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Modeling 3-D compliant blood flow with FOSLS.

Blood flow in large vessels is typically modeled using the Navier-Stokes equations for the fluid domain and elasticity equations for the vessel wall. As the wall deforms, additional complications are introduced because the shape of the fluid domain changes, necessitating the use of a re-mapping or re-griding process for the fluid region. Typically, this system (fluid, solid, mapping) is solved using an iterative approach in which the fluid, elastic, and mapping equations are solved in series until the iterations converge. We present a new approach based on multilevel minimization of the finite element approximation error using a least-squares (LS) norm. This approach allows for minimization of the error for the entire system or in selected parts. The multilevel LS approach overcomes many shortcomings of standard techniques. Most notably, the computational cost of solving the problem increases linearly with the degrees of freedom and the associated least-squares functional provides an a posteriori error measure. This paper compares the LS finite element approach to other popular numerical methods, specifically, the commercial package CFD-ACE. The focus of the comparison is on accuracy, computational cost, scalability (both parallel and serial), and flexibility. We show that the multilevel LS finite element approach scales optimally (i.e., linearly in serial environments), while the other methods degrade substantially as the problem size increases.

Algorithms↗

Demonstration of software programs for estimating multilevel measurement model parameters.

A brief overview of the relevant parameterizations of the Rasch measurement model will first be provided. Next, the use of five different hierarchical linear modeling software programs (SAS, MLWIN, S-PLUS, R and HLM) using a heuristic data set will be demonstrated. For each program, researchers will be offered: 1) instructions describing the way to set up data sets, as well as 2) directions for running each program, 3) guidelines to assist with the appropriate interpretation of the output. Last, testing of the local independence assumption will be discussed. All data and code for each of the models run in this analysis may be downloaded from the website: http://www.hlm-online.com/papers/mmmpaper.htm/.

Data Interpretation, Statistical↗

The regulation of collagen in fetal skin wounds: mRNA localization and analysis.

The deposition of collagen in fetal skin wounds has been shown in several animal models. The authors used a radiolabeled RNA antisense probe, complementary to the mRNA for the alpha-1 chain of human procollagen type I, to assess regulation of this collagen species in fetal and adult rabbit wounds. Dorsal skin wounds were placed on fetal and maternal animals at the beginning of the third trimester, and were harvested 3, 5, and 7 days later. In situ RNA/RNA hybridization was performed on suitable specimens, and morphometric analysis was carried out with a computerized LECO image analyzer. Fetal wounds exhibited an inflow of mesenchymal cells that produced collagen type I at levels higher than the surrounding tissue; this activity was highest on days 3 and 5 after wounding. Adult wounds had increased fibroblast presence by day 7, producing collagen type I at levels higher than those of adjacent unwounded tissue. Morphometric analysis of the signal produced by in situ hybridization and of the number of cells producing the signal in a given field showed that fetal wounds appear to produce collagen type I by an increase in the number of cells in the area of the wound--not by induction of the gene for procollagen type I. In contrast, adult wounds had both fibroblast migration and induction of procollagen type I mRNA synthesis. These findings imply multilevel regulation of collagen production in the adult and posttranslational regulation in the fetus.

Animals↗

Decentred comparative research: Context sensitive analysis of maternal health care.

Cross-national comparison is an important tool for health care research, but too often those who use this method fail to consider important inter-national differences in the social organisation of health care and in the relationship between health care practices and social experience. In this article we make the case for a context-sensitive and reflexive analysis of health care that allows researchers to understand the important ways that health care systems and practices are situated in time and place. Our approach--decentred comparative research--addresses the often unacknowledged ethnocentrism of traditional comparative research. Decentred cross-national research is a method that draws on the socially situated and distributed expertise of an international research team to develop key concepts and research questions. We used the decentred method to fashion a multilevel framework that used the meso level of organisation (i.e., health care organisations, professional groups and other concrete organisations) as an analytical starting point in our international study of maternity care in eight countries. Our method departs from traditional comparative health systems research that is most often conducted at the macro level. Our approach will help researchers develop new and socially robust knowledge about health care.

Delivery of Health Care↗

Regulated expression of proenkephalin A during ontogenic development of mesenchymal derivative tissues.

Proenkephalin A (PEA), a neuropeptide-encoding gene, is widely expressed in the nervous and endocrine systems. Recently, we demonstrated that in addition to its abundance in fetal brain tissue; PEA is markedly expressed in nondifferentiated mesodermal cells of developing fetuses. To evaluate the implication of these findings for the normal development of tissues of mesodermal origin, we examined the expression of PEA in rat mesenchymal tissues during pre- and postnatal development. Using in situ hybridization analysis combined with RNA blots and a Met-enkephalin-specific radioimmunoassay, we showed that (i) PEA mRNA levels in embryonic and newborn mesenchymal derivative tissues were as high as in the developing brain, (ii) PEA mRNA concentrations in these tissues dropped to undetectable levels shortly after birth, and (iii) this mRNA was translated and processed differentially among different mesenchymal tissues, yielding a tissue-specific pattern of PEA-derived peptides. Our results demonstrate multilevel regulation of PEA gene expression during ontogenic development of mesenchymal derivative tissues. The transient expression and the correlation between PEA mRNA and tissue maturation support the notion that peptides encoded by PEA play a significant role in normal development of these tissues. These findings provide a framework for examination of the mechanisms and roles of PEA gene expression during mesenchymal ontogeny.

Aging↗

Is there a "school effect" on pupil outcomes? A review of multilevel studies.

STUDY OBJECTIVE: The school environment is of importance for child outcomes. Multilevel analyses can separate determinants operating at an individual level from those operating at a contextual level. This paper aims to systematically review multilevel studies of school contextual effects on pupil outcomes. DESIGN: Key word searching of five databases yielded 17 cross sectional or longitudinal studies meeting the inclusion criteria. Results are summarised with reference to type of school contextual determinant. MAIN RESULTS: Four main school effects on pupil outcomes were identified. Having a health policy or antismoking policy, a good school climate, high average socioeconomic status, and urban location had a positive effect on pupil outcomes. Outcomes under study were smoking habits, wellbeing, problem behaviour, and school achievement. CONCLUSIONS: Despite the different pupil outcomes and the variety of determinants used in the included papers, a school effect was evident. However, to improve our understanding of school effects, presentations of results from multilevel studies need to be standardised. Intraclass correlation and explained between school variance give relevant information on factors in the school environment influencing pupil outcomes, and should be included in all multilevel studies. Inclusion of pupil level predictors in the multilevel models should be based on theoretical considerations of how schools and communities are interconnected and how pupils and their families are influenced by school contextual factors.

Achievement↗

Single stage anterior cervical reconstruction with titanium mesh cages, local bone graft, and anterior plating.

BACKGROUND CONTEXT: After cervical corpectomy, the use of tricortical autologous bone to fill the large defect is biomechanically and structurally inadequate and may lead to excessive donor site pain and morbidity. The major alternative, fibular strut allograft, has inherent problems that lead to lower rates of solid arthrodesis and graft migration. Majd et al. reported on 34 cases with a 97% solid fusion rate using titanium mesh cages and local bone graft to fill the cervical corpectomy defect. PURPOSE: With long-term results, to confirm the results previously reported by Majd et al. STUDY DESIGN/SETTING: Retrospective chart and radiological review. PATIENT SAMPLE: The first 26 patients in the senior author's practice eligible for a minimum 2-year follow-up, having had cervical corpectomy reconstructed with titanium mesh cages, local bone graft and anterior plating. OUTCOME MEASURES: Odom's criteria were used to assess clinical outcome. Anteroposterior, lateral and lateral flexion and extension radiographs were used to assess fusion. METHODS: Twenty-six patients with multilevel cervical pathology underwent successful corpectomy, decompression and fusion with titanium mesh cages filled with local bone graft. Rigid anterior plating was applied across the corpectomy defect. Preoperative, operative and postoperative chart data were collected retrospectively. Radiographic assessment included a minimum 2-year follow-up. RESULTS: Follow-up ranged from 24 to 64 months. Clinically, 21 of 26 (80.7%) had an excellent or good clinical outcome. No radiolucencies or motion were detected on radiographic analysis, yielding a fusion rate of 100% (26 of 26). Broken or pulled out screws were identified in two patients, one of whom had plate revision. All cages remained intact with no evidence of cage settling or collapse. CONCLUSIONS: The use of titanium mesh cages in conjunction with local bone graft, and rigid anterior plating is effective for cervical reconstruction after corpectomy and a viable alternative to the use of fibular strut allograft. These results confirm those previously reported by Majd et al.

Adult↗

In vitro biomechanics of cervical disc arthroplasty with the ProDisc-C total disc implant.

An in vitro biomechanical study was conducted to compare the effects of disc arthroplasty and anterior cervical fusion on cervical spine biomechanics in a multilevel human cadaveric model. Three spine conditions were studied: harvested, single-level cervical disc arthroplasty, and single-level fusion. A programmable testing apparatus was used that replicated physiological flexion/extension, lateral bending, and axial rotation. Measurements included vertebral motion, applied load, and bending moments. Relative rotations at the superior, treated, and inferior motion segment units (MSUs) were normalized with respect to the overall rotation of those three MSUs and compared using a one-way analysis of variance with Student-Newman-Keuls test (p < 0.05). Simulated fusion decreased motion across the treated site relative to the harvested and disc arthroplasty conditions. The reduced motion at the treated site was compensated at the adjacent segments by an increase in motion. For all modes of testing, use of an artificial disc prosthesis did not alter the motion patterns at either the instrumented level or adjacent segments compared with the harvested condition, except in extension.

Aged↗

The role of composite sequential bypass in the treatment of multilevel infrainguinal arterial occlusive disease.

BACKGROUND: In this study, the efficacy of composite sequential bypass is compared to that of standard in situ bypass, and to alternate prosthetic graft systems which have been used for the treatment of multilevel infrainguinal arterial occlusive disease in the absence of suitable autogenous vein. PATIENTS AND METHODS: A retrospective review of graft patency and limb salvage included 197 patients undergoing 211 bypass procedures consisting of in situ femoral-tibial (IS; n = 119); composite sequential (CS; n = 35), prosthetic femoropopliteal with single (PFP-1; n = 30) or no vessel runoff (PFP-O; n = 9), and prosthetic femoral-tibial (PFT; n = 18) bypass. RESULTS: By life-table analysis, IS bypass provided superior primary (P < 0.005) and secondary (P < 0.0005) patency over the other groups. CS bypass was similar to PFP-1, with a 2-two year primary patency of 35% and 44% (NS), respectively, and limb salvage rates of 60% and 80% (P = 0.01). PFP-O and PFT bypass procedures did considerably worse, with a 1-year patency of 19% and 22%, respectively, and associated limb salvage rates of 25% and 41% (NS). CONCLUSIONS: Composite sequential bypass is an acceptable procedure for infrainguinal arterial reconstruction when absence of autogenous vein prevents either in situ or secondary vein graft bypass procedures.

Arterial Occlusive Diseases↗

Osteogenic protein versus autologous interbody arthrodesis in the sheep thoracic spine. A comparative endoscopic study using the Bagby and Kuslich interbody fusion device.

STUDY DESIGN: Using an in vivo interbody arthrodesis model, the efficacy of the Bagby and Kuslich (BAK) device packed with recombinant human osteogenic protein-1 (rhOP-1) was evaluated. OBJECTIVES: To compare the efficacy of osteogenic protein with that of autograft for interbody arthrodesis, with fusion success based on biomechanical, histologic, and radiographic analyses. SUMMARY OF BACKGROUND DATA: The use of recombinant human bone morphogenetic proteins (rhBMPs) as osteoinductive bone graft substitutes or expanders has recently gained considerable research interest, particularly when applied in posterolateral arthrodesis. However, whether these results can be extrapolated to a successful interbody spinal arthrodesis remains uncertain. METHODS: Twelve sheep underwent a multilevel thoracic spinal decompression by thoracoscopic approach. Three noncontiguous destabilization sites (T5-T6, T7-T8, T9-T10) were prepared and randomly treated as follows. Control group treatments were nonsurgical, destabilization alone, and empty BAK. Experimental groups were treated with autograft alone, BAK device packed with autograft, or BAK device packed with rhOP-1. Four months after surgery, interbody fusion status was quantified by biomechanical testing, computed tomography, microradiography, and histomorphometry. RESULTS: Results of biomechanical analysis showed statistically higher segmental stiffness levels when comparing the control and experimental groups with four of the five testing methods (P < 0.05). Computed tomography and microradiography characterized destabilization alone as producing one fusion in six preparations; the empty BAK, two in six;, autograft alone, four in eight; BAK with autograft, five in eight; and BAK with rhOP-1 group, six in eight-all evidenced by woven trabecular bone spanning the fusion sites. Histomorphometry yielded significantly more trabecular bone formation at the fusion sites in the three experimental groups than in the two control groups (P < 0.05). CONCLUSIONS: Interbody spinal fusions showing biomechanical and histomorphometric equivalency to autologous fusions have been achieved with rhOP-1. The functional unit stability and histologic osteointegration evidenced by the BAK/rhOP-1 complex shows this interbody arthrodesis technique to be a viable alternative toconventional autologous iliac crest, thereby obviating the need for an iliac crest donor site and associated patient morbidity.

Analysis of Variance↗

Failed anterior cervical discectomy and arthrodesis. Analysis and treatment of thirty-five patients.

Thirty-five patients were managed operatively after failure of an anterior cervical discectomy and arthrodesis. Failure was classified as the absence of fusion without deformity but with neck pain or radiculopathy, or both; the absence of fusion after anterior or posterior dislodgment of the graft; or kyphosis due to collapse of the graft or to an unrecognized posterior soft-tissue injury. Twenty-three patients had failure of the arthrodesis without deformity (with neck pain only, neck and arm pain, radiculopathy, or myelopathy). Four patients had dislodgment of the graft; in two of them the graft migrated anteriorly after a multilevel Robinson arthrodesis, and in two it migrated posteriorly after a Cloward arthrodesis. Eight patients had a failure because of a kyphotic deformity. Five of them had had a Cloward arthrodesis; one, a discectomy; and two, a Robinson arthrodesis. Six had received allograft bone. Operative treatment of the pseudarthrosis consisted of repeat resection of the disc space in the area of the failed arthrodesis followed by repeat anterior Robinson arthrodesis with decompression of the nerve root if the patient had radiculopathy. It consisted of anterior corpectomy or vertebral-body resection and strut-grafting with reduction of the deformity if the patient had migration of the graft and kyphosis. The reoperations were performed four months to fourteen years (average, thirty-two months) after the initial operation. The duration of follow-up after the second operation averaged forty-four months (range, twenty-four to 216 months). The result was excellent for twenty-nine patients, good for one, fair for four, and poor for one. We concluded that, in patients who have persistent symptoms after an anterior cervical arthrodesis, an excellent result can be achieved with repeat anterior decompression and autogenous bone-grafting.

Adult↗

Spatial correlation analysis of isotropic microvessels: methodology and application to thyroid capillaries.

The study of relations between structural organization and functions of microcirculatory networks is a major aim of modern microangiology. Such a structural aspect of microvessels (MVs) as their spatial arrangement has substantial influence on their transport and other functional properties. This paper describes a methodology of spatial correlation analysis for isotropic blood and lymphatic MVs which is based on a stereological estimator of the pair correlation function [g3D(r)] created recently by the authors for systems of elongated objects. The following main features of the methodology are presented: (i) interpretation of the shape of g3D(r) curves, (ii) their quantitative description by numerical parameters, and (iii) limitations of the method arising from statistical requirements to MVs under investigation. The methodology is considered in the light of multilevel sampling designs, which are typical for biomedical morphology. The estimator with its methodological framework is applied to perifollicular blood capillaries in the adult rat thyroid. Related methods for studying the spatial arrangement of MVs are thoroughly discussed in the paper.

Albinism↗

Expression of the gene for mitoribosomal protein S12 is controlled in human cells at the levels of transcription, RNA splicing, and translation.

The human gene RPMS12 encodes a protein similar to bacterial ribosomal protein S12 and is proposed to represent the human mitochondrial orthologue. RPMS12 reporter gene expression in cultured human cells supports the idea that the gene product is mitochondrial and is localized to the inner membrane. Human cells contain at least four structurally distinct RPMS12 mRNAs that differ in their 5'-untranslated region (5'-UTR) as a result of alternate splicing and of 5' end heterogeneity. All of them encode the same polypeptide. The full 5'-UTR contains two types of sequence element implicated elsewhere in translational regulation as follows: a short upstream open reading frame and an oligopyrimidine tract similar to that found at the 5' end of mRNAs encoding other growth-regulated proteins, including those of cytosolic ribosomes. The fully spliced (short) mRNA is the predominant form in all cell types studied and is translationally down-regulated in cultured cells in response to serum starvation, even though it lacks both of the putative translational regulatory elements. By contrast, other splice variants containing one or both of these elements are not translationally regulated by growth status but are translated poorly in both growing and non-growing cells. Reporter analysis identified a 26-nucleotide tract of the 5'-UTR of the short mRNA that is essential for translational down-regulation in growth-inhibited cells. Such experiments also confirmed that the 5'-UTR of the longer mRNA variants contains negative regulatory elements for translation. Tissue representation of RPMS12 mRNA is highly variable, following a typical mitochondrial pattern, but the relative levels of the different splice variants are similar in different tissues. These findings indicate a complex, multilevel regulation of RPMS12 gene expression in response to signals mediating growth, tissue specialization, and probably metabolic needs.

Animals↗

Biomechanical testing of an artificial cervical joint and an anterior cervical plate.

An in vitro biomechanical study was conducted to determine the effects of fusion and nonfusion anterior cervical instrumentation on cervical spine biomechanics in a multilevel human cadaveric model. Three spine conditions were studied: harvested, single-level artificial cervical joint, and single-level graft with anterior cervical plate. A programmable testing apparatus was used that replicated physiologic flexion/extension and lateral bending. Measurements included vertebral motion, applied load, and bending moments. Relative rotations at the superior, implanted, and inferior motion segment units (MSUs) were normalized with respect to the overall rotation of those three MSUs and compared using a one-way analysis of variance (P < 0.05). Application of an anterior cervical plate decreased motion across the fusion site relative to the harvested and artificial joint spine conditions. The reduced motion was compensated for by an increase in motion at the adjacent segments. Use of an artificial cervical joint did not alter the motion patterns at either the instrumented level or the adjacent segments compared with the harvested condition for all modes of testing.

Aged↗

COVASIAM: an image analysis method that allows detection of confluent microbial colonies and colonies of various sizes for automated counting.

In this work we introduce the confluent and various sizes image analysis method (COVASIAM), an automated colony count technique that uses digital imaging technology for detection and separation of confluent microbial colonies and colonies of various sizes growing on petri dishes. The proposed method takes advantage of the optical properties of the surfaces of most microbial colonies. Colonies in the petri dish are epi-illuminated in order to direct the reflection of concentrated light coming from a halogen lamp towards an image-sensing device. In conjunction, a multilevel threshold algorithm is proposed for colony separation and counting. These procedures improved the quantification of colonies showing confluence or differences in size. We tested COVASIAM with a sample set of microorganisms that form colonies with contrasting physical properties: Saccharomyces cerevisiae, Aspergillus nidulans, Escherichia coli, Azotobacter vinelandii, Pseudomonas aeruginosa, and Rhizobium etli. These physical properties range from smooth to hairy, from bright to opaque, and from high to low convexities. COVASIAM estimated an average of 95.47% (sigma = 8.55%) of the manually counted colonies, while an automated method based on a single-threshold segmentation procedure estimated an average of 76% (sigma = 16.27) of the manually counted colonies. This method can be easily transposed to almost every image-processing analyzer since the procedures to compile it are generically standard.

Aspergillus nidulans↗

Surgical management of osseous hemangioblastoma of the thoracic spine: technical case report.

OBJECTIVE AND IMPORTANCE: Spinal hemangioblastomas usually occur as isolated, intramedullary, central nervous system masses, often as a component of von Hippel-Lindau syndrome. They may occasionally occur extradurally and give the appearance of vertebral hemangioma. Rarely, they may be purely osseous lesions. The surgical management of these lesions has not been elaborated. We present a case and discuss the management of multilevel osseous hemangioblastoma of the thoracic spine. CLINICAL PRESENTATION: A 50-year-old woman with a history of thoracic hemangioblastoma 3 years earlier presented with progressive paraparesis. Imaging revealed circumferential tumor involvement of T7 to T9, inclusive. There was severe spinal cord compression. INTERVENTION: The patient underwent surgery via a bilateral lateral extracavitary approach to the tumor. This permitted a complete spondylectomy of T7, T8, and T9; complete tumor removal; and decompression of the spinal cord. Pathological analysis confirmed hemangioblastoma. The spine was reconstructed with an interbody expandable cage and pedicle screw fixation, all placed via the dorsal approach. The patient improved neurologically after the operation. CONCLUSION: Although extremely rare, hemangioblastomas may occur in a purely osseous location. They may resemble vertebral hemangioma. Treatment should include aggressive surgical removal, although arduous, if appropriate. A bilateral lateral extracavitary approach is ideal for complete spondylectomy. With this technique, ventral and dorsal reconstruction of the spine through the same incision is possible.

Female↗

An improved biomechanical testing protocol for evaluating spinal arthroplasty and motion preservation devices in a multilevel human cadaveric cervical model.

OBJECT: An experimental study was performed to determine the biomechanical end-mounting configurations that replicate in vivo physiological motion of the cervical spine in a multiple-level human cadaveric model. The vertebral motion response for the modified testing protocol was compared to in vivo motion data and traditional pure-moment testing methods. METHODS: Biomechanical tests were performed on fresh human cadaveric cervical spines (C2-T1) mounted in a programmable testing apparatus. Three different end-mounting conditions were studied: pinned-pinned, pinned-fixed, and translational/pinned-fixed. The motion response of the individual segmental vertebral rotations was statistically compared using one-way analysis of variance and Student-Newman-Keuls tests (p < 0.05 unless otherwise stated) to determine differences in the motion responses for different testing methods. CONCLUSIONS: A translational/pinned-fixed mounting configuration induced a bending-moment distribution across the cervical spine, resulting in a motion response that closely matched the in vivo case. In contrast, application of pure-moment loading did not reproduce the physiological response and is less suitable for studying disc arthroplasty and nonfusion devices.

Aged↗

Combining segmental systolic pressures and plethysmography to diagnose arterial occlusive disease of the legs.

Computer-assisted analysis of the data from SLP and PVR study of the legs with angiographically documented arterial occlusive disease, projected against a background of normal limbs, was used to assess the diagnostic value of each study, including its individual variables, as well as their varied combinations. The accuracy of both SLP and PVR interpretation was significantly improved by standarization against brachial values, but even with the aid of superimposed physician interpretation, each only reached 86 per cent when cases with multilevel occlusive disease were included. The combination of these two studies, which compensate for each other's limitations in several respects, achieved an overall accuracy of 97 per cent, with no errors observed in diagnosing either normal limbs or those with isolated occlusive disease. Objective diagnostic criteria for both SLP and PVR interpreatation are presented in algorithmic form.

Arterial Occlusive Diseases↗