A Cell-Centred CVD-MPFA Finite Volume Method for Two-Phase Fluid Flow Problems with Capillary Heterogeneity and Discontinuity

A novel finite-volume method is presented for porous media flow simulation that is applicable to discontinuous capillary pressure fields. The method crucially retains the optimal single of freedom per control-volume being developed within the flux-continuous control-volume distributed multi-point flux approximation (CVD-MPFA) framework (Edwards and Rogers in Comput Geosci 02(04):259–290, 1998; Friis et al. in SIAM J Sci Comput 31(02):1192–1220, 2008) . The new methods enable critical subsurface flow processes involving oil and gas trapping to be correctly resolved on structured and unstructured grids. The results demonstrate the ability of the method to resolve flow with oil/gas trapping in the presence of a discontinuous capillary pressure field for diagonal and full-tensor permeability fields. In addition to an upwind approximation for the saturation equation flux, the importance of upwinding on capillary pressure flux via a novel hybrid formulation is demonstrated

Higher resolution total velocity Vt and Va finite-volume formulations on cell-centred structured and unstructured grids

Novel cell-centred finite-volume formulations are presented for incompressible and immiscible two-phase flow with both gravity and capillary pressure effects on structured and unstructured grids. The Darcy-flux is approximated by a control-volume distributed multipoint flux approximation (CVD-MPFA) coupled with a higher resolution approximation for convective transport. The CVD-MPFA method is used for Darcy-flux approximation involving pressure, gravity, and capillary pressure flux operators. Two IMPES formulations for coupling the pressure equation with fluid transport are presented. The first is based on the classical total velocity Vt fractional flow (Buckley Leverett) formulation, and the second is based on a more recent Va formulation. The CVD-MPFA method is employed for both Vt and Va formulations. The advantages of both coupled formulations are contrasted. The methods are tested on a range of structured and unstructured quadrilateral and triangular grids. The tests show that the resulting methods are found to be comparable for a number of classical cases, including channel flow problems. However, when gravity is present, flow regimes are identified where the Va formulation becomes locally unstable, in contrast to the total velocity formulation. The test cases also show the advantages of the higher resolution method compared to standard first-order single-point upstream weighting

Out-of-hours care in western countries: assessment of different organizational models

Contains fulltext : 81655.pdf (publisher's version ) (Open Access)BACKGROUND: Internationally, different organizational models are used for providing out-of-hours care. The aim of this study was to assess prevailing models in order to identify their potential strengths and weaknesses. METHODS: An international web-based survey was done in 2007 in a sample of purposefully selected key informants from 25 western countries. The questions concerned prevailing organizational models for out-of-hours care, the most dominant model in each country, perceived weaknesses, and national plans for changes in out-of-hours care. RESULTS: A total of 71 key informants from 25 countries provided answers. In most countries several different models existed alongside each other. The Accident and Emergency department was the organizational model most frequently used. Perceived weaknesses of this model concerned the coordination and continuity of care, its efficiency and accessibility. In about a third of the countries, the rota group was the most dominant organizational model for out-of-hours care. A perceived weakness of this model was lowered job satisfaction of physicians. The GP cooperative existed in a majority of the participating countries; no weaknesses were mentioned with respect to this model. Most of the countries had plans to change the out-of-hours care, mainly toward large scale organizations. CONCLUSION: GP cooperatives combine size of scale advantages with organizational features of strong primary care, such as high accessibility, continuity and coordination of care. While specific patients require other organizational models, the co-existence of different organizational models for out-of-hours care in a country may be less efficient for health systems

Exponential Random Graph Modeling for Complex Brain Networks

Exponential random graph models (ERGMs), also known as p* models, have been utilized extensively in the social science literature to study complex networks and how their global structure depends on underlying structural components. However, the literature on their use in biological networks (especially brain networks) has remained sparse. Descriptive models based on a specific feature of the graph (clustering coefficient, degree distribution, etc.) have dominated connectivity research in neuroscience. Corresponding generative models have been developed to reproduce one of these features. However, the complexity inherent in whole-brain network data necessitates the development and use of tools that allow the systematic exploration of several features simultaneously and how they interact to form the global network architecture. ERGMs provide a statistically principled approach to the assessment of how a set of interacting local brain network features gives rise to the global structure. We illustrate the utility of ERGMs for modeling, analyzing, and simulating complex whole-brain networks with network data from normal subjects. We also provide a foundation for the selection of important local features through the implementation and assessment of three selection approaches: a traditional p-value based backward selection approach, an information criterion approach (AIC), and a graphical goodness of fit (GOF) approach. The graphical GOF approach serves as the best method given the scientific interest in being able to capture and reproduce the structure of fitted brain networks

Disentangling the genetic overlap and causal relationships between primary open-angle glaucoma, brain morphology and four major neurodegenerative disorders

BACKGROUND: Primary open-angle glaucoma (POAG) is an optic neuropathy characterized by progressive degeneration of the optic nerve that leads to irreversible visual impairment. Multiple epidemiological studies suggest an association between POAG and major neurodegenerative disorders (Alzheimer's disease, amyotrophic lateral sclerosis, frontotemporal dementia, and Parkinson's disease). However, the nature of the overlap between neurodegenerative disorders, brain morphology and glaucoma remains inconclusive. METHOD: In this study, we performed a comprehensive assessment of the genetic and causal relationship between POAG and neurodegenerative disorders, leveraging genome-wide association data from studies of magnetic resonance imaging of the brain, POAG, and four major neurodegenerative disorders. FINDINGS: This study found a genetic overlap and causal relationship between POAG and its related phenotypes (i.e., intraocular pressure and optic nerve morphology traits) and brain morphology in 19 regions. We also identified 11 loci with a significant local genetic correlation and a high probability of sharing the same causal variant between neurodegenerative disorders and POAG or its related phenotypes. Of interest, a region on chromosome 17 corresponding to MAPT, a well-known risk locus for Alzheimer's and Parkinson's disease, was shared between POAG, optic nerve degeneration traits, and Alzheimer's and Parkinson's diseases. Despite these local genetic overlaps, we did not identify strong evidence of a causal association between these neurodegenerative disorders and glaucoma. INTERPRETATION: Our findings indicate a distinctive and likely independent neurodegenerative process for POAG involving several brain regions although several POAG or optic nerve degeneration risk loci are shared with neurodegenerative disorders, consistent with a pleiotropic effect rather than a causal relationship between these traits. FUNDING: PG was supported by an NHMRC Investigator Grant (#1173390), SM by an NHMRC Senior Research Fellowship and an NHMRC Program Grant (APP1150144), DM by an NHMRC Fellowship, LP is funded by the NEI EY015473 and EY032559 grants, SS is supported by an NIH-Oxford Cambridge Fellowship and NIH T32 grant (GM136577), APK is supported by a UK Research and Innovation Future Leaders Fellowship, an Alcon Research Institute Young Investigator Award and a Lister Institute for Preventive Medicine Award

Modifiable risk factors for dementia and dementia risk profiling. A user manual for Brain Health Services-part 2 of 6

We envisage the development of new Brain Health Services to achieve primary and secondary dementia prevention. These services will complement existing memory clinics by targeting cognitively unimpaired individuals, where the focus is on risk profiling and personalized risk reduction interventions rather than diagnosing and treating late-stage disease. In this article, we review key potentially modifiable risk factors and genetic risk factors and discuss assessment of risk factors as well as additional fluid and imaging biomarkers that may enhance risk profiling. We then outline multidomain measures and risk profiling and provide practical guidelines for Brain Health Services, with consideration of outstanding uncertainties and challenges. Users of Brain Health Services should undergo risk profiling tailored to their age, level of risk, and availability of local resources. Initial risk assessment should incorporate a multidomain risk profiling measure. For users aged 39-64, we recommend the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) Dementia Risk Score, whereas for users aged 65 and older, we recommend the Brief Dementia Screening Indicator (BDSI) and the Australian National University Alzheimer's Disease Risk Index (ANU-ADRI). The initial assessment should also include potentially modifiable risk factors including sociodemographic, lifestyle, and health factors. If resources allow, apolipoprotein E ɛ4 status testing and structural magnetic resonance imaging should be conducted. If this initial assessment indicates a low dementia risk, then low intensity interventions can be implemented. If the user has a high dementia risk, additional investigations should be considered if local resources allow. Common variant polygenic risk of late-onset AD can be tested in middle-aged or older adults. Rare variants should only be investigated in users with a family history of early-onset dementia in a first degree relative. Advanced imaging with 18-fluorodeoxyglucose positron emission tomography (FDG-PET) or amyloid PET may be informative in high risk users to clarify the nature and burden of their underlying pathologies. Cerebrospinal fluid biomarkers are not recommended for this setting, and blood-based biomarkers need further validation before clinical use. As new technologies become available, advances in artificial intelligence are likely to improve our ability to combine diverse data to further enhance risk profiling. Ultimately, Brain Health Services have the potential to reduce the future burden of dementia through risk profiling, risk communication, personalized risk reduction, and cognitive enhancement interventions