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Predicting malaria infection in Gambian children from satellite data and bed net use surveys: the importance of spatial correlation in the interpretation of results.

In line with the renewed World Health Organization Global Malaria Control Strategy, we have advocated the use of satellite imagery by control services to provide environmental information for malaria stratification, monitoring, and early warning. To achieve this operationally, appropriate methodologies must be developed for integrating environmental and epidemiologic data into models that can be used by decision-makers for improved resource allocation. Using methodologies developed for the Famine Early Warning Systems and spatial statistics, we show a significant association between age related malaria infection in Gambian children and the amount of seasonal environmental greenness as measured using the normalized difference vegetation index derived from satellite data. The resulting model is used to predict changes in malaria prevalence rates in children resulting from different bed net control scenarios.

Animals↗

Experimental and in silico analyses of glycolytic flux control in bloodstream form Trypanosoma brucei.

A mathematical model of glycolysis in bloodstream form Trypanosoma brucei was developed previously on the basis of all available enzyme kinetic data (Bakker, B. M., Michels, P. A. M., Opperdoes, F. R., and Westerhoff, H. V. (1997) J. Biol. Chem. 272, 3207-3215). The model predicted correctly the fluxes and cellular metabolite concentrations as measured in non-growing trypanosomes and the major contribution to the flux control exerted by the plasma membrane glucose transporter. Surprisingly, a large overcapacity was predicted for hexokinase (HXK), phosphofructokinase (PFK), and pyruvate kinase (PYK). Here, we present our further analysis of the control of glycolytic flux in bloodstream form T. brucei. First, the model was optimized and extended with recent information about the kinetics of enzymes and their activities as measured in lysates of in vitro cultured growing trypanosomes. Second, the concentrations of five glycolytic enzymes (HXK, PFK, phosphoglycerate mutase, enolase, and PYK) in trypanosomes were changed by RNA interference. The effects of the knockdown of these enzymes on the growth, activities, and levels of various enzymes and glycolytic flux were studied and compared with model predictions. Data thus obtained support the conclusion from the in silico analysis that HXK, PFK, and PYK are in excess, albeit less than predicted. Interestingly, depletion of PFK and enolase had an effect on the activity (but not, or to a lesser extent, expression) of some other glycolytic enzymes. Enzymes located both in the glycosomes (the peroxisome-like organelles harboring the first seven enzymes of the glycolytic pathway of trypanosomes) and in the cytosol were affected. These data suggest the existence of novel regulatory mechanisms operating in trypanosome glycolysis.

Animals↗

Predictors of early grade retention among children in the United States.

BACKGROUND: Despite increasing concerns regarding school readiness, little is known about child health correlates of early school failure among the general child population. The results of this study, conducted to investigate health and social factors associated with early grade retention in a nationally representative sample of children in the United States, are reported here. DESIGN: Analyses of data derived from interviews with parents of 9996 children ages 7 to 17 years who participated in the Child Health Supplement to the 1988 National Health Interview Survey. MAIN OUTCOME MEASURES: History of repeating kindergarten or first grade. RESULTS: Nationally, 7.6% of children repeated kindergarten or first grade. In a logistic regression model, factors independently associated with increased risk of grade retention were: poverty [Odds Ratio (OR) 1.7, 95% confidence interval (CI) 1.4, 2.1], male gender (OR 1.5, CI 1.3, 1.9), low maternal education (OR 1.4, CI 1.1, 1.8); deafness (OR 1.9, CI 1.4, 2.6), speech defects (OR 1.7, CI 1.1, 2.6), low birth weight (OR 1.6, CI 1.2, 2.2), enuresis (OR 1.6, CI 1.1, 2.2), and exposure to household smoking (OR 1.4, CI 1.1, 1.7). High maternal education (OR 0.6 CI 0.4, 0.9) and residence with both biological parents at age 6 years (OR 0.7, CI 0.6, 0.9) were independently associated with a decreased risk of retention. Recurrent otitis media, black race, and low maternal age, although associated with early grade retention in bivariate analyses, were not independently associated with grade retention in a model that controls for these other factors and for the age cohort of the child. Although omitted from the above predictive model because of uncertainty about its temporal relation to early grade retention in this dataset, behavior problems at the time of interview have a strong independent association (OR 1.9, CI 1.5, 2.5) with prior early retention. CONCLUSIONS: This is the first study that uses national data to investigate how health and social factors individually and collectively contribute to early grade retention. It demonstrates that early retention is common, that a number of extremely common child health problems are independently associated with it, and that the magnitude of the heightened risk associated with these problems is similar to that of many of the well-recognized and difficult to change family and social risk factors for early retention. The successful implementations of Pub L 99-457 (The Education for All Handicapped Children Act Amendments of 1986) services in communities nationwide, and the improvement in the educational performance of large numbers of children will be facilitated by pediatricians' advocacy and surveillance for problems that place children at risk for educational failure, and by effective referral to and collaboration with nonpediatric child and family services.

Adolescent↗

Protection and vulnerability processes relevant for early onset of substance use: a test among African American children.

This research tested predictions from a self-regulation model of factors relevant for early onset of tobacco and alcohol use with a community sample of 889 African American children (mean age = 10.5 years). Criterion variables were peer substance use, willingness to use substances, and resistance efficacy (intention to refuse substance offers). Structural modeling indicated effects of temperament dimensions were mediated through self-control and risk-taking constructs, which were related to school involvement, life events, and perceived vulnerability to harmful effects of substances. Peer use was predicted by life events, poor self-control, and parent-child conflict; willingness was predicted by life events, risk taking, and (inversely) parental support; and resistance efficacy was predicted by perceived vulnerability and (inversely) poor self-control. Findings are discussed with reference to theoretical models of early protection and vulnerability processes.

Black or African American↗

Disclosure of HIV status and sexual orientation independently predicts increased absolute CD4 cell counts over time for psychiatric patients.

OBJECTIVE: The objective of this study was to replicate the relationship between disclosure of sexual orientation and immune functioning in HIV-positive persons and to extend those findings to a different type of disclosure (HIV status) and a different population (psychiatric outpatients in a publicly funded HIV/AIDS clinic). METHODS: A sample of psychiatric outpatients (N = 373) from a large, urban HIV clinic was assessed for level of sexual orientation and HIV status disclosure as well as absolute CD4 cell counts over time. Mixed-effects random regression analysis was used to build a predictor model that included biobehavioral covariates. RESULTS: Consistent disclosure of both sexual orientation and HIV status independently predicted increased CD4 cell counts over time controlling for important biobehavioral covariates. The only other significant effects in the model were baseline CD4 cell count and number of days between assessment of disclosure and assessment of CD4 cell count. CONCLUSIONS: Relieving potential psychological distress by disclosing sexual orientation and HIV status has a positive impact on CD4 cell counts over time even among outpatients stressed by psychiatric illness and economic disadvantage. Additional research is needed to understand whether and under what conditions disclosure should be part of HIV disease management.

Adult↗

Quantitative analysis of the CD8+ T-cell response to readily eliminated and persistent viruses.

The recent development of techniques for the direct staining of peptide-specific CD8+ T cells has revolutionized the analysis of cell-mediated immunity (CMI) in virus infections. This approach has been used to quantify the acute and long-term consequences of infecting laboratory mice with the readily eliminated influenza A viruses (fluA) and a persistent gammaherpesvirus (gammaHV). It is now, for the first time, possible to work with real numbers in the analysis of CD8+ T CMI, and to define various characteristics of the responding lymphocytes both by direct flow cytometric analysis and by sorting for further in vitro manipulation. Relatively little has yet been done from the latter aspect, though we are rapidly accumulating a mass of numerical data. The acute, antigen-driven phases of the fluA and gammaHV-specific response look rather similar, but CD8+ T-cell numbers are maintained in the long term at a higher 'set point' in the persistent infection. Similarly, these 'memory' T cells continue to divide at a much greater rate in the gammaHV-infected mice. New insights have also been generated on the nature of the recall response following secondary challenge in both experimental systems, and the extent of protection conferred by large numbers of virus-specific CD8+ T cells has been determined. However, there are still many parameters that have received little attention, partly because they are difficult to measure. These include the rate of antigen-specific CD8+ T-cell loss, the extent of the lymphocyte 'diaspora' to other tissues, and the diversity of functional characteristics, turnover rates, clonal life spans and recirculation profiles. The basic question for immunologists remains how we reconcile the extraordinary plasticity of the immune system with the mechanisms that maintain a stable milieu interieur. This new capacity to quantify CD8+ T-cell responses in readily manipulated mouse models has obvious potential for illuminating homeostatic control, particularly if the experimental approaches to the problem are designed in the context of appropriate predictive models.

Animals↗

Comparison of an in vitro cellular phototoxicity model against controlled clinical trials of fluoroquinolone skin phototoxicity.

Many therapeutic drugs induce phototoxic skin responses following exposure to solar or artificial ultraviolet radiation sources. Several in vitro model systems have been developed to predict drug phototoxicity but none have been conducted in parallel with controlled clinical phototoxicity studies on systemically administered pharmaceuticals. The in vitro phototoxicity of eight fluoroquinolone (FQ) antibiotics (ciprofloxacin, grepafloxacin, lomefloxacin, norfloxacin, ofloxacin, trovafloxacin, BAYy3118, moxifloxacin) was determined by exposing Chinese hamster fibroblasts to UVA radiation. Cell damage was quantified with standard MTT or neutral red assays and an in vitro phototoxic index calculated (PI(vit)=% cell viability with UVA alone /% cell viability with UVA+FQ) for each endpoint. Clinical photosensitizing ability of the eight systemically administered FQ was investigated using double-blind, placebo and positive controlled, clinical skin phototesting of normal subjects. Minimal erythema doses at 365+/-30nm were determined before and after 6-7 days of FQ ingestion and PI(clin) (minimal erythema dose without FQ/minimal erythema dose with FQ) calculated. Linear regression analysis of PI(vit) vs PI(clin) gave correlations of up to 0.893. Principal components analysis of PI(vit), daily dose, plasma levels and photophysical (absorption) properties of the eight FQ showed that phototoxic (arbitrarily defined as PI(clin)> or =2) and non-phototoxic (PI(clin)<2) FQ could be completely discriminated using these parameters, and that the in vitro models were able to rank the relative phototoxic potential of the eight FQ.

Animals↗

Familial aggregation in the night eating syndrome.

OBJECTIVE: This study examined the extent to which the night eating syndrome (NES) affects first-degree relatives of NES and control probands. METHOD: NES participants and controls were assessed with the Night Eating Questionnaire (NEQ), the Night Eating Syndrome History and Inventory (NESHI), 10 day sleep and food records, the Eating Disorder Examination (EDE), the Structured Clinical Interview for DSM IV Axis I Disorders (SCID I), and a Family History Questionnaire (FHQ) to assess the presence of NES among first-degree relatives. A proband predictive model, using logistic regression analyses and the generalized estimating equation to control for correlation among observations within families was used to assess familial aggregation. RESULTS: The odds of an NES proband having an affected first-degree relative were significantly greater than that of a control proband (odds ratio=4.9, p<.001). A number of covariates were included in the model: proband body mass index (BMI) (kg/m2), proband gender, proband age, proband ethnicity, first-degree relative gender, relationship to proband (i.e., mother, father, or sibling), and the interaction between relationship to proband and proband status (night eater or control); none was statistically significant (p>.05). CONCLUSION: The study showed a strong aggregation of NES in families.

Adult↗

On allosteric control model of bone turnover cycle containing osteocyte regulation loop.

One approach to developing a mathematical model that predicts osteoactivity both in bio-scaffolds, as well as the in bone tissue in vivo, is based on a bio-cybernetic vision of basic multicellular unit (BMU) action. In the case of the model presented in this paper, some of the loops of regulation have been modified to reflect the range of allosteric control mechanisms: Michaelis-Menten, Hill, Adair, Koshland-Nemethy-Filmer (KNF), Monod-Wyman-Changeux (MWC). This approach has resulted in a four-dimensional system that shows steady cyclic behaviour using a range of constants with clear biological meaning. The initial findings suggesting that a steady state appears as a cycle in multidimensional phase space and this is discussed in this paper. The existence of this cycle in the osteoclasts-osteoblasts-osteocytes-bone subspace indicates that there is a conservative value along steady trajectories for this dynamic system. Biophysical interpretation of this conservative value has been proposed as a kind of substrate-energy regenerative potential of the bone remodelling system with a similarity to the classical physical value-energy. Such a recovery "potential" is directed against both mechanical and biomechanical damage to the bone. The current model has credibility when compared to the normal bone remodelling process. In the framework of widely recognised Michaelis-Menten mechanisms of allosteric regulation the cyclic attractor, described formerly for a pure cellular model, prevails for different forms of feedback control. This finding demonstrates the viability of the suggestion of the subsistence of conservative value (analogous to energy) that characterises the recovery potential of the bone remodelling cycle. The results indicate that the robust behaviour of the model is maintained from the simple cellular level to the molecular biochemical level of regulation.

Allosteric Site↗

Predicting the emission rate of volatile organic compounds from vinyl flooring.

A model for predicting the rate at which a volatile organic compound (VOC) is emitted from a diffusion-controlled material is validated for three contaminants (n-pentadecane, n-tetradecane, and phenol) found in vinyl flooring (VF). Model parameters are the initial VOC concentration in the material phase (C0), the material/air partition coefficient (K), and the material-phase diffusion coefficient (D). The model was verified by comparing predicted gas-phase concentrations to data obtained during small-scale chamber tests and by comparing predicted material-phase concentrations to those measured at the conclusion of the chamber tests. Chamber tests were conducted with the VF placed top-side-up and bottom-side-up. With the exception of phenol and within the limits of experimental precision, the mass of VOCs recovered in the gas-phase balances the mass emitted from the material phase. The model parameters (C0, K, and D) were measured using procedures completely independent of the chamber test. Gas- and material-phase predictions compare well to the bottom-side-up chamber data. The lower emission rates for the top-side-up orientation may be explained by the presence of a low-permeability surface layer. The sink effect of the stainless steel chamber surface was shown to be negligible.

Air Pollution, Indoor↗

[Changes in phospho-calcium metabolic factors in function of the rate of bone turnover. Epidemiologic study of osteoporosis (part 2)].

BACKGROUND: The recent development of highly accurate and precise osseous mass quantitative evaluation methodology, permits the conduction, in the sphere of osteoporosis, of epidemiologic investigations no longer limited solely to fracture complications, but also based on the definition of osseous mass. Fractures being only complications, possible but not certain, of the advanced stages of the disease, the studies based on their incidence allow one to underestimate the global entity of prevalence and incidence, besides building only a partially useful reference in view of primary and secondary prevention. METHODS: The main points of our study are the following: 1) evaluation of the incidence of the primary risk factors for osteoporosis as they appear in the literature, on the bone mass values of examined subjects, utilizing static mineralometric data as a reference standard; 2) study of biohumoral data relative to phospho-calcium metabolism and to sexual function, to show the possibility of their use as early identifying markers of subjects at risk; reference values represented by dynamic mineralometric data. The principal conclusions that emerged in the course of the study are the following. RESULTS: In relation to the use of phospho-calcium metabolic biohumoral and hormonal variables, as a predictive function on the variations of bone turnover, the variables; osteocalcin, alkaline phosphatase, alkaline phosphatase bone isoenzyme, hydroxyprolinuria/ creatininuria, have resulted significantly different in the comparison between high and low turnover subjects. The degree of quantitative correlation of such variables with the entity of percentage decrement of bone mass has been modest. The overall value of R-square of the predictive model, besides the variables mentioned the value of bone mass at 1 degree control visit, was 0.38 (osteocalcin: 0.27; osteocalcin+hydroxyprolinuria/ creatininuria: 0.33; preceding variables+bone mass at 1st control: 0.36; preceding variables+alkaline phosphatase: 0.37; preceding variables+alkaline phosphatase bone isoenzyme: 0.38). CONCLUSIONS: The single value osteocalcin may furnish indications on the future variations of bone turnover and consequently on the early identification of the subjects at risk for osteoporosis at high turnover; the addition of the other variables indicated in our predictive model allows an increase of the possibilities of individualizing of these subjects.

Adult↗

Optimal posture control of a musculo-skeletal arm model.

In this paper maximal performance posture control of the human arm is investigated by means of model simulations. Recent experiments (F.C.T. van der Helm, submitted, 2000) have shown that the reflexive feedback during postural control varies with the bandwidth of the applied force disturbances. This paper focusses on the influence of the frequency content of force disturbances on the reflexive feedback gains by means of optimization. The arm is modelled by a nonlinear musculo-skeletal model with two degrees of freedom and six muscles. To facilitate the optimization of the model parameters, the arm model is linearized. A performance criterion is minimized for stochastic force disturbances in a two-step procedure: (1) optimization of static muscle activations using an additional energy criterion to obtain a unique and energy-efficient solution; antid (2) optimization of reflex gains using an additional control effort criterion to obtain a unique solution. The optimization reveals that for the given task and posture, the shoulder muscles have the largest contribution, whereas the bi-articular muscles have a relatively small contribution to the behaviour. The dynamics at the endpoint level are estimated so that a comparison can be made with the experiments. Compared to the experiments, the intrinsic damping of the model is relatively large (about 150%), whereas the intrinsic stiffness is relatively small (about 60%). These differences can be attributed to unmodelled mechanical effects of crossbridges in Hill-type muscle models. The optimized reflex gains show remarkable similarities with the values found in the experiments, implying that humans can adjust their reflexive feedback gains in an optimal way, weighting the performance and energy. The approach in this paper could be useful in the study of various posture tasks, for example in the prediction of the relation between the control parameters of various musculo-skeletal models and different experimental variables.

Arm↗

Insulin kinetics, models, and delivery schedules.

Several insulin models are examined as to their responses to various insulin inputs and glucose utilization and production control. It is shown that the action of insulin on glucose utilization correlates best with model compartments having a 30--50-min delay compared with plasma, whereas glucose production control is rapid. It is further shown that whereas the predicted plasma insulin response curves are nearly the same for various models, the responses at possible sites of action (e.g., receptors or slowly exchanging tissues) can differ considerably for the different models. By determining the parameter values for the glucose-insulin system in a patient through isotope kinetics studies, it is possible to use the patient's model either as a direct algorithm for insulin delivery or as a tool for studying glucose control under various conditions and thus aid in the design of appropriate algorithms or schedules for insulin delivery.

Animals↗

Metalearning and neuromodulation.

This paper presents a computational theory on the roles of the ascending neuromodulatory systems from the viewpoint that they mediate the global signals that regulate the distributed learning mechanisms in the brain. Based on the review of experimental data and theoretical models, it is proposed that dopamine signals the error in reward prediction, serotonin controls the time scale of reward prediction, noradrenaline controls the randomness in action selection, and acetylcholine controls the speed of memory update. The possible interactions between those neuromodulators and the environment are predicted on the basis of computational theory of metalearning.

Algorithms↗

To verify four 5-year-old mathematical models to predict the outcome of ICU patients.

AIM: The aim of this study is to verify calibration and discrimination after 5 years in the case mix of patients admitted to the Intensive Care Unit (ICU) during the year 2000. In this way we want to perform a quality control of our ICU in order to justify the increased amount of money spent for intensive care. METHODS: A prospective study has been made on the 357 patients admitted to the ICU during the year 2000. The Apache II score was calculated within the first 24 hours and, depending on the length of stay in the ICU, on the 5(th), 10(th) and 15(th) day after ICU admission. On the basis of the 4 mathematical models death risk has been calculated for each of the 4 times. The Hosmer-Lemeshow test was performed for calibration and ROC curves for discrimination, always for each of the 4 mathematical models. RESULTS: The 1(st) model, at 24 hours from ICU admission, showed a bad calibration (p=0.000088), while the ROC curve was 0.744+/-0.32. Also the 2(nd) model, at the 5(th) day from admission, showed a bad calibration (p=0.000588), with ROC curve of 0.827+/-0.04. The 3(rd) model (10(th) day), was well calibrated (p=0.112247) and discriminating (ROC=0.888 +/-0.04). Finally the models at 15 days showed again a bad calibration (p=0.001422) but a very good discrimination (area=0.906+/-0.06). CONCLUSION: Developing mathematical models to predict mortality within ICUs can be useful to assess quality of care, even if these models should not be the only ICU quality controls, but must be accompanied by other indicators, looking at quality of life of the patients after ICU discharge.

Critical Care↗

Domain and facet personality predictors of all-cause mortality among Medicare patients aged 65 to 100.

OBJECTIVES: Our objectives were to test whether Conscientiousness, the other 4 domains of the Five-Factor Model, and their facets predicted mortality in older, frail individuals. METHODS: Controlling for demographic and health measures, we used Cox regression to test whether the NEO Five-Factor Inventory (NEO-FFI) Neuroticism, Extraversion, Openness to Experience, Agreeableness, and Conscientiousness domains predicted all-cause mortality over 5 years in 1076 65- to 100-year-old participants who took part in a Medicare Demonstration study. Supplementary analyses on 597 participants aged 66 to 102 who were reassessed 2 years later were conducted to determine whether any of the Revised NEO Personality Inventory (NEO-PI-R) facets were related to mortality. RESULTS: When personality domains were treated as continuous variables, NEO-FFI Neuroticism and Agreeableness were significant protective factors. When personality domains were trichotomized, NEO-FFI Conscientiousness was a protective factor. In a third analysis, Agreeableness was not a significant predictor in a model that included the continuous Neuroticism and trichotomized Conscientiousness variables. Analysis of the NEO-PI-R Neuroticism, Agreeableness, and Conscientiousness factors showed that Agreeableness and Conscientiousness were protective and that there was a trend for a similar effect of Neuroticism. Facet-level analyses revealed that the Impulsiveness, Straightforwardness, and Self-Discipline facets of Neuroticism, Agreeableness, and Conscientiousness, respectively, were prospectively related to greater survival over a 3-year interval. CONCLUSION: The effects of Neuroticism and Agreeableness on mortality are inconsistent across previous studies. This study indicates that, in a sample of older, frail participants, high Neuroticism and Agreeableness scores are protective and that more specific effects are primarily the result of the Impulsiveness and Straightforwardness facet scales. The Conscientiousness findings are consistent with those in earlier studies and demonstrate the importance of the Self-Discipline facet.

Activities of Daily Living↗

Solubilization rates of oils in surfactant solutions and their relationship to mass transport in emulsions.

Information on solubilization rates of oils in aqueous micellar solutions is reviewed. For ionic surfactants electrostatic repulsion prevents close approach of micelles to the oil-water interface, so that solubilization results from oil molecules dissolving individually in the solution and being taken up by micelles during and/or after transport across a diffusion boundary layer to the bulk solution. Experiments with SDS solutions and single oil drops having low (but not negligible) solubility indicate that mass transfer is often not rate-controlling. Instead phenomena near the oil-water interface including, but not limited to, the rates of micellar uptake of oil from the aqueous solution seem to control the solubilization rate. In contrast, Ostwald ripening experiments involving multiple oil drops in SDS solutions are often interpreted in terms of molecular dissolution and diffusion alone since ripening rates are typically only slightly different from those observed in the absence of surfactant micelles, where this mechanism is considered to hold. For many nonionic surfactant systems and oils of low or negligible solubility the principal mechanism of solubilization is incorporation of surfactant at the oil-water interface from micelles, which coalesce or "adsorb" at the interface or else dissociate nearby, permitting individual surfactant molecules to be adsorbed. Subsequently the excess surfactant is emitted as oil-containing micelles. Most experiments have indicated that this process, which appears in the analyses as an interfacial resistance, is rate controlling. New results are presented here supporting this model and showing that resistance to mass transfer is often quite low because natural convection can arise near an oil drop owing to the density change produced by solubilized oil in micelles near the drop surface. Provided that polydispersity of drop sizes is properly accounted for, experiments on solubilization and compositional ripening in emulsions stabilized with nonionic surfactants can be interpreted using the interfacial resistance model with values of resistance obtained from single-drop experiments. However, it is unclear whether mass transfer, interfacial resistance or perhaps some combined mechanism controls the rate of Ostwald ripening. One uncertainty limiting predictions of the interfacial resistance model is the lack of information on the oil-to-surfactant ratio in micelles when the concentration of individually dissolved oil molecules slightly exceeds the equilibrium value for a plane oil-water interface, the situation during Ostwald ripening.

Journal Article↗

Safety evaluation of sous vide-processed products with respect to nonproteolytic Clostridium botulinum by use of challenge studies and predictive microbiological models.

Sixteen different types of sous vide-processed products were evaluated for safety with respect to nonproteolytic group II Clostridium botulinum by using challenge tests with low (2. 0-log-CFU/kg) and high (5.3-log-CFU/kg) inocula and two currently available predictive microbiological models, Food MicroModel (FMM) and Pathogen Modeling Program (PMP). After thermal processing, the products were stored at 4 and 8 degrees C and examined for the presence of botulinal spores and neurotoxin on the sell-by date and 7 days after the sell-by date. Most of the thermal processes were found to be inadequate for eliminating spores, even in low-inoculum samples. Only 2 of the 16 products were found to be negative for botulinal spores and neurotoxin at both sampling times. Two products at the high inoculum level showed toxigenesis during storage at 8 degrees C, one of them at the sell-by date. The predictions generated by both the FMM thermal death model and the FMM and PMP growth models were found to be inconsistent with the observed results in a majority of the challenges. The inaccurate predictions were caused by the limited number and range of the controlling factors in the models. Based on this study, it was concluded that the safety of sous vide products needs to be carefully evaluated product by product. Time-temperature combinations used in thermal treatments should be reevaluated to increase the efficiency of processing, and the use of additional antibotulinal hurdles, such as biopreservatives, should be assessed.

Botulinum Toxins↗