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At least 595 records · Page 33Linked to original sources
PubMed1999

Insufficient evidence: the problems of evidence-based nursing.

Evidence-based medicine was first proposed in the early 1990s as a means of integrating clinical expertise with the best evidence from research. It has recently gained a foothold in nursing, where despite calls for a broad and nursing-oriented definition of what should count as evidence, it appears to be propounding the randomized controlled trial (RCT) as the gold standard. This paper challenges the wisdom of basing nursing practice on the findings of large-scale statistical research studies, and offers a number of logical objections to the underpinning philosophy of evidence-based nursing and the randomized controlled trial. It concludes by arguing for a rethinking of what should count as evidence, and suggests a quasi-legal model based on reflection rather than research, in which evidence is employed to understand and justify practice after the event rather than being used deterministically to plan practice in advance.

Clinical Competence↗
PubMed2004

External and internal limitations in amplitude-modulation processing.

Three experiments are presented to explore the relative role of "external" signal variability and "internal" resolution limitations of the auditory system in the detection and discrimination of amplitude modulations (AM). In the first experiment, AM-depth discrimination performance was determined using sinusoidally modulated broadband-noise and pure-tone carriers. The AM index, m, of the standard ranged from -28 to -3 dB (expressed as 20 log m). AM-depth discrimination thresholds were found to be a fraction of the AM depth of the standard for standards down to -18 dB, in the case of the pure-tone carrier, and down to -8 dB, in the case of the broadband-noise carrier. For smaller standards, AM-depth discrimination required a fixed increase in AM depth, independent of the AM depth of the standard. In the second experiment, AM-detection thresholds were obtained for signal-modulation frequencies of 4, 16, 64, and 256 Hz, applied to either a band-limited random-noise carrier or a deterministic ("frozen") noise carrier, as a function of carrier bandwidth (8 to 2048 Hz). In general, detection thresholds were higher for the random- than for the frozen-noise carriers. For both carrier types, thresholds followed the pattern expected from frequency-selective processing of the stimulus envelope. The third experiment investigated AM masking at 4, 16, and 64 Hz in the presence of a narrow-band masker modulation. The variability of the masker was changed from entirely frozen to entirely random, while the long-term average envelope power spectrum was held constant. The experiment examined the validity of a long-term average quantity as the decision variable, and the role of memory in experiments with frozen-noise maskers. The empirical results were compared to predictions obtained with two modulation-filterbank models. The predictions revealed that AM-depth discrimination and AM detection are limited by a combination of the external signal variability and an internal "Weber-fraction" noise process.

Acoustic Stimulation↗
PubMed2006

Experimental and numerical study of heterogeneous pressure-temperature-induced lethal and sublethal injury of Lactococcus lactis in a medium scale high-pressure autoclave.

The present contribution is dedicated to experimental and theoretical assessment of microbiological process heterogeneities of the high-pressure (HP) inactivation of Lactococcus lactis ssp. cremoris MG 1363. The inactivation kinetics are determined in dependence of pressure, process time, temperature and absence or presence of co-solutes in the buffer system namely 4 M sodium chloride and 1.5 M sucrose. The kinetic analysis is carried out in a 0.1-L autoclave in order to minimise thermal and convective effects. Upon these data, a deterministic inactivation model is formulated with the logistic equation. Its independent variables represent the counts of viable cells (viable but injured) and of the stress-resistant cells (viable and not injured). This model is then coupled to a thermo-fluiddynamical simulation method, high-pressure computer fluid dynamics technique (HP-CFD), which yields spatiotemporal temperature and flow fields occurring during the HP application inside any considered autoclave. Besides the thermo-fluiddynamic quantities, the coupled model predicts also the spatiotemporal distribution of both viable (VC) and stress-resistant cell counts (SRC). In order to assess the process non-uniformity of the microbial inactivation in a 3.3-L autoclave experimentally, microbial samples are placed at two distinct locations and are exposed to various process conditions. It can be shown with both, experimental and theoretical models that thermal heterogeneities induce process non-uniformities of more than one decimal power in the counts of the viable cells at the end of the treatment.

Biotechnology↗
PubMed2005

A population-based Bayesian approach to the minimal model of glucose and insulin homeostasis.

The minimal model was proposed in the late 1970s by Bergman et al. (Am. J. Physiol. 1979; 236(6):E667) as a powerful model consisting of three differential equations describing the glucose and insulin kinetics of a single individual. Considering the glucose and insulin simultaneously, the minimal model is a highly ill-posed estimation problem, where the reconstruction most often has been done by non-linear least squares techniques separately for each entity. The minimal model was originally specified for a single individual and does not combine several individuals with the advantage of estimating the metabolic portrait for a whole population. Traditionally it has been analysed in a deterministic set-up with only error terms on the measurements. In this work we adopt a Bayesian graphical model to describe the coupled minimal model that accounts for both measurement and process variability, and the model is extended to a population-based model. The estimation of the parameters are efficiently implemented in a Bayesian approach where posterior inference is made through the use of Markov chain Monte Carlo techniques. Hereby we obtain a powerful and flexible modelling framework for regularizing the ill-posed estimation problem often inherited in coupled stochastic differential equations. We demonstrate the method on experimental data from intravenous glucose tolerance tests performed on 19 normal glucose-tolerant subjects.

Adult↗
PubMed2006

Error thresholds in a mutation-selection model with Hopfield-type fitness.

The deterministic limit of a Hopfield-type mutation-selection model in the sequence space approach is investigated. Genotypes are identified with two-letter sequences. Mutation is modelled as a Markov process, fitness functions are of Hopfield type, where the fitness of a sequence is determined by the Hamming distances to a number of predefined patterns. Using a maximum principle for the population mean fitness in equilibrium, the error threshold phenomenon is studied for quadratic Hopfield-type fitness functions with small numbers of patterns. Different from previous investigations of the Hopfield model, the system shows error threshold behaviour not for all fitness functions, but only for certain parameter values.

Algorithms↗
PubMed2006

The neurobiology of aggressive behaviour.

Neurobiological research on aggressive behaviour comes up against particular difficulties that stem from the multifactorial origin of any social behaviour and from the fact that it evolves over time under the shaping influence of experience. From a historical point of view, the conceptual framework progressively switched from a deterministic causality based on the spatial distribution of a specifically-related 'neural substrate' to a probabilistic causality taking into account all the multiple contextual and developmental determinants with their underlying brain processes and mechanisms. With regard to ethical issues, the role and the weight ascribed to biological determinants in the generation of aggressive behaviour greatly influence the way in which one plans to fight against such behaviour.

Aggression↗
PubMed2006

PEGylated phospholipid nanomicelles interact with beta-amyloid((1-42)) and mitigate its beta-sheet formation, aggregation and neurotoxicity in vitro.

beta-Amyloid (Abeta) is a hydrophobic peptide that drives the pathogenesis of Alzheimer's disease (AD) due to its aberrant aggregation. Inhibition of Abeta aggregation process is one of the most promising strategies for therapeutic intervention in AD. Here, we demonstrate that sterically stabilized (PEGylated) phospholipid nanomicelles (SSM) are effective in mitigating Abeta-42 aggregation using several deterministic techniques such as (1) Turbidimetry (2) Congo red binding (3) Thioflavine-T binding (4) Laser light scattering and (5) Electron Microscopy. alpha-Helicity of Abeta-42 is significantly augmented in the presence of SSM as demonstrated by circular dichroism (p<0.05). Cytotoxicity studies, employing human neuroblastoma SHSY-5Y cells, established that PEGylated phospholipid associated peptide demonstrated significantly lower neurotoxicity compared to lipid untreated Abeta-42 (p<0.05). Collectively, our results establish that PEGylated phospholipids abrogate transformation of Abeta-42 to amyloidogenic beta-sheeted form and impart neuroprotection in vitro. This study provides a foundation for designing nanoconstructs of PEGylated phospholipid nanomicelles in conjunction with a therapeutic agent for multitargeting the different pathophysiologies associated with AD.

Amyloid beta-Peptides↗
PubMed1990

Receptor-mediated cell attachment and detachment kinetics. I. Probabilistic model and analysis.

The kinetics of receptor-mediated cell adhesion to a ligand-coated surface play a key role in many physiological and biotechnology-related processes. We present a probabilistic model of receptor-ligand bond formation between a cell and surface to describe the probability of adhesion in a fluid shear field. Our model extends the deterministic model of Hammer and Lauffenburger (Hammer, D.A., and D.A. Lauffenburger. 1987. Biophys. J. 52:475-487) to a probabilistic framework, in which we calculate the probability that a certain number of bonds between a cell and surface exists at any given time. The probabilistic framework is used to account for deviations from ideal, deterministic behavior, inherent in chemical reactions involving relatively small numbers of reacting molecules. Two situations are investigated: first, cell attachment in the absence of fluid stress; and, second, cell detachment in the presence of fluid stress. In the attachment case, we examine the expected variance in bond formation as a function of attachment time; this also provides an initial condition for the detachment case. Focusing then on detachment, we predict transient behavior as a function of key system parameters, such as the distractive fluid force, the receptor-ligand bond affinity and rate constants, and the receptor and ligand densities. We compare the predictions of the probabilistic model with those of a deterministic model, and show how a deterministic approach can yield some inaccurate results; e.g., it cannot account for temporally continuous cell attach mentor detachment, it can underestimate the time needed for cell attachment, it can overestimate the time required for cell detachment for a given level of force, and it can overestimate the force necessary for cell detachment.

Biophysical Phenomena↗
PubMed2000

Hitchhiking under positive Darwinian selection.

Positive selection can be inferred from its effect on linked neutral variation. In the restrictive case when there is no recombination, all linked variation is removed. If recombination is present but rare, both deterministic and stochastic models of positive selection show that linked variation hitchhikes to either low or high frequencies. While the frequency distribution of variation can be influenced by a number of evolutionary processes, an excess of derived variants at high frequency is a unique pattern produced by hitchhiking (derived refers to the nonancestral state as determined from an outgroup). We adopt a statistic, H, to measure an excess of high compared to intermediate frequency variants. Only a few high-frequency variants are needed to detect hitchhiking since not many are expected under neutrality. This is of particular utility in regions of low recombination where there is not much variation and in regions of normal or high recombination, where the hitchhiking effect can be limited to a small (<1 kb) region. Application of the H test to published surveys of Drosophila variation reveals an excess of high frequency variants that are likely to have been influenced by positive selection.

Animals↗
PubMed2001

Bridge from diffusion-limited aggregation to the Saffman-Taylor problem.

We introduce a Monte Carlo mean-field scheme for the diffusion-limited aggregation (DLA) model, in order to simulate processes of viscous fingering. The patterns obtained demonstrate a striking resemblance to natural shapes in Hele-Shaw cells, reproducing the Saffman-Taylor analytical solutions in the stable regime. The corresponding deterministic equations of the mean-field DLA scheme are derived and studied.

Journal Article↗
PubMed2026

A step-wise, deterministic and fatal mouse model of myeloid neoplasm with spontaneous acquisition of patient-relevant RTK-RAS mutations.

Leukaemia arises through the stepwise transformation of healthy haematopoietic cells, yet the asymptomatic premalignant phase and its progression to overt disease remain poorly understood. To model this process, we engineered a patient-derived CEBPA mutation into Hoxb8-FL multipotent murine progenitors and transplanted them into syngeneic mice, capturing a clinically silent premalignant stage. All recipients developed overt disease after ~12 months with 100% penetrance and all acquired secondary RTK-RAS mutations, often with identical amino acid changes to those in patients. Single-cell transcriptomics and phenotypic profiling showed that premalignant mutant cells adopt a plasmacytoid dendritic progenitor-like state in vitro which generates both myeloid and B-lymphoid lineages during premalignancy in vivo, with individual tumours restricted to one lineage. The specificity for RTK-RAS mutations coupled with ongoing differentiation, reflects clinically relevant biological contexts thus providing a tractable model of myeloid neoplasm for mechanistic studies and drug discovery.

Journal Article↗
PubMed1995

Dynamical analysis of neuromuscular transmission jitter.

Utilizing prolonged axonal stimulation single fiber EMG, neuromuscular transmission becomes a time-series of interpotential intervals (IPIs). In this form, the underlying processes of neuromuscular transmission can be studied using standard numerical techniques to determine whether these processes can be described by a simple mathematical model. In particular, neuromuscular transmission jitter can be examined in this way. In this article, we attempt to determine whether healthy jitter is noise or deterministic chaos. The presence of deterministic chaos was assessed by analysis of the IPI time-series using visual inspection of both phase-space plots and their principal component dimensions, and using the Grassberger-Procaccia algorithm to determine the correlation dimension of the time-series dynamics. These graphical and mathematical techniques provided little evidence for the existence of deterministic chaos. Linear autoregression time-series prediction also failed to account for the variability of the data and IPI histograms exhibited simple gaussian distributions. These results suggest normal neuromuscular transmission jitter is the result of intrinsic noise.

Action Potentials↗
PubMed1991

A stochastic model for the development of an AIDS epidemic in a heterosexual population.

A non-age-dependent model, describing the evolution of a bisexual population, is developed in this paper and applied to projecting an AIDS epidemic in a heterosexual population. Included in the formulation are frequency- and non-frequency-dependent rules of partnership formation as well as five states of HIV disease, affecting the probability of infection per sexual contact. Results from computer experiments, designed to study the development of an AIDS epidemic in a heterosexual population fed by single males with a 50% prevalence of HIV infection prior to becoming active in heterosexual partnerships, are reported. In these experiments, the only source of HIV infection for females was sexual contacts with infected males within partnerships. Data on the probability of infection per sexual contact with an infected partner and the number of sexual contacts per month were incorporated into the model. However, the numbers used for the initial population of singles, couples, and those becoming sexually active per month were hypothetical. Even though the prevalence of HIV infection among males entering heterosexual partnerships was high, after 30 years the projected prevalence of HIV infection among females ranged from about 10 to 15% depending in part on the expected duration of partnerships and on whether the frequency- or non-frequency-dependent model was used. In these experiments, solutions of the embedded, nonlinear, deterministic equations for the incidence of HIV infection and the cumulative number of deaths due to AIDS proved to be good measures of central tendency for the sample functions of the stochastic population process.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Quantal noise and decision rules in dynamic models of light adaptation.

To evaluate some of the consequences of including probabilistic processes (e.g. quantal noise) in a computable model of light-adaptation dynamics, we considered the behavior of a general class of models. These models contain four stages: (1) early noise; (2) a deterministic filtering and gain-changing stage; (3) late noise; (4) a decision rule that is either an ideal (signal-known-exactly) detector or a peak-trough detector. With the ideal detector and without late noise, the observer's sensitivity as a function of mean luminance and temporal frequency is not affected by the filtering and gain-changing stage. Consequently, if the early noise is entirely quantal fluctuations, sensitivity will always be a square-root function of mean luminance and a uniform (flat) function of temporal frequency. This latter prediction is contradicted by all known data; either the ideal-detector is the wrong decision rule or sensitivity is almost always limited by sources of noise other than quantal fluctuations. With the peak-trough detector, however, with or without late noise, the observer's sensitivity as a function of temporal frequency does reflect the sensitivity of the low-level filtering and gain-changing stage. Late noise is needed, however, if the observer's sensitivity as a function of mean luminance is to go through both a square-root and a Weber region. Comparing these conclusions to similar work on the spatial frequency dimension highlights differences between the spatial and temporal frequency domains. Finally, on the basis of these analyses and evidence from the literature, we question whether quantal fluctuations limit visual sensitivity under any condition.

Adaptation, Ocular↗
PubMed2006

Propagation and control of stochastic signals through universal learning networks.

The way of propagating and control of stochastic signals through Universal Learning Networks (ULNs) and its applications are proposed. ULNs have been already developed to form a superset of neural networks and have been applied as a universal framework for modeling and control of non-linear large-scale complex systems. However, the ULNs cannot deal with stochastic variables. Deterministic signals can be propagated through a ULN, but the ULN does not provide any stochastic characteristics of the signals propagating through it. The proposed method named Probabilistic Universal Learning Networks (PrULNs) can process stochastic variables and can train network parameters so that the signals behave with the pre-specified stochastic properties. As examples of applications of the proposed method, control and identification of non-linear dynamic systems with noises are studied, and it is shown that the method are useful for dealing with the control and identification of the non-linear stochastic systems contaminated with noises.

Artificial Intelligence↗
PubMed2005

Parallel biomolecular computation on surfaces with advanced finite automata.

A biomolecular, programmable 3-symbol-3-state finite automaton is reported. This automaton computes autonomously with all of its components, including hardware, software, input, and output being biomolecules mixed together in solution. The hardware consisted of two enzymes: an endonuclease, BbvI, and T4 DNA ligase. The software (transition rules represented by transition molecules) and the input were double-stranded (ds) DNA oligomers. Computation was carried out by autonomous processing of the input molecules via repetitive cycles of restriction, hybridization, and ligation reactions to produce a final-state output in the form of a dsDNA molecule. The 3-symbol-3-state deterministic automaton is an extension of the 2-symbol-2-state automaton previously reported, and theoretically it can be further expanded to a 37-symbol-3-state automaton. The applicability of this design was further amplified by employing surface-anchored input molecules, using the surface plasmon resonance technology to monitor the computation steps in real time. Computation was performed by alternating the feed solutions between endonuclease and a solution containing the ligase, ATP, and appropriate transition molecules. The output detection involved final ligation with one of three soluble detection molecules. Parallel computation and stepwise detection were carried out automatically with a Biacore chip that was loaded with four different inputs.

Adenosine Triphosphate↗
PubMed2001

Non-thermal melting in semiconductors measured at femtosecond resolution.

Ultrafast time-resolved optical spectroscopy has revealed new classes of physical, chemical and biological reactions, in which directed, deterministic motions of atoms have a key role. This contrasts with the random, diffusive motion of atoms across activation barriers that typically determines kinetic rates on slower timescales. An example of these new processes is the ultrafast melting of semiconductors, which is believed to arise from a strong modification of the inter-atomic forces owing to laser-induced promotion of a large fraction (10% or more) of the valence electrons to the conduction band. The atoms immediately begin to move and rapidly gain sufficient kinetic energy to induce melting--much faster than the several picoseconds required to convert the electronic energy into thermal motions. Here we present measurements of the characteristic melting time of InSb with a recently developed technique of ultrafast time-resolved X-ray diffraction that, in contrast to optical spectroscopy, provides a direct probe of the changing atomic structure. The data establish unambiguously a loss of long-range order up to 900 A inside the crystal, with time constants as short as 350 femtoseconds. This ability to obtain the quantitative structural characterization of non-thermal processes should find widespread application in the study of ultrafast dynamics in other physical, chemical and biological systems.

Journal Article↗
PubMed2003

A two-stage interval-stochastic programming model for waste management under uncertainty.

This study introduces a two-stage interval-stochastic programming (TISP) model for the planning of solid-waste management systems under uncertainty. The model is derived by incorporating the concept of two-stage stochastic programming within an interval-parameter optimization framework. The approach has the advantage that policy determined by the authorities, and uncertain information expressed as intervals and probability distributions, can be effectively communicated into the optimization processes and resulting solutions. In the modeling formulation, penalties are imposed when policies expressed as allowable waste-loading levels are violated. In its solution algorithm, the TISP model is converted into two deterministic submodels, which correspond to the lower and upper bounds for the desired objective-function value. Interval solutions, which are stable in the given decision space with associated levels of system-failure risk, can then be obtained by solving the two submodels sequentially. Two special characteristics of the proposed approach make it unique compared with other optimization techniques that deal with uncertainties. First, the TISP model provides a linkage to predefined policies determined by authorities that have to be respected when a modeling effort is undertaken; second, it furnishes the reflection of uncertainties presented as both probabilities and intervals. The developed model is applied to a hypothetical case study of regional solid-waste management. The results indicate that reasonable solutions have been generated. They provide desired waste-flow patterns with minimized system costs and maximized system feasibility. The solutions present as stable interval solutions with different risk levels in violating the waste-loading criterion and can be used for generating decision alternatives.

Environment↗