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Dome osteotomy for posttraumatic cubitus varus: a surgical technique to avoid lateral condylar prominence.

The indication for surgery in most children with posttraumatic cubitus varus is the presence of an unsightly deformity. The function of the limb is generally not impaired. Lateral closing-wedge supracondylar osteotomy, although a widely used corrective procedure, tends to produce lateral condylar prominence, thus jeopardizing the cosmetic outcome. The authors used the dome supracondylar osteotomy, as described by Tien et al, as the corrective procedure for cubitus varus in 12 consecutive children. The average follow-up was 2.3 (range 1-4) years. The objective evaluation was done by one of the authors by measuring the pre- and postoperative lateral condylar prominence index, carrying angle, and the range of movement at the elbow. The patients and parents were also asked to self-assess the cosmetic outcome. There were seven excellent and five good results. None of the children showed a prominent lateral humeral condyle. Hypertrophic scar formation and ulnar neurapraxia were seen in one patient each. These results were comparable to the published results of lateral closing-wedge osteotomy in terms of correction of carrying angle and preservation of elbow motion and were superior to those of the lateral closing-wedge osteotomy in terms of the prominence of lateral humeral condyle, acceptability of the scar, and cosmesis. The authors offer independent verification of the observation that the technique of dome osteotomy as described by Tien et al for the correction of the posttraumatic cubitus varus is a simple, safe, and technically sound procedure that prevents the lateral condyle from becoming prominent and yields an excellent cosmetic outcome.

Adolescent↗

Toward a scientifically rigorous basis for developing mapped ecological regions.

Despite the wide use of ecological regions in conservation and resource-management evaluations and assessments, a commonly accepted theoretical basis for ecological regionalization does not exist. This fact, along with the paucity of focus on ecological regionalization by professional associations, journals, and faculties, has inhibited the advancement of a broadly acceptable scientific basis for the development, use, and verification of ecological regions. The central contention of this article is that ecological regions should improve our understanding of geographic and ecological phenomena associated with biotic and abiotic processes occurring in individual regions and also of processes characteristic of interactions and dependencies among multiple regions. Research associated with any ecoregional framework should facilitate development of hypotheses about ecological phenomena and dominant landscape elements associated with these phenomena, how these phenomena are structured in space, and how they function in a hierarchy. Success in addressing the research recommendations outlined in this article cannot occur within an ad hoc, largely uncoordinated research environment. Successful implementation of this plan will require activities--coordination, funding, and education--that are both scientific and administrative in nature. Perhaps the most important element of an infrastructure to support the scientific work of ecoregionalization would be a national or international authority similar to the Water and Science Technology Board of the National Academy of Sciences.

Conservation of Natural Resources↗

Use of percollTM in the isolation and purification of rabbit small intestinal brush border membranes.

(1) Intestinal absorption is altered under a variety of circumstances in health and disease and to determine a possible relationship between intestinal absorptive function and intestinal brush border membrane composition, we undertook the isolation and purification of rabbit jejunal and ileal brush borders, to allow further studies of their lipid composition under varied experimental conditions. (2) A modification of an established method (Schmitz, J., Preiser, H., Maestracci, D., Ghosh, B.K., Cerda, J.J. and Crane, R.K. (1973) Biochim. Biophys. Acta 323, 98-112) utilized CaCl2 aggregation and sequential centrifugation followed by purification of the brush border pellet (P2) at 27,000 X g on a PercollTM (Pharmacia) self-forming gradient. The PercollTM was removed by ultracentrifugation for 30 min at 100 000 X g, utilizing a batch rotor in the Beckman airfugeTM. (3) Pure brush border membrane vesicles were obtained and characterized by specific marker analysis and electron microscopy. Comparative marker analyses performed on P2 and final PercollTM preparations from animals showed that the purification achieved was 8-11-fold greater when compared to the original homogenates. Verification of purity was also demonstrated by the absence of DNA and very low levels of Beta-gluconridase and (Na+ + K+)-ATPase in the PercollTM preparations. (4) Comparative lipid analyses of P2 and final PercollTM preparations showed that levels of total phospholipid and free fatty acids were several-fold higher in the PercollTM preparations on a per mg protein basis. (5) A comparison of the activity of enzyme markers and the levels of total free fatty acids in P2 pellets obtained after Cacl2 and MgCl2 aggregation showed that CaCl2 aggregation gave the more consistently reproducible results. (6) Although standard procedures of membrane preparations not involving density gradient separation provide membranes of reasonable purity for the estimation of lipid components, we consider the final purification step of density gradient separation using PercollTM is essential for determining small quantitative changes which might occur in the membrane lipid composition under experimental conditions were intestinal absorptive function is altered.

Alkaline Phosphatase↗

The temperature-composition phase diagram and mesophase structure characterization of monopentadecenoin in water.

The temperature-composition phase diagram of monopentadecenoin, a monoacylglycerol with a cis monounsaturated fatty acid 15 carbon atoms long (C15:1c10) in water was constructed using x-ray diffraction. Low- and wide-angle diffraction patterns were collected from samples of fixed hydration as a function of temperature in the heating direction on x-ray-sensitive film. The temperature and hydration ranges investigated were 0-104 degrees C and 0-60% (w/w) water, respectively. The phases identified in the system include the lamellar crystalline phase, the lamellar liquid crystalline phase, the fluid isotropic phase, and two inverted cubic phases belonging to space groups la3d (Q230) and Pn3m (Q244). Particular attention has been devoted to the issues of phase equilibrium, phase boundary verification, and structure characterization. The phase diagrams of monopentadecenoin, monomyristolein (C14:1c9), and monoolein (C18:1c9) are compared, and the impact of molecular structure on mesophase stability and structure is discussed.

Fatty Acids, Monounsaturated↗

The efficiency of various thermoluminescence dosemeter types to heavy ions.

Dose verification in heavy-ion beams using passive dosemeter systems, e.g. thermoluminescence dosemeters (TLDs), is crucial due to the changing efficiency of the dosemeters for different ion species and linear energy transfer (LET) values. This behaviour leads to a falsification of absorbed dose that can be significant for many applications, e.g. in space or radiotherapeutic dosimetry. TLDs can only be established as a 'reference' system in heavy-ion beams or other radiation fields if the efficiency functions for all contributing ion species and LET values are provided. In the framework of a research project of the Atominstitute of the Austrian Universities irradiations with various ions were performed in the years 2001-2003 at the Heavy Ion Medical Accelerator (HIMAC) of the National Institute for Radiological Sciences (NIRS) in Chiba, Japan. Efficiency values were recorded in dependence on ion species and LET in a range from 2 to 400 keV microm(-1). The efficiencies of five different commercially available TLD materials namely TLD 600, TLD 700, TLD 700H, TLD 300 and TLD 200 were investigated.

Dose-Response Relationship, Radiation↗

Hospital reorganization after merger.

Major organizational changes among hospitals, like system affiliation, merger, and closure, would seem to offer substantial opportunities for hospitals and health systems to be strategic in the local reconfiguration of health services. This report presents the results of a unique survey on what happened to hospitals after mergers occurring between 1983 and 1988, inclusive. Building on an ongoing verification process of the American Hospital Association, surviving institutions from all 74 mergers that occurred during the study frame were surveyed in the fall of 1991. Responses were received from 60 of the 74 mergers (81%), regarding the primary, postmerger use of the hospitals involved. Topics surveyed included the premerger competition between the hospitals and in their environment, and what happened to the hospitals after their mergers. Mergers frequently served to convert acute, inpatient capacity to other functions, with less than half of acquired hospitals continuing acute services after merger. In the context of health care reform, mergers may offer an expeditious way locally to restructure health services. Evidence on the postmerger uses of hospitals and about the reasons given for merger suggests that mergers may reflect two general strategies: elimination of direct acute competitors or expansion of acute care networks.

Data Collection↗

Patient position verification using CT images.

The use of ions in the radiotherapy of cancer patients requires an accurate patient positioning in order to exploit its potential benefits. Using CT images as the basis for the setup verification offers the advantage of a high in-plane resolution in combination with a geometrically accurate, volumetric information. Before each fraction a single CT slice is acquired at the isocenter level after the positioning procedure. This single slice is registered to the planning CT cube using automated image registration algorithms. Thus any erreonous translation or rotation can be detected and quantified. The registration process involves the interpolation of the volumetric data, the calculation of an energy function, and the minimization of this energy function. Several data interpolation functions as well as minimization algorithms were compared. CT studies with a head phantom were performed in which defined translations and rotations were simulated by moving a motor-driven treatment chair. Different slice thicknesses and anatomical sites were studied to investigate their potential influence on the registration accuracy. The accuracy of the registration was found to be a fraction of a voxel size for suitable combinations of algorithms (typically better than 0.16 mm/deg). A significant dependancy of the registration accuracy on the CT slice thickness and the anatomical site was found (the accuracy ranges from 0.05 mm/deg to 0.16 mm/deg depending on the site). The calculation time is dependant on the used algorithms and the magnitude of the setup error. For the standard combination of algorithms as proposed by the authors (Downhill Simplex minimization with Trilinear interpolation) the typical calculation time is about 20 s for a Sun UltraSPARC processor. Taking into account the mechanical accuracy of the setup device (motor-driven chair) the registration of CT images is thus a useful tool for detecting and quantifying any significant error in the patient position.

Algorithms↗

[Classification of clinico-electroencephalographic syndromes in epilepsy in the developmental age].

The author describes the clinical-electroencephalographic classification of eleven syndromes of epilepsy in developmental age used by himself, based on verification of 3613 successive patients aged from 0 to 18 years who were treated in the years 1970-1976 and followed up for 5 years in the Poznań Epilepsy Treatment Centre. On the ground of clinical status (seizures and neuropsychiatric findings) and serial EEG records 2746 patients (76%) could have been classified into these epilepsy types. The practical aim of the classification was identification of the focus and circuit of the seizure at a given structural-functional level or organization of the developing brain for guided comprehensive therapy.

Adolescent↗

Verification bias-corrected estimators of the relative true and false positive rates of two binary screening tests.

The relative accuracy of two binary screening tests can be quantified by estimating the relative true positive rate (rTPR) and relative false positive rate (rFPR) between the two tests. Ideally all study subjects are administered both screening tests as well as a gold standard to determine disease status. In practice, however, often the gold standard is so invasive or costly that only a percentage of study subjects receive disease verification and the percentage differs depending on the results of the two screening tests. This is known as verification-biased sampling and may be by design or due to differential patient dropout or refusal to have the gold standard test administered. In this paper, maximum likelihood estimators of rTPR and rFPR and corresponding confidence intervals are developed for studies with verification-biased sampling assuming that disease status is missing at random (MAR). Simulation studies are used to show that if the MAR assumption holds, then the verification bias-corrected point estimators have little small sample bias and the confidence intervals have good coverage probabilities. Simulation studies also demonstrate that the verification bias-corrected point estimators may not be robust to violation of the MAR assumption. The proposed methods are illustrated using data from a study comparing the accuracy of Papanicolaou and human papillomavirus tests for detecting cervical cancer.

Adolescent↗

Effects of selected serotonin 5-HT(1) and 5-HT(2) receptor agonists on feeding behavior: possible mechanisms of action.

Serotonin (5-HT) receptor agonists with high affinity for the different subtypes (i.e. 5-HT(1A-1F), 5-HT(2A-2C)) of the 5-HT(1)- and 5-HT(2) receptor families have been shown to affect ingestive behavior. It has been assumed that: (1) stimulation of hypothalamic 5-HT(2C) or 5-HT(1B) receptors leads to a behaviorally specific hypophagic effect by accelerating satiety processes; (2) stimulation of 5-HT(2A) receptors leads to a disruption of the feeding cascade; and (3) stimulation of 5-HT(1A) and 5-HT(2B) receptors leads to a hyperphagic effect. The present paper reviews studies performed with the relatively selective receptor agonists ipsapirone (5-HT(1A)), CP-94,253 (5-HT(1B)), BW 723C86 (5-HT(2B)) and ORG 37684 (5-HT(2C)), as well as the nonselective receptor agonists TFMPP (5-HT(1B/2C)), m-CPP (5-HT(2C/1B)) and DOI (5-HT(2A/2C)) in a variety of feeding paradigms in rats, both after systemic and local injection. These studies support a role for other neuroanatomical regions (i.e. brain stem) and behavioral mechanisms (i.e. appetitive processes) in the hypophagic effects of these compounds, possibly as a function of the administered dose. Studies with 5-HT receptor antagonists indicate that the proposed role of particular 5-HT(1/2) receptor subtypes in the hypophagic effects of these 5-HT receptor agonists may be more complicated than originally thought. Further characterization of the role of 5-HT(1/2) receptor subtypes in the control of ingestive behavior will require extensive pharmacological and behavioral studies, using more selective receptor agonists and antagonists and different behavioral procedures, as well as verification in transgenic animals.

Animals↗

Framework for the environmental damage assessment of an industrial process chain.

On the basis of the life cycle approach, a framework for the assessment of the environmental damages generated by an industrial process chain is established. In order to consider all the processes of the life cycle, a methodology is developed based on an eco-matrix formed by chemical process eco-vectors containing all their environmental loads. To perform the impact assessment, environmental damage indicators are estimated in the most accurate way possible for each process. For this, site-specific evaluation is carried out applying damage functions and, hence, for each damage indicator, a damage matrix is obtained. In order to make the methodology more practical, options like dominance analysis are presented. Because of the large number of environmental loads, the focus is on the priority pollutants and then the final estimations are done with one indicator per safeguard subject. The damage indicators selected in this paper are damage costs, ecological damage parameter (both site-specific) and global damage estimates. As for the verification of the methodology, a study has been carried out based on the life cycle of the electricity produced by a municipal waste incinerator.

Animals↗

Continuous cultivation of the diatom Nitzschia laevis for eicosapentaenoic acid production: physiological study and process optimization.

The continuous cultures of the diatom Nitzschia laevis were performed at different dilution rates (D) and feed glucose concentrations (S(0)) to investigate cellular physiological responses and its production potential of eicosapentaenoic acid (EPA). Steady-state cell dry weight, residual glucose concentration, cell growth yield, specific glucose consumption rate, and fatty acid profiles were investigated within the range of D from 0.1 to 1.0 day(-1) (S(0) fixed at 20 g/L) and the range of S(0) from 5 to 35 g/L (D fixed at 0.3 day(-1)), respectively. The highest EPA productivity of 73 mg L(-1) day(-1) was obtained at D = 0.5 day(-1) and S(0) = 20 g/L. However, when the continuous culture achieved high productivities of EPA at certain dilution rates and feed glucose concentrations, glucose in the feed could not be consumed completely. Accordingly, the continuous culture was evaluated in terms of both EPA productivity (P) and glucose assimilation efficiency (E). The parameter eta, defined as the product of P and E, was used as an overall performance index. Since eta is a function of the two independent variables D and S(0), we employed a central composite design to optimize D and S(0) for the highest eta value. Based on the experimental results of the design, a second-order polynomial equation was established to represent the relationship between eta and D and S(0). The optimal values of D and S(0) were subsequently determined as 0.481 day(-1) and 15.56 g/L, respectively by the empirical model. The verification experiment confirmed the validity of the model. Under the optimal conditions, eta value reached 46.5 mg L(-1) day(-1), suggesting a considerably high efficiency of the continuous culture of N. laevis in terms of EPA production and glucose utilization.

Bioreactors↗

Loss of detoxification in inflammatory bowel disease: dysregulation of pregnane X receptor target genes.

BACKGROUND & AIMS: Phase 1, phase 2, and cellular efflux transporters are critical components in intestinal barrier function against xenobiotics and bacteria. We therefore performed global gene expression profiling in patients with ulcerative colitis (UC) and Crohn's disease as well as control specimens, with a special emphasis on genes involved in detoxification and epithelial membrane integrity. METHODS: Mucosal biopsy specimens from nonaffected regions of the colon and the terminal ileum were subjected to DNA microarray analysis and pathway-related data mining. Real-time reverse-transcription polymerase chain reaction was used for verification of selected regulated candidate genes in larger inflammatory bowel disease sample numbers and intestinal cell lines. RESULTS: Several dysregulated genes were identified in both disease groups and tissues. A set of genes coordinately down-regulated in the colon of patients with UC was composed of cellular detoxification and defense genes, which are target genes for the transcription factor pregnane X receptor (PXR). Messenger RNA expression of ABCB1 (MDR1) and PXR was significantly reduced in the colon of patients with UC but was unaffected in patients with Crohn's disease. In contrast to some of its target genes, the expression of PXR was not sensitive to tumor necrosis factor alpha stimulation of intestinal cell lines. CONCLUSIONS: A disease- and tissue-specific decrease in the expression of detoxification enzymes and ABC transporters was observed, which may be explained by a loss of PXR expression. Thus, dysregulation of xenobiotic metabolism and PXR activity in the gut is likely to contribute to the pathophysiology of UC.

ATP-Binding Cassette Transporters↗

A filtering approach based on Gaussian-powerlaw convolutions for local PET verification of proton radiotherapy.

Because proton beams activate positron emitters in patients, positron emission tomography (PET) has the potential to play a unique role in the in vivo verification of proton radiotherapy. Unfortunately, the PET image is not directly proportional to the delivered radiation dose distribution. Current treatment verification strategies using PET therefore compare the actual PET image with full-blown Monte Carlo simulations of the PET signal. In this paper, we describe a simpler and more direct way to reconstruct the expected PET signal from the local radiation dose distribution near the distal fall-off region, which is calculated by the treatment planning programme. Under reasonable assumptions, the PET image can be described as a convolution of the dose distribution with a filter function. We develop a formalism to derive the filter function analytically. The main concept is the introduction of 'Q' functions defined as the convolution of a Gaussian with a powerlaw function. Special Q functions are the Gaussian itself and the error function. The convolution of two Q functions is another Q function. By fitting elementary dose distributions and their corresponding PET signals with Q functions, we derive the Q function approximation of the filter. The new filtering method has been validated through comparisons with Monte Carlo calculations and, in one case, with measured data. While the basic concept is developed under idealized conditions assuming that the absorbing medium is homogeneous near the distal fall-off region, a generalization to inhomogeneous situations is also described. As a result, the method can determine the distal fall-off region of the PET signal, and consequently the range of the proton beam, with millimetre accuracy. Quantification of the produced activity is possible. In conclusion, the PET activity resulting from a proton beam treatment can be determined by locally filtering the dose distribution as obtained from the treatment planning system. The filter function can be calculated analytically using convolutions of Gaussians and powerlaw functions.

Algorithms↗

Predicting gene regulation by sigma factors in Bacillus subtilis from genome-wide data.

MOTIVATION: Sigma factors regulate the expression of genes in Bacillus subtilis at the transcriptional level. We assess the accuracy of a fold-change analysis, Bayesian networks, dynamic models and supervised learning based on coregulation in predicting gene regulation by sigma factors from gene expression data. To improve the prediction accuracy, we combine sequence information with expression data by adding their log-likelihood scores and by using a logistic regression model. We use the resulting score function to discover currently unknown gene regulations by sigma factors. RESULTS: The coregulation-based supervised learning method gave the most accurate prediction of sigma factors from expression data. We found that the logistic regression model effectively combines expression data with sequence information. In a genome-wide search, highly significant logistic regression scores were found for several genes whose transcriptional regulation is currently unknown. We provide the corresponding RNA polymerase binding sites to enable a straightforward experimental verification of these predictions.

Algorithms↗

Evaluation of electronic portal imaging device for missing tissue compensator design and verification.

The purpose of this investigation is to determine if electronic portal imaging devices (EPIDs) can be used for the design and verification of compensating filters. In order to do this, we investigated the operating characteristics of a commercially available EPID and the variation in transmitted dose for various measurement situations. We performed four initial tests to determine the EPID response specific to compensator situations. The tests determined EPID response to variable patient SSDs, different gantry angles, positions of an inhomogeneity within a phantom, and the sensitivity variation of different parts of the imager. After these tests, we determined the attenuation functions relating EPID response to phantom thickness for various phantom materials. With these functions, we tested simple compensation situations to demonstrate that missing tissue compensators can both be designed and verified using EPIDs.

Biophysical Phenomena↗

RUN-CBFbeta interaction in C. elegans: computational prediction and experimental verification.

The Runt domain proteins are eukaryotic transcription factors that regulate major developmental pathways. All members of this family contain a highly-conserved sequence-specific DNA binding domain: the Runt domain (RD). Structural and biochemical studies have shown that the Runt domain undergoes a conformational transition upon binding to DNA and that this process is regulated by an unrelated partner protein CBFbeta that enhances the DNA binding affinity of RD. Most of the reported studies on the Runt domain transcription factors were performed on proteins from mammals and Drosophila whereas very little has been known about the C. elegans RD protein, RUN, which provides the simplest model system for understanding the function of this class of transcription factors. We performed computational studies on RD domains from various species including C. elegans, Drosophila, and human, using the atom-atom contact surface area scoring method. The scoring analysis indicates that the DNA binding regulation of the C. elegans RD protein (CeRD) occurs via its interaction with a CBFbeta-like partner, as found for the human proteins, whereas a different mode of regulation may occur in the Drosophila system. Sequence, secondary structure and fold analyses of a putative CBFbeta protein identified in the C. elegans genome, CeCBFbeta, sharing a 22% identity with the human protein, predict a similar structure of this protein to that of the human CBFbeta protein. We produced the C. elegans proteins CeRD and CeCBFbeta in bacteria and confirmed their physical interaction as well as cross interactions with the corresponding human proteins. We also confirmed the structural similarity of CBFbeta and CeCBFbeta by circular dichroism analysis. The combined results suggest that a similar mechanism of regulation operates for the human and the C. elegans RD proteins despite the low sequence identity between their CBFbeta proteins and the evolutionary distance between the two systems.

Amino Acid Sequence↗

MENDL2 and IEAF2001 nuclide production yields databases verification in inter-medium energy range.

This work presents results of computer simulation of two experiments which aim at measuring the threshold activation reaction rates in 12C, 19F, 27Al, 59Co, 63Cu, 65Cu, 64Zn, 93Nb, 115In, 169Tm, 181Ta, 197Au, and thin samples placed inside and outside a 0.8 GeV proton-irradiated 4-cm thick W target and a 92-cm-thick W-Na composite target of 15 cm diameter both. In total, more than 1000 values of activation reaction were determined in both the experiments. The measured reaction rates were compared with the rates simulated by the LAHET code with the use of several nuclear databases for the respective excitation functions, namely, MENDL2 together with MENDL2P for cross sections of protons and neutrons up to 100 MeV, and with the recently developed IEAF-2001 that provides neutron cross sections up to 150 MeV. A comparison of simulation-to-experiment agreement obtained with MENDL2 and IEAF-2001 is presented. The agreement between simulation and experiment has been found general satisfactory for both databases. However, further studies should be done to improve the simulation of production of secondary protons and high-energy neutrons, as well as the high-energy neutron elastic scattering. Our results allow to conclude about the reliability of the transport codes and databases used to simulate the accelerator driven systems (ADS), particularly with Na-cooled W targets. High-energy threshold excitation functions to be used in the activation-based unfolding of neutron spectra inside the ADS can also be inferred from these results.

Algorithms↗