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Brachytherapy of stage II mobile tongue carcinoma. Prediction of local control and QOL.

BACKGROUND: There is no consensus as to the prognostic model for brachytherapy of tongue carcinoma. This study was designed to evaluate the prognostic factors for local control based on a large population under a unified treatment policy. RESULTS: Between 1970 and 1998, 433 patients with stage II tongue squamous cell carcinoma were treated by low-dose-rate brachytherapy. This series included 277 patients treated with a linear source with a minimum follow-up of 3 years. A spacer was introduced in 1987. The primary local control rates were 85.6%. CONCLUSION: In the multivariate analysis, an invasive growth pattern was a significant factor for local recurrence. The disease-related survival was influenced by old age and an invasive growth pattern. A spacer lowered mandibular bone complications. The growth pattern was the most important factor for recurrence. Brachytherapy was associated with a high cure rate and the use of spacers brought about good quality of life (QOL).

Adult↗

Grasp stability during manipulative actions.

The control of adequate contact forces between the skin and an object (grasp stability) is examined for two classes of prehensile actions that employ a precision grip: lifting objects that are "passive" (subject only to inertial forces and gravity) and preventing "active" objects from moving. For manipulating either passive or active objects the relevant fingertip forces are determined by at least two control processes. "Anticipatory parameter control" is a feedforward controller that specifies the values for motor command parameters on the basis of predictions of critical characteristics, such as object weight and skin-object friction, and initial condition information. Through vision, for instance, common objects can be identified in terms of the fingertip forces necessary for a successful lift according to previous experiences. After contact with the object, sensory information representing discrete mechanical events at the fingertips can (i) automatically modify the motor commands, (ii) update sensorimotor memories supporting the anticipatory parameter control policy, (iii) inform the central nervous system about completion of the goal for each action phase, and (iv) trigger commands for the task's sequential phases. Hence, the central nervous system monitors specific, more or less expected peripheral sensory events to produce control signals that are appropriate for the task at its current phase. The control is based on neural modelling of the entire dynamics of the control process that predicts the appropriate output for several steps ahead. This "discrete-event, sensor-driven control" is distinguished from feedback or other continuous regulation. Using these two control processes, slips are avoided at each digit by independent control mechanisms that specify commands and process sensory information on a local, digit-specific basis. This scheme obviates explicit coordination of the digits and is employed when independent nervous systems lift objects. The force coordination across digits is an emergent property of the local control mechanisms operating over the same time span.

Hand↗

Carotenoid dynamics in Atlantic salmon.

BACKGROUND: Carotenoids are pigment molecules produced mainly in plants and heavily exploited by a wide range of organisms higher up in the food-chain. The fundamental processes regulating how carotenoids are absorbed and metabolized in vertebrates are still not fully understood. We try to further this understanding here by presenting a dynamic ODE (ordinary differential equation) model to describe and analyse the uptake, deposition, and utilization of a carotenoid at the whole-organism level. The model focuses on the pigment astaxanthin in Atlantic salmon because of the commercial importance of understanding carotenoid dynamics in this species, and because deposition of carotenoids in the flesh is likely to play an important life history role in anadromous salmonids. RESULTS: The model is capable of mimicking feed experiments analyzing astaxanthin uptake and retention over short and long time periods (hours, days and years) under various conditions. A sensitivity analysis of the model provides information on where to look for possible genetic determinants underlying the observed phenotypic variation in muscle carotenoid retention. Finally, the model framework is used to predict that a specific regulatory system controlling the release of astaxanthin from the muscle is not likely to exist, and that the release of the pigment into the blood is instead caused by the androgen-initiated autolytic degradation of the muscle in the sexually mature salmon. CONCLUSION: The results show that a dynamic model describing a complex trait can be instrumental in the early stages of a project trying to uncover underlying determinants. The model provides a heuristic basis for an experimental research programme, as well as defining a scaffold for modelling carotenoid dynamics in mammalian systems.

Animals↗

Evaluation of the efficacy of extrapolation population modeling to predict the dynamics of Americamysis bahia populations in the laboratory.

An age-classified projection matrix model has been developed to extrapolate the chronic (28-35 d) demographic responses of Americamysis bahia (formerly Mysidopsis bahia) to population-level response. This study was conducted to evaluate the efficacy of this model for predicting the population behavior of A. bahia held (for more than three generations) under controlled laboratory exposure conditions. The research involved the performance of a standard life-cycle test and a multigenerational (greater than three mysid generations, 55 d) assay using A. bahia to experimentally evaluate model predictions regarding population-level risks of chemical exposure. The organic compound para-nonylphenol was chosen as the chemical stressor in assays. This compound is a ubiquitous contaminant and suspected endocrine disruptor. Utilizing data obtained during the standard life-cycle test, aggregate estimates of population growth rate (lambda) and measured p-nonylphenol concentration were used to develop an exposure-response model of population-level effects. These estimates provided the basis of predictions for the long-term dynamics of mysid populations exposed to p-nonylphenol. The veracity of the mysid population model was evaluated through quantitative comparisons of model predictions based on the life-cycle test with dynamics of the experimental populations (multigenerational assay results). The results indicate that the population model was able to project within a few micrograms per liter the concentration where population-level effects would begin to occur (projected 16 micrograms/L from the model vs measured 19 micrograms/L from the multigenerational assay).

Aging↗

Open loop control of multiple drug effects in anesthesia.

Current open-loop computer-controlled infusion pumps do not explicitly control the transient adverse side effects of intravenous drugs during anesthesia. We used optimal control principles to synthesize a single-input multiple-output controller that regulates concentrations at the site of desirable drug effect while penalizing excessive side-effect drug concentrations. The cost function incorporates model-based predictions of future effect-site concentrations, and the capability of the anesthesiologist to anticipate upcoming surgical events. The controller was evaluated and then compared with alternative control strategies through computer simulation of a physiologically based pharmacokinetic model for the intravenous drug alfentanil. Multiple-effect control offers an analytic approach to limit the overshoot in adverse side-effect concentrations at the consequence of increasing the time to achieve the desired drug effect.

Alfentanil↗

Malignant hypertensive crisis induced by chronic intrarenal norepinephrine infusion.

The purpose of the present study was to develop a controllable experimental model in the dog that would consistently and predictably produce a malignant hypertensive crisis, and to determine the sequential changes in renal function, salt and water balance, and hormones that are involved in the transition from benign to accelerated hypertension. Norepinephrine (NE) was infused continuously into the renal artery of unilaterally nephrectomized dogs that were maintained on 50 mEq sodium/day. The infusion rate of NE was increased each day according to the following schedule: 0.05, 0.1, 0.2, 0.3, 0.4, and 0.5 microgram/kg/min. During the first 4 to 5 days of intrarenal NE infusion, there was a progressive decrease in glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), and increases in plasma renin activity (PRA), mean arterial pressure (MAP), and filtration fraction. At the end of this period of benign hypertension, MAP had risen from a control value of 91 +/- 4 to 132 +/- 8 mm Hg, in association with approximately a 10-fold increase in PRA and a 40% reduction in renal function. Then, suddenly, during the subsequent 24-hour infusion period, the MAP increased abruptly in all animals (MAP = 156 +/- 8 mm Hg), and a hypertensive crisis occurred. This crisis was associated with the following: salt and water depletion, hyponatremia, hypovolemia and hemoconcentration, polydipsia, marked activation of the renin-angiotensin-aldosterone system, increased plasma cortisol concentration, hemolysis, marked impairment in renal function, lethargy, and vomiting.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗

Task effects on three-dimensional dynamic postures during seated reaching movements: an investigative scheme and illustration.

In this paper we describe a new scheme for empirically investigating the effects of task factors on three-dimensional (3D) dynamic postures during seated reaching movements. The scheme relies on an underlying model that integrates two statistical procedures: (a) a regression description of the relationship between the time-varying hand location and postural angles to characterize the movement data and (b) a series of analyses of variance to test the hypothesized task effects using representative instantaneous postures. The use of this scheme is illustrated by an experiment that examines two generic task factors: hand motion direction and motion completion time. Results suggest that hand motion direction is a significant task factor in determining instantaneous postures, whereas a distinctive difference in the time to complete a motion does not appear to have a significant effect. We discuss the concept of an instantaneous posture and its utility in dynamic studies of movements, some insights into human reaching movement control strategy, and implications for the development of a 3D dynamic posture prediction model.

Adult↗

Controlled attention sharing influences time estimation.

A seminal attentional model of time estimation predicts that subjective duration will be positively correlated to the amount of attention given to temporal processing. This prediction holds under prospective conditions, in which one is forewarned that judgments of time will be asked, in contrast to retrospective conditions, in which such judgments are required after the relevant period without any prior warning. In three experiments, an attention-sharing method was used. Subjects were asked to control the amount of attention that they devoted to one or the other component of a dual-task paradigm. The first experiment involved word categorization and reproduction of duration. The following experiments, based on signal detection theory, required discrimination of both the duration and the intensity of a single stimulus, in the visual (Experiment 2) or the auditory (Experiment 3) modality. The results indicate that when the attention is directly controlled by the subject, the subjective duration shortens as the amount of attention devoted to the temporal task diminishes. The implications of these results for the possible existence of an internal timer are considered.

Adult↗

Polymorphisms in nucleotide excision repair genes and DNA repair capacity phenotype in sisters discordant for breast cancer.

Interindividual differences in DNA repair capacity (DRC) may play a critical role in breast cancer risk. Previously, we determined that DRC measured via removal of in vitro-induced benzo[a]pyrene diolepoxide-DNA adducts in lymphoblastoid cell lines was lower in cases compared with controls among sisters discordant for breast cancer from the Metropolitan New York Registry of Breast Cancer Families. We have now determined genotypes for seven single nucleotide polymorphisms in five nucleotide excision repair genes, including Xeroderma pigmentosum complementation group A (XPA +62T>C), group C (XPC Lys939Gln and Ala499Val), group D (XPD Asp312Asn and Lys751Gln), and group G (XPG His1104Asp) and ERCC1 (8092 C>A) in a total of 160 sister pairs for whom DRC phenotype data were available. Overall, there were no statistically significant differences in average DRC for most of the genotypes. A final multivariate conditional logistic model, including three single nucleotide polymorphisms (XPA +62T>C, XPC Ala499Val, and XPG His1104Asp) and smoking status, only modestly predicted DRC after adjusting for case-control status and age of blood donation. The overall predictive accuracy was 61% in the model with a sensitivity of 78% and specificity of 39%. These findings suggest that those polymorphisms we have investigated to date in nucleotide excision repair pathway genes explain only a small amount of the variability in DRC.

Adult↗

Predictability of El Niño over the past 148 years.

Forecasts of El Niño climate events are routinely provided and distributed, but the limits of El Niño predictability are still the subject of debate. Some recent studies suggest that the predictability is largely limited by the effects of high-frequency atmospheric 'noise', whereas others emphasize limitations arising from the growth of initial errors in model simulations. Here we present retrospective forecasts of the interannual climate fluctuations in the tropical Pacific Ocean for the period 1857 to 2003, using a coupled ocean-atmosphere model. The model successfully predicts all prominent El Niño events within this period at lead times of up to two years. Our analysis suggests that the evolution of El Niño is controlled to a larger degree by self-sustaining internal dynamics than by stochastic forcing. Model-based prediction of El Niño therefore depends more on the initial conditions than on unpredictable atmospheric noise. We conclude that throughout the past century, El Niño has been more predictable than previously envisaged.

Journal Article↗

Ultrafast electron-transfer and solvent adiabaticity effects in viologen charge-transfer complexes.

We report ultrafast electron transfer (ET) in charge-transfer complexes that shows solvent relaxation effects consistent with adiabatic crossover models of nonadiabatic ET. The complexes of either dimethyl viologen (MV) or diheptyl viologen (HV) with 4,4'-biphenol (BP) (MVBP or HVBP complexes) have identical charge-transfer spectra and kinetics in ethylene glycol with approximately 900 fs ET decay. We assign this decay time as largely due to adiabatic control of a predicted approximately 40 fs nonadiabatic ET. The MVBP decay in methanol of 470 fs is reduced in mixtures having low (2-20%) concentrations of acetonitrile to as short as 330 fs; these effects are associated with faster relaxation time in methanol and its mixtures. In contrast, HVBP has much longer ET decay in methanol (730 fs) and mixture effects that only reduce its decay to 550 fs. We identify the heptyl substituent as creating major perturbations to solvent relaxation times in the methanol solvation shell of HVBP. These charge-transfer systems have reasonably well-defined geometry with weak electronic coupling where the electronic transitions are not dependent on intramolecular motions. We used a nonadiabatic ET model with several models for adiabatic crossover predictions to discuss the small variation of energy gap with solvent and the ET rates derived from adiabatic solvent control. A time correlation model of solvent relaxation was used to define the solvent relaxation times for this case of approximately zero-barrier ET.

Journal Article↗

Predictors of hypoxaemia in hospital admissions with acute lower respiratory tract infection in a developing country.

Since oxygen has to be given to most children in developing countries on the basis of clinical signs without performing blood gas analyses, possible clinical predictors of hypoxaemia were studied. Sixty nine children between the ages of 2 months and 5 years admitted to hospital with acute lower respiratory tract infection and an oxygen saturation (Sao2) < 90% were compared with 67 children matched for age and diagnosis from the same referral hospital with an Sao2 of 90% or above (control group 1), and 44 unreferred children admitted to a secondary care hospital with acute lower respiratory infection (control group 2). Using multiple logistic regression analysis, sleepiness, arousal, quality of cry, cyanosis, head nodding, decreased air entry, nasal flaring, and upper arm circumference were found to be independent predictors of hypoxaemia on comparison of the cases with control group 1. Using a simple model of cyanosis or head nodding or not crying, the sensitivity to predict hypoxaemia was 59%, and the specificity 94% and 93% compared to control groups 1 and 2, respectively; 80% of the children with an Sao2 < 80% were identified by the combination of these signs. Over half of the children with hypoxaemia could be identified with a combination of three signs: extreme respiratory distress, cyanosis, and severely compromised general status. Further prospective validation of this model with other datasets is warranted. No other signs improved the sensitivity without compromising specificity. If a higher sensitivity is required, pulse oximetry has to be used.

Acute Disease↗

Activating patients for smoking cessation through physician autonomy support.

OBJECTIVE: Test whether physicians' counseling patients for smoking cessation with an autonomy supportive rather than controlling style would increase patients' active involvement in the counseling session and increase maintained abstinence. DESIGN: Randomized trial of 27 community-based physicians using two interview styles, with observer ratings of patient active involvement and assessments of patient smoking status at 6 months, 12 months, and 30 months. PATIENTS: Adult smokers: 336 recruited; 249 for final analyses. INTERVENTION: Physicians used an autonomy- supportive or controlling interpersonal style, randomly assigned within physician, to briefly counsel patients about smoking cessation, using the National Cancer Institute's 4-A's model. MEASUREMENT: Patient active involvement was rated from audio tapes of the interviews. Continuous abstinence came from self-reports at 6 months, 12 months, and 30 months, CO validated at 6 months or 12 months and at 30 months. RESULTS: Physician style did not have a significant direct effect on smoking cessation but did significantly increase patient active involvement in the interview. Active involvement, in turn, increased smoking cessation. Structural equation modeling confirmed a theoretical model in which the intervention positively predicted patient active involvement after controlling for patient reports of wanting to stop smoking, and active involvement significantly predicted continuous abstinence after controlling for previous quit attempts. CONCLUSIONS: Although physicians' autonomy- supportive style while counseling smokers to quit did not have a direct effect on smoking cessation, it increased patients' active involvement in the counseling session which in turn increased continuous abstinence over 30 months. Further research should clarify the direct effects of physician interpersonal style on health outcomes.

Adult↗

Selective versus non-selective antiarrhythmic approach for prevention of atrial fibrillation after coronary surgery: is there a need for pre-operative risk stratification? A prospective placebo-controlled study using low-dose sotalol.

AIM: This study evaluated the advantages of 'selective' over 'non-selective' antiarrhythmic prevention of atrial fibrillation after coronary surgery based on a new risk prediction algorithm. METHODS AND RESULTS: In a retrospective analysis of a prospective randomized trial, a model for risk prediction was determined based on clinical data of the control group (A; n = 107) and tested in a test group (B; n = 107, treated with low dose sotalol). Using this algorithm, the effect of a 'selective' antiarrhythmic approach in high-risk patients was compared to a 'non-selective' approach, where all patients were treated. In total, 75 (35%) patients developed atrial fibrillation and 14 (7%) side-effects led to discontinuation of study medication. Based on the risk prediction algorithm, 36% of group A patients were classified as high-risk patients with an incidence of atrial fibrillation of 76% compared to 26% in low-risk patients (P < 0.0001). The selective approach, i.e. treatment of high-risk patients only reduced the incidence of atrial fibrillation from 76% to 50% (P = 0.0295) compared to a reduction from 44% to 26% (P = 0.0065) when all patients were treated. More importantly, with the non-selective approach 100% of patients were exposed to the possible side-effects of sotalol and costs compared to 24% only with the selective approach (P < 0.0001). CONCLUSIONS: Thus, a selective approach based on a clinical risk prediction algorithm should improve the cost-effectiveness and safety of low-dose sotalol in the prevention of atrial fibrillation after coronary bypass surgery.

Adult↗

Age- and size-related trends in woody plant shoot development: regulatory pathways and evidence for genetic control.

Woody plants exhibit significant and predictable patterns of change in morphology and physiology as they become older and larger. Four models of potential pathways controlling these changes are presented: a stimulus-response model in which fully developed organs respond to changes in environment (defined here as everything external to the organ); an extrinsic model in which the attributes of developing organs are determined by environmental factors; an intrinsic model in which changes are a result of programmed changes in gene expression; and an extrinsic-intrinsic model in which changes in gene expression are induced by environmental factors. We review evidence that a genetic component is involved in controlling age- and size-related changes in foliar morphology and physiology and discuss the possibility of complex interactions among model pathways.

Models, Biological↗

Mathematical modelling of the cellular mechanics of plants.

The complex mechanical behaviour of plant tissues reflects the complexity of their structure and material properties. Modelling has been widely used in studies of how cell walls, single cells and tissue respond to loading, both externally applied loading and loads on the cell wall resulting from changes in the pressure within fluid-filled cells. This paper reviews what approaches have been taken to modelling and simulation of cell wall, cell and tissue mechanics, and to what extent models have been successful in predicting mechanical behaviour. Advances in understanding of cell wall ultrastructure and the control of cell growth present opportunities for modelling to clarify how growth-related mechanical properties arise from wall polymeric structure and biochemistry.

Biomechanical Phenomena↗