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Plasmid-borne or chromosomally mediated resistance by Tn7 is the most common response to ubiquitous use of trimethoprim.

The folic acid analog trimethoprim has been in clinical use for more than 10 years. The use of it in Sweden has doubled in the last 6 to 7 years, and from the distribution statistics it can be calculated that during 1 year 4 to 5% of the population in Sweden are given this drug. The bacterial resistance mechanisms to be found in response to such a selection pressure were investigated in a relatively isolated population in northern Sweden (the county of Jämtland), in which one centrally located bacteriological laboratory serves the area. Trimethoprim-resistant strains were collected during an 8-month period from consecutive specimens of bacteria from the urinary tracts of patients. Among the highly resistant strains of enteric bacteria, trimethoprim resistance mediated by transposon-borne dihydrofolate reductase of type I was found to dominate. The corresponding Tn7-like transposon was found to be localized both on the chromosome of isolated Escherichia coli strains and also on a 50-kilobase IncI transferable plasmid which was found in several different serotypes of E. coli. In two enterobacterial strains, resistance to more than 10(3) micrograms of trimethoprim per ml was furthermore found to be caused by a ca. 80-fold increase in the formation of chromosomal dihydrofolate reductase.

Chromosomes, Bacterial↗

In vitro antimicrobial activity of MSI-78, a magainin analog.

MSI-78 is a cationic peptide with broad-spectrum antimicrobial activity and is being developed as a topical agent. We compared the in vitro activity of MSI-78 with those of ofloxacin and other antibiotics against fresh clinical isolates. Based on MIC distribution statistics, strains for which the MSI-78 MIC was < or = 64 micro/ml were assumed to be susceptible for purposes of this report. Of 411 aerobic isolates tested, 91% were susceptible to MSI-78, compared to 91% for ofloxacin and 92% for ciprofloxacin. Only enterococci consistently required > or = 64 microg of MSI-78/ml for inhibition. MSI-78 demonstrated bactericidal activity equivalent to that of ofloxacin. Of 61 anaerobes, 97% were susceptible to MSI-78. Of 10 isolates of Candida albicans, 3 were inhibited by MSI-78 at 24 h. Further studies of this compound appear to be warranted.

Anti-Infective Agents↗

Monte Carlo simulation of pathogen behavior during the sprout production process.

Food-borne disease outbreaks linked to the consumption of raw sprouts have become a concern over the past decade. A Monte Carlo simulation model of the sprout production process was created to determine the most-effective points for pathogen control. Published literature was reviewed, and relevant data were compiled. Appropriate statistical distributions were determined and used to create the Monte Carlo model with Analytica software. Factors modeled included initial pathogen concentration and prevalence, seed disinfection effectiveness, and sampling of seeds prior to sprouting, sampling of irrigation water, or sampling of the finished product. Pathogen concentration and uniformity of seed contamination had a large effect on the fraction of contaminated batches predicted by the simulation. The model predicted that sprout sampling and irrigation water sampling at the end of the sprouting process would be more effective in pathogen detection than seed sampling prior to production. Day of sampling and type of sample (sprout or water) taken had a minimal effect on rate of detection. Seed disinfection reduced the proportion of contaminated batches, but in some cases it also reduced the ability to detect the pathogen when it was present, because cell numbers were reduced below the detection limit. Both the amount sampled and the pathogen detection limit were shown to be important variables in determining sampling effectiveness. This simulation can also be used to guide further research and compare the levels of effectiveness of different risk reduction strategies.

Colony Count, Microbial↗

Focus formation by a murine sarcoma leukemia virus complex. I. Theoretical analysis.

The transformation of cells in culture by a murine sarcoma-leukemia virus complex leads to the formation of identifiable foci. Titration patterns of focus counts vs. virus dilutions have been explained as being due to the interactions of three virions: leukemia, defective sarcoma, and competent hybrid. This interaction is analyzed quantitatively and equations are derived which permit determination of the composition of a sarcoma virus pseudotype as well as use of the technique for the assay of exogeneous leukemia virus. The analysis is based on the statistical distribution of virions in the culture cells and assumes that all virions have equal probability of infecting a cell and that transformation of any one cell will lead to focus formation. Limitations of the assumptions and expected measurement accuracy are discussed.

Cell Transformation, Neoplastic↗

An introduction to statistical inference--3.

Statistics inference is used to make comments about a population based upon data from a sample. In a similar manner it can be applied to a population to make an estimate about a sample. It is commonly seen in medical publications when the null hypothesis is being tested. This calculates the probability (p value) of a type I error--that is, that a particular finding is attributable to chance. It is also important to be aware of the chances of a type II error--that is, accepting the null hypothesis when it does not apply. Sample size, point estimate and variability are common factors that will affect the chances of making these two types of errors. Interpreting results therefore needs to take these factors into account as well as the clinical relevance of the findings. Statistical significance does not necessarily mean clinical significance.

Emergency Service, Hospital↗

Variability in biological monitoring of solvent exposure. I. Development of a population physiological model.

Biological indicators of exposure to solvents are often characterised by a high variability that may be due either to fluctuations in exposure or individual differences in the workers. To describe and understand this variability better a physiological model for differing workers under variable industrial environments has been developed. Standard statistical distributions are used to simulate variability in exposure concentration, physical workload, body build, liver function, and renal clearance. For groups of workers exposed daily, the model calculates air monitoring indicators and biological monitoring results (expired air, blood, and urine). The results obtained are discussed and compared with measured data, both physiological (body build, cardiac output, alveolar ventilation) and toxicokinetic for six solvents: 1,1,1-trichloroethane, trichloroethylene, tetrachloroethylene, benzene, toluene, styrene, and their main metabolites. Possible applications of this population physiological model are presented.

Adipose Tissue↗

Experimental study of cracking induced by desiccation in 1-dimensional systems.

We designed a simple experiment to study both the dynamical and statistical properties of cracking that occurs in a one-dimensional system composed of wet clay (or similar material) exposed to shrinkage induced by desiccation. We study both the dynamical formation of cracks and the statistical characteristics of the final cracks pattern. We observe that the drying rate has a strong influence on the way cracks appear and grow. We find that the final crack width is related to the order of apparition of the cracks. We discuss the statistical distributions of cracks width and separation between two adjacent cracks. We also study the correlations between these two quantities. Our results are compared to the predictions of existing models. Finally, a comparison with another kind of clay is made.

Journal Article↗

Cavity growth in soft adhesives.

The growth process of cavities nucleated at the interface between a rigid surface and a soft adhesive layer has been investigated with a probe method. A tensile stress was applied to the highly confined layer resulting in a negative hydrostatic pressure in the layer. The statistics of appearance and rate of growth of cavities as a function of applied negative stress were monitored with a CCD camera. If large germs of cavities were initially present, most of the cavities became optically visible above a critical level of stress independent of layer thickness. Cavities grew simultaneously and at the same expansion rate as a function of applied stress. In the absence of large germs, cavities became optically visible one after another, reaching a limiting size controlled by the thickness of the layer independently and very rapidly. Although, for each sample, we observed a statistical distribution of critical stress levels where a cavity expanded, the mean cavitation stress depended both on surface topography and more surprisingly on layer thickness. We believe that this new and somewhat surprising result can be interpreted with a model for the growth of small germs in finite size layers (J. Dollhofer, A. Chiche, V. Muralidharan et al., Int. J. Solids Struct. 41, 6111 (2004)). This model is mainly based on the dual notion of an energy activated transition from an unexpanded metastable state to an expanded stable state and to the proportionality of the activation energy with the elastic energy stored in the adhesive layer.

Adhesiveness↗

Integrating undergraduate laboratories into the curriculum.

Developing a curriculum that integrates laboratory, field, and nonlaboratory experiences requires solid planning, cooperation, and compromise among the faculty members in a department. This is especially true for laboratory experiences where basic skills and familiarity with the different groups of plants and animals carry over to upper-division courses. In an introductory Principles of Biology laboratory, for example, exercises can be designed to give students a clear idea of a statistical distribution and the consequences of random molecular motion. Both concepts are used in nearly all upper-division courses to some extent. Some important but "mechanical" features of courses within a curriculum, such as adopting within the department a single format for writing a scientific paper, will go a long way in tying together different laboratory experiences. Other similar but simpler ideas are to develop appendexes to laboratory exercises that can be used in introductory and upper-division courses, e.g., how to do dilutions, the use of SI units, etc. The latter may be a good way to stimulate departments to think more carefully about continuity and consistency in the design of the overall curriculum. Continuity of instruction from lower-division to upper-division courses and among upper-division courses requires communication between instructors at all levels.

Animals↗

Learning to move amid uncertainty.

We studied how subjects learned to make movements against unpredictable perturbations. Twelve healthy human subjects made goal-directed reaching movements in the horizontal plane while holding the handle of a two-joint robotic manipulator. The robot generated viscous force fields that perturbed the limb perpendicular to the desired direction of movement. The amplitude (but not the direction) of the viscous field varied randomly from trial to trial. Systems identification techniques were employed to characterize how subjects adapted to these random perturbations. Subject performance was quantified primarily using the peak deviation from a straight-line hand path. Subjects adapted their arm movements to the sequence of random force-field amplitudes. This adaptive response compensated for the approximate mean from the random sequence of perturbations and did not depend on the statistical distribution of that sequence. Subjects did not adapt by directly counteracting the mean field strength itself on each trial but rather by using information about perturbations and movement errors from a limited number of previous trials to adjust motor commands on subsequent trials. This strategy permitted subjects to achieve near-optimal performance (defined as minimizing movement errors in a least-squares sense) while maintaining computational efficiency. A simple model using information about movement errors and perturbation amplitudes from a single previous trial predicted subject performance in stochastic environments with a high degree of fidelity and further predicted key performance features observed in nonstochastic environments. This suggests that the neural structures modified during motor adaptation require only short-term memory. Explicit representations regarding movements made more than a few trials in the past are not used in generating optimal motor responses on any given trial.

Adaptation, Physiological↗

Mapping genes for polygenic disorders: considerations for study design in the complex trait of inflammatory bowel disease.

While the methodology for the mapping of Mendelian disorders is well established, the practical and theoretical steps required for successful gene identification in a complex trait are still difficult to predict. A number of analytical models and simulations based on repetitive drawings from predefined statistical distributions are available. To supplement these analytical models, we developed an integrated simulation approach by directly simulating entire populations under a disease model based on epidemiological data. Random mating, nonoverlapping populations and the absence of differential fitness were assumed. Samples were drawn from these homogeneous and heterogeneous populations and analyzed with established analysis tools. We investigated the properties of linkage and association studies in inflammatory bowel disease - modeled as a six-locus polygenic disorder - as an example of this approach. In nonparametric linkage studies, lod scores varied widely, with the median required sample size depending on the locus-specific relative sibling risk. A fine mapping resolution <4 cM was found to require nonparametric lod scores >10. Family-based association studies (TDT test) and case-control studies showed a similar sensitivity and can identify risk loci in populations with moderate levels of linkage disequilibrium in sample sizes of 500-800 triplets. Case-control association studies were prone to false-positive results if applied in heterogeneous populations, with the false-positive rate increasing with sample size because population heterogeneity is detected with increasing power.

Alleles↗

[Efficacy of experimental renal embolization with microspheres. Additionally, a critical report on the complication rate of intra-arterial embolization with particles (author's transl)].

Renal embolization was performed in 12 dogs using the Seldinger technique and microspheres 250 +/- 40 micrometer in diameter. Periodical arteriography, microangiographies and histological analysis was carried out to control the efficacy of embolization. As a result, renal arteries could be embolized wi. th microspheres, however, because of statistical distribution there were histologically anemic and normal parenchyma situated closely together. In more than 50% there was a reflux of microspheres which could only be detected by histological examination, while angiographies showed a totally normal vascular pattern. Microspheres should not be used in clinical embolization. Experimental investigation of embolization materials must almost embrace histological analysis.

Animals↗

Maternal deaths related to abortions in Sweden, 1931-1980.

Deaths related to abortion accounted for 20% of all maternal mortality in Sweden during the period 1931-80. The risk of dying as a consequence of abortion, per 100,000 pregnancies, declined with a factor of 160 during the study period. Three main reasons for the improvement are discussed. The introduction of antibiotics reduced mortality due to illegal abortions, but during the 1950s and 1960s sepsis and air embolism resulting from illegal abortion still accounted for the bulk of the abortional mortality. Liberal legislation and abortional practice subsequently eliminated illegal abortions, and resulted in a more accurate and favorable statistical distribution of abortions by pregnancy week. This together with new technology reduced the legal abortions mortality rate to one-fiftieth over the last 30 years even though the number of legal abortions increased 7-fold.

Abortion, Illegal↗

A biophysicist's view of ovum transport.

Experimental evidence justifying the selection of primary variables in ovum isthmic transport is evaluated. Peristaltic pumping alone cannot account for the observed ovum motions, however, the theory of pressure forcing of pellets through narrow tubes when combined with the dynamic and motile properties of the mucosal and muscular layers of the isthmus, appears capable of modeling the physiological mechanism. In this model the hormonally dependent tubal compliance is a controlling element of transport rate. The contractile activity statistically distributed both spatially and temporally, provides a persistent though irregular directionality to the movement.

Animals↗

Evolution of QRS-T relationship from birth to adolescence in Frank-lead orthogonal electrocardiograms of 1492 normal children.

Patterns of evolution of QRS-T relationship were investigated by determining statistical distributions of QRS and STT integral vectors and the ventricular gradient vector in 1492 normal children divided into 12 age groups from birth to the age of 16 years. From birth to the age of 4 days, the ventricular gradient vector shifts posteriorly and to the left due to posterior shift of the STT integral vector and an increase in the spatial angle between QRS and STT integral vectors to a mean value of 103 degrees. These early neonatal changes in QRS-T relationship probably reflect the sudden reduction of hemodynamic load and the subsequent postnatal atrophy of the right ventricle while the left ventricular load slowly increases. The magnitude of the ventricular gradient vector increases from age 3 weeks until about 7 years. The increase appears to be related to a gradual increase in the magnitude of the QRS and STT integral vectors and a drastic decrease in the spatial angle between them. The spatial angle between QRS and STT integral vectors reaches it minimum (22 degrees) in the age group 1.5--4.5 years, suggesting that at that age the average direction of ventricular excitation and repolarization wavefronts are nearly opposite to each other. In addition to the shifting balance between the left and right ventricular hemodynamic load, other factors, such as the maturation of the sympathetic nervous system, may be important in determining spatial gradients in the duration of action potentials, thus influencing the relationship between ventricular excitation and repolarization.

Action Potentials↗

Reference values for 24-hour ambulatory blood pressure monitoring based on a prognostic criterion: the Ohasama Study.

Although reference values for ambulatory blood pressure (ABP) monitoring have been investigated in several population studies, these values were derived from cross-sectional observations and were based merely on the statistical distribution of blood pressure values. Therefore, we conducted a prospective cohort study to identify reference values for 24-hour ABP in relation to prognosis. We obtained measurements of 24-hour ABP for 1542 subjects (565 men) aged 40 years and over in a general population of a rural Japanese community and then followed-up their survival status. There were 117 deaths during the follow-up period (mean, 6.2 years). The association between baseline 24-hour ABP values and mortality, examined by the Cox proportional hazards regression model adjusted for possible confounding factors, showed a better fit with a second-degree equation than with a first-degree equation. On the basis of the results of this analysis, we identified the following reference values as the optimal blood pressure ranges that predict the best prognosis: 120 to 133 mm Hg for systolic blood pressure and 65 to 78 mm Hg for diastolic blood pressure. 24-Hour ABP values >134/79 mm Hg and <119/64 mm Hg were related to increased risks for cardiovascular and noncardiovascular mortality, respectively. This is the first report to propose reference values for 24-hour ABP based on a prognostic criterion.

Adult↗

Common neural basis for phoneme processing in infants and adults.

Investigating the degree of similarity between infants' and adults' representation of speech is critical to our understanding of infants' ability to acquire language. Phoneme perception plays a crucial role in language processing, and numerous behavioral studies have demonstrated similar capacities in infants and adults, but are these subserved by the same neural substrates or networks? In this article, we review event-related potential (ERP) results obtained in infants during phoneme discrimination tasks and compare them to results from the adult literature. The striking similarities observed both in behavior and ERPs between initial and mature stages suggest a continuity in processing and neural structure. We argue that infants have access at the beginning of life to phonemic representations, which are modified without training or implicit instruction, but by the statistical distributions of speech input in order to converge to the native phonemic categories.

Acoustic Stimulation↗