients with HIV/AIDS at the Inpatient Unit of a South African Hospice Implementing the ICHC Model

Background: Seventy-five per cent of the world's HIV/AIDS population resides in Sub-Saharan Africa. South Africa; along with the rest of Sub-Saharan Africa; is experiencing an increasing disease and palliative care burden as a result of the HIV/AIDS pandemic. At present there is no cure for AIDS and access to antiretroviral treatment is limited.HIV/AIDS is the largest single cause of death in South Africa; accounting for 30 per cent of deaths in 2000. An estimated 20 000 of the approximately 5 350 000 infected South Africans receive antiretroviral treatment. To cope with the rising need for AIDS-related health services; a comprehensive; integrated approach to health care is advocated; with a shift in focus from hospital care to home-based care. The Department of Health supports a community home-based care (ICHC) model as one of five models of care. It is based on similar principles to palliative care and was piloted at seven hospices in South Africa. This study was conducted in the inpatient unit (IPU) of a hospice participating in the ICHC pilot project. This model requires that the hospice provide the overall management of the home-based care programme; as well as various forms of support. Care provision is shared between professional nurses and non-professional community-based caregivers; who are trained by Hospice. For challenging symptoms; respite or terminal care; the hospice has a six-bed IPU to which patients can be admitted for short periods. The AIDS patients admitted to the IPU of the study hospice were all cared for under the ICHC model.Method: This study was a retrospective case-control study conducted in a hospice in South Africa. Cases were consecutive deaths related to AIDS. Controls were cancer patients matched for socioeconomic status.Results: Five days before their death; morphine for pain control was given to three of the 29 (10) AIDS patients and to 20 of 29 (69) cancer patients (p 0.001). On the day of their death; morphine for pain control was given to 17 (59) of the AIDS patients and 25 (86) of the cancer patients (p 0.05). Eleven (65) of the 17 AIDS patients who were given morphine died within 48 hours of commencing with the treatment. The morphine starting dosages were within the lower therapeutic range.Conclusions: The palliative care of dying cancer patients met internationally recognised standards. The results suggest that the pain of AIDS patients admitted to the IPU was under treated in terms of both dosage and duration. It is unlikely that the use of opiates or sedatives hastened death in dying AIDS (or cancer) patients. All the AIDS patients admitted to the IPU were cared for under the integrated community home-based care (ICHC) model. This raises the following questions: Is the ICHC model as implemented by this hospice achieving the symptom relief intended? And; is this typical of palliative care for AIDS patients in South Africa?

Degenerative mucinotic mural folliculitis in cats.

A novel form of mural folliculitis is described in seven cats. Clinically, all cats exhibited generalized alopecia with scaling or crusting that was more pronounced over the head, neck, and shoulders. The face and muzzle of all cats was unusually thickened. Six of seven cats were progressively lethargic but did not demonstrate any other consistent systemic abnormalities. Histologically, there was severe mixed inflammation of the wall of the follicular isthmus in all cats, accompanied by some follicular destruction in five cats. Sebaceous glands were not affected. All cats had variable, but often striking, follicular mucin deposition, as well as epidermal hyperkeratosis and crusting. The cause of the severe mural folliculitis was not identified, and all cats responded poorly to immunomodulating therapy. Follicular mucinosis may be a nonspecific finding, likely reflective of the follicular lymphocytic milieu, and does not always herald follicular lymphoma.

The London and Liverpool Schools of Tropical Medicine 1898-1998.

In June 1866, Patrick Manson (1844-1922), newly qualified in medicine at Aberdeen University, arrived in Formosa (Taiwan) to begin a career in the service of the Chinese Imperial Maritime customs. His five years there, and subsequently at Amoy on the Chinese mainland, set in train a sequence of events that has been called 'the birth of the science of tropical medicine'. For it was there that Manson began his solitary painstaking studies of the filarial larvae of elephantiasis, and of mosquitoes transmitting filarial infections. It was there that he first realised and acknowledged his own shortcomings in diagnosing and treating the 'tropical diseases' affecting his Chinese patients. These shortcomings were shared by many British colleagues, sent to outposts of the Empire, with no formal knowledge of diseases of hot climates, which did not then form part of the curriculum in British medical schools.

The role of chemotherapy in early malaria control and eradication programmes in Thailand.

The use of synthetic antimalarial compounds played a secondary role to the use of residual insecticides in post World War II antimalarial control and eradication campaigns. The discovery of chloroquine-resistant malaria in South East Asia and South America prompted an intensification of antimosquito measures, rather than a thorough investigation of resistance. It was the failure of the antimosquito measures which primarily called a halt to malaria eradication and a return to control. A focus on the role of synthetic antimalarials in Thailand thus aims to provide a complementary view to those histories being constructed around the antimosquito measures.

Bone remodelling using sensitivity analysis.

A boundary element formulation is presented for analysing the surface bone remodelling. The formulation is based on sensitivity analysis and utilises design parameters which are related to the shape of the bone. An application of the method to the modelling of bone ingrowth into a slot of an implant is presented.

Selected feline eosinophilic skin diseases.

Eosinophilic plaque and mosquito-bite dermatitis are recognized hypersensitivity reactions. The pathogenesis of eosinophilic granuloma and indolent ulcer are not as clearly understood. Each of these syndromes is distinctive from a clinical and histopathologic view point. Accurate diagnosis depends on history, physical findings, and histopathologic evaluation. Understanding of feline dermatology will be furthered by including these syndromes in a broader grouping that encompasses all the feline eosinophilic dermatoses.