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Wear patterns on tibial plateau from varus osteoarthritic knees.

BACKGROUND: The knowledge of cartilage wear patterns at the medial tibial plateau is important to understand the main causes of arthritis in varus knees. The most important factors influencing knee arthritis in fact seem to be the severity of the degenerative changes determined by the lower limb mechanical axis and the abnormal knee joint kinematics which frequently results from dysfunction of the anterior cruciate ligament. METHODS: We studied the wear patterns of cartilage damage in 70 medial tibial plateaus resected at operation during total knee arthroplasty indicated for varus osteoarthritic knee. Anterior cruciate ligament and medial meniscus integrity was assessed intra-operatively. Calibrated digital images were used to measure the wear patterns with a standard software tool. The medial compartment of the tibial plateau was divided into six zones, and the amount of cartilage and bone destruction in each zone was classified into two grades. FINDINGS: The wear pattern was found to be highly dependent upon knee varus deformity (Mann Whitney P<0.001) and anterior cruciate ligament integrity (Friedman P<0.0005). Anterior cruciate ligament was found intact in 35.7% of the cases. Wear patterns on intact anterior cruciate ligament knees occurred in the central to medial aspect of the tibial plateau. Anterior cruciate ligament deficient knees had significantly larger wear patterns anteriorly and posteriorly in the most medial region of the medial plateau. INTERPRETATION: These observations suggest altered joint mechanics exist in anterior cruciate ligament deficient varus knees, which would worsen cartilage degeneration and osteoarthritis progression.

Adult↗

The registration of CT image to the patient head by using an automated laser surface scanning system--a phantom study.

In this paper, a practical methodology of surface-based registration supported by an automated laser surface scanning system to achieve good mapping performance is reported. The laser scanning system is used to digitize the facial feature of a phantom so as to mesh the physical space into triangular frame. The image space is established by translating the corresponding CT image into point set through using the medical image software tools. The image-to-physical registration task is carried out by a direct searching mechanism together with the objective function in an optimal fashion. The unconstrained nonlinear optimization algorithm performs the optimal searching iteration to find those parameters in the rigid-body transformation until the sum of the squared normal distances is minimized. Considering mapping the massive points in registration task would consume the computation time, there is only a suitable sample size to stand for the entire population with sufficient confidence and accuracy are extracted statistically from the CT point space to map to the laser scanning space. Registration results evaluated by gauging the position errors of the landmarks on phantom forehead show the proposed methodology has good ability to perform the image-to-physical registration.

Algorithms↗

The suitable restriction enzymes for pulsed-field gel electrophoresis analysis of Bordetella pertussis.

We searched the restriction enzymes with rare cutting sites on the genome of Bordetella pertussis strain Tohama I using the Restriction Digest Tool software provided in the Institute for Genomic Research web site. The usefulness of 5 enzymes for pulsed-field gel electrophoresis (PFGE) analysis was evaluated with 68 B. pertussis isolates. The results indicated that AflII, DraI, SpeI, and XbaI were useful enzymes, and AflII was the best one for PFGE analysis of B. pertussis isolates.

Bordetella pertussis↗

Findings from a survey on GIS use in the UK National Health Service: organisational challenges and opportunities.

The use of geographical information systems (GIS) in a variety of application areas points to an increasing interest in the spatial aspects of health policies. Despite the fact that most public sector organisations in the United Kingdom (UK) have access to such software tools, there has not been a comprehensive review of take-up within the health sector. In this paper, we report on a recently completed mixed-method research project that has examined the current levels of GIS use in the UK National Health Service, and focus our discussion on health authorities (HAs). Couched within the context of previous studies that have been concerned with outlining the types of factors influencing IT implementation in the health sector, we illuminate the importance of behavioural, cultural and organisational factors on the diffusion of GIS in the UK National Health Service. It is noted that very few organisations had a GIS strategy and we contend that if GIS is to play a wider role in addressing issues surrounding 'joined-up' government, more advice and guidance is needed on policies promoting the exchange of geographical data between agencies concerned with tackling health issues. We conclude by drawing attention to the perceived lack of national guidance on GIS matters, more generally, within the UK health sector.

Data Collection↗

Prediction of cyclosporine blood levels in heart transplantation patients using a pharmacokinetic model identified by evolutionary algorithms.

BACKGROUND: Artificial intelligence (AI)-based computation methods have been recently shown to be applicable in several clinical diagnostic fields. The purpose of this study was to introduce a novel AI method called evolutionary algorithms (EAs) to clinical predictions. The technique was used to create a pharmacokinetic model for the prediction of whole blood levels of cyclosporine (CyA). METHODS: One hundred one adult cardiac transplant recipients were randomly selected and included in this study. All patients had been receiving oral cyclosporine twice daily, and the trough levels in whole blood were measured by monoclonal-specific radioimmunoassay. An evolutionary algorithm (EA)-based software tool was trained with pre- and post-operative variables from 64 patients. The results of this process were then tested on data sets from 37 patients. RESULTS: The mean value of the predicted CyA level throughout the measurement period for the test data was 175 +/- 27 ng/ml, which compared well with the mean observed CyA level of 180 +/- 31 ng/ml. The system bias expressed as the mean percent error (MPE) for the training and test data sets were 7.1 +/- 5.4% (0.1% to 26.7%) and 8.0 +/- 6.7% (0.8% to 28.8%), respectively. The prediction accuracy ranged from 80% to 90%. The correlation coefficient between predicted and observed CyA concentration for the training data were 0.93 (p < 0.001) and for the test data were 0.85 (p < 0.001), respectively. CONCLUSIONS: The results of this study suggest that the use of evolutionary algorithms to identify pharmacokinetic models yields accurate prediction of cyclosporine whole blood levels in heart transplant recipients. This and other similar technologies should be considered as future clinical tools to reduce costs in our health systems.

Adult↗

Implications of radiation dosimetry of the mandible in patients with carcinomas of the oral cavity and nasopharynx treated with intensity modulated radiation therapy.

Intensity modulated radiation therapy (IMRT) is a newer method of delivering highly conformal, salivary gland sparing radiation treatment that is finding increasing applications in head and neck malignancies. However, the radiation dose distribution to the mandible is rarely considered with IMRT, and the potential risks of osteoradionecrosis or osseointegrated implant failure are not well characterized for this modality. In a series of 10 patients with oral cavity and nasopharyngeal cancers who previously underwent IMRT, examination of the three-dimensional mandibular dose distribution was undertaken. The findings indicate a modest potential risk of osteoradionecrosis and osseointegrated implant failure in cases where IMRT optimization constraints are not specifically aimed at sparing the mandibular bone. Significantly higher mandibular doses (P < 0.04) were received in cases of oral cavity as opposed to nasopharyngeal cancers with IMRT. Efforts to optimize IMRT to further reduce doses to the mandible should be considered, and development of software tools to integrate three-dimensional dose distributions into planning of post-radiotherapy osseointegration would be beneficial.

Carcinoma↗

Automated functional image-guided radiation treatment planning for rectal cancer.

PURPOSE: Computer tomography-based (CT-based) tumor-volume definition is time consuming and is subject to clinical interpretation. CT is not accessible for standardized algorithms for the purpose of treatment-volume planning. We have evaluated the accuracy of target-volume definition based on the positron emission tomography (PET) data from an integrated PET/CT system with 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG) for standardized target-volume delineation. MATERIALS AND METHODS: Eleven patients with rectal cancer who were undergoing preoperative radiation therapy (RT) were studied. A standardized region-growing algorithm was tested to replace the CT-derived gross tumor volume by the PET-derived gross tumor volume (PET-GTV) or the biologic target volume (BTV). A software tool was developed to automatically delineate the appropriate tumor volume as defined by the FDG signal, the PET-GTV, and the planning target volume (PTV). The PET-derived volumes were compared with the target volumes from CT. RESULTS: The BTV defined for appropriate GTV assessment was set at a single peak threshold of 40% of the signal of interest. Immediate treatment volume definition based on the choice of a single-tumor volume-derived PET-voxel resulted in a tumor volume that strongly correlated with the CT-derived GTV (r(2) = 0.84; p < 0.01) and the volume as assessed on subsequent anatomic-pathologic analysis (r(2) = 0.77; p < 0.01). In providing sufficient extension margins from the CT-derived GTV and the PET-derived GTV, to PTV, respectively, the correlation of the CT-derived and PET-derived PTV was sufficiently accurate for PTV definition for external-beam therapy (r(2) = 0.96; p < 0.01). CONCLUSION: Automated segmentation of the PET signal from rectal cancer may allow immediate and sufficiently accurate definition of a preliminary working PTV for preoperative RT. If required, correction for anatomic precision and geometric resolution may be applied in a second step. Computed PET-based target-volume definition could be useful for the definition of standardized simultaneous internal-boost volumes for intensity-modulated radiation therapy (IMRT) based on biologic target volumes.

Fluorodeoxyglucose F18↗

Identifying important concepts from medical documents.

Automated medical concept recognition is important for medical informatics such as medical document retrieval and text mining research. In this paper, we present a software tool called keyphrase identification program (KIP) for identifying topical concepts from medical documents. KIP combines two functions: noun phrase extraction and keyphrase identification. The former automatically extracts noun phrases from medical literature as keyphrase candidates. The latter assigns weights to extracted noun phrases for a medical document based on how important they are to that document and how domain specific they are in the medical domain. The experimental results show that our noun phrase extractor is effective in identifying noun phrases from medical documents, so is the keyphrase extractor in identifying important medical conceptual terms. They both performed better than the systems they were compared to.

Algorithms↗

Process economics of industrial monoclonal antibody manufacture.

Pressures for cost-effective manufacture of antibodies are growing given their high doses and increasing market potential that have resulted in significant increases in total site capacities of up to 200,000 L. This paper focuses on the process economic issues associated with manufacturing antibodies and reviews the cost studies published in the literature; many of the issues highlighted are not only specific to antibodies but also apply to recombinant proteins. Data collated at UCL suggest current benchmark investment costs of $660-$1580/ft2 ($7130-$17,000/m2) and $1765-$4220/L for antibody manufacturing facilities with total site capacities in the range of 20,000-200,000 L; the limitations of the data are highlighted. The complications with deriving benchmark cost of goods per gram (COG/g) values are discussed, stressing the importance of stating the annual production rate and either titre or fermentation capacity with the cost so as to allow comparisons. The uses and limitations of the methods for cost analysis and the available software tools for process economics are presented. Specific examples found in the literature of process economic studies related to antibody manufacture for different expression systems are reviewed. The key economic drivers are identified; factors such as fermentation titre and overall yield are critical determinants of economic success. Future trends in antibody manufacture that are driven by economic pressures are discussed, such as the use of alternative expression systems (e.g. transgenics, E. coli and yeast), disposables, and improvements to downstream technology. The hidden costs and the challenges in each case are highlighted.

Animals↗

Preoperative simulation of postoperative iris-fixated phakic intraocular lens position and simulation of aging using high-resolution Scheimpflug imaging.

To increase postoperative safety after implantation of iris-fixated phakic intraocular lenses (pIOLs), optimal preoperative evaluation and patient selection is mandatory. We present a new software tool in a high-resolution Scheimpflug imaging device that precisely simulates the postoperative position of an iris-fixated pIOL and also simulates the effect of aging on the pIOL's position.

Adult↗

A decision support system for managing forest fire casualties.

Southern Europe is exposed to anthropogenic and natural forest fires. These result in loss of lives, goods and infrastructure, but also deteriorate the natural environment and degrade ecosystems. The early detection and combating of such catastrophes requires the use of a decision support system (DSS) for emergency management. The current literature reports on a series of efforts aimed to deliver DSSs for the management of the forest fires by utilising technologies like remote sensing and geographical information systems (GIS), yet no integrated system exists. This manuscript presents the results of scientific research aiming to the development of a DSS for managing forest fires. The system provides a series of software tools for the assessment of the propagation and combating of forest fires based on Arc/Info, ArcView, Arc Spatial Analyst, Arc Avenue, and Visual C++ technologies. The system integrates GIS technologies under the same data environment and utilises a common user interface to produce an integrated computer system based on semi-automatic satellite image processing (fuel maps), socio-economic risk modelling and probabilistic models that would serve as a useful tool for forest fire prevention, planning and management. Its performance has been demonstrated via real time up-to-date accurate information on the position and evolution of the fire. The system can assist emergency assessment, management and combating of the incident. A site demonstration and validation has been accomplished for the island of Evoia, Greece, an area particularly vulnerable to forest fires due to its ecological characteristics and prevailing wind patterns.

Decision Support Techniques↗

Solution structure of a Hck SH3 domain ligand complex reveals novel interaction modes.

We studied the interaction of hematopoietic cell kinase SH3 domain (HckSH3) with an artificial 12-residue proline-rich peptide PD1 (HSKYPLPPLPSL) identified as high affinity ligand (K(D)=0.2 muM). PD1 shows an unusual ligand sequence for SH3 binding in type I orientation because it lacks the typical basic anchor residue at position P(-3), but instead has a tyrosine residue at this position. A basic lysine residue, however, is present at position P(-4). The solution structure of the HckSH3:PD1 complex, which is the first HckSH3 complex structure available, clearly reveals that the P(-3) tyrosine residue of PD1 does not take the position of the typical anchor residue but rather forms additional van der Waals interactions with the HckSH3 RT loop. Instead, lysine at position P(-4) of PD1 substitutes the function of the P(-3) anchor residue. This finding expands the well known ligand consensus sequence +xxPpxP by +xxxPpxP. Thus, software tools like iSPOT fail to identify PD1 as a high-affinity HckSH3 ligand so far. In addition, a short antiparallel beta-sheet in the RT loop of HckSH3 is observed upon PD1 binding. The structure of the HckSH3:PD1 complex reveals novel features of SH3 ligand binding and yields new insights into the structural basics of SH3-ligand interactions. Consequences for computational prediction tools adressing SH3-ligand interactions as well as the biological relevance of our findings are discussed.

Amides↗

Effect of zinc deficiency on the mRNA expression pattern in liver and jejunum of adult rats: monitoring gene expression using cDNA microarrays combined with real-time RT-PCR.

In the study presented here, the effect of zinc deficiency on mRNA expression levels in liver and jejunum of adult rats was analyzed. Feed intake was restricted to 8 g/day. The semi-synthetic diet was fortified with pure phytate and contained either 2 microg Zn/g (Zn deficiency, n = 6) or 58 microg Zn/g (control, n = 7). After 29 days of Zn depletion feeding, entire jejunum and liver were retrieved and total RNA was extracted. Tissue specific expression pattern were screened and quantified by microarray analysis and verified individually via real-time RT-PCR. A relative quantification was performed with the newly developed Relative Expression Software Tool Copyright on numerous candidate genes which showed a differential expression. This study provides the first comparative view of gene expression regulation and fully quantitative expression analysis of 35 candidate genes in a non-growing Zn deficient adult rat model. The expression results indicate the existence of individual expression pattern in liver and jejunum and their tissue specific regulation under Zn deficiency. In addition, in jejunum a number of B-cell related genes could be demonstrated to be suppressed at Zn deficiency. In liver, metallothionein subtype 1 and 2 (MT-1 and MT-2) genes could be shown to be dramatically repressed and therefore represent putative markers for Zn deficiency. Expression results imply that some genes are expressed constitutively, whereas others are highly regulated in tissues responsible for Zn homeostasis.

Animals↗

An improved algorithm for anisotropic nonlinear diffusion for denoising cryo-tomograms.

Cryo-electron tomography is an imaging technique with an unique potential for visualizing large complex biological specimens. It ensures preservation of the biological material but the resulting cryotomograms are extremely noisy. Sophisticated denoising techniques are thus essential for allowing the visualization and interpretation of the information contained in the cryotomograms. Here a software tool based on anisotropic nonlinear diffusion is described for filtering cryotomograms. The approach reduces local noise and meanwhile enhances both curvilinear and planar structures. In the program a novel solution of the partial differential equation has been implemented, which allows a reliable estimation of derivatives and, furthermore, reduces computation time and memory requirements. Several criteria have been included to automatically select the optimal stopping time. The behaviour of the denoising approach is tested for visualizing filamentous structures in cryotomograms.

Algorithms↗

Metrological validation for 3D modeling of dental plaster casts.

The contribution of this paper is twofold: (1) it presents an automatic 3D modeling technique and (2) it advances a procedure for its metrological evaluation in the context of a medical application, the 3D modeling of dental plaster casts. The motivation for this work is the creation of a "virtual gypsotheque" where cumbersome dental plaster casts can be replaced by numerical 3D models, thereby alleviating storage and access problems and allowing dentists and orthodontists the use of novel and unprecedented software tools for their medical evaluations. Modeling free-form surfaces of anatomical interest is an intriguing mixture of open issues concerning 3D modeling, geometrical metrology, and medicine. Of general interest is both the fact that a widespread use of 3D modeling in non-engineering applications requires automatic procedures of the kind presented in this work and the adopted validation paradigm for free-form surfaces, rather useful for practical purposes. In this latter respect, the metrological analysis we advance is the first seminal attempt in the field of 3D modeling and can be readily extended to contexts other than the medical one discussed in this paper.

Computer Simulation↗

Automation of NMR structure determination of proteins.

The automation of protein structure determination using NMR is coming of age. The tedious processes of resonance assignment, followed by assignment of NOE (nuclear Overhauser enhancement) interactions (now intertwined with structure calculation), assembly of input files for structure calculation, intermediate analyses of incorrect assignments and bad input data, and finally structure validation are all being automated with sophisticated software tools. The robustness of the different approaches continues to deal with problems of completeness and uniqueness; nevertheless, the future is very bright for automation of NMR structure generation to approach the levels found in X-ray crystallography. Currently, near completely automated structure determination is possible for small proteins, and the prospect for medium-sized and large proteins is good.

Automation↗

Déjà vu all over again: finding and analyzing protein structure similarities.

Structure comparison is a crucial aspect of structural biology today. The field of structure comparison is developing rapidly, with the development of new algorithms, similarity scores, and statistical scores. The predicted large increase of experimental structures and structural models made possible by high-throughput efforts means that structural comparison and searching of structural databases using automated methods will become increasingly common. This Ways & Means article is meant to guide the structural biologist in the basics of structural alignment, and to provide an overview of the available software tools. The main purpose is to encourage users to gain some understanding of the strengths and limitations of structural alignment, and to take these factors into account when interpreting the results of different programs.

Algorithms↗

Assessing sensory function in locomotor systems using neuro-mechanical simulations.

Computer simulations are being used increasingly to gain an understanding of the complex interactions between the neuronal, sensory, muscular and mechanical components of locomotor systems. Recent neuro-mechanical simulations of walking in humans, cats and insects, and of swimming in lampreys, have provided new information on the functional role of specific groups of sensory receptors in regulating locomotion. As we discuss in this review, these studies also make it clear that a full understanding of the neural and mechanical mechanisms that underlie locomotion can be achieved only by using simulations in parallel with physiological investigations. The widespread implementation of this approach would be enhanced by the development of freely available and easy-to-use software tools.

Animals↗