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PubMed1993

Assessment of past occupational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin using blood lipid analyses.

Current 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) concentrations were determined in blood samples for 138 persons who had been involved in assessment, clean-up and demolition activities after the 1953 BASF trichlorophenol reactor accident. From these data and detailed descriptions of the circumstances and duration of individual exposure, a regression model was developed for describing the relationships between various exposure situations and TCDD concentration. The model explained 65% of the variability in log (TCDD) concentration. Using half-life assumptions and the regression model parameters we estimated cumulative TCDD concentrations back-calculated to the time of exposure for all 254 members of the accident cohort. The geometric mean cumulative TCDD concentration for all cohort members averaged 137.7 ppt. Estimated cumulative TCDD concentrations correlated well with chloracne severity. The mean TCDD concentrations were 38.4 ppt for the no chloracne subgroup (n = 139), 420.8 ppt for the moderate chloracne subgroup (n = 59) and 1008 ppt for the severe chloracne subgroup (n = 56). The estimation procedure should be helpful in assessing the relationships between various health outcomes and TCDD exposure in this cohort.

Acne Vulgaris↗

PubMed2002

The effect of PACS on the time required for technologists to produce radiographic images in the emergency department radiology suite.

The purpose of this study was to evaluate the effect of a switch to a filmless image management system on the time required for technologists to produce radiographic images in the emergency department (ED) after controlling for exam difficulty and a variable workload. Time and motion data were collected on patients who had radiographic images taken while being treated in the emergency department over the 3 1/2-year period from April 1997 to November 2000. Event times and demographic data were obtained from the radiology information system, from the hospital information system, from emergency department records, or by observation by research coordinators. Multiple least squares regression analysis identified several independent predictors of the time required for technologists to produce radiographic images. These variables included the level of technologist experience, the number of trauma-alert patient arrivals, and whether a filmless image management system was used (all P <.05). Our regression model explained 22% of the variability in technologist time (R2 Adjusted, 0.22; F = 24.01; P <.0001). The regression model predicted a time saving of 2 to 3 minutes per patient in the elapsed time from notification of a needed examination until image availability because of the implementation of PACS, a delay of 4 to 6 minutes per patient who were imaged by technologists who spent less than 10% of their work assignments within the ED, and a delay of 18 to 27 minutes in radiology workflow because of the arrival of a trauma alert patient. A filmless system decreased the amount of time required to produce radiographs. The arrival of a trauma alert patient delayed radiology workflow in the ED. Inexperienced technologists require 4 to 6 minutes of additional time per patient to complete the same amount of work accomplished by an experienced technologist.

Allied Health Personnel↗

PubMed1996

Spatial properties of filters underlying vernier acuity revealed by masking: evidence for collator mechanisms.

Models of vernier acuity based on the differential response of oriented filters receive support from the finding that vernier threshold elevation peaks for grating mask orientations which are slightly different from the orientation of the vernier bars. We replicate this effect using long, abutting vernier bars, and masks which possess gaps up to 22.5' wide (Experiments 1 and 3); a surprising result considering that vernier acuity improves little for bars longer than 10'. To account for this we suggest the involvement of elongated mechanisms (referred to as collators or collectors) that "integrate" responses of numerous smaller filters along the axis of their common orientation. The collator model explains patterns of threshold elevation obtained with a variety of mask-vernier configurations. In particular, the model predicts that masks located midway between separated vernier bars will interfere with integrative processes occurring over the entire region encompassing both bars (Experiment 2). In confirmation of this prediction we find that centrally placed masks produce significant orientation-specific threshold elevation. In suggesting a contribution to vernier acuity from integrative mechanisms, our results, along with others, emphasize the importance of global processes in vernier acuity.

Filtration↗

PubMed1988

Classical genetic analysis of GABA-related seizures.

Differences in resistance to 3-mercaptopropionic acid (MP)-induced seizures exist between DBA/2Ibg and C57BL/6Ibg inbred strains of mice; C57BL/6Ibg mice are more resistant to MP-induced seizures. To determine the mode of inheritance for seizure resistance, a classical genetic analysis was conducted using these two parental strains, their F1, F2, and backcross generations. Latencies to seizure onset and tonus after intraperitoneal (IP) injections of MP (25-40 mg/kg) were quantified. For all populations mean latencies to onset and tonus decreased in a dose dependent manner with the hybrid generations exhibiting a seizure resistant phenotype resembling the C57BL/6Ibg strain. In general, female mice were less resistant to MP-induced seizures than males; however, a significant degree of resistance was retained by the C57BL/6Ibg females and their female progeny. A quantitative assessment of the pattern of inheritance for seizure resistance using a weighted least-squares regression approach indicated that an additive-dominance model explained latency to seizure onset data at 25, 35 and 40 mg/kg. However, at 30 mg/kg, the model required the addition of an epistatic parameter to best describe mean scores at this dose. The results of these analyses suggest that resistance to MP-induced seizures is transmitted in a dominant manner.

3-Mercaptopropionic Acid↗

PubMed2004

Theoretical model to determine the effects of geometrical factors on the resorption of calcium phosphate bone substitutes.

A theoretical approach was used to determine the effect of geometrical factors on the resorption rate of calcium phosphate bone substitutes that are either dense, microporous, and/or contain spherical macropores. Two cases were considered: (a) macroporous blocks that can be invaded by resorbing cells either directly because the structure is fully open-porous, or indirectly after some resorption of the macropores walls and/or interconnections. (b) Microporous or dense blocks/granules that cannot be invaded by resorbing cells, i.e. can only be resorbed from the outside to the inside, layer by layer. The theoretical approach was based on five assumptions: (i) the pores are spherical; (ii) the pores are ordered according to a face-centered cubic packing; (iii) the resorption is surface-controlled; (iv) the resorption is only possible if the surface can be accessed by blood vessels of 50 microm in diameter; and (v) the resorption time of a given amount of calcium phosphate is proportional to the net amount of material. Based on these assumptions, the calculations showed that the resorption time of a macroporous block could be minimized at a specific pore radius. This pore radius depended (i) on the size of the bone substitute and (ii) on the interpore distance. Typical radii were in the range of 100-400 microm. These values are similar to the numerous pore size optima mentioned in the scientific literature. For microporous or dense blocks/granules, the model suggested that a relatively small radius should be preferred. Such a radius leads to an optimum combination of a high surface area favorizing resorption and the presence of large intergranular gaps favorizing blood vessel ingrowth. In that case, the optimum of granule radius is around 100-200 microm. Finally, a very good agreement was found between the predictions of the model and experimental data, i.e. the model explained in all but two cases the results with an accuracy superior to 80%. In conclusion, the model appears to be a useful tool to better understand in vivo results, and possibly better define the geometry and distribution of the pores as well as the size of a bone substitute.

Absorbable Implants↗

PubMed2005

Modelling 137Cs uptake in plants from undisturbed soil monoliths.

A model predicting 137Cs uptake in plants was applied on data from artificially contaminated lysimeters. The lysimeter data involve three different crops (beans, ryegrass and lettuce) grown on five different soils between 3 and 5 years after contamination and where soil solution composition was monitored. The mechanistic model predicts plant uptake of 137Cs from soil solution composition. Predicted K concentrations in the rhizosphere were up to 50-fold below that in the bulk soil solution whereas corresponding 137Cs concentration gradients were always less pronounced. Predictions of crop 137Cs content based on rhizosphere soil solution compositions were generally closer to observations than those based on bulk soil solution composition. The model explained 17% (beans) to 91% (lettuce) of the variation in 137Cs activity concentrations in the plants. The model failed to predict the 137Cs activity concentration in ryegrass where uptake of the 5-year-old 137Cs from 3 soils was about 40-fold larger than predicted. The model generally underpredicted crop 137Cs concentrations at soil solution K concentration below about 1.0 mM. It is concluded that 137Cs uptake can be predicted from the soil solution composition at adequate K nutrition but that significant uncertainties remain when soil solution K is below 1 mM.

Cesium Radioisotopes↗

PubMed1994

Molecular models and structural comparisons of native and mutant class I filamentous bacteriophages Ff (fd, f1, M13), If1 and IKe.

The filamentous bacteriophages are flexible rods about 1 to 2 microns long and 6 nm in diameter, with a helical shell of protein subunits surrounding a DNA core. The approximately 50-residue coat protein subunit is largely alpha-helix and the axis of the alpha-helix makes a small angle with the axis of the virion. The protein shell can be considered in three sections: the outer surface, occupied by the N-terminal region of the subunit, rich in acidic residues that interact with the surrounding solvent and give the virion a low isoelectric point; the interior of the shell, including a 19-residue stretch of apolar side-chains, where protein subunits interact mainly with each other; and the inner surface, occupied by the C-terminal region of the subunit, rich in basic residues that interact with the DNA core. The fact that virtually all protein side-chain interactions are between different subunits in the coat protein array, rather than within subunits, makes this a useful model system for studies of interactions between alpha-helix subunits in a macromolecular assembly. We describe molecular models of the class I filamentous bacteriophages. This class includes strains fd, f1, M13 (these 3 very similar strains are members of the Ff group), If1 and IKe. Our model of fd has been refined to fit quantitative X-ray fibre diffraction data to 30 A resolution in the meridional direction and 7 A resolution in the equatorial direction. A simulated 3.3 A resolution diffraction pattern from this model has the same general distribution of intensity as the experimental diffraction pattern. The observed diffraction data at 7 A resolution are fitted much better by the calculated diffraction pattern of our molecular model than by that of a model in which the alpha-helix subunit is represented by a rod of uniform density. The fact that our fd model explains the fd diffraction data is only part of our structure analysis. The atomic details of the model are supported by non-diffraction data, in part previously published and in part newly reported here. These data include information about permitted or forbidden side-chain replacements, about the effect of chemical modification, and about spectroscopic experiments.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

PubMed1985

A model for chromosome movement based on lateral interaction of spindle microtubules.

Quantitative morphological studies of meiotic spindles in the crane fly Pales ferruginea (Fuge, 1980, 1984, 1985) were the basis for the development of a model explaining anaphase chromosome transport in higher eukaryotes. Two main features of chromosome fibres were important for the model: (1) the existence of microtubules oriented obliquely with respect to kinetochore microtubules, and (2) a higher degree of disorder in fibres exerting a pulling force. It is postulated that microtubules of the same polarity being inclined to each other at a certain angle are able to slide past each other by means of mechano-chemically active side-arms working in alternate succession. Sliding is suggested to lead to a displacement of microtubules and chromosomes in direction towards the poles. Furthermore, it is suggested that the chromosome fibre in anaphase becomes progressively disintegrated by fragmentation and disassembly of microtubules. Fragmentation may be induced by bending stress within the dynamic system.

Anaphase↗

PubMed2000

A critical reappraisal of the fossil record of the bilaterian phyla.

It has long been assumed that the extant bilaterian phyla generally have their origin in the Cambrian explosion, when they appear in an essentially modern form. Both these assumptions are questionable. A strict application of stem- and crown-group concepts to phyla shows that although the branching points of many clades may have occurred in the Early Cambrian or before, the appearance of the modern body plans was in most cases later: very few bilaterian phyla sensu stricto have demonstrable representatives in the earliest Cambrian. Given that the early branching points of major clades is an inevitable result of the geometry of clade diversification, the alleged phenomenon of phyla appearing early and remaining morphologically static is seen not to require particular explanation. Confusion in the definition of a phylum has thus led to attempts to explain (especially from a developmental perspective) a feature that is partly inevitable, partly illusory. We critically discuss models for Proterozoic diversification based on small body size, limited developmental capacity and poor preservation and cryptic habits, and show that the prospect of lineage diversification occurring early in the Proterozoic can be seen to be unlikely on grounds of both parsimony and functional morphology. Indeed, the combination of the body and trace fossil record demonstrates a progressive diversification through the end of the Proterozoic well into the Cambrian and beyond, a picture consistent with body plans being assembled during this time. Body-plan characters are likely to have been acquired monophyletically in the history of the bilaterians, and a model explaining the diversity in just one of them, the coelom, is presented. This analysis points to the requirement for a careful application of systematic methodology before explanations are sought for alleged patterns of constraint and flexibility.

Animals↗

PubMed2005

Opinion: migrating cancer stem cells - an integrated concept of malignant tumour progression.

The dissemination of tumour cells is the prerequisite of metastases and is correlated with a loss of epithelial differentiation and the acquisition of a migratory phenotype, a hallmark of malignant tumour progression. A stepwise, irreversible accumulation of genetic alterations is considered to be the responsible driving force. But strikingly, metastases of most carcinomas recapitulate the organization of their primary tumours. Although current models explain distinct and important aspects of carcinogenesis, each alone can not explain the sum of the cellular changes apparent in human cancer progression. We suggest an extended, integrated model that is consistent with all aspects of human tumour progression - the 'migrating cancer stem (MCS)-cell' concept.

Animals↗

PubMed2006

A lock-and-key model for protein-protein interactions.

MOTIVATION: Protein-protein interaction networks are one of the major post-genomic data sources available to molecular biologists. They provide a comprehensive view of the global interaction structure of an organism's proteome, as well as detailed information on specific interactions. Here we suggest a physical model of protein interactions that can be used to extract additional information at an intermediate level: It enables us to identify proteins which share biological interaction motifs, and also to identify potentially missing or spurious interactions. RESULTS: Our new graph model explains observed interactions between proteins by an underlying interaction of complementary binding domains (lock-and-key model). This leads to a novel graph-theoretical algorithm to identify bipartite subgraphs within protein-protein interaction networks where the underlying data are taken from yeast two-hybrid experimental results. By testing on synthetic data, we demonstrate that under certain modelling assumptions, the algorithm will return correct domain information about each protein in the network. Tests on data from various model organisms show that the local and global patterns predicted by the model are indeed found in experimental data. Using functional and protein structure annotations, we show that bipartite subnetworks can be identified that correspond to biologically relevant interaction motifs. Some of these are novel and we discuss an example involving SH3 domains from the Saccharomyces cerevisiae interactome. AVAILABILITY: The algorithm (in Matlab format) is available (see http://www.maths.strath.ac.uk/~aas96106/lock_key.html).

Algorithms↗

PubMed2003

Trust and risk perception in western Europe: a cross-national study.

The relationship between trust and risk perception was investigated, within and across four European countries (Sweden, Spain, United Kingdom, and France). Survey data were collected in 1996; total number of respondents was approximately 1,000 (United Kingdom and Spain), 1,350 (France), and 2,050 (Sweden). Trust was a significant predictor of perceived risk within countries, but the strength of the relationship varied from weak (Spain and France) to moderate (United Kingdom and Sweden). General trust was also a significant source of variation in perceived risk among countries, but much of the variation in perceived risk remained unexplained. Correlations between trust and risk perception also varied depending on the type of risk (i.e., nuclear risks were more influenced by trust) and trust measure (i.e., general trust explained perceived risk better than specific trust). It is concluded that trust may be an element in models explaining risk perception, but it is not as powerful as often argued in the risk perception literature.

France↗

PubMedDate not supplied

Student pharmacist perspectives of rural pharmacy practice.

OBJECTIVE: To evaluate the level of interest of upper-level doctor of pharmacy students in rural pharmacy practice, rural pharmacy ownership, and a proposed rural pharmacy practice model. DESIGN: Cross-sectional study. SETTING: Minnesota, North Dakota, and South Dakota in October through December 2003. PARTICIPANTS: Third- and fourth-year professional student pharmacists at the University of Minnesota, North Dakota State University, and South Dakota State University. INTERVENTION: Self-administered questionnaire completed by study participants. MAIN OUTCOME MEASURES: Student interest in rural pharmacy practice and potential future directions for maintaining access to medications and the knowledge of pharmacists in rural communities. RESULTS: Of 177 respondents, 62.7% has given serious consideration to practice in rural communities with populations of 5,000 or fewer residents. Of these 111 students, 81% would be interested in the proposed practice model explained in the survey. Of the 108 total students expressing interest in the proposed rural pharmacy practice model, 63% had not previously given serious consideration to pursuing ownership (full or partnership) of a community pharmacy. CONCLUSION: Students from the schools that have traditionally supplied the majority of Minnesota rural pharmacists indicated an interest in practicing in rural areas as long as opportunities align with their personal and professional interests.

Community Pharmacy Services↗

PubMed1990

Predicting marijuana use among adolescents.

The present paper (1) contrasts the prevalence of marijuana use and involvement with marijuana among 194 delinquent and 405 nondelinquent adolescents, (2) examines the utility of an expanded version of Jessor and Jessor's (1977) problem behavior model in predicting adolescent marijuana use, and (3) tests the relative importance of the predictors of marijuana use. Personality variables that were added to the Jessor problem behavior model included: (1) stimulus reducing - augmenting, (2) ego strength, (3) anxiety, and (4) field dependence. Results showed that delinquents reported using marijuana more often than nondelinquents. In the multiple regression analyses the expanded model explained a slightly greater percentage of the variance in adolescent marijuana use than the Jessor and Jessor model. Of the added personality variables, the Vando (1969) Reducer--Augmenter dimension seemed to be a particularly significant predictor. In addition, reducing--augmenting seemed to be a better predictor of involvement with marijuana than several previously used personality and demographic variables since it replaced these in the final regression equation. Perceived environment variables measuring pressure from friends to use marijuana and friends as models for marijuana use were the best predictors of marijuana use.

Adolescent↗

PubMedDate not supplied

[Oscillator generator in the lower portion of the glycolytic system].

A mathematical model explaining the mechanism of autooscillation generation in the lower part of the glycolytic system is suggested. The model is based on substrate inhibition of glyceraldehydephosphatedehydrigenase (GAPDH) with glyceraldehydephosphate (GAP). Pyrimidinenucleotides (NADplus and NADH) are shown not to play an important role in the given oscillation mechanism and can not be considered to simplify the model.

Glyceraldehyde-3-Phosphate Dehydrogenases↗

PubMed1987

A methodology for predicting lengths of stay for spinal cord injury patients.

Although the focus of Medicare's prospective payment system is on acute care hospitalization, other health care delivery systems are likely to be included in the future. In this paper, we report on a model for predicting length of stay (LOS) for spinal cord injury patients requiring hospitalization and rehabilitation services. Using multiple regression on data on 2,169 patients from the National Spinal Cord Injury Statistical Center data base, we predicted LOS for seven injury severity groups, and then validated our results with a second sample of 505 patients. Our predictive model explained a robust 45% of the variance in LOS and adjusted hospital charges. We conclude that our model would be useful in projecting LOS for patients whose injuries or illnesses require extensive rehabilitation services after acute care.

Adult↗

PubMedDate not supplied

Psychiatric symptoms in multiple chemical sensitivity.

Neuropsychiatric symptoms are among the most prominent manifestations of generalized chemical sensitivity. Patients, clinicians, and researchers are in agreement that symptoms such as depression, irritability, and mood instability are prominent among the distressing and disabling symptoms occurring in response to low-level chemical exposure. Beyond that point, however, agreement is difficult. The pathophysiology and clinical management of these symptoms remain quite controversial. This paper will review available data on the prevalence and form of psychiatric symptoms among those suffering from multiple chemical sensitivity. Various models explaining the relationship of psychiatric symptoms to chemical sensitivity will be discussed. Finally, the implications of these models for clinical management and future research will be reviewed.

Humans↗

PubMed2004

Complex III releases superoxide to both sides of the inner mitochondrial membrane.

Mechanisms of mitochondrial superoxide formation remain poorly understood despite considerable medical interest in oxidative stress. Superoxide is produced from both Complexes I and III of the electron transport chain, and once in its anionic form it is too strongly charged to readily cross the inner mitochondrial membrane. Thus, superoxide production exhibits a distinct membrane sidedness or "topology." In the present work, using measurements of hydrogen peroxide (Amplex red) as well as superoxide (modified Cypridina luciferin analog and aconitase), we demonstrate that Complex I-dependent superoxide is exclusively released into the matrix and that no detectable levels escape from intact mitochondria. This finding fits well with the proposed site of electron leak at Complex I, namely the iron-sulfur clusters of the (matrix-protruding) hydrophilic arm. Our data on Complex III show direct extramitochondrial release of superoxide, but measurements of hydrogen peroxide production revealed that this could only account for approximately 50% of the total electron leak even in mitochondria lacking CuZn-superoxide dismutase. We posit that the remaining approximately 50% of the electron leak must be due to superoxide released to the matrix. Measurements of (mitochondrial matrix) aconitase inhibition, performed in the presence of exogenous superoxide dismutase and catalase, confirmed this hypothesis. Our data indicate that Complex III can release superoxide to both sides of the inner mitochondrial membrane. The locus of superoxide production in Complex III, the ubiquinol oxidation site, is situated immediately next to the intermembrane space. This explains extramitochondrial release of superoxide but raises the question of how superoxide could reach the matrix. We discuss two models explaining this result.

Aconitate Hydratase↗