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Influence of bacterial resistances on the efficiency of antibiotic treatments for community-acquired pneumonia.

The objective of this paper is to perform a cost-effectiveness analysis of the oral antibiotics used in Spain for the ambulatory treatment of community-acquired pneumonia. Our analysis takes into account the influence of bacterial resistances on the cost-effectiveness ratio of antibiotic alternatives from the viewpoint of the public insurer. A deterministic decision analysis model is used to simulate the impact of treatment alternatives on both patients' health and resource consumption. Amoxicillin 1 g may be the most efficient therapy for treating typical pneumonia, as long as the physician is able to discriminate clinically the aetiology of the process with a high degree of reliability. However, for those pathological pictures in which the aetiology cannot be discriminated clinically, and for those in which the consequences of incorrect diagnosis are serious according to clinical criteria, moxifloxacin is the most effective and efficient option.

Anti-Bacterial Agents↗

Density dependence and the control of helminth parasites.

1. The transient dynamics and stability of a population are determined by the interplay between species density, its spatial distribution and the positive and negative density-dependent processes regulating population growth. 2. Using the human-helminth parasite system as an example, we propose that the life-stage upon which negative density dependence operates will influence the rate of host reinfection following anthelmintic chemotherapy, and the likely success of control programmes. 3. Simple deterministic models are developed which highlight how a parasite species whose population size is down-regulated by density-dependent establishment will reinfect a host population at a faster rate than a species with density-dependent parasite fecundity. 4. Different forms of density dependence can produce the same equilibrium behaviour but different transient dynamics. Under-representing the nature and magnitude of density-dependent mechanisms, and in particular those operating upon establishing life-stages, may cause the resilience of the parasite population to a control perturbation to be underestimated.

Animals↗

Wrong and missing sire information affects genetic gain in the Angeln dairy cattle population.

In the present study, molecular genetic markers were used to help estimate the degree of wrong sire information in the German Angeln dairy cattle population. Sixteen polymorphic microsatellite markers were genotyped on 5 different paternal half-sib families with a total of 805 daughters. For the genotyping process, blood samples of the daughters and semen samples of the sires were used. Allelic frequencies and exclusion probabilities were estimated. The simultaneous effect of wrong (WSI) and missing sire information (MSI) on the reliability of estimated breeding values and on the genetic gain was investigated using deterministic simulations. For these simulations, different values for the number of daughters per sire, heritability, WSI, and MSI were chosen. The estimated proportion of the WSI was 7% in the German Angeln dairy cattle population. The combined impact of WSI and MSI on the genetic gain was relatively large, especially in the case of small progeny size per sire and low heritability. The impact of WSI was more harmful than MSI on response to selection.

Alleles↗

A comparison of record linkage yield for health research using different variable sets.

As part of a study on childbearing and survival, we linked records of young women with invasive breast cancer identified through three population-based cancer registries, to state birth certificate records. In Michigan prior to 1989, only maternal social security number (SSN) was available for matching; other data became available in 1989 including name, birth date, address, and infant's surname. To examine the quality of the linkage using SSN as the sole matching criterion, we conducted two procedures using data for 1989-1994 to compare linkages identified by SSN, to linkages identified using other available variables. Linkage was conducted using a deterministic approach based on seven variables and 14 steps. In each step a string of relevant variables was created and in successive phases selected variables were substituted or removed with decreasingly stringent requirements. A manual review was done to check for accuracy. Utilizing all available variables, the linkage process yielded 793 matches (live births) among 4496 patients, 780 [98%] of which would have been identified using SSN alone. Five of seven matches identified by SSN were not confirmed by manual review. SSN appears to be fairly accurate for linkage and can be valuable for linking cancer registries to other data sources.

Adult↗

A space radiation transport method development.

Improved spacecraft shield design requires early entry of radiation constraints into the design process to maximize performance and minimize costs. As a result, we have been investigating high-speed computational procedures to allow shield analysis from the preliminary design concepts to the final design. In particular, we will discuss the progress towards a full three-dimensional and computationally efficient deterministic code for which the current HZETRN evaluates the lowest-order asymptotic term. HZETRN is the first deterministic solution to the Boltzmann equation allowing field mapping within the International Space Station (ISS) in tens of minutes using standard finite element method (FEM) geometry common to engineering design practice enabling development of integrated multidisciplinary design optimization methods. A single ray trace in ISS FEM geometry requires 14 ms and severely limits application of Monte Carlo methods to such engineering models. A potential means of improving the Monte Carlo efficiency in coupling to spacecraft geometry is given in terms of re-configurable computing and could be utilized in the final design as verification of the deterministic method optimized design.

Cosmids↗

A maximum principle for the mutation-selection equilibrium of nucleotide sequences.

We study the equilibrium behaviour of a deterministic four-state mutation-selection model as a model for the evolution of a population of nucleotide sequences in sequence space. The mutation model is the Kimura 3ST mutation scheme, and the selection scheme is assumed to be invariant under permutation of sites. Considering the evolution process both forward and backward in time, we use the ancestral distribution as the stationary state of the backward process to derive an expression for the mutational loss (as the difference between ancestral and population mean fitness), and we prove a maximum principle that determines the population mean fitness in mutation-selection balance.

Animals↗

Parameterization of individual-based models: comparisons with deterministic mean-field models.

The relating of deterministic, mean-field models into network models, where epidemic spread occurs between interconnected susceptible and infectious individuals or populations, requires careful consideration. Here, we discuss models that consider differently the manner in which contact rate and infectiousness change over time, with different algorithms suitable for different underlying processes. Though these models give coincidental results to the mean-field in the case of large, highly connected networks, the results when sparsely connected networks are considered may differ. Different subsets of the parameters from the mean-field epidemic (R(0), generation time, infectiousness, etc.) are preserved in each case. Despite these differences, simulated epidemics generated under some model architectures are insensitive to the average degree of contact amongst nodes, k. Model-based estimates of k may be model dependent, and must therefore be viewed with caution.

Algorithms↗

Noise-assisted traffic of spikes through neuronal junctions.

The presence of noise, i.e., random fluctuations, in the nervous system raises at least two different questions. First, is there a constructive role noise can play for signal transmission in a neuron channel? Second, what is the advantage of the power spectra observed for the neuron activity to be shaped like 1/f(k)? To address these questions a simple stochastic model for a junction in neural spike traffic channels is presented. Side channel traffic enters main channel traffic depending on the spike rate of the latter one. The main channel traffic itself is triggered by various noise processes such as Poissonian noise or the zero crossings of Gaussian 1/f(k) noise whereas the variation of the exponent k gives rise to a maximum of the overall traffic efficiency. It is shown that the colored noise is superior to the Poissonian and, in certain cases, to deterministic, periodically ordered traffic. Further, if this periodicity itself is modulated by Gaussian noise with different spectral exponents k, then such modulation can lead to noise-assisted traffic as well. The model presented can also be used to consider car traffic at a junction between a main and a side road and to show how randomness can enhance the traffic efficiency in a network. (c) 2001 American Institute of Physics.

Journal Article↗

Use of multiple logistic analysis in twin zygosity diagnosis.

Stochastic methods were applied to the diagnosis of twin zygosity by mailed questionnaire in a study on adult twins. Multiple logistic discriminant analysis was able to classify twin pairs previously left unclassified (XZ) by a deterministic method, and accuracy of classification was verified by blood testing. The mean intrapair differences of height and weight of XZ pairs were in between dizygotic and monozygotic pairs, but the frequency of personal contact between XZ twins was significantly less than that of MZ or DZ pairs. Both classification methods, when used separately with the same questions, left unclassified 6.5-7.6% of all 11,542 respondent pairs in the Finnish Twin Registry, but deterministic classification followed by logistic analysis misclassified only 1.9% of all twin pairs.

Adult↗

The neurobiological context of autism.

Autistic disorder (AD) is a complex neuropsychiatric disorder of neurodevelopmental origin, where multiple genetic and environmental factors may interact, resulting in a clinical continuum. The genetic component is best described by a multilocus model that takes into account epistatic interactions between several susceptibility genes. In the past ten years enormous progress has been made in identifying chromosomal regions in linkage with AD, but moving from chromosomal regions to candidate genes has proven to be tremendously difficult. Neuroanatomical findings point to early dysgenetic events taking place in the cerebral cortex, cerebellum, and brainstem. At the cellular level, disease mechanisms may include altered cell migration, increased cell proliferation, decreased cell death, or altered synapse elimination. Neurochemical findings in AD point to involvement of multiple neurotransmitter systems. The serotoninergic system has been intensively investigated in AD, but other neurotransmitter systems (e.g., the GABAergic and the cholinergic system) are also coming under closer scrutiny. The role of environmental factors is still poorly characterized. It is not clear yet whether environmental factors act merely as precipitating agents, always requiring an underlying genetic liability, or whether they represent an essential component of a pathogenetic process where genetic liability alone does not lead to the full-blown autism phenotype. A third potential player in the pathogenesis of autism, in addition to genetic and environmental factors, is developmental variability due to "random" factors, e.g. small fluctuations of gene expression and complex, non-deterministic interactions between genes during brain development. These considerations suggest that a non-deterministic conceptual framework is highly appropriate for autism research.

Animals↗

[Morphological studies in the theory of the chromosomal determination of sex: 1880-1912].

This article analyses morphological research on sex determination from the late nineteenth-century to the discovery of sex chromosomes and the theory of sex determination by chromosomes. It describes the links between Morphology and Zoology through their development in Germany and North America, as main producer countries. Cytological research, carried ou on a wide spectrum of zoological species, led to an understanding of important problems regarding the number, appearance and behaviour of chromosomes, supporting determinist hypotheses against those defending the importance of environmental or cytoplasmic factors in the control of development.

Cell Biology↗

Utilization of developmental basic science principles in the evaluation of reproductive risks from pre- and postconception environmental radiation exposures.

The subject of the reproductive toxicity of various forms of radiation can be anxiety provoking to the public on two accounts, since reproductive failure engenders an unusual level of guilt and anger in the affected families, and radiation effects are misunderstood and feared by the public. Reproductive problems include an array of genetic and acquired diseases affecting parents and their offspring. Many of these problems are associated with the risk of being induced by preconception and/or postconception exposures to environmental agents. For the various forms of radiation, namely, ionizing radiation, ultrasound, low-frequency electromagnetic fields (EMF), and microwaves, the potential for producing reproductive effects varies considerably with the form of "radiation" and, of course, the dose. Whether the exposure occurs preconceptionally or postconceptionally is another major consideration. In evaluating the actual reproductive risks, we rely on accurate dosimetry and information obtained in epidemiological studies and animal studies. Epidemiological studies must demonstrate consistency of the reproductive finding, and animal studies should be designed to add to the findings of the epidemiological studies. Most importantly, the conclusions must not contradict the basic principles of teratology, genetics, and reproductive biology, and they should be biologically plausible. But frequently important basic science principles are ignored in the evaluation process. Yet developmental basic science principles can be instrumental in refuting or supporting the concern about possible risks. Although there is some overlap with regard to the preconception and intrauterine effects of ionizing radiation, there are significant differences. Preconception effects are mainly stochastic effects, while intrauterine effects are mainly deterministic effects. The stochastic genetic risks are lower than the deterministic risks at equivalent exposures. Thus, it is frequently difficult to demonstrate the occurrence of stochastic effects in populations that have received low preconception exposures to ionizing radiation. The reproductive effects from preconception and intrauterine exposures to electromagnetic fields (low-frequency EMF, video display terminals, microwaves) and ultrasound represent much different problems, since the main effects of microwaves and ultrasound occur because of their hyperthermic effects at high exposures. Low-frequency EMF does not have the capacity to produce hyperthermia, and none of these forms of nonionizing radiation has the specificity to damage the DNA comparable to the specificity of ionizing radiation. Not only do they not have targeted mutagenic effects at the usual exposures that populations receive, they are not cytotoxic at these exposure levels as well. From the viewpoint of biological plausibility, these other forms of radiation are much less likely to have the potential for producing reproductive toxicity at the usual population exposures.

Abnormalities, Radiation-Induced↗

A simplified predictive control algorithm for disturbance rejection.

Model predictive control (MPC) offers several advantages for control of chemical processes. However, the standard MPC may do a poor job in suppressing the effects of certain disturbances. This shortcoming is mainly due to the assumption that disturbances remain constant over the prediction horizon. In this paper, a simple disturbance predictor (SDP) is developed to provide predictions of the unmodeled deterministic disturbances for a simplified MPC algorithm. The prediction is developed by curve fitting of the past information. A tuning parameter is employed to handle a variety of disturbance dynamics and a procedure is presented to find an optimum value of the tuning parameter online. A comparison is made with the commonly used disturbance prediction on three example problems. The results show that an improved regulatory performance and zero offset can be achieved under both regular and ramp output disturbances by using the proposed disturbance predictor.

Journal Article↗

Toward an integration of interpersonal and biological processes: evolutionary psychiatry as an empirically testable framework for psychiatric research.

Phenomenological, biological, and interpersonal aspects of psychiatric disorders lack an integrative empirical framework. In this paper evolutionary psychiatry is proposed as a meta-theory to integrate biological and interpersonal aspects of psychopathology. Pathological cognition, emotions, and behaviors may be examined according to specific biosocial goals originally pursued to increase the individual's inclusive fitness, similar to the ways that "normal" processes have been analyzed by evolutionary psychology. Sex-specific differences in prevalence rates and symptomatology of psychiatric disorders may also be better understood if divergent problems of adaptation for men and women in human evolutionary history are taken into account. Instead of mistaking the evolutionary approach for being deterministic and empirically untestable, it may rather be appropriate to provide a functional classification which adds to the contemporary psychiatric nosology through analysis according to specific conflicts of adaptation (at the ultimate level), the pursuit of biosocial goals, and proximate specifiers such as genetic, developmental, and interpersonal causes of disorders.

Adaptation, Psychological↗

Verification of the optimal probabilistic basis of aural processing in pitch of complex tones.

Periodicity pitch for complex tones has been quantitatively accounted for by a two-stage process of Fourier-frequency analysis subject to random errors and significant nonlinearities, followed by an harmonic pattern recognizer that makes an optimum probabilistic estimate of the fundamental period of musical and speech sounds. The theory predicts that periodicity pitch is a multimodal probabilistic function of a given stimulus. A clear and empirically supported distinction is made between limitations on the pitch mechanism caused by the stochastic nature of aural frequency representation and by the deterministic resolution bandwidths of aural frequency analysis. This model was developed earlier [J. L. Goldstein, J. Acoust. Soc. Am 54, 1496-1516 (1973)] to account for probabilistic data on pitch errors [A. J. M. Houtsma and J. L. Goldstein, J. Acoust. Soc. Am. 51, 520 (1972)] measured with periodic stimuli comprising two successive harmonics. This paper presents new predictions by the theory that were calculated, with computer simulation where needed, for known probabilistic pitch data from stimuli comprising three to six successive harmonics. Predicted pitch errors increase with increasing errors in estimating the frequencies of stimulus harmonics and decrease as more harmonics are added to the stimulus. Optimum processor theory fully accounts for the multicomponent pitch data on the basis of similar errors in estimating component stimulus frequencies as reported earlier, thus providing further evidence for the optimum probabilistic basis of aural signal processing in pitch of complex tones.

Auditory Cortex↗

No accident: genetic codes freeze in error-correcting patterns of the standard genetic code.

The standard genetic code poses a challenge in understanding the evolution of information processing at a fundamental level of biological organization. Genetic codes are generally coadapted with, or 'frozen' by, the protein-coding genes that they translate, and so cannot easily change by natural selection. Yet the standard code has a significantly non-random pattern that corrects common errors in the transmission of information in protein-coding genes. Because of the freezing effect and for other reasons, this pattern has been proposed not to be due to selection but rather to be incidental to other evolutionary forces or even entirely accidental. We present results from a deterministic population genetic model of code-message coevolution. We explicitly represent the freezing effect of genes on genetic codes and the perturbative effect of changes in genetic codes on genes. We incorporate characteristic patterns of mutation and translational error, namely, transition bias and positional asymmetry, respectively. Repeated selection over small successive changes produces genetic codes that are substantially, but not optimally, error correcting. In particular, our model reproduces the error-correcting patterns of the standard genetic code. Aspects of our model and results may be applicable to the general problem of adaptation to error in other natural information-processing systems.

Animals↗

Stochastic von Bertalanffy models, with applications to fish recruitment.

We consider three individual-based models describing growth in stochastic environments. Stochastic differential equations (SDEs) with identical von Bertalanffy deterministic parts are formulated, with a stochastic term which decreases, remains constant, or increases with organism size, respectively. Probability density functions for hitting times are evaluated in the context of fish growth and mortality. Solving the hitting time problem analytically or numerically shows that stochasticity can have a large positive impact on fish recruitment probability. It is also demonstrated that the observed mean growth rate of surviving individuals always exceeds the mean population growth rate, which itself exceeds the growth rate of the equivalent deterministic model. The consequences of these results in more general biological situations are discussed.

Animals↗

Concentration dependence of the subunit association of oligomers and viruses and the modification of the latter by urea binding.

A theoretical model is presented that accounts for the facilitation of the pressure dissociation of R17 phage, and for the partial restoration of the concentration dependence of the dissociation, by the presence of subdenaturing concentrations of urea. As an indifferent osmolyte urea should promote the stability of the protein aggregates under pressure, and the decrease in pressure stability with urea concentration demonstrates that such indirect solvent effects are not significant for this case, and that the progressive destabilization is the result of direct protein-urea interactions. By acting as a "homogenizer" of the properties of the phage particles, urea addition converts the pressure-induced deterministic dissociation of the phage into a limited stochastic equilibrium. The model establishes the origin of the uniform progression from the stochastic equilibrium of dimers, to the temperature-dependent and partially concentration-dependent association of tetramers, to the fully deterministic equilibrium observed in many multimers and in the virus capsids.

Bacteriophages↗