131 research outputs found
Multilevel convergence analysis of multigrid-reduction-in-time
This paper presents a multilevel convergence framework for
multigrid-reduction-in-time (MGRIT) as a generalization of previous two-grid
estimates. The framework provides a priori upper bounds on the convergence of
MGRIT V- and F-cycles, with different relaxation schemes, by deriving the
respective residual and error propagation operators. The residual and error
operators are functions of the time stepping operator, analyzed directly and
bounded in norm, both numerically and analytically. We present various upper
bounds of different computational cost and varying sharpness. These upper
bounds are complemented by proposing analytic formulae for the approximate
convergence factor of V-cycle algorithms that take the number of fine grid time
points, the temporal coarsening factors, and the eigenvalues of the time
stepping operator as parameters.
The paper concludes with supporting numerical investigations of parabolic
(anisotropic diffusion) and hyperbolic (wave equation) model problems. We
assess the sharpness of the bounds and the quality of the approximate
convergence factors. Observations from these numerical investigations
demonstrate the value of the proposed multilevel convergence framework for
estimating MGRIT convergence a priori and for the design of a convergent
algorithm. We further highlight that observations in the literature are
captured by the theory, including that two-level Parareal and multilevel MGRIT
with F-relaxation do not yield scalable algorithms and the benefit of a
stronger relaxation scheme. An important observation is that with increasing
numbers of levels MGRIT convergence deteriorates for the hyperbolic model
problem, while constant convergence factors can be achieved for the diffusion
equation. The theory also indicates that L-stable Runge-Kutta schemes are more
amendable to multilevel parallel-in-time integration with MGRIT than A-stable
Runge-Kutta schemes.Comment: 26 pages; 17 pages Supplementary Material
Hoarding disorder: A new obsessive-compulsive related disorder in DSM-5
Obsessive-compulsive disorder (OCD) and related disorders have been the subject of significant revisions in the fifth edition of the Diagnostic and Statistical Manual (DSM-5). One of these major changes has been the removal of OCD from the \u2018Anxi- ety Disorders\u2019 section and its instalment in a new and distinct Obsessive-Compulsive and Related Disorders (OCRDs) chap- ter. However, it is the instatement of Hoarding Disorder (HD) as a new OCRD that marks the most significant change. Previously considered a symptom of OCPD, and subsequently linked to OCD, it is now acknowledged that hoarding can emerge inde- pendently from any alternative condition. The present paper provides an updated review of recent investigations supporting the status of HD as an independent nosological entity. Specifi- cally, we will present the new DSM-5 diagnostic criteria and examine the literature pertaining to the psychopathological and phenomenological aspects of the disorder, with particular atten- tion to practical strategies that can help clinicians to recognise and differentiate HD from OCD. Finally, the available assess- ment and treatment strategies for HD are summarised
The association between heterosexual anal intercourse and HIV acquisition in three prospective cohorts of women
The extent to which receptive anal intercourse (RAI) increases the HIV acquisition risk of women compared to receptive vaginal intercourse (RVI) is poorly understood. We evaluated RAI practice over time and its association with HIV incidence during three prospective HIV cohorts of women: RV217, MTN-003 (VOICE), and HVTN 907. At baseline, 16% (RV 217), 18% (VOICE) of women reported RAI in the past 3 months and 27% (HVTN 907) in the past 6 months, with RAI declining during follow-up by around 3-fold. HIV incidence in the three cohorts was positively associated with reporting RAI at baseline, albeit not always significantly. The adjusted hazard rate ratios for potential confounders (aHR) were 1.1 (95% Confidence interval: 0.8-1.5) for VOICE and 3.3 (1.6-6.8) for RV 217, whereas the ratio of cumulative HIV incidence by RAI practice was 1.9 (0.6-6.0) for HVTN 907. For VOICE, the estimated magnitude of association increased slightly when using a time-varying RAI exposure definition (aHR = 1.2; 0.9-1.6), and for women reporting RAI at every follow-up survey (aHR = 2.0 (1.3-3.1)), though not for women reporting higher RAI frequency (> 30% acts being RAI vs. no RAI in the past 3 months; aHR = 0.7 (0.4-1.1)). Findings indicated precise estimation of the RAI/HIV association, following multiple RVI/RAI exposures, is sensitive to RAI exposure definition, which remain imperfectly measured. Information on RAI practices, RAI/RVI frequency, and condom use should be more systematically and precisely recorded and reported in studies looking at sexual behaviors and HIV seroconversions; standardized measures would aid comparability across geographies and over time
Multiphysics computational modeling in <i>C</i>Heart
From basic science to translation, modern biomedical research demands computational models which integrate several interacting physical systems. This paper describes the infrastructural framework for generic multiphysics integration implemented in the software , a finite-element code for biomedical research. To generalize the coupling of physics systems, we introduce a framework in which the geometric and operator relationships between the constituent systems are rigorously defined. We then introduce the notion of topological interfaces and define specific operators encompassing many common model coupling requirements. These interfaces enable the evaluation of weak form integrals between mesh subregions of arbitrary finite-element bases' orders, types, and spatial dimensions. Equation maps are introduced which provide abstract representations of the individual physics systems that can be automatically combined to permit a monolithic matrix assembly. Flexible solution strategies for the resulting coupled systems are implemented, permitting fine-tuning of solution updates during fixed point iterations, and subgrouping where several problems are being solved together. Partitioning of coupled mesh domains for optimal load balancing is also supported, taking into account the per-processor cost of the entire coupled problem within the graph problem. The demonstration of the performance is illustrated through important real-world multiphysics problems relevant to cardiac physiology
Modeling the heart
Quantitative prediction over multiple space and time scales using computer models of the electrical activity in the mammalian heart, based on membrane and intracellular ion transport and binding dynamics, digital histology, and three-dimensional cardiac anatomy and architecture
The effect of starch-based biomaterials on leukocyte adhesion and activation in vitro
Leukocyte adhesion to biomaterials has long been recognised as a key element to
determine their inflammatory potential. Results regarding leukocyte adhesion and
activation are contradictory in some aspects of the material’s effect in determining these
events. It is clear that together with the wettability or hydrophilicity/hydrophobicity, the
roughness of a substrate has a major effect on leukocyte adhesion. Both the chemical and
physical properties of a material influence the adsorbed proteins layer which in turn
determines the adhesion of cells.
In this work polymorphonuclear (PMN) cells and a mixed population of
monocytes/macrophages and lymphocytes (mononuclear cells) were cultured separately
with a range of starch-based materials and composites with hydroxyapatite (HA). A
combination of both reflected light microscopy and scanning electron microscopy (SEM)
was used in order to study the leukocyte morphology. The quantification of the enzyme
lactate dehydrogenase (LDH) was used to determine the number of viable cells adhered to
the polymers. Cell adhesion and activation was characterised by immunocytochemistry
based on the expression of several adhesion molecules, crucial in the progress of an
inflammatory response.
This work supports previous in vitro studies with PMN and monocytes/macrophages,
which demonstrated that there are several properties of the materials that can influence
and determine their biological response. From our study, monocytes/macrophages and
lymphocytes adhere in similar amounts to more hydrophobic (SPCL) and to moderately
hydrophilic (SEVA-C) surfaces and do not preferentially adhere to rougher substrates
(SCA). Contrarily, more hydrophilic surfaces (SCA) induced higher PMN adhesion and
lower activation. In addition, the hydroxyapatite reinforcement induces changes in cell
behaviour for some materials but not for others.
The observed response to starch-based biodegradable polymers was not significantly
different from the control materials. Thus, the results reported herein indicate the low
potential of the starch-based biodegradable polymers to induce inflammation especially
the HA reinforced composite materials
Characterization of the physical and mechanical properties of femoral bone defects filled with polyanionic collagen scaffolds in ovariectomized rats
X-Ray Phase-Contrast Tomography of Renal Ischemia-Reperfusion Damage
Purpose: The aim of the study was to investigate microstructural changes occurring in unilateral renal ischemia-reperfusion injury in a murine animal model using synchrotron radiation. Material and Methods: The effects of renal ischemia-reperfusion were investigated in a murine animal model of unilateral ischemia. Kidney samples were harvested on day 18. Grating-Based Phase-Contrast Imaging (GB-PCI) of the paraffin-embedded kidney samples was performed at a Synchrotron Radiation Facility (beam energy of 19 keV). To obtain phase information, a two-grating Talbot interferometer was used applying the phase stepping technique. The imaging system provided an effective pixel size of 7.5 mu m. The resulting attenuation and differential phase projections were tomographically reconstructed using filtered back-projection. Semi-automated segmentation and volumetry and correlation to histopathology were performed. Results: GB-PCI provided good discrimination of the cortex, outer and inner medulla in non-ischemic control kidneys. Post-ischemic kidneys showed a reduced compartmental differentiation, particularly of the outer stripe of the outer medulla, which could not be differentiated from the inner stripe. Compared to the contralateral kidney, after ischemia a volume loss was detected, while the inner medulla mainly retained its volume (ratio 0.94). Post-ischemic kidneys exhibited severe tissue damage as evidenced by tubular atrophy and dilatation, moderate inflammatory infiltration, loss of brush borders and tubular protein cylinders. Conclusion: In conclusion GB-PCI with synchrotron radiation allows for non-destructive microstructural assessment of parenchymal kidney disease and vessel architecture. If translation to lab-based approaches generates sufficient density resolution, and with a time-optimized image analysis protocol, GB-PCI may ultimately serve as a non-invasive, non-enhanced alternative for imaging of pathological changes of the kidney
The peroxisome proliferator-activated receptor (PPAR) alpha agonist fenofibrate maintains bone mass, while the PPAR gamma agonist pioglitazone exaggerates bone loss, in ovariectomized rats
<p>Abstract</p> <p>Background</p> <p>Activation of peroxisome proliferator-activated receptor (PPAR)gamma is associated with bone loss and increased fracture risk, while PPARalpha activation seems to have positive skeletal effects. To further explore these effects we have examined the effect of the PPARalpha agonists fenofibrate and Wyeth 14643, and the PPARgamma agonist pioglitazone, on bone mineral density (BMD), bone architecture and biomechanical strength in ovariectomized rats.</p> <p>Methods</p> <p>Fifty-five female Sprague-Dawley rats were assigned to five groups. One group was sham-operated and given vehicle (methylcellulose), the other groups were ovariectomized and given vehicle, fenofibrate, Wyeth 14643 and pioglitazone, respectively, daily for four months. Whole body and femoral BMD were measured by dual X-ray absorptiometry (DXA), and biomechanical testing of femurs, and micro-computed tomography (microCT) of the femoral shaft and head, were performed.</p> <p>Results</p> <p>Whole body and femoral BMD were significantly higher in sham controls and ovariectomized animals given fenofibrate, compared to ovariectomized controls. Ovariectomized rats given Wyeth 14643, maintained whole body BMD at sham levels, while rats on pioglitazone had lower whole body and femoral BMD, impaired bone quality and less mechanical strength compared to sham and ovariectomized controls. In contrast, cortical volume, trabecular bone volume and thickness, and endocortical volume were maintained at sham levels in rats given fenofibrate.</p> <p>Conclusions</p> <p>The PPARalpha agonist fenofibrate, and to a lesser extent the PPARaplha agonist Wyeth 14643, maintained BMD and bone architecture at sham levels, while the PPARgamma agonist pioglitazone exaggerated bone loss and negatively affected bone architecture, in ovariectomized rats.</p
Altered mRNA expression of genes related to nerve cell activity in the fracture callus of older rats: A randomized, controlled, microarray study
BACKGROUND: The time required for radiographic union following femoral fracture increases with age in both humans and rats for unknown reasons. Since abnormalities in fracture innervation will slow skeletal healing, we explored whether abnormal mRNA expression of genes related to nerve cell activity in the older rats was associated with the slowing of skeletal repair. METHODS: Simple, transverse, mid-shaft, femoral fractures with intramedullary rod fixation were induced in anaesthetized female Sprague-Dawley rats at 6, 26, and 52 weeks of age. At 0, 0.4, 1, 2, 4, and 6 weeks after fracture, a bony segment, one-third the length of the femur, centered on the fracture site, including the external callus, cortical bone, and marrow elements, was harvested. cRNA was prepared and hybridized to 54 Affymetrix U34A microarrays (3/age/time point). RESULTS: The mRNA levels of 62 genes related to neural function were affected by fracture. Of the total, 38 genes were altered by fracture to a similar extent at the three ages. In contrast, eight neural genes showed prolonged down-regulation in the older rats compared to the more rapid return to pre-fracture levels in younger rats. Seven genes were up-regulated by fracture more in the younger rats than in the older rats, while nine genes were up-regulated more in the older rats than in the younger. CONCLUSIONS: mRNA of 24 nerve-related genes responded differently to fracture in older rats compared to young rats. This differential expression may reflect altered cell function at the fracture site that may be causally related to the slowing of fracture healing with age or may be an effect of the delayed healing
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