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PubMed2005

Studying protein aggregation by programmed flow field-flow fractionation using ceramic hollow fibers.

Ceramic hollow fibers have been used as separation channels for flow field-flow fractionation. The fibers were made of alpha-alumina, with a gamma-alumina layer on the inside wall acting as a semipermeable (ultrafiltration) membrane. The fibers and the separation system were tested by determining the diffusion coefficients of a series of standard proteins under various experimental conditions. Even for the smallest protein studied, a complete recovery from the fiber was obtained. A single fiber could be used for several months without problems such as leakage or fouling. The precision of the diffusion coefficient measurements was in the order of 5-10%. A good agreement with literature data was found. Programming of the cross-flow, with a time-delayed exponential decay program, was applied to extend the accessible size range for the sample components. With flow programming, the observed retention times increased linearly with the logarithm of the molar mass of proteins and aggregates, as predicted by theory. Heat-induced aggregation of beta-lactoglobulin (beta-LG) in aqueous solution was studied with the system. Upon heating, not only the extent of aggregation but also the size of the beta-LG aggregates was found to increase with the original concentration of beta-LG in solution and with the heating time. After heating in the presence of salt, very large aggregates were formed, with molar masses over 100 million. A multiangle light scattering detector was used to estimate molar masses and sizes of the protein aggregates. From the relation between the apparent diffusion coefficients and the molar masses of the aggregates, as well as from the ratio of the rms (scattering) and the hydrodyamic radii, it was concluded that the larger beta-LG aggregates behave as flexible chains in solution.

Ceramics↗
PubMed1998

Life-style factors associated with changes in serum lipids in a follow-up study of cardiovascular risk factors.

We studied some life-style characteristics that may predict changes in total serum cholesterol and cholesterol bound to high density lipoproteins (HDL-cholesterol) in a sample of 980 healthy Spanish employees of both sexes who were followed for three years. All workers participated in a multifactorial program aimed at preventing cardiovascular disease. Linear regression models were fitted with changes in total and HDL-cholesterol as the dependent variables, after eliminating variability due to the influence of basal values. The association between lifestyle factors and lipid changes was controlled for dietary modifications. In the multivariate analysis, decreases in body mass index, and in alcohol consumption were associated with significant reductions in total serum cholesterol. Maintaining sports at post-test or starting to practice them in the interim was also significantly and independently associated with favourable changes in serum cholesterol. Leisure-time exercise (p = 0.002) and giving up smoking (p = 0.06) were each associated with increased HDL-cholesterol.

Adolescent↗
PubMed1986

Age-dependent cyclosporine: pharmacokinetics in marrow transplant recipients.

We evaluated the effect of age on cyclosporine pharmacokinetics in 69 nonobese patients aged 10 months to 56 years (median 22 years) undergoing allogeneic bone marrow transplantation for treatment of aplastic anemia or hematologic malignancy. Cyclosporine pharmacokinetics were studied during the first 2 posttransplant weeks after an intravenous dose of 2.6 to 3.5 mg/kg. Serum cyclosporine concentrations were measured by HPLC. Cyclosporine concentration-time data were fitted to a two-compartment model with a nonlinear regression program. There was a significant inverse linear correlation between age and both total systemic clearance (CL) (r = 0.42; P less than 0.001) and volume of distribution at steady-state (Vss) (r = 0.33; P less than 0.01). Mean (+/- SE) cyclosporine CL was 82 +/- 21, 45 +/- 5, 38 +/- 9, 44 +/- 8, and 20 +/- 3 ml/min/kg and mean cyclosporine Vss was 34 +/- 11, 28 +/- 10, 15 +/- 4, 14 +/- 5, and 4.7 +/- 0.7 L/kg in patients 0 to 10 (n = 12), 11 to 20 (n = 19), 21 to 30 (n = 12), 31 to 40 (n = 17), and greater than 40 (n = 9) years old, respectively. Patients 0 to 10 years old had a significantly higher cyclosporine CL than those 11 to 40 or greater than 40 years old and also had a significantly larger Vss than those greater than 40 yrs old (P less than 0.05). Age-related differences in CL or Vss were also observed when these parameters were normalized by body surface area.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMedDate not supplied

A comparison of two models of health-promoting lifestyle in rural elderly Taiwanese women.

The purposes of this study were to: (1) examine the relations among age, marital status, social class, perceived health, self-care agency, health-promoting lifestyle, and well-being in two groups of rural elderly Taiwanese women and (2) validate and compare two models using the two age groups of rural elderly Taiwanese women. Based on the conceptualizations of the major study variables in Orem's self-care model (1995), Pender's health promotion model (1987), and other scholars' ideas (Hartweg, 1990; Simmons, 1990), a theoretical model of health-promoting lifestyle was proposed for this study. A survey-interview method was used for data collection. Two groups of elderly women were recruited for data analysis: 168 in the younger group and 116 in the older group. The mean age was 64.66 in the younger group and 75.59 in the older group. Two models of health-promoting lifestyle were tested with a path analysis, using the Linear Structural Relations 8 (LISREL 8) program. The resultant models yielded chi2 of 13.69 with 9 degrees of freedom (p = 0.13) in the younger group and chi2 of 15.76 with 10 degrees of freedom (p = 0.11) in the older group. Other fit indices also indicate the two models fit the data well. Community nurses can assess, identify, and use effective interventions for rural elderly women on a basis of the resulting models.

Age Factors↗
PubMed2005

The application of infrared spectroscopy to probe the surface morphology of alumina-supported palladium catalysts.

Five alumina-supported palladium catalysts have been prepared from a range of precursor compounds [palladium(II) nitrate, palladium(II) chloride, palladium(II) acetylacetonate, and tetraamminepalladium(II) tetraazidopalladate(II)] and at different metal loadings (1-7.3 wt %). Collectively, this series of catalysts provides a range of metal particle sizes (1.2-8.5 nm) that emphasize different morphological aspects of the palladium crystallites. The infrared spectra of chemisorbed CO applied under pulse-flow conditions reveal distinct groupings between metal crystallites dominated by low index planes and those that feature predominantly corner/edge atoms. Temperature-programmed infrared spectroscopy establishes that the linear CO band can be resolved into contributions from corner atoms and a combination of (111)(111) and (111)(100) particle edges. Propene hydrogenation has been used as a preliminary assessment of catalytic performance for the 1 wt % loaded catalysts, with the relative inactivity of the catalyst prepared from palladium(II) chloride attributed to a diminished hydrogen supply due to decoration of edge sites by chlorine originating from the preparative process. It is anticipated that refinements linking the vibrational spectrum of a probe molecule with surface structure and accessible adsorption sites for such a versatile catalytic substrate provide a platform against which structure/reactivity relationships can be usefully developed.

Journal Article↗
PubMed1994

A decentralized process for finding equilibria given by linear equations.

I present a decentralized process for finding the equilibria of an economy characterized by a finite number of linear equilibrium conditions. The process finds all equilibria or, if there are none, reports that, in a finite number of steps at most equal to the number of equations. The communication and computational complexity compare favorably with other decentralized processes. The process may also be interpreted as an algorithm for solving a distributed system of linear equations. Comparisons with the Linpack program for LU (lower and upper triangular decomposition of the matrix of the equation system, a version of Gaussian elimination) are presented.

Journal Article↗
PubMed2004

[Metal logarithmic scale titration as a tool for complexing ligand distribution determination: an application by DPASV].

A new logarithmic scale titration is proposed for the characterisation of natural organic matter-trace metals interactions in natural systems. The Suwannee River Fulvic Acid complexation with Cd and Pb ions has been analysed by this technique, using Differential Pulse Anodic Stripping Voltammetry (DPASV) for labile metal concentrations measurement. Results of titrations have been modelled by four ligands. Their complexing properties (CLi, Ki(Cd), Ki(Pb)) have been determined by a non-linear optimisation based on the speciation program MINEQL, coupled with a simplex. These ligands were called "very weak, weak, strong and very strong" with respect to their complexing constants (Ki(Cd), Ki(Pb)) ranging from 10(4) to 10(11). The obtained ligands concentrations (CLi) are respectively 1.9 microM, 150 nM, 25.1 nM and 21.1 nM for a 7.9 ppm carbon content. Moreover, this model takes account of the pH dependency and metals competition respectively by experiments at pH 7.8 and 4.6, and by definition of stability constants for each ligand toward each analysed metal. As a conclusion, the authors suggest a systematic use of the logarithmic scale titrations when full characterisation of the metal-organic matter interactions is necessary.

Cadmium↗
PubMed2006

Hyperlipidemia guideline adherence and association with patient gender.

BACKGROUND: Gender disparities in cardiovascular disease (CVD) management have become increasingly apparent in recent years. Previous research has focused on inpatient disparities, but little is known about how patient gender affects assessment, treatment, and management of patients for hyperlipidemia and cardiovascular risk in primary care settings. Patients with coronary artery disease (CAD) and hyperlipidemia are at high risk for cardiovascular and cerebrovascular morbidity. We sought to examine the effect of patient gender on assessment, treatment, and target maintenance of hyperlipidemia among patients with CAD in a primary care setting. METHODS: Chart abstraction was done for 715 patients with CAD in 55 family practices in New Jersey and eastern Pennsylvania as part of the Using Learning Teams for Reflective Adaptation (ULTRA) project. Hyperlipidemia assessment, treatment, and target adherence scores were determined for those at-risk patients based on National Heart, Lung, and Blood Institute (NHLBI) recommended National Cholesterol Education Program (NCEP) ATP III guidelines. Generalized linear models were used to determine the association of hyperlipidemia guideline adherence with patient gender, using comorbidities and age as confounders. RESULTS: After controlling for comorbidities and age, women were less likely to be assessed for lipids (p = 0.0462). There was no difference in treatment (p = 0.1074) or target laboratory values (p = 0.3949). CONCLUSIONS: Women with CAD are less often assessed for lipids than men in primary care practices. More intensive efforts may be necessary to educate physicians and patients about cardiovascular risk for women.

Adult↗
PubMed1999

Local sequence alignments with monotonic gap penalties.

MOTIVATION: Sequence alignments obtained using affine gap penalties are not always biologically correct, because the insertion of long gaps is over-penalised. There is a need for an efficient algorithm which can find local alignments using non-linear gap penalties. RESULTS: A dynamic programming algorithm is described which computes optimal local sequence alignments for arbitrary, monotonically increasing gap penalties, i.e. where the cost g(k) of inserting a gap of k symbols is such that g(k) >/= g(k-1). The running time of the algorithm is dependent on the scoring scheme; if the expected score of an alignment between random, unrelated sequences of lengths m, n is proportional to log mn, then with one exception, the algorithm has expected running time O(mn). Elsewhere, the running time is no greater than O(mn(m+n)). Optimisations are described which appear to reduce the worst-case run-time to O(mn) in many cases. We show how using a non-affine gap penalty can dramatically increase the probability of detecting a similarity containing a long gap. AVAILABILITY: The source code is available to academic collaborators under licence.

Algorithms↗
PubMed2004

DPRml: distributed phylogeny reconstruction by maximum likelihood.

MOTIVATION: In recent years there has been increased interest in producing large and accurate phylogenetic trees using statistical approaches. However for a large number of taxa, it is not feasible to construct large and accurate trees using only a single processor. A number of specialized parallel programs have been produced in an attempt to address the huge computational requirements of maximum likelihood. We express a number of concerns about the current set of parallel phylogenetic programs which are currently severely limiting the widespread availability and use of parallel computing in maximum likelihood-based phylogenetic analysis. RESULTS: We have identified the suitability of phylogenetic analysis to large-scale heterogeneous distributed computing. We have completed a distributed and fully cross-platform phylogenetic tree building program called distributed phylogeny reconstruction by maximum likelihood. It uses an already proven maximum likelihood-based tree building algorithm and a popular phylogenetic analysis library for all its likelihood calculations. It offers one of the most extensive sets of DNA substitution models currently available. We are the first, to our knowledge, to report the completion of a distributed phylogenetic tree building program that can achieve near-linear speedup while only using the idle clock cycles of machines. For those in an academic or corporate environment with hundreds of idle desktop machines, we have shown how distributed computing can deliver a 'free' ML supercomputer.

Algorithms↗
PubMed2005

Craniofacial changes in Icelandic children between 6 and 16 years of age - a longitudinal study.

The aim of the present study was to describe the craniofacial changes between 6 and 16 years of age in a sample of Icelandic children. Complete sets of lateral cephalometric radiographs were available from 95 males and 87 females. Twenty-two reference points were digitized and processed by standard methods, using the Dentofacial Planner computer software program. Thirty-three angular and linear variables were calculated, including: basal sagittal and vertical measurements, facial ratio, and dental, cranial base and mandibular measurements. For the angular measurements, gender differences were not statistically different for any of the measurements, in either age group, except for the variable s-n-na, which was larger in the 16-year-old boys (P < or = 0.001). Linear variables were consistently larger in the boys compared with the girls at both age levels. During the observation period mandibular prognathism increased but the basal sagittal jaw relationship, the jaw angle, the mandibular plane angle and cranial base flexure (n-s-ba) decreased in both genders (P < or = 0.001). Maxillary prognathism increased only in the boys from 6 to 16 years. Inclination of the lower incisors and all the cranial base dimensions increased in both genders during the observation period. When the Icelandic sample was compared with a similar Norwegian sample, small differences could be noted in the maxillary prognathism, mandibular plane angle and in the inclination of the maxilla. Larger differences were identified in the inclination of the lower incisors. These findings could be used as normative cephalometric standards for 6- and 16-year-old Icelandic children.

Adolescent↗
PubMed2003

Three-dimensional surgical planning for maxillary and midface distraction osteogenesis.

Computerized surgical planning protocols for distraction osteogenesis are still in their rudimentary phase. The authors have developed a system to plan distraction osteogenesis in craniofacial and maxillofacial surgery that uses three-dimensional computed tomography scans and computer simulation in a virtual reality environment. This involves the creation of a three-dimensional bone model of the craniofacial skeleton, which incorporates virtual globes. Virtual osteotomies are performed on the bone model and the movements of the bone segments are simulated. The program generates a recipe for the linear and the angular changes necessary to achieve the desired outcome. The purpose of this article is to present this surgical planning process and discuss its use in maxillary and midface distraction.

Child↗
PubMed2003

Domestic violence: increasing knowledge and improving skills with a four-hour workshop using standardized patients.

PURPOSE: Domestic violence (DV) is common, yet physicians feel unprepared to address it. Educational interventions may improve the care provided to DV victims, yet the effectiveness of interventions is often unproven. METHOD: Written questions and DV-specific standardized patient (SP) checklist items from an end-of-clerkship and fourth-year comprehensive multispecialty (the Clinical Performance Examination or CPX) examinations of medical students participating in a DV workshop using SPs was compared with nonparticipants. RESULTS: DV workshop participants' and nonparticipants' written question mean scores were 93.2% and 85.8%, respectively, p =.02. End-of-clerkship SP examination DV-specific checklist scores for participants and nonparticipants was 76.3% and 60.0%, respectively, p =.002. Workshop participants scored 44.1% on the CPX DV-specific checklist items versus 35.6% for the nonparticipants, p =.01. CONCLUSION: A DV workshop improved knowledge and skills assessed four and an average of 27 weeks later.

Clinical Clerkship↗
PubMed1980

Numerical integration simulation programs for the microcomputer.

Programs for use with the Apple II Plus microcomputer that generate graphic simulations of various linear and Michaelis-Menten pharmacokinetic models are described. The programs numerically integrate sets of differential equations for appropriate pharmacokinetic models. Multiple oral (or intramuscular), intravenous bolus, or infusion doses (continuous or discontinuous) may be administered in any combination. Doses as well as pharmacokinetic parameters may be changed at the end of each simulated dosing interval. The programs can be easily modified by users familiar with the BASIC programming language and offer an economical approach to pharmacokinetic simulation.

Computers↗
PubMed2003

Tolerable hearing aid delays. III. Effects on speech production and perception of across-frequency variation in delay.

OBJECTIVE: Signal processing strategies that attempt to mimic the frequency resolution of the healthy cochlea require finer frequency resolution at low frequencies than at high. The filtering required will cause more delay to the low-frequency end of the spectrum than to the high-frequency end, which may have disturbing effects. In a real-time application, making the delay constant across frequency would require the higher frequency components to be subjected to a compensating delay, leading to a larger overall delay, which may also give rise to disturbing effects (Stone & Moore, 1999, 2002). This experiment assessed the effects of frequency-dependent delay on subjective and objective measures of speech production and perception. DESIGN: Digital filtering was used to introduce across-frequency delays of 0, 4, 9, 15, or 24 msec. The low frequencies were always more delayed than the high frequencies, with a smooth variation in delay between the low and the high frequencies. In addition, there was a 2.5 msec delay that did not vary with frequency arising from the processes of analog-digital-analog conversion and equalization. Ten subjects with symmetric, bilateral, moderate hearing impairment of cochlear origin were fitted binaurally with Phonak PicoNet2 BTE linear hearing aids. The aids were programmed to provide insertion gains closely approximating the NAL (RP) (Byrne & Dillon, 1986) prescription for each subject and ear. The output of an omnidirectional microphone, attached on top of each aid, fed a digital filtering unit that introduced the across-frequency delay. Audio shoes reintroduced the signal back into the BTE aids. Subjects were tested in a counterbalanced order for their identification of vowel-consonant-vowel (VCV) syllables. In a second session, the same subjects spoke from a script: their utterances were recorded on tape, speech production rates were measured and subjective ratings of the disturbance of the delay were obtained. Subjects required some training to recognize the effects of the delay and rate them consistently. RESULTS: Subjective disturbance increased progressively with increasing across-frequency delay. A 9-msec delay was significantly more disturbing than a 0-msec delay. A delay of about 20 msec led to a mean rating of "disturbing." VCV identification decreased significantly once the across-frequency delay was 15 msec or greater. However, word production rates were not significantly affected by across-frequency delay over the range tested. CONCLUSIONS: Relatively small across-frequency delays (9 to 15 msec) give rise to significant changes in speech identification and subjective disturbance. A delay of 9 to 15 msec, constant across frequency, would have a smaller effect (Stone & Moore, 1999). It appears desirable to compensate, at least in part, for across-frequency delays introduced by any processing.

Aged↗
PubMed2006

Investigation of transverse oscillation method.

Conventional ultrasound scanners can display only the axial component of the blood velocity vector, which is a significant limitation when vessels nearly parallel to the skin surface are scanned. The transverse oscillation (TO) method overcomes this limitation by introducing a TO and an axial oscillation in the pulse echo field. The theory behind the creation of the double oscillation pulse echo field is explained as well as the theory behind the estimation of the vector velocity. A parameter study of the method is performed, using the ultrasound simulation program Field II. A virtual linear-array transducer with center frequency 7 MHz and 128 active elements is created, and a virtual blood vessel of radius 6.4 mm is simulated. The performance of the TO method is found around an initial point in the parameter space. The parameters varied are: flow angle, transmit focus depth, receive apodization, pulse length, transverse wave length, number of emissions, signal-to-noise ratio (SNR), and type of echo-canceling filter used. Using an experimental scanner, the performance of the TO method is evaluated. An experimental flowrig is used to create laminar parabolic flow in a blood mimicking fluid, and the fluid is scanned under different flow-to-beam angles. The relative standard deviation on the transverse velocity estimate is found to be less than 10% for all angles between 50 degrees and 90 degrees. Furthermore, the TO method is evaluated in the flowrig using pulsatile flow, which resembles the flow in the femoral artery. The estimated volume flow as a function of time is compared to the volume flow derived from a conventional axial method at a flow-to-beam angle of 60 degrees. It is found that the method is highly sensitive to the angle between the flow and the beam direction. Also, the choice of echo canceling filter affects the performance significantly.

Algorithms↗
PubMed2004

Population pharmacokinetic modeling of steady state clearance of carbamazepine and its epoxide metabolite from sparse routine clinical data.

OBJECTIVE: To develop a population pharmacokinetic model to evaluate the effects of variety of covariates on clearance of carbamazepine (CBZ) and its main metabolite carbamazepine-10,11-epoxide (CBZE) in Chinese population. METHODS: Serum samples at steady trough state (n = 459) were collected prospectively from 408 compliant outpatients during their routine clinical care. CBZ and CBZE concentrations were simultaneously determined by high performance liquid chromatography. Population clearance (CL) of CBZ and CBZE were estimated by non-linear mixed effect modeling and NONMEM program with a one-compartment model of first-order absorption and elimination. RESULTS: Total body weight (TBW), dose and concomitant medication were all important determinants of CL of CBZ and CBZE. The final regression model for CBZ was: where VPA = 1 for patients comedicated with valproic acid and its dose greater than 18 mg/kg, otherwise VPA = 0; PHT = 1 for patients comedicated with phenytoin, otherwise PHT = 0; PB = 1 for patients comedicated with phenytoin, otherwise PB = 0. The final regression CL model for the CBZE was: where VPA = 1 for patients comedicated with valproic acid, otherwise VPA = 0. CONCLUSION: The current models, which describe CL of CBZ and CBZE in terms of patient specific details, can be used as a reference to optimize CBZ therapy in Chinese epilepsy patients.

Administration, Oral↗
PubMed1992

Mathematical description of the concentration of oxytetracycline and penicillin-G in tissue cages in calves as related to the serum concentration.

A mathematical model based on Fick's laws of diffusion describing the concentration of drug in tissue cage models was elaborated. The model takes into account differences in protein binding, tissue cage geometry and serum pharmacokinetics. The validity of the model was tested against experimental data obtained from a tissue cage model in calves by simultaneous fitting to serum and tissue cage fluid (TCF) data in a non-linear least-squares regression computer program. Concentrations of penicillin-G (pen-G) in serum and TCF following intravenous (i.v.) administration of potassium pen-G were adequately described by the mathematical model. Concentrations in TCF after intramuscular (i.m.) administration of the same drug and of procaine pen-G could be predicted by the mathematical model. Concentrations of oxytetracycline (OTC) in serum and TCF following i.v. administration and continuous i.v. infusions were also adequately described by the model, and TCF concentrations after i.m. administration of the same drug could be roughly predicted. The results indicate that pen-G and OTC have the same permeability coefficient for transport from serum to TCF.

Animals↗