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PubMed2006

Structural plasticity of single chromatin fibers revealed by torsional manipulation.

Magnetic tweezers were used to study the mechanical response under torsion of single nucleosome arrays reconstituted on tandem repeats of 5S positioning sequences. Regular arrays are extremely resilient and can reversibly accommodate a large amount of supercoiling without much change in length. This behavior is quantitatively described by a molecular model of the chromatin three-dimensional architecture. In this model, we assume the existence of a dynamic equilibrium between three conformations of the nucleosome, corresponding to different crossing statuses of the entry/exit DNAs (positive, null or negative, respectively). Torsional strain displaces that equilibrium, leading to an extensive reorganization of the fiber's architecture. The model explains a number of long-standing topological questions regarding DNA in chromatin and may provide the basis to better understand the dynamic binding of chromatin-associated proteins.Note: In the supplementary information initially published online to accompany this article, Supplementary Figure 2 was mistakenly replaced by Supplementary Equation 2. The error has been corrected online.

Biomimetic Materials↗

PubMed2006

Developing a predictive model for vertigo using demographic and laboratory data: An evidence-based medicine approach.

CONCLUSION: The approach described in this paper may be helpful in establishing an early-warning, evidence-based mechanism for diagnosing vertigo, which can be utilized in medical education to reduce medical uncertainty. OBJECTIVE: To use an evidence-based medicine approach to evaluate the probability of having vertigo using laboratory and demographic data. MATERIAL AND METHODS: The study was conducted on 22 working days during July 2002. Targeted cases who visited a general hospital in southern Taiwan for routine physical examinations were asked to participate in the study and agreed to take additional tests during their visits. A total of 200 subjects were systematically and randomly selected from this data pool. We ran binary logistic regression on all these cases. RESULTS: The logistic regression model explained 71.3% of the variance in having vertigo or not. The equation for having vertigo was as follows: -21.855 + (1.132 x male gender) + (0.071 x age) + (-0.023 x systolic blood pressure) + (0.057 x diastolic blood pressure) + (0.048 x fasting glucose) + (0.051 x cholesterol) + (-0.005 x triglycerides) + (-0.361 x presence of cardiovascular diseases).

Adult↗

PubMed1986

The use of acoustical test fixtures for the measurement of hearing protector attenuation. Part II: Modeling the external ear, simulating bone conduction, and comparing test fixture and real-ear data.

This paper investigates two main features of the human head which influence the measured attenuation of circumaural and intraaural hearing protection devices (HPDs): the external ear and the different pathways of bone conduction. A theoretical model for the external ear shows that its influence on the insertion loss of HPDs, on the sensitivity level of headphones or earphones, and on the insertion gain of hearing aids, all can be described by one equation. While it is not necessary to simulate the eardrum impedance in order to measure the insertion loss of earmuffs and the sensitivity level of headphones with acoustical test fixtures (ATFs), the required accuracy of an ear simulator is more stringent when the same measurements are performed on intraaural devices. For the evaluation of HPDs, bone conduction plays an important role. We have developed a model to estimate HPD-dependent bone conduction effects. The model includes two bone conduction sources: one in the external ear and one in the middle ear. The model explains, for example, the occlusion effect of HPDs and the masking error at low frequencies due to physiological noise that arises when real-ear attenuation at threshold (REAT) measurements are made. Consequently, objectively measured insertion loss can now be used to predict REAT with improved accuracy. ATF and REAT data are compared using nine earmuffs and nine earplugs. In the majority of cases, the two sets of data agree well. Discrepancies are discussed.

Auditory Threshold↗

PubMed1988

A mathematical study of human intracranial hydrodynamics. Part 1--The cerebrospinal fluid pulse pressure.

An original mathematical model of human intracranial hydrodynamics is proposed. Equations able to mimic the behavior of the intracranial arterial vascular bed, intracranial venous vascular bed, cerebrospinal fluid absorption and production processes, and the constancy of overall intracranial volume are separately presented and discussed. The model parameters were given normal values computed using physiological considerations and recent anatomical data. In this paper the model is used to simulate the genesis and morphology of the intracranial pressure pulse wave. In particular, dependence of the intracranial pressure pulse amplitude on mean intracranial pressure, obtained from the model, shows excellent agreement with recent experimental findings. The model explains the intracranial pressure pulse wave as the result of the pulsating changes in cerebral blood volume (related to cerebrovascular compliance) which occur within a rigid space (i.e., the craniospinal compartment). At low and medium values of intracranial pressure, the intracranial pressure pulse amplitude mainly reflects the cerebral pressure-volume relationship. However, during severe intracranial hypertension, an abrupt increase in the cerebrovascular compliance becomes evident, which is reflected in an abrupt increase in the intracranial pressure pulse wave.

Cerebrospinal Fluid↗

PubMed2005

Linear indices of the 'macromolecular graph's nucleotides adjacency matrix' as a promising approach for bioinformatics studies. Part 1: prediction of paromomycin's affinity constant with HIV-1 psi-RNA packaging region.

The design of novel anti-HIV compounds has now become a crucial area for scientists around the world. In this paper a new set of macromolecular descriptors (that are calculated from the macromolecular graph's nucleotide adjacency matrix) of relevance to nucleic acid QSAR/QSPR studies, nucleic acids' linear indices. A study of the interaction of the antibiotic Paromomycin with the packaging region of the HIV-1 psi-RNA has been performed as example of this approach. A multiple linear regression model predicted the local binding affinity constants [Log K (10(-4) M(-1))] between a specific nucleotide and the aforementioned antibiotic. The linear model explains more than 87% of the variance of the experimental Log K (R = 0.93 and s = 0.102 x 10(-4) M(-1)) and leave-one-out press statistics evidenced its predictive ability (q2 = 0.82 and s(cv) = 0.108 x 10(-4) M(-1)). The comparison with other approaches (macromolecular quadratic indices, Markovian Negentropies and 'stochastic' spectral moments) reveals a good behavior of our method.

Anti-Bacterial Agents↗

PubMed2006

A simple steady-state model for carry-over of aflatoxins from feed to cow's milk.

A simple steady-state model is derived from two kinetic one-compartment models for the disposition of aflatoxin B1 (AFB1) and aflatoxin M1 (AFM1) in the lactating cow. The model relates daily intake of AFB1 in feed of dairy cattle and the cow's lactation status to resulting concentrations of AFM1 in milk. Moreover, assuming a linear relationship between the cow's lactation status and feed intake, the model relates daily milk production and AFB1 concentration in total feed to AFM1 levels in milk. The model explains similar experimental outcomes from different investigations into carry-over of aflatoxins from feed to milk. Although it is difficult to set a permanent limit for AFB1 in feed, the European Union (EU) limit of 5 microg AFB1 kg(-1) concentrate has proved, thus far, to be an appropriate level in preventing the EU limit of 0.05 microg AFM1 kg(-1) milk being exceeded.

Aflatoxin B1↗

PubMed1995

Predictors of fixed orthodontic treatment in 15-year-old adolescents in South Australia.

An understanding of the determinants of the provision of fixed orthodontic treatment would be beneficial in the planning of any system aimed at rationalising supply. The aim of this longitudinal study was to determine those factors which were predictive of the provision of fixed orthodontic treatment in adolescents. Baseline data, at age 13 years, on oral health, the history of orthodontic consultation and interceptive orthodontic care, a dental appearance score (DAI), socio-demographic characteristics and self and parental perceptions of both dental appearance and need for fixed orthodontic treatment were obtained from 2793 adolescents under the care of the South Australian School Dental Service who had not undergone fixed orthodontic treatment. Data on the orthodontic care provided to these adolescents in the ensuing 2 years were collected. At the end of the 24-month period 433 adolescents (15.5%) had undergone fixed orthodontic treatment. Significant bivariate associations were found between the provision of fixed orthodontic treatment and the DAI score, sex of the adolescent, familial history of fixed orthodontic treatment, income, private insurance, orthodontic consultation and interceptive orthodontic care before the age of 13 years and self and parental perceptions of both dental appearance and the need for fixed orthodontic treatment. Logistic regression was used to produce a predictive model of fixed orthodontic treatment. The model explained 30.2% of the variance, with a specificity of 0.94, a sensitivity of 0.49 and a hit rate of 0.84%. Odds ratios greater than one were found for the DAI score, private insurance, females, self and parental perception of need, higher incomes and orthodontic consultation and interceptive orthodontic care before the age of 13 years.

Adolescent↗

PubMed2004

Can psychological factors help us to determine adherence to CPAP? A prospective study.

The present study objective was to establish whether pretreatment social cognitive variables may contribute to the explanation of variance in adherence to continuous positive airway pressure (CPAP) treatment for patients with obstructive sleep apnoea/hypopnoea syndrome (OSAHS). A total of 119 of 180 consecutive OSAHS patients were recruited to the study prior to initial CPAP titration. Patients completed psychological measures of health value, health locus of control (incorporating internality, chance, powerful others) and self-efficacy prior to CPAP titration. Objective adherence data were measured by CPAP unit time clocks and collected at 3-month follow-up. Average nightly use was calculated over this period. Logistic regression of prospective predictors of adherence produced a model comprising psychological (health value, internality, powerful others), as well as clinical variables (Epworth score, body mass index, apnoea/hypopnoea index, CPAP pressure). This model explained 24% of the variance in CPAP use, and correctly identified 75% of adherers and 53% of nonadherers. Although the psychological variables explained only a small amount of the overall variance in adherence behaviour, this result provides further support for the hypothesis that psychological variables contribute, in part, to continuous positive airway pressure adherence. Future research should focus on highlighting discrete variables, which may helpfully inform psychologically based interventions aimed at improving the use of continuous positive airway pressure by patients with obstructive sleep apnoea/hypopnoea syndrome at risk of discontinuance.

Continuous Positive Airway Pressure↗

PubMed1995

Predicting hospital costs among older decedents over time.

To explain the variation in total real hospital costs among elderly patients who died between 1984 and 1991, a cohort analytic study of the nationally representative sample of elderly subjects included in the Longitudinal Study on Aging (N = 7,527) was carried out. The cohort comprised the subset of 1,778 community-dwelling Americans who were age 70 years and older in 1984, had one or more subsequent hospital episodes, and died by 1991. Hospital charges for 1984 through 1991 were taken from the Medicare Automated Data Retrieval System. Annual hospital charges were adjusted for inflation (restated in 1984 dollars) using the hospital market basket component of the consumer price index. The natural logarithm of aggregated real charges was used in the analysis. Mean total real hospital charges were $24,956 (SD = $27,847). A standard multivariable regression model explained 9.7% of the variance in real total hospital charges. After incorporating additional measures reflecting a respondent's distribution (mean and standard deviation) of comorbidities (as measured by the number of ICD-9-CM codes [truncated at five]) during all hospitalizations in the observation window, the cause of death, and the concentration of charges in the last year of life, the explained variance increased to 29.3%. The most important explanatory factors were the two variables controlling for the distribution of comorbidity, the variable controlling for population density, and the dichotomous variable indicating that the patient's death was related to an acute myocardial infarction. Total real hospital resources consumed by elderly decedents vary substantially. The concentration of resources consumed in the last year of a respondent's life was only marginally significant in predicting total real hospital charges over an 8-year observation window.

Aged↗

PubMed1980

A model of cell activation and desensitization by surface immunoglobin: the case of histamine release from human basophils.

We present a model for the control of immunoglobulin E (IgE)-mediated histamine release from human basophils. We suggest that there is a calcium gating factor which interacts with crosslinked IgE to form a short-lived open calcium channel. After formation of the channel the activated gating factor rapidly decays to an inactive form. It is the loss of the active gating factor which causes the basophil to desensitize nonspecifically. We propose that the crosslinked IgE molecules are deactivated by a mechanism, such as endocytosis or shedding, which is independent of the mechanism which inactivates the calcium gating factor. This loss of functional IgE leads to specific desensitization. The mathematical formulation of the model explains the relationship of specific and nonspecific desensitization to the amount of specific IgE on the basophil surface; explains why there are two types of antigen excess inhibition; explains the relationship between antigen excess inhibition and desensitization; explains why, for a fixed antigen concentration, increasing the concentration of cell surface IgE increases histamine release until an optimal concentration is reached, then decreases histamine release; predicts the effects that changing the external calcium will have on the dose response curve; and predicts that increasing the amount of specific IgE on the cell surface will cause the dose response curve to undergo a transition from a curve with a single maximum to a curve with two maxima.

Basophils↗

PubMedDate not supplied

Cost of AIDS care in Mexico: what are its main individual predictors?

BACKGROUND: The Mexican government is offering universal access to antiretroviral (ARV) drugs. The cost of doing so, despite aggressive price negotiation with the pharmaceutical industry, remains high. Even with a low prevalence, about 150,000 Mexicans are estimated to be living with HIV and will require ARV treatment. Estimating the resources needed to fund this gap should consider how patient and provider characteristics affect health care costs. METHODS: Using a sample of patients from 11 facilities in three Mexican cities representing a large proportion of AIDS patients in the country, we developed a fixed-effect model, which by controlling the facilities and individual heterogeneity estimates predicted costs using patient demographic and socioeconomic characteristics as well as physician training. RESULTS: The estimated model explains about 45% of the variation in costs. Additional education is significantly and positively associated with cost. Increasing age is also associated with higher costs. CONCLUSIONS: Socioeconomic status and demographic characteristics explain an important proportion of variation in care costs for AIDS, despite AIDS being such a heterogeneous disease. Such characteristics will need to be taken into account when resource needs are estimated. A priority-setting process considering the principles of equity in the fair distribution of resources is needed to help reduce the social burden of HIV/AIDS in Mexico.

Acquired Immunodeficiency Syndrome↗

PubMed1993

Functional status outcomes in rehabilitation. Implications for prospective payment.

Previous studies have demonstrated that functional status is a significant predictor of resource utilization for rehabilitation patients. Before implementing a prospective payment system (PPS) for rehabilitation, it is important to first: 1) develop an underlying conceptual framework of rehabilitation resource use; and 2) understand how the role of functional status may vary by rehabilitation condition. In this study, a theoretical model of rehabilitation is presented that proposes relationships between patient and provider characteristics, rehabilitation treatment, costs, and clinical outcomes of rehabilitation. Also presented are regression analyses based on this model for a key outcome of rehabilitation, change in functional status, for nine rehabilitation conditions using variables that minimize adverse incentives by providers in selecting patients for admission to rehabilitation. The change-in-functional-status model explained the most variance for back injury, cardiopulmonary, and arthritis, and less variance for stroke, spinal cord injury, and neurologic impairment. The significant predictors of change in functional status varied by condition. Results support the use of functional status measurements in a PPS for rehabilitation services, the need to refine the measurement of functional status, and the use of condition-specific activities of daily living (ADL) items to include in summary indices.

Activities of Daily Living↗

PubMed1991

Balancing acute and long-term care: the mathematics of throughput in departments of geriatric medicine.

The empirical distribution of length of stay of patients in departments of geriatric medicine is fit extremely well by a sum of two exponentials. Most of the patients in a geriatric department are rehabilitated and discharged or they die within a few weeks of admission, but the few who become long-stay patients remain for months or even years. A model is presented for the flow of patients through a geriatric department, which has analogies to models of drug flow in pharmacokinetics. The theoretical model explains why the empirical pattern of length of stay in the occupied beds fits a sum of two exponentials; conversely, the empirical distribution, obtained from the midnight bed state report, can be used to study the effect of various policy decisions on both immediate and future admission rates for the department, and shows the benefits of policies which reduce long-stay patient numbers by improving long-stay rehabilitation.

Acute Disease↗

PubMed1985

Influence of urinary pH on pethidine kinetics in healthy volunteer subjects.

The kinetics of intravenous pethidine (150 micrograms kg-1) were determined in 10 healthy Caucasian subjects under uncontrolled and controlled (acidic and alkaline) urinary pH. Although large variations in the 48 hr urinary recovery of pethidine and norpethidine (26.9 +/- 5.9% & 23.4 +/- 4.6%, 0.6 +/- 0.3% & 3.6 +/- 1.6%, 6.9 +/- 3.2% & 17.4 +/- 6.6%, respectively, under acidic, alkaline and uncontrolled urinary pH were induced by change in urinary pH, the terminal t1/2 (7-8 hr), the AUC and the plasma concentration-time profiles were not affected. Under all these conditions, the disappearance of pethidine from the plasma was described by a triexponential function. A 3-compartment open model with input into the central compartment and elimination from both the central and the fast accessible (metabolising) compartment was proposed to interpret pethidine distribution in the body. This model explains the complimentary elimination of pethidine by renal excretion and metabolism. Under alkaline urinary pH, the hydrolytic route predominates as recovery of pethidine and norpethidine in the urine is significantly lower under this condition. Acidification of the urine may increase body clearance of the unchanged drug due mainly to greater renal clearance, and this may be useful clinically to treat acute pethidine poisoning and when the complimentary hepatic metabolism is impaired.

Adult↗

PubMed1995

Modeling direction selectivity of simple cells in striate visual cortex within the framework of the canonical microcircuit.

Nearly all models of direction selectivity (DS) in visual cortex are based on feedforward connection schemes, where geniculate input provides all excitatory synaptic input to both pyramidal and inhibitory neurons. Feedforward inhibition then suppresses feedforward excitation for nonoptimal stimuli. Anatomically, however, the majority of asymmetric, excitatory, synaptic contacts onto cortical cells is provided by other cortical neurons, as embodied in the Canonical Microcircuit of Douglas and Martin (1991). In this view, weak geniculate input is strongly amplified in the preferred direction by the action of intracortical excitatory connections, while in the null direction inhibition reduces geniculate-induced excitation. We investigate analytically and through biologically realistic computer simulations the functioning of a cortical network based on massive excitatory, cortico-cortical feedback. The behavior of this network is compared to physiological data as well as to the behavior of a purely feedforward model of DS based on nonlagged input. Our model explains a number of puzzling features of direction selective simple cells, including the small somatic input conductance changes that have been measured experimentally during stimulation in the null direction, and the persistence of DS while fully blocking inhibition in a single cell. Although the operation at the heart of our network is amplification, the network passes the linearity test of (Jagadeesh et al., 1993). We make specific predictions concerning the effect of selective blockade of cortical inhibition on the velocity-response curve.

Animals↗

PubMed1996

[Nurses' representations of the managerial function, what professional commitment does this mean?].

THE SUBJECT OF THIS RESEARCH: "What idea nurses have about the managerial function; from a professional point of view what commitments does this function entail?" is connected with: The fact that at a legislative level there is no reglementation of the managerial function. From a legal point of view, the nature of the commitments in connection with this function is not accurate enough as there is no law explaining exactly what does the job of charge nurse consist in. Therefore, the opinions the whole medical profession have about the managerial function are various. On the other hand, taking into consideration what charge nurses think about their own function can help to explain the behaviour as, usually the ideas determine the practice (cf. ABRIC 1994). The methodology used was based on a scientific procedure and first of all I had to break with my prejudices and wrong opinions which only give you the illusion that you can understand the matters. Readings and exploratory talks helped me in that way and so I could formulate the problem. I worked within this theoretical context and I practically tested the facts by means of semi-directed interviews. The result of the analysis invalidated the hypothesis put forward at the beginning. As regards to the idea nurses have about the managerial function, the difference expressed is more regarding the connection between the nurses values and those ones of the charge nurses, rather than regarding the adequacy between the function and the place of the charge nurse. This is somewhere the notion of project according to ARDOI-NO (1984) in which it is necessary to define the aim of the project first and to establish the means used for the realization after. To formulate the problem only--in our research: the job description--is not enough. It must be developped. So, this procedure enable me, first, to consider the problems differently and to study complicated situations in which we can feel uncertain. The question is at the same time to anticipate and to accept to discover something different. Therefore, there is no model explaining how to understand the complexity of a problem. The charge nurse who is, on one hand, responsible of a conformity must accept to discover, on the other hand, something new: it is one of the paradox of this function.

Attitude of Health Personnel↗

PubMed2004

Characterization of calcium and magnesium binding domains of human 5-lipoxygenase.

Two calcium binding sites, separated by about 9.3A, present in the loops that connect the beta-sheets of N-terminal domain contain the ligating residues F14, A15, G16, D79, and D18, D19, L76, respectively. Magnesium is found to bind in regions, which are marginally different owing to the disparity in the ionic radii of Ca2+ and Mg2+. The entropy analysis on the loops of 5-lipoxygenase, implementing the wormlike chain model, explains that the N-terminal beta-barrel is well suited to accommodate calcium binding sites. The large buried side chain area of W102 (compared to W13 and W75) and comparatively smaller fraction of side chain exposed to polar atoms corroborate the calcium induced higher affinity to phosphatidylcholine (PC). However, W80 lying in close proximity of the calcium binding sites is expected to have considerable PC affinity but negligible calcium induced effect on PC binding.

Amino Acid Sequence↗

PubMed2001

Computer modeling of human angiogenin-dinucleotide substrate interaction.

Structures of substrate bound human angiogenin complexes have been obtained for the first time by computer modeling. The dinucleotides CpA and UpA have been docked onto human angiogenin using a systematic grid search procedure in torsion and Eulerian angle space. The docking was guided throughout by the similarity of angiogenin-substrate interactions with interactions of RNase A and its substrate. The models were subjected to 1 nanosecond of molecular dynamics to access their stability. Structures extracted from MD simulations were refined by simulated annealing. Stable hydrogen bonds that bridged protein and ligand residues during the MD simulations were taken as restraints for simulated annealing. Our analysis on the MD structures and annealed models explains the substrate specificity of human angiogenin and is in agreement with experimental results. This study also predicts the B2 binding site residues of angiogenin, for which no experimental information is available so far. In the case of one of the substrates, CpA, we have also identified the presence of a water molecule that invariantly bridges the B2 base with the protein. We have compared our results to the RNase A-substrate complex and highlight the similarities and differences.

Amino Acid Sequence↗