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PubMed1995

Second-order analysis of space-time clustering.

We consider the problem of detecting and describing space-time interaction in point process data. We extend existing second-order methods for purely spatial point process data to the spatial-temporal setting. This extension allows us to estimate space-time interaction as a function of spatial and temporal separation, and provides a useful reinterpretation of a popular test, due to Knox, for space-time interaction. Applications to simulated and real data indicate the method's potential.

Cluster Analysis↗
PubMed2004

Assessing anti-rabies baiting--what happens on the ground?

BACKGROUND: Rabies is one of the most hazardous zoonoses in the world. Oral mass vaccination has developed into the most effective management method to control fox rabies. The future need to control the disease in large countries (i.e. Eastern Europe and the Americas) forces cost-benefit discussions. The 'Increase bait density' option refers to the usual management assumption that more baits per km2 could compensate for high fox abundance and override the imperfect supply of bait pieces to the individual fox. METHODS: We use a spatial simulation, which combines explicitly fox space use (tessellation polygons) and aeroplane flight lines (straight lines). The number of baits actually falling into each polygon is measured. The manager's strategic options are converted into changes of the resulting bait distribution on the ground. The comparison enables the rating of the options with respect to the management aim (i.e. accessibility of baits). RESULTS: Above 5% (approx. 10%) of all fox groups without any bait (at most 5 baits) relate to the baiting strategy applied in the field (1 km spaced parallel flight lines, 20 baits per km2 distributed) under habitat conditions comparable to middle and western Europe (fox group home-range 1 km2, 2.5 adults; reference strategy). Increasing the bait density on the same flight-line pattern neither reduces the number of under-baited fox group home-ranges, nor improves the management outcome and hence wastes resources. However, reducing the flight line distance provides a more even bait distribution and thus compensates for missed fox groups or extra high fox density.The reference strategy's bait density can be reduced when accounting for the missed fox groups. The management result with the proper strategy is likely the same but with reduced costs. CONCLUSION: There is no overall optimal strategy for the bait distribution in large areas. For major parts of the landscape, the reference strategy will be more competitive. In situations where set backs are attributed to non-homogeneous bait accessibility the distribution scheme has to be refined zone-based (i.e. increase of the flight line length per unit area). However, increase in bait density above the reference strategy appears inappropriate at least for non-urban abundance conditions of the red fox.

Administration, Oral↗
PubMed2002

Image transfer through cirrus clouds. II. Wave-front segmentation and imaging.

A hybrid technique to simulate the imaging of space-based objects through cirrus clouds is presented. The method makes use of standard Huygens-Fresnel propagation beyond the cloud boundary and a novel vector trace approach within the cloud. At the top of the cloud, the wave front is divided into an array of input gradient vectors, which are in turn transmitted through the cloud model by use of the Coherent Illumination Ray Trace and Imaging Software for Cirrus. At the bottom of the cloud, the output vector distribution is used to reconstruct a wave front that continues propagating to the ground receiver. Images of the object as seen through cirrus clouds with different optical depths are compared with a diffraction-limited image. Turbulence effects from the atmospheric propagation are not included.

Journal Article↗
PubMed2006

An empirical Bayes method for updating inferences in analysis of quantitative trait loci using information from related genome scans.

Individual genome scans for quantitative trait loci (QTL) mapping often suffer from low statistical power and imprecise estimates of QTL location and effect. This lack of precision yields large confidence intervals for QTL location, which are problematic for subsequent fine mapping and positional cloning. In prioritizing areas for follow-up after an initial genome scan and in evaluating the credibility of apparent linkage signals, investigators typically examine the results of other genome scans of the same phenotype and informally update their beliefs about which linkage signals in their scan most merit confidence and follow-up via a subjective-intuitive integration approach. A method that acknowledges the wisdom of this general paradigm but formally borrows information from other scans to increase confidence in objectivity would be a benefit. We developed an empirical Bayes analytic method to integrate information from multiple genome scans. The linkage statistic obtained from a single genome scan study is updated by incorporating statistics from other genome scans as prior information. This technique does not require that all studies have an identical marker map or a common estimated QTL effect. The updated linkage statistic can then be used for the estimation of QTL location and effect. We evaluate the performance of our method by using extensive simulations based on actual marker spacing and allele frequencies from available data. Results indicate that the empirical Bayes method can account for between-study heterogeneity, estimate the QTL location and effect more precisely, and provide narrower confidence intervals than results from any single individual study. We also compared the empirical Bayes method with a method originally developed for meta-analysis (a closely related but distinct purpose). In the face of marked heterogeneity among studies, the empirical Bayes method outperforms the comparator.

Chromosome Mapping↗
PubMedDate not supplied

Dentin bond strength and marginal adaptation: direct composite resins vs ceramic inlays.

The aim of this in vitro study was to compare the dentin bond strength and marginal adaptation of directly and indirectly inserted restorations. A conically modified push-out test was designed to consider polymerization shrinkage and facilitate inlay placement. A total of 260 cavities were prepared into disks of freshly extracted human third molars and filled with direct composite resins or with adhesively luted ceramic inlays. Dentin adhesives of the third--(with self-etching primer: ART Bond, Syntac Classic), fourth--(with total etching: Scotchbond Multi-Purpose Plus), and fifth-generation (one-bottle adhesives: Syntac Single Component, Prime & Bond 2.1) were used in combination with one hybrid composite (Tetric) or luting composite (Variolink Low). Control groups did not use an adhesive. Polymerization of the bonding agent was carried out prior to insertion of the filling/inlay or afterwards simultaneously with the composite/luting composite. The thickness of the adhesive layer and luting composite was recorded, and after 7 days of storage and 24 hours of thermocycling (1150 cycles) replicas were made and extrusion testing performed. Fracture modes were determined and replicas were examined regarding marginal adaptation using SEM (X200 magnification). Precuring of the bonding resin increased dentin bond strength independent of the material combination or insertion mode (P < 0.05). In general, third- and fourth-generation dentin adhesives produced better results in bond strength and marginal adaptation than one-bottle systems (P < 0.05). In the third generation, ART Bond achieved significantly higher push-out values than Syntac (P < 0.05), but no better marginal adaptation. Cohesive fractures within the dentin were only observed in the inlay groups with precured resin. Precuring of the bonding resin is an important factor for both direct and indirect restorations. Nevertheless, precuring of the bonding resin prior to insertion of adhesive inlays cannot be recommended clinically, because the 120-micron luting spaces were too large. In simulated cavities, direct composite fillings with precuring achieved bond strengths similar to inlays without precuring. One-bottle adhesive systems performed poorly compared with multi-step adhesives of the third and fourth generation.

Analysis of Variance↗
PubMedDate not supplied

[Antiorthostatic hypokinesia as an approximate model of weightlessness].

Eight test subjects were exposed to a five-day bed rest experiment in the recumbent and head-down position (at an angle of 0 degrees,--4 degrees,--8 degrees, and--12 degrees) to study the physiological effects of the exposure. The head-down tilting at--4 degrees and--12 degrees was shown to simulate physiological effects of real space flight better than bed rest at 0 degrees. The results made it possible to model an acute stage of weightlessness adaptation and to assay the contribution of gravity-induced blood redistribution to the physiological reactions.

Adult↗
PubMed1983

[Combined treatment of malignant gliomas].

A controlled study of 226 age-matched patients with histologically proven grade 3 and 4 supratentorial gliomas with maximum feasible tumour resection, postoperative Karnofsky performance over 50 and minimum survival of 8 weeks compares the results of supportive care (45 cases), high-dose irradiation of 40 to 66 Gy (59 cases), COMP protocol (CCNU, procarbazine, vincristine, methotrexate, prednisone in 15 day cycles-42 cases) and simultaneous irradiation and COMP chemotherapy (80 cases including 30 survivors). Median recurrent-free intervals in the treatment groups (7 to 11.7 months) were significantly longer than after supportive care (4.4 months). Median survival with supportive care (6.7 months) was significantly shorter than after radiation or COMP treatment (11.7 and 12.3 months) and 14.9 to over 19.9 months with combined treatment, where the two-year survival rates were 33 and 67% (for survivors), and the 3-year survival rates 13 to 30%. Toxic side effects of multimodality treatment were more frequent than after chemotherapy. In addition to space-occupying intracranial cysts often simulating tumour recurrence (12%) and rare radiation necrosis, about 15% of long-term survivors developed progressive intellectual dysfunction with brain atrophy, in the absence of tumour regrowth. Despite some promising results of multimodality approaches towards the management of malignant supratentorial gliomas, the overall results are unsatisfactory and need further optimization.

Adult↗
PubMed1993

[Quantitative ultrastructure of the myocardium of Japanese quail after long-term hypodynamia].

Quantitative ultrastructural myocardial changes of myocardium of the japanese quail (Coturnix coturnix japonica) were studied during an immobilization stress (hypodynamia) lasting 9, 30, 60 and 90 days. Hypodynamic quails were fixed by waistcoats to the feeding place simulating conditions of long lasting space flight which the quails were determined for. The surveyed morphological parametres were: mitochondrial rate, mitochondrial volume in % of cytoplasm, volume of myofibres in % of cytoplasm, volume of single mitochondria, extent of cristolysis. Progressive mitochondrial hydratation and even local oedema were observed during the experiment. It led to a progressive increase of mitochondrial volume and simultaneous decrease of volume of myofilaments as a sign of intracellular atrophy of myofibres. The results correlated well with a decreased mass of myofibres observed in experimental quails from space flight on the orbital station MIR.

Animals↗
PubMedDate not supplied

Intermittent loading of teeth restored using prefabricated carbon fiber posts.

This in vivo study evaluated the fracture resistance of bovine teeth with prefabricated carbon fiber posts. Fourteen bovine teeth having similar lengths and dimensions were mounted in an acrylic resin block having a simulated periodontal ligament. The post space was prepared using two calibrated drills that provided an 8.5-mm post length. The prefabricated carbon fiber post was luted with a resin luting agent, and the core was made using the system's autopolymerizing resin core material. A crown was luted to each prepared tooth. Each test specimen was intermittently loaded (250 N) at an angulation of 45 degrees to the long axis of the tooth at a frequency of 2 loads per second. Four of the roots had an incomplete longitudinal fracture after loading. The results of this study were compared to a previous study by the authors that had been conducted under similar conditions with prefabricated parallel-sided posts (Para-Post) and tapered, individually cast posts. The failure rates of the two types of posts from the previous study were significantly higher (Logrank test; P<.02) than those of the carbon fiber posts.

Animals↗
PubMed2004

Population resistance to climate change: modelling the effects of low recruitment in open populations.

Isolated populations or those at the edge of their distribution are usually more sensitive to changes in the environment, such as climate change. For the barnacle Semibalanus balanoides (L.), one possible effect of climate change is that unpredictable spring weather could lead to the mismatching of larval release with spring phytoplankton bloom, hence reducing the recruitment. In this paper, model simulations of a variable open population with space limited recruitment were used to investigate the effects of low and zero recruitment on population abundance in S. balanoides. Data for model parameters was taken from an isolated population in the Isle of Man, British Isles. Model simulations with observed frequencies of years with low recruitment showed only small changes in population dynamics. Increased frequencies of low recruitment had large effects on the variation in population growth rate and free space and on population structure. Furthermore, populations with intermediate to high frequencies of low recruitment appeared more sensitive to additional changes in recruitment. Exchanging low recruitment with zero recruitment severely increased the risk of local extinctions. Simulations with consecutive years of low recruitment showed a substantial increase in free space and an increase in the time taken to recover to normal densities. In conclusion, model simulations indicate that variable populations can be well buffered to changes in the demography caused by introduced environmental noise, but also, that intermediate to high frequencies of disturbance can lead to a swift change in population dynamics, which in turn, may affect the dynamics of whole communities.

Animals↗
PubMed1987

[Stress distribution in the brain--numerical simulation by the finite element method].

The analysis of the deformation of brain and distribution of stress caused by the compression from outside would be interesting and also useful for the better understanding of the pathophysiology in the cases of intracranial hematoma and other space occupying lesions. The computerized numerical simulation using the finite element method was carried out to analyze these problems. A simple brain model of two dimensions, that was composed of the inner surface of skull, brain and lateral ventricles, was utilized and it was divided into 101 triangular elements for the calculation of finite element method by a 16-bit personal computer. The model of brain was compressed in two different ways; one was a subdural hematoma type where the force of compression was distributed over relatively wide area and the other was a epidural hematoma type where compression was localized to smaller area. In both types, the brain was compressed on the left fronto-temporal region. The deformation of brain in the subdural hematoma type model was that corresponding to the hematoma of crescent shape just as seen on the CT scan of actual case. The lateral ventricle of affected side was deformed more markedly than that of contralateral side. The midline structure of the brain was shifted to normal side and shift was larger in the portion anterior to the lateral ventricles. The stress was distributed from the area beneath the hematoma to remote location in the affected hemisphere but the propagation of stress was blocked by the falx and it was very small in the contralateral hemisphere.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain↗
PubMed2006

X-ray diffraction "fingerprinting" of DNA structure in solution for quantitative evaluation of molecular dynamics simulation.

Solution state x-ray diffraction fingerprinting is demonstrated as a method for experimentally assessing the accuracy of molecular dynamics (MD) simulations. Fourier transforms of coordinate data from MD simulations are used to produce reciprocal space "fingerprints" of atomic pair distance correlations that are characteristic of the ensemble and are the direct numerical analogues of experimental solution x-ray diffraction (SXD). SXD experiments and MD simulations were carried out to test the ability of experiment and simulation to resolve sequence-dependent modifications in helix conformation for B-form DNA. SXD experiments demonstrated that solution-state poly(AT) and poly(A)-poly(T) duplex DNA sequences exist in ensembles close to canonical B-form and B'-form structures, respectively. In contrast, MD simulations analyzed in terms of SXD fingerprints are shown to deviate from experiment, most significantly for poly(A)-poly(T) duplex DNA. Compared with experiment, MD simulation shortcomings were found to include both mismatches in simulated conformer structures and number population within the ensembles. This work demonstrates an experimental approach for quantitatively evaluating MD simulations and other coordinate models to simulate biopolymer structure in solution and suggests opportunities to use solution diffraction data as experimental benchmarks for developing supramolecular force fields optimized for a range of in situ applications.

DNA↗
PubMed1995

Side-chain prediction by neural networks and simulated annealing optimization.

The prediction of the side-chain positions of proteins of known tertiary backbone structure was accomplished by a combination of neural networks and a simulated annealing method. Neural networks were used to generate distributions of side-chain dihedral angles. By eliminating network outputs with low activities, we were able to generate a reduced conformational space in which Monte Carlo-simulated annealing was carried out to optimize side-chain positions. In this study of 12 proteins, the average fractions of correct chi 1, chi 2 and combined chi 1 and chi 2 (to within 40 degrees of actual structure) were 82, 72 and 68% respectively.

Amino Acids↗
PubMed1994

[Mineral metabolism in man under altered gravitation].

The book contains data about the functions and the metabolism of mineralized tissues, and the results of investigations of bone tissue and calcium metabolism during manned space missions and ground-based simulations. Consideration is given to the bone strength characteristics under experimental hypo- and hypergravity. The role of hormonal and physical/chemical factors in the mechanisms of iron control alterations in man during space missions of various lengths is analyzed. Evaluated is the efficiency of different countermeasures opposing the shifts in electrolyte exchange and bone mineral losses in these conditions. A concept is proposed for hypogravity-induced changes in the mineral metabolism and bone tissue status. The book is addressed to biologists, physiologists, biochemists, specialists in space biology and aerospace medicine.

Aerospace Medicine↗
PubMed1999

Biomedical study on combined effects of simulated weightlessness and emergent depressurization of spacecraft.

Cabin emergent depressurization (CED) may occur in spacecraft during manned space flight. The purpose of this paper was to study the combined effects of simulated weightlessness (SW) and CED factors on humans and animals. It was found that the amplitude of T wave of human electrocardiograms (ECG) significantly decreased in bed rest and hypoxia compared with the control condition (P<0.05), and that suspension with pure O2 induced severer edema in the lungs of rats than that in only a pure O2 environment. SW and pure O2 caused middle ear congestion and decreased the barofunction during pressure changes. These results indicate that human response to CED factors become more serious under SW because of the blood redistribution.

Aerospace Medicine↗
PubMed1996

Cognitive fatigue and complex decision making under prolonged isolation and confinement.

Cognitive fatigue and subjective state were assessed in four healthy subject (three males and one female), confined for a period of 60 days in a hyperbaric chamber stimulating a space station environment. They were required to carry out daily a working memory/decision-making test, simulating the management of the levels of contaminants present in a spacecraft atmosphere. Information about a set of contaminants is presented on a 'reference screen.' This has to be memorized, then used to make decisions about the need for corrective action across a sequence of four 'status screens.' Subjects may check back to the reference information at any time. A low error rate was emphasized in the instructions and training. In addition to error rate, performance was also measured in terms of the time taken to make decisions and checks of reference screens (decision time and check time). Subjective measures were also made of workload and environmental resources (personal control and support), levels of anxiety and fatigue before the task, and cognitive effort expended during the task. The search for decrements during the second half of the isolation period was complicated by evidence of a continued learning process during the first half, probably because of insufficient practice before isolation. Learning curves (negative exponential functions) were fitted to the data points for the first half of the isolation period, and residuals between predicted and observed data for the second four weeks were analyzed. All subjects showed increases in decision time and check time during the last weeks of isolation, with one subject also showing an increase in errors. Workload levels were reported as moderate, but varied across the four subjects, The same was true for resources. Anxiety was low and relatively stable over the entire 60-day period, but fatigue levels were elevated during the second half. This was particularly true for the two subjects who maintained the required low error rate. Effort was also quite stable, through it tended to follow changes in work demands and fatigue. Individual subjects are seen to adapt to the stress of prolonged isolation in different ways. Two subjects maintained low error rates under increasing subjective demands by additional cognitive effort and slowing of performance. The other two subjects exhibit more widespread decrement, including high error rates, without increase in subjective demands. The analysis of individual patterns of adaptation is recommended as a way of understanding and predicting the impact of isolation and confinement during spaceflights.

Adaptation, Psychological↗
PubMed2002

The effect of malignant effusions on methotrexate disposition.

PURPOSE: The purpose of this study was to evaluate the effect of malignant effusions on the pharmacokinetics of methotrexate (MTX). METHODS: Simulated drug concentrations in blood, tissues and effusion fluid spaces were generated using a previously published physiologically based pharmacokinetic (PBPK) model for MTX in humans. The model was expanded to incorporate effusion spaces with permeability rate-limited drug transport. The model was used first to simulate MTX plasma concentrations in patients without effusions. Then the effects of cardiac, peritoneal and pleural effusions on MTX plasma concentrations were investigated followed by an examination of the influence of effusion volume, binding in the effusate, and effusion space permeability clearance (PA) on MTX plasma pharmacokinetics. In addition, the effect of the disposition characteristics (e.g. volume of distribution) of the anticancer drug on the overall influence of an effusate was evaluated. Finally, the simulations were compared with MTX concentrations observed in the plasma and pleural fluid of a patient with a pleural effusion treated with MTX. RESULTS: There was good agreement between the PBPK-simulated MTX plasma concentrations and observed values in patients without effusions. There was also a remarkable similarity between simulated and measured plasma and effusion MTX concentrations in a pediatric patient with a malignant pleural effusion. The physiological characteristics of an effusion, i.e. fluid volume, protein binding and membrane permeability clearance, modulate the influence of an effusion on the drug plasma concentration-time course. In general, effusions cause an increase in the steady-state volume of distribution but no change in the overall clearance of a drug. Malignant effusions were noticeable only in the disposition phase of MTX resulting in an apparent "third space." This was most prominent when the effusion fluid volume was large, the binding of MTX in the effusion fluid was greater than in plasma and the PA value was low. The percentage change in terminal half-life due to an effusion is significant for drugs with small volumes of distribution (332%) but not for those with large volumes of distribution (1.29%). In the case of MTX, and probably other anticancer drugs, the resulting increase in half-life may be associated with unanticipated toxicity.

Antimetabolites, Antineoplastic↗
PubMed1996

Ethological analysis of crew member behavior: distances, orientations, and postures.

The purpose of this study was to investigate the spatial behavior towards each other of a group of three males and one female isolated and confined for a period of 60 days. Video recordings of the individual crew members in the habitat, laboratory, and transfer modules for a 4-hr period once weekly during the isolation period provided the material for analysis. The observed parameters were: inter-individual distance, orientation (number of other subjects laced), and posture. Three distinct periods are noted. The initial period was characterized by a rather constant spatial behavior of the crew with few changes in inter-individual distances. The middle period of isolation (particularly weeks 5 and 6) showed a tendency towards closer grouping with decreased inter-individual distances (personal and social space). The final period (weeks 7-9) was marked by a dispersion of the crew members with increased inter-individual distances (public space) and more frequent isolated positions. Individual differences in behavioral strategy were noted. The Commander (subject B) kept the largest number of other crew members in his visual field. The orientation of the other subjects showed more variation. Dominant posture were: seated, standing, lying. Here also there were individual differences, for example, the female subject H frequently assumed a very grouped posture. During the second half of the isolation period stretched body positions became more frequent, suggesting reduced tension and stress. The observed spatial behavior indicates a weak cohesion of the crew with little tendency towards formation of a true social group in the course of isolation. The crew remained a group of individuals constituted for the purpose of the experiment. From her closer positions to the other subjects, it appears that the female crew member had a positive effect on group cohesiveness through an active social role. However, it seems that a longer period of confinement would be needed to turn the four crew members into a cohesive crew. The findings from these simulation studies and in earlier spaceflight observations suggest a possible use of ethological observation during space missions for the purpose of optimizing performance, physical and psychological fitness of the individual astronauts and group dynamics of the entire crew. It might be possible to establish a set of individual standards allowing detection of slight behavioral disturbances in an astronaut during the mission.

Astronauts↗