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Use of predictive modeling to evaluate the manipulation of milking frequency, temperature, and oxygen tension on growth of Escherichia coli in an artificial intramammary environment.

A method was developed to evaluate frequent milking as a means of controlling intramammary infection. An artificial intramammary environment was used to determine growth responses of Escherichia coli (P4) to natural changes in the mammary gland resulting from bacterial invasion. Physical conditions manipulated in this model were growth medium, temperature, and oxygen tension. Mathematical modeling was then incorporated to generate predictions concerning growth dynamics of the organism when milking frequency was changed. To test accuracy of the model, initial predictions were derived from bacterial growth data in which E coli was incubated in tryptose soy broth for 12 hours at 37 C and PO2 equal to 23.3 mm of Hg. These predictions matched closely with experimental data in which 12-, 4-, and 2-hour milking intervals were simulated in the artificial intramammary environment. The mathematical model was then used to characterize growth rate data from in vitro experiments in ultra-high temperature-treated milk and in vivo experimental infection data generated with E coli (P4). Predictions generated from this model suggested that increasing milking frequency to 4 or 6 times daily controls growth of E coli for a prolonged period and that 12 times daily milking may lead to elimination of the bacterium.

Animals↗

Temperature regulation of bud-burst phenology within and among years in a young Douglas-fir (Pseudotsuga menziesii) plantation in western Washington, USA.

Past research has established that terminal buds of Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco) seedlings from many seed sources have a chilling requirement of about 1200 h at 0-5 degrees C; once chilled, temperatures > 5 degrees C force bud burst via accumulation of heat units. We tested this sequential bud-burst model in the field to determine whether terminal buds of trees in cooler microsites, which receive less heat forcing, develop more slowly than those in warmer microsites. For three years we monitored terminal bud development in young saplings as well as soil and air temperatures on large, replicated plots in a harvest unit; plots differed in microclimate based on amount of harvest residue and shade from neighboring stands. In two of three years, trees on cooler microsites broke bud 2 to 4 days earlier than those on warmer microsites, despite receiving less heat forcing from March to May each year. A simple sequential model did not predict cooler sites having earlier bud burst nor did it correctly predict the order of bud burst across the three years. We modified the basic heat-forcing model to initialize, or reset to zero, the accumulation of heat units whenever significant freezing temperature events (> or = 3 degree-hours day(-1) < 0 degrees C) occurred; this modified model correctly predicted the sequence of bud burst across years. Soil temperature alone or in combination with air temperature did not improve our predictions of bud burst. Past models of bud burst have relied heavily on data from controlled experiments with simple temperature patterns; analysis of more variable temperature patterns from our 3-year field trial, however, indicated that simple models of bud burst are inaccurate. More complex models that incorporate chilling hours, heat forcing, photoperiod and the occurrence of freeze events in the spring may be needed to predict effects of future silvicultural treatments as well to interpret the implications of climate-change scenarios. Developing and testing new models will require data from both field and controlled-environment experiments.

Ecosystem↗

Cost-effectiveness of primary prevention of coronary heart disease through risk factor intervention in 60-year-old men from the county of Stockholm--a stochastic model of exercise and dietary advice.

BACKGROUND: Recent screenings show a high prevalence of cardiovascular risk factors in the county of Stockholm. Primary prevention may be a way to lower the risk burden of coronary heart disease, but we must establish that preventive programs are cost-effective. METHODS: Through the use of a stochastic Markov model, which predicts reduction in coronary heart disease events based on risk factor reductions, this study evaluates the results of a previous controlled trial in middle-aged men comparing dietary advice, exercise, and the combination of both applied to an observed cohort of 60-year-old men in the county of Stockholm. RESULTS: The model predicts lower costs and higher effectiveness for dietary advice compared to the alternatives. Assuming a declining effect of the intervention, dietary advice saves 0.0228 life-years compared to no intervention. If no decline is assumed, the corresponding figure is 0.0997 life-years. From the societal perspective, the added costs are 2,892 Swedish Kronor (SEK) and 14,106 SEK for the two modeling assumptions, resulting in a cost-effectiveness of 127,065 SEK per life-year gained (LYG) and 141,555 SEK/LYG. These figures are below what is generally thought of as cost-effective. CONCLUSION: Based on the model, dietary advice appears to be the most cost-effective of the studied interventions.

Adult↗

Mixed modelling to characterize genotype-phenotype associations.

We propose using mixed effects models to characterize the association between multiple gene polymorphisms, environmental factors and measures of disease progression. Characterizing high-order gene-gene and gene-environment interactions presents an analytic challenge due to the large number of candidate genes and the complex, undescribed interactions among them. Several approaches have been proposed recently to reduce the number of candidate genes and post hoc approaches to identify gene-gene interactions are described. However, these approaches may be inadequate for identifying high-order interactions in the absence of main effects and generally do not permit us to control for potential confounders. We describe how mixed effects models and related testing procedures overcome these limitations and apply this approach to data from a cohort of subjects at risk for cardiovascular disease. Four (4) genetic polymorphisms in three genes of the same gene family are considered. The proposed modelling approach allows us first to test whether there is a significant genetic contribution to the variability observed in our disease outcome. This contribution may be through main effects of multi-locus genotypes or through an interaction between genotype and environmental factors. This approach also enables us to identify specific multi-locus genotypes that interact with environmental factors in predicting the outcome. Mixed effects models provide a flexible statistical framework for controlling for potential confounders and identifying interactions among multiple genes and environmental factors that explain the variability in measures of disease progression.

Adult↗

Is alexithymia distinct from health locus of control?

OBJECTIVE: Both locus of control and alexithymia have been considered personality factors fostering health concerns and behaviors. This study investigates the relationship between the health locus of control and alexithymia. METHOD: Seventy-eight psychiatric outpatients were administered the Wallston Health Locus of Control Scale (HLC), the Toronto Alexithymia Scale (HLC), and the Five Factor Inventory, which measures neuroticism, extraversion, openness, agreeableness, and conscientiousness. Depressive and anxious affect was also measured. Regression models were developed to assess the influence of the above variables upon alexithymia. RESULTS: Although there was a significant bivariant correlation between an external locus of control and increased alexithymia, regression models found that HLC did not significantly predict TAS. Neuroticism, however, provided the most significant contribution to predict increased alexithymia. CONCLUSION: Neuroticism may link HLC and TAS due to the face validity of each construct. A sense of vulnerability is stated in each measure. This may foster somatic preoccupation. The data suggest HLC and TAS to be separate phenomena and further support the validity of alexithymia as a unique personality trait.

Adult↗

Model utility in the study of cardiorespiratory control.

This study investigates the utility of differing modeling approaches to the study of cardiorespiratory control. Models are classified in terms of intended purpose. A structural model predicts behavior based on a hypothetical physiological structure. An empirical model summarizes observed behavior. A functional model attempts to relate physiological structure to observed behavior. Models from the literature for exercising man illustrate these concepts and motivate the importance of experimental design in terms of the dynamic variation of a work-rate input.

Biomedical Engineering↗

Predicting progression to AIDS. An evaluation of two approaches.

This study evaluated the predictive validity of two clinical staging systems for HIV infection (the Rabeneck and Royce systems) using data obtained from the Department of Veterans Affairs Cooperative Study Number 298, a randomized clinical trial involving 335 symptomatic patients with CD4 counts of 200 to 500/mm3. The relation between the HIV clinical stages and progression to AIDS was examined using Kaplan-Meier estimates, and Cox models were used to determine if the stages remained predictive after controlling for CD4 count. Both systems were significant independent predictors of progression to AIDS. This work demonstrates that simple, valid staging systems for HIV infection can be developed that provide greater prognostic distinction than the CD4 count alone.

Acquired Immunodeficiency Syndrome↗

Toward quantifying water pollution abatement in response to installing buffers on crop land.

The scientific research literature is reviewed (i) for evidence of how much reduction in nonpoint source pollution can be achieved by installing buffers on crop land, (ii) to summarize important factors that can affect this response, and (iii) to identify remaining major information gaps that limit our ability to make probable estimates. This review is intended to clarify the current scientific foundation of the USDA and similar buffer programs designed in part for water pollution abatement and to highlight important research needs. At this time, research reports are lacking that quantify a change in pollutant amounts (concentration and/or load) in streams or lakes in response to converting portions of cropped land to buffers. Most evidence that such a change should occur is indirect, coming from site-scale studies of individual functions of buffers that act to retain pollutants from runoff: (1) reduce surface runoff from fields, (2) filter surface runoff from fields, (3) filter groundwater runoff from fields, (4) reduce bank erosion, and (5) filter stream water. The term filter is used here to encompass the range of specific processes that act to reduce pollutant amounts in runoff flow. A consensus of experimental research on functions of buffers clearly shows that they can substantially limit sediment runoff from fields, retain sediment and sediment-bound pollutants from surface runoff, and remove nitrate N from groundwater runoff. Less certain is the magnitude of these functions compared to the cultivated crop condition that buffers would replace within the context of buffer installation programs. Other evidence suggests that buffer installation can substantially reduce bank erosion sources of sediment under certain circumstances. Studies have yet to address the degree to which buffer installation can enhance channel processes that remove pollutants from stream flow. Mathematical models offer an alternative way to develop estimates for water quality changes in response to buffer installation. Numerous site conditions and buffer design factors have been identified that can determine the magnitude of each buffer function. Accurate models must be able to account for and integrate these functions and factors over whole watersheds. At this time, only pollutant runoff and surface filtration functions have been modeled to this extent. Capability is increasing as research data is produced, models become more comprehensive, and new techniques provide means to describe variable conditions across watersheds. A great deal of professional judgment is still required to extrapolate current knowledge of buffer functions into broadly accurate estimates of water pollution abatement in response to buffer installation on crop land. Much important research remains to be done to improve this capability. The greatest need is to produce direct quantitative evidence of this response. Such data would confirm the hypothesis and enable direct testing of watershed-scale prediction models as they become available. Further study of individual pollution control functions is also needed, particularly to generate comparative evidence for how much they can be manipulated through buffer installation and management.

Agriculture↗

Early antecedents of adult work stress: social-emotional competence and anger in adolescence.

We hypothesized that youth with elevated coronary heart disease (CHD) risk who exhibit diminished social-emotional competence and frequent anger in adolescence experience increased occupational stress after becoming adults. Perceived job control and support from coworkers in 57 young Black and White men and women were regressed on measures of social problem-solving skill (SPS) and anger arousal (AR) obtained 5 years earlier when participants were in high school. In models controlling for grade point average (GPA), SPS and GPA independently predicted coworker support in adulthood; anger in high school predicted diminished job control. These findings suggest that occupational stress may have identifiable social-emotional antecedents early in life.

Adolescent↗

Home blood pressure teletransmission for better diagnosis and treatment.

The rate of control of high blood pressure is disappointing, and noncompliance is one factor that contributes to this. The reasons for poor compliance are complex and include factors related to the patient, the healthcare provider, and the medical system. In general, the lack of regular communication between the patient and the physician, as occurs in the traditional model of clinic-based care, predicts a low rate of blood pressure control. In addition, clinic-based blood pressure rates are notoriously unreliable. A solution to this dilemma is teletransmission of self- measured blood pressure readings, which offers the dual advantages of more reliable measurements, and the establishment of regular telephone communication between the patient and the healthcare provider. Preliminary evidence with this type of system suggests that blood pressure control can be improved substantially.

Antihypertensive Agents↗

Structure/function relationships of muscarinic acetylcholine receptors.

The regions of muscarinic receptors that specify G-protein-coupling and ligand-binding have been defined in several recent studies. Overall, these studies have shown that amino acids within the third cytoplasmic loop of the receptors define their selectivity for different G-proteins, and that multiple, discontinuous epitopes contribute to their selectivities for different ligands. In fact, several competitive and allosteric antagonists can be classified into groups based on which of these epitopes contribute to their subtype selectivity. Site-directed mutagenesis, combined with covalent-labeling studies have suggested that ligands bind to a hydrophobic core of the receptors that is formed by multiple transmembrane (TM) domains. An aspartic acid located in TM3 is likely to bind to the ammonium headgroup of muscarinic ligands, and multiple hydroxyl-containing amino acids contribute to agonist but not antagonist binding. These data are discussed in the context of a computational model of a muscarinic receptor. Our model is based on a sequence alignment with bacteriorhodopsin, a seven TM protein for which a higher resolution structure is available. Most of the mutagenic data can be rationalized in the context of this model, and predict testable hypotheses concerning the mechanism by which ligands control the activity of muscarinic receptors.

Animals↗

Risk assessment of antibiotic residues of beta-lactams and macrolides in food products with regard to their immuno-allergic potential.

In human medicine drug allergy is a well-established side-effect of the therapeutic use of antibiotics, especially the beta-lactams. Side-effects caused by macrolides are uncommon and only a very few of these seem to be caused by allergic mechanisms. Clinically, drug allergy is characterized by a spectrum of reactions ranging from mild skin rashes to angio-oedema or life-threatening anaphylaxis. Concern has been expressed that antibiotic residues in meat and other foods might be responsible for similar hypersensitivity reactions in a small number of individuals. This review assesses the potential risk of such reactions in general, but focuses on allergy to penicillin and macrolide residues in particular. In relation to the risk of primary sensitization, it is unlikely that residues could contribute to the overall immune response in view of the very low levels that are likely to be encountered in comparison with the high levels received during therapeutic use. No evidence has been found that any individual has become sensitized by residues of either penicillins or macrolides. Furthermore, the oral route is much less sensitizing than parenteral administration and immunochemical studies with penicillin indicate that hapten-protein complexes formed in vivo are unlikely to be immunogenic because of their low dose, low epitope density and binding to autologous carrier proteins. For performed allergens, the epitope density was also too low to be immunogenic. Because of the ubiquitous nature of penicillin-producing moulds in nature and the extensive use of beta-lactam antibiotics in human medicine, it is unlikely that epidemiological studies could be undertaken that could allow quantification of the minimal risk. The risk of allergic reactions in pre-sensitized individuals can be assessed similarly and again it is concluded that factors such as dose, oral administration and low epitope density make it unlikely that a significantly antigenic derivative could be formed. However, a review of the literature on penicillin hypersensitivity revealed a very small number of previously sensitized individuals from whom there is reasonable clinical and documentary evidence that penicillin residues in milk triggered an allergic reaction, usually a rash. Although these cases are very rare (less than 10 cases reported in the last 25 years), they illustrate the continuing need to control antibiotic residues vigilantly. Animal models have not proved useful for predicting the risk of hypersensitivity reactions to drugs, since allergy in man is determined by genetic and other factors and no validated methods exist to determine a no-effect level.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Radioresponsiveness, sublethal damage repair and stem cell rate in spheroids from three human tumor lines: comparison with xenograft data.

Dose-control curves after fractionated irradiation were generated for small oxic spheroids from the two human glioma cell lines, U87 and A7, as well as the squamous cell carcinoma line FaDu. These data were fitted by the linear quadratic model assuming Poisson statistics. The alpha/beta values of A7, U87, and FaDu spheroids, respectively were 10.3 (8.1-12.9) Gy, 17.8 (15.1-21.1) Gy, and 37.9 (29.1-51.5) Gy. These data were compared with those previously published by Suit et al. (31) and Zietman et al. (40) for 6 mm xenografts of U87 and FaDu after fractionated irradiation and for A7 after single dose irradiation under clamped conditions. A good agreement in the alpha/beta values was observed for U87 and Fadu xenografts and spheroids assuming an oxygen enhancement ratio (OER) of 2.7. In addition, the ranking according to the single doses needed to control 50% of the tumors agreed for xenografts and spheroids from the three cell lines. U87 was the most resistant line in both model systems, followed by A7 and FaDu. However, the absolute values of alpha and beta, obtained from the direct fit to the dose-control data were only about half as high for U87 and FaDu xenografts than for the spheroids. Monte Carlo simulations showed that this discrepancy can be explained by a greater tumor heterogeneity of the xenografts. While the number of critical stem cells or spheroid rescuing units equaled the number of cells per spheroid for the three cell lines, the percentage of tumor rescuing units for Fadu and U87 xenografts was estimated to be below 1%. In a next step, survival curves were generated for exponentially growing cells of the three lines. A7 cells were significantly more radioresistant when plated on tissue plastic than in soft agar. Using the most resistance-promoting colony assay conditions for each cell line, a good agreement was observed for the alpha and SF2Gy values calculated from the colony and spheroid control data. This study shows that the spheroid model can quantitatively predict the repair capacity of sublethal damage as well as the rank order of radiation sensitivity of in vivo tumors.

Animals↗

Modeling aggressive driver behavior at unsignalized intersections.

The processing of vehicles at unsignalized intersections is a complex and highly interactive process, whereby each driver makes individual decisions about when, where, and how to complete the required maneuver, subject to his perceptions of distances, velocities, and own car's performance. Typically, the performance of priority-unsignalized intersections has been modeled with probabilistic approaches that consider the distribution of gaps in the major-traffic stream and their acceptance by the drivers of minor street vehicles based on the driver's "critical gap". This paper investigates the aggressive behavior of minor street vehicles at intersections that are priority-unsignalized but operate with little respect of control measures. The objective is to formulate a behavioral model that predicts the probability that a driver performs an aggressive maneuver as a function of a set of driver and traffic attributes. Parameters that were tested and modeled include driver characteristics (gender and age), car characteristics (performance and model year), and traffic attributes (number of rejected gaps, total waiting time at head of queue, and major-traffic speed). Binary probit models are developed and tested, based on a collected data set from an unsignalized intersection in the city of Beirut, to determine which of the studied variables are statistically significant in determining the aggressiveness of a specific driver. Primary conclusions reveal that age, car performance, and average speed on the major road are the major determinants of aggressive behavior. Another striking conclusion is that the total waiting time of the driver while waiting for an acceptable gap is of little significance in incurring the "forcing" behavior. The obtained model is incorporated in a simple simulation framework that reflects driver behavior and traffic stream interactions in estimating delay and conflict measures at unsignalized intersections. The simulation results were then compared against real world observations, representing an important step in validating the model of aggressive driver behavior at unsignalized intersections.

Age Factors↗

Adhesion design maps for bio-inspired attachment systems.

Fibrous surface structures can improve the adhesion of objects to other surfaces. Animals, such as flies and geckos, take advantage of this principle by developing "hairy" contact structures which ensure controlled and repeatable adhesion and detachment. Mathematical models for fiber adhesion predict pronounced dependencies of contact performance on the geometry and the elastic properties of the fibers. In this paper the limits of such contacts imposed by fiber strength, fiber condensation, compliance, and ideal contact strength are modeled for spherical contact tips. Based on this, we introduce the concept of "adhesion design maps" which visualize the predicted mechanical behavior. The maps are useful for understanding biological systems and for guiding experimentation to achieve optimum artificial contacts.

Adhesiveness↗

Skin cholesterol content identifies increased carotid intima-media thickness in asymptomatic adults.

BACKGROUND: A noninvasive assay to measure skin Tc recently has become available for use in the outpatient setting as a cardiovascular (CV) risk prediction tool. The purpose of this study was to determine whether skin tissue cholesterol content (skin Tc) levels are associated with increased carotid intima-media thickness (CIMT) after adjusting for known CV risk factors and Framingham CV risk. METHODS: Consecutive patients without known vascular disease who were referred for determination of CIMT underwent B-mode ultrasonography of the carotid arteries and measurement of skin Tc using a noninvasive assay. Use of medications, cardiac risk factors, and Framingham 10-year CV risk were determined prospectively. Multivariable regression was used to determine predictors of increased CIMT. RESULTS: Among 81 subjects, the mean (SD) age was 55.6 (7.7) years and the mean skin Tc was 95.9 (18.3) U. Carotid intima-media thickness was significantly higher among individuals in the highest quartile of skin Tc (0.87 vs 0.76 mm, P = .011). In multivariable analyses, skin Tc was associated with increased CIMT even after adjusting for age, sex, glucose, systolic blood pressure, total/high-density lipoprotein cholesterol ratio, and use of lipid-lowering therapy (odds ratio [OR] per 10-unit increase = 1.590, 95% CI 1.525-1.658, P = .031). Skin Tc also was associated with increased CIMT after adjustment for Framingham risk (OR = 1.341, 95% CI 1.302-1.380, P = .048). CONCLUSIONS: Skin Tc is an easy-to-measure, noninvasive marker that can help identify subclinical atherosclerosis in asymptomatic middle-aged adults, even after controlling for risk factors and CV risk predicted by the Framingham model.

Adult↗

Operative mortality after conventional versus coronary revascularization without cardiopulmonary bypass.

OBJECTIVE: Off-pump coronary artery bypass (CABG) is a safe revascularization option with comparable or superior results to the conventional on-pump CABG. However, comparative analysis of the type of surgical approach on the mortality rate is largely unknown. This study sought to investigate whether CABG without cardiopulmonary bypass (off-pump CABG) is associated with lower operative mortality than the conventional on-cardiopulmonary bypass (on-pump) approach. METHODS: From October 1998 to June 2001, off-pump CABG was performed on 2477 patients and on-pump CABG was performed on 3077 patients. The patients undergoing off-pump CABG were randomly matched to on-pump patients via propensity score. Seventy-four percent of the off-pump CABG patients were matched with on-pump patients via propensity scores. A logistic regression model was used to test the difference in the postoperative mortality rate between off-pump CABG and on-pump CABG, controlling the correlation between matched sets. A multiple logistic regression model predicting the risk of mortality adjusted by risk factors of mortality and operation type was computed. RESULTS: Results from the general estimating equation showed that patients who had on-pump CABG were 1.6 (95% confidence intervals (CI)=1.2-2.0, P<0.01) times more likely to die during the first 30 days after surgery than patients who had off-pump CABG. Independent predictors of 30-day mortality identified from the multiple logistic model included on-pump CABG (versus off-pump CABG), advanced age, female gender, carotid artery disease, chronic renal failure, depressed ejection fraction, reoperative CABG, preoperative intraaortic balloon counterpulsation, and recent myocardial infarction. CONCLUSION: Excellent clinical results and a lower operative mortality rate can be achieved with the off-pump CABG technique compared with the conventional on-pump approach.

Aged↗

Outcomes for women with co-occurring disorders and trauma: program and person-level effects.

Six-month outcomes are evaluated from a 9-site quasi-experimental study of women with mental health and substance use disorders who have experienced physical or sexual abuse who enrolled in either comprehensive, integrated, trauma-informed, and consumer/survivor/recovering person-involved services (N = 1023) or usual care (N = 983). Mental health, post-traumatic stress symptoms, and substance use outcomes are assessed with multilevel regression models, controlling for program and personal characteristics. Person-level variables predict outcomes independent of intervention condition and, to a small extent, moderate intervention and program effects. In sites where the intervention condition provided more integrated counseling than the comparison condition, there are increased effects on mental health and substance use outcomes; these effects are partially mediated by person-level variables. These results encourage further research to identify the longer-term effects of integrated counseling for women with co-occurring disorders and trauma histories.

Adult↗