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PubMed1997

Ganglioside hydration study by 2H-NMR: dependence on temperature and water/lipid ratio.

Dynamic properties of 2H2O in samples of ganglioside aggregates hydrated at water/lipid ratios ranging from 25:1 to 8000:1 mole/mole were studied by using deuterium nuclear magnetic resonance (2H-NMR). We present a physical model for the interpretation of the measured spin-spin relaxation times (T2). For all the concentrations studied the model provides evidence for the existence of at least two kinds of water environments: one in which the rotational correlation time is in the range of 10(-9) to 10(-8) s, and a second in which it lies between 10(-11) to 10(-10) s. A detailed study on the temperature dependence was performed for two of the concentrations, one corresponding to the hexagonal phase (100:1 mole/mole) and the other involving a micellar phase (200:1 mole/mole). In the 100:1 2H2O/ganglioside molar ratio sample, most of the water is tightly bound to long cylindrical structures. For the 200: 1 sample, there are on average approximately 30 water molecules tightly bound to the polar head group of each ganglioside molecule. The relative number and dynamics of molecules in this environment are essentially insensitive to temperature variations in the range 220-300K The rest of water molecules are also influenced by the aggregate, having a different mobility from that observed in the free liquid state.

Animals↗

PubMed1994

Modeling methodology for vascular input impedance determination and interpretation.

The significance of pulse wave reflections in the pulmonary vascular system is elaborated using a new method to determine the broadband frequency response of input impedance up to frequencies of 100 Hz. A simple data model, based on the signal construct of a wavelet, is used to generalize and reconcile the common approaches to vascular frequency response estimation so that an accurate response can be calculated from physiological waveforms. Input impedance interpretation is accomplished using a structural and functional modeling methodology. To identify internal structural system properties, the methodology of inverse scattering is used to relate observed pulse wave echoes in the frequency response to a longitudinal distribution of reflection sites of anatomic significance. To identify functional interactions with pulmonary vascular wave mechanics, a time series analysis methodology is proposed to describe vascular interactions using a generalized principle of superposition. The methods of determination and interpretation are applied to a sample pressure-flow data set from the pulmonary circulation of a lamb experiencing vascular-ventilatory interaction. The example suggests that the frequency response is consistent with a discrete longitudinal distribution of reflection sites that may be affected by the ventilator.

Animals↗

PubMed2001

Graph models of oncogenesis with an application to melanoma.

We describe several analytical techniques for use in developing genetic models of oncogenesis including: methods for the selection of important genetic events, construction of graph models (including distance-based trees, branching trees, contingency trees and directed acyclic graph models) from these events and methods for interpretation of the resulting models. The models can be used to make predictions about: which genetic events tend to occur early, which events tend to occur together and the likely order of events. Unlike simple path models of oncogenesis, our models allow dependencies to exist between specific genetic changes and allow for multiple, divergent paths in tumor progression. A variety of genetic events can be used with the graph models including chromosome breaks, losses or gains of large DNA regions, small mutations and changes in methylation. As an application of the techniques, we use a recently published cytogenetic analysis of 206 melanoma cases [Nelson et al. (2000), Cancer Genet. Cytogenet.122, 101-109] to derive graph models for chromosome breaks in melanoma. Among our predictions are: (1) breaks in 6q1 and 1q1 are early events, with 6q1 preferentially occurring first and increasing the probability of a break in 1q1 and (2) breaks in the two sets [1p1, 1p2, 9q1] and [1q1, 7p2, 9p2] tend to occur together. This study illustrates that the application of graph models to genetic data from tumor sets provide new information on the interrelationships among genetic changes during tumor progression.

Chromosome Breakage↗

PubMed2003

Roles and responsibilities of the interpreter in interactions with speech-language pathologists, parents, and students.

The Individuals with Disabilities Education Act Amendments of 1997 (IDEA '97) specify that students must be assessed in their primary language. With the ever-increasing number of diverse languages spoken by students, it is very unlikely that even an English-bilingual speech-language pathologist's other language will match that of a student who is referred for a speech-language assessment. Knowing how to work effectively with an interpreter is, therefore, essential for all speech-language pathologists. This article reviews the process of interpretation during parent conferences and student assessments. It describes the specific roles and responsibilities of the speech-language pathologist-interpreter team, with a focus on the linguistic, cultural, and professional skills that the interpreter should have to ensure a successful outcome. Data obtained from bilingual Spanish/English-speaking speech-language pathologists are provided to confirm and describe some important features desired in an interpreter who collaborates with a speech-language pathologist. Suggestions for training and certifying future interpreters are outlined. Finally, models are presented for successful interactions with interpreters.

Communication Barriers↗

PubMed1993

A biomechanical analysis of the last stride, touch-down and take-off characteristics of the women's long jump.

This study was concerned with the measurement of a selection of performance variables from competitors in the women's long jump final of the World Student Games held in Sheffield, UK in July 1991. Several performances of each of six finalists were recorded on cine-film at 100 Hz. Resulting planar kinematic data were obtained for the last stride, touch-down and take-off. For the analysis, the point of maximum knee flexion was established and this was used to represent the point at which the compression phase had ended. A variety of variables describing the position, velocity and angular changes are presented as descriptive data. In addition, these were used to compute energies on the basis of a whole body model. The data were interpreted on the basis of a technique model of long jumping established from the literature. It was confirmed that take-off velocity was a function of touch-down velocity, and that there was an increase in vertical velocity at the expense of a reduction of horizontal velocity. An attempt was made to identify the mechanisms acting during the touch-down to take-off phase which were responsible for generating vertical velocity. It was concluded that there was evidence for mechanical, biomechanical and muscular mechanisms. The former relates to the generation of vertical velocity by the body riding over the base of support; the second is the elastic re-utilization of energy; and the third is the contribution by concentric muscular contraction.

Biomechanical Phenomena↗

PubMed1996

Nurses' health study: log-incidence mathematical model of breast cancer incidence.

BACKGROUND: In 1983, Pike et al. developed a mathematical model to quantify the effects of reproductive risk factors on the incidence of breast cancer. In 1994, we modified that model to correct some deficiencies in the original model, including a lack of terms for spacing of births and an inability to easily accommodate births after age 40 years. Our extended Pike model, while improving on the original, still has serious disadvantages, such as difficulty in translating model parameters into relative risks (RRs) and an incomplete fit to data that slightly overestimated incidence for premenopausal women with an early age at first birth and that underestimated incidence for post-menopausal women with a late age at first birth. PURPOSE: We undertook both the development of a new mathematical model to quantify the effects of reproductive risk factors on breast cancer incidence and validation of the model. METHODS: A new log-incidence model of breast cancer incidence was developed using nonlinear regression methods, and a study population consisting of 89,132 women in the Nurses' Health Study from which a total of 2249 incident cases of breast cancer were identified. Subjects were followed from the return of the 1976 Nurses' Health Study questionnaire until June 1, 1990, or until the last questionnaire was returned, until the development of any cancer, or until death, yielding 1,148,593 person-years of follow-up. The log-incidence models were fitted using iteratively reweighted least squares analysis. RESULTS: The log-incidence model provided a better fit to that data than the extended Pike model, with parameter estimates interpretable in terms of RRs. This new model can be fitted using standard commercially available statistical software. In the model, younger parous women are generally at slightly higher risk than nulliparous women, which is true for both the observed and expected RRs, and older parous women, aged 55-64 years with an early age at first birth, are at lower risk than nulliparous women,while older women with a late age at first birth are at substantially higher risk than nulliparous women. CONCLUSION: Log-incidence models, such as this one, provide an efficient framework for modeling the effect of lifestyle risk factors on breast cancer incidence that may be specifically targeted to certain time periods of a woman's reproductive life.

Adult↗

PubMed1995

A chemoreflex model of relation between blood pressure and heart rate in sleep apnea syndrome.

In obstructive sleep apnea syndrome (OSAS), pronounced low-frequency (LF) oscillations of blood pressure and interbeat interval (I) occur during recurrent apneas. We investigated the time relations between LF oscillations of diastolic pressure (D) and I in 12 patients with OSAS by means of spectral analysis. A high coherency between I and D was found, allowing a description of the relation by gain and phase. Oscillations in I and D were almost in counterphase in the LF range. Simple physiological models were implemented to interpret the observed features of LF oscillations. Model 1 describes the vagal and sympathetic influence by the carotid body chemoreflex on the circulation. From derivation of the frequency response of this model, gain and phase relations were obtained as would be expected from the action of the chemoreflex. We found that a range of phase relations can be induced by this reflex, depending on the relative vagal and sympathetic efferent influence on the circulation. This range of phase relations was indeed observed in 10 patients. Extended models that also included the orienting reflex (model 1a) or the baroreflex and a mechanical influence of breathing on the circulation (model 2) could not fit the data without a major contribution of the chemoreflex. We conclude that the relation between LF oscillations in I and D in OSAS can be explained by assuming that stimulation of the carotid body chemoreflex is the main source of these oscillations.

Adult↗

PubMedDate not supplied

Concussions in college football. A multivariate analysis.

The purpose of this investigation was to examine risk patterns of concussion in college football. Multivariate models were used to interpret the data. Specifically, log-linear modeling and analysis techniques were incorporated into the investigation. An average of 49 college teams were studied over the 8 year period 1975 to 1982. This represented over 36,000 athlete-seasons and 395 team-seasons. The data selected were limited to 1,005 game-related concussions. The general hypotheses tested were the null hypothesis that the variables of team (offense and defense), player position, situation (rushing and passing), and activity (block and tackle) had no effect on the occurrence of these game-related concussions. It was found that concussions were a persistent and regular but relatively infrequent type of injury in college football. Concussions accounted for 75% of the total number of injuries on or about the head. The injuries were examined relative to player position, situation, and activity using a log-linear modeling technique, with interactions among the variables also established. The contribution of each variable was not always equal or completely interactive. Generally, the highest risk of concussion was associated with offensive and defensive players involved in a block on a rushing play. Specifically, running backs demonstrated the highest risk of concussion, regardless of activity. The lowest risk was for offensive linemen and quarterbacks while blocking on any type of play. On defense, the secondary exhibited the highest risk of concussion while being blocked on a running play. Similarly, linemen experienced their greatest risk while being blocked on plays run inside the tackle.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

PubMed1992

The unbooked maternity patient in an academic hospital in Durban.

This paper examines the unbooked maternity patient in an academic hospital in Durban, Natal. This hospital is the biggest hospital serving the underprivileged population of this area. Of the 16,000 annual deliveries in this hospital, about 12% are unbooked patients. The health belief model of Rosenstock, as interpreted by Mikhail, and Cox's interaction model of client health behaviour were used as a theoretical framework for this research. A qualitative case study methodology was undertaken and semi-structured interviews were conducted with unbooked mothers who had utilized appropriate health services in a previous pregnancy. The aim of such interviews was to explore reasons given by mothers for non-use of facilities in the current pregnancy. The basic trends reflected in the findings regarding non-utilization of health services were client instability, health service failure and socio-cultural constraints. The study is innovative and addresses the problem from a social-cultural and midwifery perspective.

Adolescent↗

PubMed1987

Laparotomy enhances intraperitoneal tumor growth and abrogates the antitumor effects of interleukin-2 and lymphokine-activated killer cells.

The interrelationship between host resistance to cancer and the trauma of a surgical procedure is the subject of much speculation. Extensive study of animal models and human subjects is required to define these effects and to provide a theoretical model by which to interpret these data. We used a murine model of intraperitoneal cancer to demonstrate the augmentation of tumor growth by surgical trauma. In this intraperitoneal tumor model, a surgical procedure that included entry into the abdominal cavity resulted in augmented tumor growth; a surgical incision on the skin of the animal's back did not promote tumor growth. The immunotherapeutic effects of interleukin-2 and lymphokine-activated killer cells were significantly reduced by the performance of a laparotomy. This abrogation of the effects of the immunotherapeutic regimen was observed for up to 14 days after laparotomy but was lost by days 35 to 42. Healing tissue may promote tumor growth, and these effects are dominant over immunotherapy with interleukin-2 plus lymphokine-activated killer cells.

Animals↗

PubMed1995

Model inconsistency, illustrated by the Cox proportional hazards model.

We consider problems involving the comparison of two or more treatments where we have the opportunity to adjust for relevant covariates either conditionally in a regression model or implicitly in repeated measures data, for example, in crossover trials. It is seen that for data arising from non-Normal distributions there is the possibility that models adjusting for covariates and those not adjusting for covariates will be inconsistent, that is, at most one of the models can be valid. Alternatively, even if conditional and unconditional models are valid, parameters in each model may have different interpretations. We note that this presents difficulties for the specification and interpretation of the analysis. It is also clear that model validation is critical. Specific attention is paid to survival data analysed by the Cox proportional hazards model.

Analysis of Variance↗

PubMed1994

Quantitative radial imaging of porous particles beds with varying water contents.

Radial imaging protocols suitable for monitoring water transport in biopolymer and food materials during processes such as drying and rehydration are developed and tested on a well-characterized model sample. This model consisted of a randomly packed bed of Sephadex beads with varying water content. The results are interpreted with theoretical models for the dependence of the initial water magnetization, transverse relaxation, and diffusive attenuation on water content for two slice-selective radial imaging pulse sequences. It is shown that volume shrinkage and changes in packing density complicate the dependence of the initial magnetization on water content, so that the transverse relaxation rate provides the most reliable monitor of water content. Radial imaging is shown to offer many advantages over conventional two-dimensional imaging whenever the sample can be made with cylindrical symmetry.

Algorithms↗

PubMed2004

Cell-type specific regulation of calreticulin and Bcl-2 expression by mood stabilizer drugs.

Recent studies in rat brain and cell cultures have demonstrated that expression of the peptide-folding chaperone protein calreticulin is increased by valproate treatment, while the anti-apoptotic Bcl-2 is increased by both lithium and valproate. We asked whether a similar pattern of regulation by these drugs is evident in human neuronal and glial cells. One-week treatment with 1 mM valproate induced a significant (90%) increase in calreticulin mRNA and protein levels in SVG, a glial cell line, but reduced its mRNA levels by 38% in hNT neuronal cells. Valproate also markedly increased Bcl-2 mRNA levels by 260%, but only in hNT neurons. In contrast, lithium had no significant effect in either cell type. Valproate-induced increases in calreticulin may therefore show glial specificity in humans, while changes in Bcl-2 levels may be neuron specific. These results highlight the cell model dependence of outcomes in molecular studies of mood stabilizer effects and the need for caution in interpreting findings in model systems.

Analysis of Variance↗

PubMed2003

Modelling the combined effect of temperature, pH and aw on the growth rate of Monascus ruber, a heat-resistant fungus isolated from green table olives.

AIMS: Growth modes predicting the effect of pH (3.5-5.0), NaCl (2-10%), i.e. aw (0.937-0.970) and temperature (20-40 degrees C) on the colony growth rate of Monascus ruber, a fungus isolated from thermally-processed olives of the Conservolea variety, were developed on a solid culture medium. METHODS AND RESULTS: Fungal growth was measured as colony diameter on a daily basis. The primary predictive model of Baranyi was used to fit the growth data and estimate the maximum specific growth rates. Combined secondary predictive models were developed and comparatively evaluated based on polynomial, Davey, gamma concept and Rosso equations. The data-set was fitted successfully in all models. However, models with biological interpretable parameters (gamma concept and Rosso equation) were highly rated compared with the polynomial equation and Davey model and gave realistic cardinal pHs, temperatures and aw. CONCLUSIONS: The combined effect of temperature, pH and aw on growth responses of M. ruber could be satisfactorily predicted under the current experimental conditions, and the models examined could serve as tools for this purpose. SIGNIFICANCE AND IMPACT OF THE STUDY: The results can be successfully employed by the industry to predict the extent of fungal growth on table olives.

Colony Count, Microbial↗

PubMed2003

Bivariate longitudinal model for the analysis of the evolution of HIV RNA and CD4 cell count in HIV infection taking into account left censoring of HIV RNA measures.

We present a bivariate linear mixed model taking into account censored measures of the response variable due to lower quantification limit of the assays. It allows an estimate of the correlation between the two response variables and takes into account this correlation for the estimation of other model parameters. This model was applied in a large cohort study (APROCO Cohort) to study the evolution under antiretroviral treatment of the two major biomarkers of the progression of Human Immunodeficiency Virus (HIV) infection: plasma HIV RNA and CD4+ T lymphocytes cell count. In a sample of 929 patients who started an highly active antiretroviral therapy, we illustrate the superiority in terms of likelihood of a bivariate model compared to two univariate models and the impact of taking into account the left-censoring of HIV-RNA. Moreover, interpretation of the model parameters allows confirmation of correlation between these two markers throughout the whole follow-up and the continuous decrease of plasma HIV RNA on average. Despite some limitations (distribution assumption, ignorance of missingness process), such a model appeared to be very useful to correctly describe the current evolution of important biomarkers in HIV infection.

CD4 Lymphocyte Count↗

PubMed2005

Modeling of protein signaling networks in clinical proteomics.

Molecular interactions that underlie pathophysiological states are being elucidated using techniques that profile proteomic endpoints in cellular systems. Within the field of cancer research, protein interaction networks play pivotal roles in the establishment and maintenance of the hallmarks of malignancy, including cell division, invasion, and migration. Multiple complementary tools enable a multifaceted view of how signal protein pathway alterations contribute to pathophysiological states. One pivotal technique is signal pathway profiling of patient tissue specimens. This microanalysis technology provides a proteomic snapshot at one point in time of cells directly procured from the native context of a tumor microenvironment. To study the adaptive patterns of signal pathway events over time, before and after experimental therapy, it is necessary to obtain biopsies from patients before, during, and after therapy. A complementary approach is the profiling of cultured cell lines with and without treatment. Cultured cell models provide the opportunity to study short-term signal changes occurring over minutes to hours. Through this type of system, the effects of particular pharmacological agents may be used to test the effects of signal pathway inhibition or activation on multiple endpoints within a pathway. The complexity of the data generated has necessitated the development of mathematical models for optimal interpretation of interrelated signaling pathways. In combination, clinical proteomic biopsy profiling, tissue culture proteomic profiling, and mathematical modeling synergistically enable a deeper understanding of how protein associations lead to disease states and present new insights into the design of therapeutic regimens.

Humans↗

PubMed1993

Dynamic properties of cortical evoked (10 Hz) oscillations: theory and experiment.

Experiments probed the dynamic properties of stimulus-evoked (approximately 10 Hz) oscillations in somatosensory cortex of anesthetized rats. Experimental paradigms and statistical time series analysis were based on theoretical ideas from a dynamic approach to temporal patterns of neuronal activity. From the results of a double-stimulus paradigm we conclude that the neuronal response contains two components with different dynamics and different coupling to the stimulus. Based on this result a quantitative dynamic model is derived, making use of normal form theory for bifurcating vector fields. The variables used are abstract, but measurable, dynamic components. The model parameters capture the dynamic properties of neuronal response and are related to experimental results. A structural interpretation of the model can be given in terms of the collective dynamics of neuronal groups, their mutual interaction, and their coupling to peripheral stimuli. The model predicts the stimulus-dependent lifetime of the oscillations as observed in experiment. We show that this prediction relies on the basic concept of dynamic bistability and does not depend on the modeling details.

Animals↗

PubMed2004

[A new statistical method on familial correlation dealing with family data from case-control studies].

OBJECTIVE: This paper presents a statistical method of familial correlation on family data from case-control studies. METHODS: Marginal mean models of the probands and the relatives conditional on the proband's disease status, as well as the marginal association model of the relatives were modeled integrately. Conditional odds-ratio and marginal odds-ratio were used to measure the familial correlation. RESULTS: The parameter's interpretation in the model was in accordance with sample characteristics. This method is more efficient due to making fully use of information of the probands and relatives. In addition, the method has all advantages of GEE2. CONCLUSION: The method in this paper efficiently and conveniently analyzes the family data from case-control studies to estimate the familial correlation on disease.

Bias↗