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PubMed2005

Prediction of smallpox outbreak and evaluation of control-measure policy in Japan, using a mathematical model.

Since the September 1 terrorist attacks and moreover, since the anthrax exposure events in 2001 in the United States, bioterrorism attacks seem to be a real threat. Of course, the public health authorities in Japan have started to prepare control measures for such events. We report here our attempts, using a mathematical model, to estimate outbreak size and to examine the most effective measures; comparing ring vaccination (contact tracing, isolation, and vaccination among contacts) and mass vaccination of the susceptible population in the area. The basic framework of the mathematical model follows a model used in previous research. The initial susceptible population is assumed to be 30 million persons. Concerning the important parameters, such as the number of initial-exposure cases, R0 (infectious power, or natural history) and, the starting day of intervention after the initial exposure, we checked the robustness of our conclusions by sensitivity analysis. We found that mass vaccination is preferable to ring vaccination when the values for the initial-exposure cases and R0 are high and when the start of intervention by public health authorities is delayed. In the base-case situation, the mass vaccination strategy needs almost 30 million vaccine doses. On the other hand, though ring vaccination needs fewer doses, it needs fewer than 50,000 doses in the worst-case scenario, that with larger first exposure, higher R0, or later start of public health authority intervention. This mathematical model can measure the prevalence of an infectious disease and can evaluate control measures for it before an outbreak. Especially, it is useful for the planning of the outbreaks of emerging diseases such as severe acute respiratory syndrome (SARS) or for bioterrorism attacks involving such diseases as smallpox. In further research, we will have to take into account the population people vaccinated of for smallpox, who account for about 70% of the total population in Japan.

Disease Outbreaks↗

PubMed2007

Disordered gambling among college students: a meta-analytic synthesis.

The purpose of this study was to use a meta-analytic procedure to synthesize the rates of disordered gambling for college students that have been reported in the research literature. In order to identify all possible studies that met stringent inclusion criteria, Medline, PsychINFO, and SocioIndex databases were searched with the terms "gambling," and "college student". This process resulted in 15 studies concerning gambling among college students that were published through July 2005. To synthesize the 15 studies, a random effects model for meta-analysis was applied. The estimated proportion of disordered gamblers among college students was 7.89%. This estimate is noteworthy because it is higher than that reported for adolescents, college students or adults in a previous study using meta-analytic procedures with studies conducted prior to 1997.

Adult↗

PubMed1991

The effect of airline deregulation on automobile fatalities.

This paper attempts to quantify the effects of airline deregulation in the United States on intercity automobile travel and consequently on the number of highway fatalities. A demand model is constructed for auto travel, which includes variables representing the price and availability of air service. A reduced form model of the airline market is then estimated. Finding that deregulation has decreased airfares and increased flights, it is estimated that auto travel has been reduced by 2.2% per year on average. Given assumptions on the characteristics of drivers switching modes and the types of roads they drove on, the number of automobile fatalities averted since 1978 is estimated to be in the range 200-300 per year.

Accidents, Aviation↗

PubMed1995

Guanosine tetraphosphate as a global regulator of bacterial RNA synthesis: a model involving RNA polymerase pausing and queuing.

A recently reported comparison of stable RNA (rRNA, tRNA) and mRNA synthesis rates in ppGpp-synthesizing and ppGpp-deficient (delta relA delta spoT) bacteria has suggested that ppGpp inhibits transcription initiation from stable RNA promoters, as well as synthesis of (bulk) mRNA. Inhibition of stable RNA synthesis occurs mainly during slow growth of bacteria when cytoplasmic levels of ppGpp are high. In contrast, inhibition of mRNA occurs mainly during fast growth when ppGpp levels are low, and it is associated with a partial inactivation of RNA polymerase. To explain these observations it has been proposed that ppGpp causes transcriptional pausing and queuing during the synthesis of mRNA. Polymerase queuing requires high rates of transcription initiation in addition to polymerase pausing, and therefore high concentrations of free RNA polymerase. These conditions are found in fast growing bacteria. Furthermore, the RNA polymerase queues lead to a promoter blocking when RNA polymerase molecules stack up from the pause site back to the (mRNA) promoter. This occurs most frequently at pause sites close to the promoter. Blocking of mRNA promoters diverts RNA polymerase to stable RNA promoters. In this manner ppGpp could indirectly stimulate synthesis of stable RNA at high growth rates. In the present work a mathematical analysis, based on the theory of queuing, is presented and applied to the global control of transcription in bacteria. This model predicts the in vivo distribution of RNA polymerase over stable RNA and mRNA genes for both ppGpp-synthesizing and ppGpp-deficient bacteria in response to different environmental conditions. It also shows how small changes in basal ppGpp concentrations can produce large changes in the rate of stable RNA synthesis.

Bacteria↗

PubMed1989

A knowledge-based support system for mechanical ventilation of the lungs. The KUSIVAR concept and prototype.

The KUSIVAR is an expert system for mechanical ventilation of adult patients suffering from respiratory insufficiency. Its main objective is to provide guidance in respirator management. The knowledge base includes both qualitative, rule-based knowledge and quantitative knowledge expressed in the form of mathematical models (expert control) which is used for prediction of arterial gas tensions and optimization purposes. The system is data driven and uses a forward chaining mechanism for rule invocation. The interaction with the user will be performed in advisory, critiquing, semi-automatic and automatic modes. The system is at present in an advanced prototype stage. Prototyping is performed using KEE (Knowledge Engineering Environment) on a Sperry Explorer workstation. For further development and clinical use the expert system will be downloaded to an advanced PC. The system is intended to support therapy with a Siemens-Elema Servoventilator 900 C.

Adult↗

PubMed2001

A model of a snorer's upper airway.

In snorers, the physiologic decrease of postural muscle tone during sleep results in increased collapsibility of the upper airway. Measurement of nasal pressure changes with prongs is increasingly used to monitor flow kinetics through a collapsing upper airway. This report presents a mathematical model to predict nasal flow profile from three critical components that control upper airway patency during sleep. The model includes the respiratory pump drive, the stiffness of the pharyngeal soft tissues, and the dynamic support of the muscles surrounding the upper airway. Depending on these three components, the proposed model is able to reproduce the characteristic changes in flow profile that are clinically observed in snorers and non-snorers during sleep.

Humans↗

PubMedDate not supplied

Why do olfactory neurons have unspecific receptive fields?

Biological olfactory neurons are deployed as a population, most responding to a large variety of chemical compounds, that is, they possess unspecific receptive fields. The question of whether this unspecificity results from some physical constraint placed upon chemical transduction, or on the other hand, is beneficial to system performance is unclear. In this paper we employ the notion of Fisher information to address this question by quantifying how both the distribution and the tunings of the receptive fields within olfactory receptor populations affect the optimal estimation performance of the system. Our results show that overlapping sensory neuron tunings that respond to common chemical compounds have better estimation performance than perfectly specific tunings. Our results suggest two phenomena that might represent general principles of organization within biological sensory systems responding to multiple stimuli: maximization of the diversity of tunings and homogeneity in the distribution of these different receptive fields across the stimulus space (independent of the statistics of the input stimuli). Our model predicts that a local randomized mechanism controlling receptor specificities generates optimal multidimensional stimulus estimation, for which there is some experimental evidence from the biology.

Olfactory Receptor Neurons↗

PubMed1980

Effects of deindividuating situational cues and aggressive models on subjective deindividuation and aggression.

This experiment demonstrated that a subjective state of deindividuation mediates the effect of deindividuating situational cues on aggression displayed by small groups (n = 4) of coacting aggressors. The deindividuated state was composed of two factors, Self-Awareness and Altered Experiencing, both of which had a causal influence on aggressive behavior. These data are interpreted in terms of deindividuation theories which assume that certain input variables reduce self-awareness and concern about social evaluation and thereby weaken the restraints against expressing antisocial behavior. Also as predicted, compared with a no-model control condition, a high-aggressive model disinhibited overt displays of aggression, whereas a low-aggressive model inhibited aggression among both individuated and deindividuated group members.

Aggression↗

PubMed2002

Adaptive divergence in experimental populations of Pseudomonas fluorescens. I. Genetic and phenotypic bases of wrinkly spreader fitness.

A central feature of all adaptive radiations is morphological divergence, but the phenotypic innovations that are responsible are rarely known. When selected in a spatially structured environment, populations of the bacterium Pseudomonas fluorescens rapidly diverge. Among the divergent morphs is a mutant type termed "wrinkly spreader" (WS) that colonizes a new niche through the formation of self-supporting biofilms. Loci contributing to the primary phenotypic innovation were sought by screening a WS transposon library for niche-defective (WS(-)) mutants. Detailed analysis of one group of mutants revealed an operon of 10 genes encoding enzymes necessary to produce a cellulose-like polymer (CLP). WS genotypes overproduce CLP and overproduction of the polymer is necessary for the distinctive morphology of WS colonies; it is also required for biofilm formation and to maximize fitness in spatially structured microcosms, but overproduction of CLP alone is not sufficient to cause WS. A working model predicts that modification of cell cycle control of CLP production is an important determinant of the phenotypic innovation. Analysis of >30 kb of DNA encoding traits required for expression of the WS phenotype, including a regulatory locus, has not revealed the mutational causes, indicating a complex genotype-phenotype map.

Adaptation, Physiological↗

PubMed2000

Estimation of base temperatures for nine weed species.

Experiments were conducted to test several methods for estimating low temperature thresholds for seed germination. Temperature responses of nine weeds common in annual agroecosystems were assessed in temperature gradient experiments. Species included summer annuals (Amaranthus albus, A. palmeri, Digitaria sanguinalis, Echinochloa crus-galli, Portulaca oleracea, and Setaria glauca), winter annuals (Hirschfeldia incana and Sonchus oleraceus), and Conyza canadensis, which is classified as a summer or winter annual. The temperature below which development ceases (Tbase) was estimated as the x-intercept of four conventional germination rate indices regressed on temperature, by repeated probit analysis, and by a mathematical approach. An overall Tbase estimate for each species was the average across indices weighted by the reciprocal of the variance associated with the estimate. Germination rates increased linearly with temperature between 15 degrees C and 30 degrees C for all species. Consistent estimates of Tbase were obtained for most species using several indices. The most statistically robust and biologically relevant method was the reciprocal time to median germination, which can also be used to estimate other biologically meaningful parameters. The mean Tbase for summer annuals (13.8 degrees C) was higher than that for winter annuals (8.3 degrees C). The two germination response characteristics, Tbase and slope (rate), influence a species' germination behaviour in the field since the germination inhibiting effects of a high Tbase may be offset by the germination promoting effects of a rapid germination response to temperature. Estimates of Tbase may be incorporated into predictive thermal time models to assist weed control practitioners in making management decisions.

Germination↗

PubMed1998

Clinical evaluation of paresthesia steering with a new system for spinal cord stimulation.

OBJECTIVE: The goal was to evaluate, in a clinical study, the predicted performance of the transverse tripolar system for spinal cord stimulation, particularly the steering of paresthesia, paresthesia coverage, and the therapeutic range of stimulation. METHODS: Six transverse tripolar electrodes were implanted in the lower thoracic region in four patients experiencing chronic neuropathic pain. Electrode positions, relative to the spinal cord, were estimated from computed tomographic scans. A dual-channel stimulator was used for initial percutaneous tests, and an implanted single-channel stimulator was used for follow-up test sessions. Nine "balance" settings and several cathode-anode combinations were used with the dual-channel and single-channel stimulator, respectively. In each test, the increase of paresthesia coverage from the perception threshold to the discomfort threshold was registered on a body map and the corresponding voltages were recorded. RESULTS: Paresthesia steering occurred in all but one patient. The normalized steering score, enabling quantitative comparisons of paresthesia steering among tests and patients, showed that maximum paresthesia steering occurred when the electrode was at least 3 mm dorsal to the spinal cord and centered <2 mm from its midline. Paresthesia coverage included 70 to 100% of the body up to the electrode level, unless the electrode migrated or had broken wires. The therapeutic range, defined as the discomfort/perception of paresthesia threshold ratio, varied from 1.6 to 4.0. CONCLUSION: The clinical performance of transverse tripolar stimulation is in accordance with the characteristics predicted by computer modeling. It enables finer control of paresthesia than that achieved by polarity changes in conventional spinal cord stimulation systems.

Adult↗

PubMed2006

Prediction of pelvic inflammatory disease among young, single, sexually active women.

OBJECTIVES: To assess prediction strategies for pelvic inflammatory disease (PID). STUDY DESIGN: One thousand one hundred seventy women were enrolled based on a high chlamydial risk score. Incident PID over a median of 3 years was diagnosed by either histologic endometritis or Centers for Disease Control and Prevention criteria. A multivariable prediction model for PID was assessed. RESULTS: Women enrolled using the risk score were young, single, sexually active, and often had prior sexually transmitted infections. Incident PID was common (8.6%). From 24 potential predictors, significant factors included age at first sex, gonococcal/chlamydial cervicitis, history of PID, family income, smoking, medroxyprogesterone acetate use, and sex with menses. The model correctly predicted 74% of incident PID; in validation models, correct prediction was only 69%. CONCLUSIONS: Our data validate a modified chlamydial risk factor scoring system for prediction of PID. Additional multivariable modeling contributed little to prediction. Women identified by a threshold value on the chlamydial risk score should undergo intensive education and screening.

Adolescent↗

PubMed2001

Down the tube: pollinators, predators, and the evolution of flower shape in the alpine skypilot, Polemonium viscosum.

We address how a conflict between pollinator attraction and avoidance of flower predation influences the evolution of flower shape in Polemonium viscosum. Flower shape in P. viscosum is the product of an isometric relationship between genetically correlated (rA = 0.70) corolla flare and length. Bumblebee pollinators preferentially visit flowers that are more flared and have longer tubes, selecting for a funnel-shaped corolla. However, flower shape also influences nectar-foraging ants that sever the style at its point of attachment to the ovary. Surveys of ant damage show that plants having flowers with flared, short corollas are most vulnerable to ant predation. Consistent with this result, the ratio of corolla length to flare is significantly greater in a krummholz (high predation risk) population than in a tundra (low predation risk) population. To explicitly test whether the evolution of a better defended flower would exact a cost in pollination, we created tubular flowers by constricting the corolla during development. Performance of tubular flowers and natural controls was compared for defensive and attractive functions. In choice trials, ants entered control flowers significantly more often than tubular ones, confirming that the evolution of tubular flowers would reduce the risk of predation. However, in a bumblebee-pollinated population, tubular flowers received significantly less pollen and set fewer seeds than controls. A fitness model incorporating these data predicts that in the absence of the genetic correlation between corolla length and flare, intermittent selection for defense could allow tubular flowers to spread in the krummholz population. However, in the tundra, where bumblebees account for nearly all pollination, the model predicts that tubular flowers should always confer a fitness disadvantage.

Animals↗

PubMed1990

The entrainment of low frequency breathing periodicity.

It has been predicted by mathematical models of the respiratory control system that the delay between the lung and the respiratory controller may determine the cycle time found in periodic breathing. We examined cycle time of periodic breathing and circulation time in 11 patients known to have circulation delay due to heart failure. We did not find a significant relationship between the amount of periodic breathing and circulation delay, but found a very high correlation between circulation delay and the cycle time of periodic breathing (r2 = 0.825; p = 0.0001).

Blood Circulation↗

PubMed2002

N-methyl-D-aspartate receptor-coupled glycineB receptors in the pathogenesis and treatment of schizophrenia: a critical review.

Glutamatergic pathways, metabotropic receptors, and ionotropic alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA), kainate and N-methyl-D-aspartate (NMDA) receptors are all implicated in the etiology and management of schizophrenia. As concerns NMDA receptors, open channel blockers (OCBs) such as phencyclidine (PCP) elicit psychotic symptoms in human subjects. This observation underpins biochemical studies indicating that a deficit in activity at NMDA receptors may be associated with psychotic states. Inasmuch as agonists at the NMDA recognition site are excitotoxic, drugs acting via the co-agonist, glycine(B) (GLY(B)) site are more promising clinical candidates as antipsychotic agents. Glycine (GLY) itself, a further endogenous agonist, D-Serine, and inhibitors of GLY reuptake are active in certain experimental models predictive of antipsychotic properties. Further, in controlled clinical trials, GLY and D-Serine enhance the ability of conventional neuroleptics such as haloperidol to improve cognitive and negative symptoms. Their actions are mimicked by the partial agonist, D-cycloserine (DCS). However, these agents exert little effect alone and may interfere with therapeutic actions of the atypical antipsychotic, clozapine. An important issue in the interpretation of drug actions at GLY(B) sites is their degree of occupation by endogenous GLY and D-Serine - although they are unlikely to be saturated. Further, distinct "subtypes" of GLY(B) site-bearing NMDA receptor may fulfill differential roles in psychotic states Finally, blockade of certain populations of NMDA receptor may be of use in the management of schizophrenia. This article reviews the complex role of GLY(B) sites/NMDA receptors and their endogenous ligands in the pathogenesis and treatment of psychotic states.

Animals↗

PubMed1977

Predation, aggression, and activity levels in food-deprived sunfish (Lepomis macrochirus and L. gibbosus): motivational interactions.

Three experiments investigated the effects of food deprivation on several behavioral categories in two species of sunfish. In Experiment 1, predatory behavior and general activity were observed under five levels of deprivation. For both species, predation measures increased in a similar negatively accelerating manner with increasing deprivation, while activity changed in a more complex fashion. Experiment 2 examined the effects of deprivation on activity in a novel environment and showed that the deprivation effects of Experiment 1 were masked by the response to the new setting. In Experiment 3, measures of aggression toward intruders of each species were recorded from resident fish of both species under three levels of food deprivation. Both species were more aggressive toward conspecifics, and bluegills were more aggressive overall. Aggression was significatly influenced by food deprivation, with the effects dependent on the species making up the pair. Theories of motivational summation, generalized drive, and activity-mediated aggression were unable to explain the differential effects of hunger on the three behavioral categories observed. A dynamic boundary-state model of behavior control was found to predict the motivational interactions observed between distinct behavioral control systems.

Aggression↗

PubMedDate not supplied

Predicting metabolic control in diabetes: a pilot study using meta-analysis to estimate a linear model.

The purpose of this pilot study was to determine the feasibility of using data from replicated descriptive studies to test a four-variable model designed to explain metabolic control in diabetes. Predictors of metabolic control selected for this analysis were knowledge; health beliefs (and the subscales of barriers, commitment, cues, expectancies, impact on lifestyle, support, and susceptibility); and compliance/adherence. A total of 17 studies, published between 1982 and 1991, were located that met inclusion criteria. Findings indicated that health beliefs have direct and indirect effects on diabetes metabolic control, depending on the individual health belief subscale analyzed. For example, commitment to the benefits of therapy was found to have a statistically significant direct effect on metabolic control; barriers had a statistically significant indirect effect through compliance. The effects of knowledge were consistent throughout the five path models explored. An inverse direct effect was noted on metabolic control and a positive indirect effect was noted on metabolic control through compliance.

Attitude to Health↗

PubMed1993

Optimizing high-dose therapy using pharmacokinetic principles.

The oncologic literature of the past decade contains numerous articles supporting the concept of "dose intensity." The hypothesis that greater intensity of effective drug therapy can result in higher cure rates is supported by the results obtained in bone marrow transplantation for leukemia, lymphoma, and, possibly, breast carcinoma. Stem cell infusion overcomes the first level of the dose-limiting toxicities, ie, bone marrow suppression. This predictable toxicity develops in all patients. Second organ toxicities, such as renal, hepatic, or cardiopulmonary toxicity, occur in a less predictable manner. This variation in individual patient tolerance may be related to wide variations in drug concentration between patients while receiving the same dose. This interpatient variability has been well described for many oncologic agents, but is not unique to oncologic therapy. Important but incompletely defined relationships of importance to high-dose therapy include (1) the relationship of drug dose to concentration within patient groups and for the individual patient and (2) the relationship of drug concentration, or other related parameter such as area under the concentration versus time curve, to toxicity and outcome. Assuming such relationships can be defined, the value of using improved methods to select drug doses for an individual patient to achieve therapeutic goals needs to be explored. The purpose is to optimize therapy. In the bone marrow transplantation setting, the ideal is to provide the greatest drug exposure without undo risk of life-threatening second organ toxicity. To solve these problems, we need models that predict and allow us to control therapy in a much more precise manner than is currently possible. This review examines the concept of dose intensity, defines this concept in terms of plasma drug concentrations, and reviews methods that can aid the control of therapy in the individual patient. The potential importance of this methodology to the individual patient is discussed.

Antineoplastic Agents↗