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PubMed2003

The second generation of the International Equine Gene Mapping Workshop half-sibling linkage map.

A low-density, male-based linkage map was constructed as one of the objectives of the International Equine Gene Mapping Workshop. Here we report the second generation map based on testing 503 half-sibling offspring from 13 sire families for 344 informative markers using the CRIMAP program. The multipoint linkage analysis localized 310 markers (90%) with 257 markers being linearly ordered. The map included 34 linkage groups representing all 31 autosomes and spanning 2262 cM with an average interval between loci of 10.1 cM. This map is a milestone in that it is the first map with linkage groups assigned to each of the 31 automosomes and a single linkage group to all but three chromosomes.

Animals↗
PubMed2002

Can specific patient variables be used to predict outcome of intracranial hemorrhage?

The study objective was to identify the demographic, physiologic, and anatomic variables associated with outcomes of patients with intracranial hemorrhages. We performed a prospective study of all patients with known or suspected intracranial hemorrhages transferred from a community hospital to the neurosurgical service of tertiary care centers in Toronto. Outcomes measured were patient disposition (admitted v discharged immediately), management (neurosurgical interventions v observation) and survival until discharge v death. Patient variables recorded pre- and post-transfer were analyzed using the statistical programs C.H.A.I.D. and C.A.R.T.(Answer-Tree Software, SPSS Inc.Headquarters, Chicago, IL). Two linear regression trees were constructed to reveal associations with each outcome. Sixty-seven patients between the ages of 24 and 89 were included in the study. Of these, 1 was referred for an epidural bleed, 20 for subdural bleeds, 21 for subarachnoid hemorrhages, and 25 for intracerebral hemorrhages. Thirteen of the patients in the study died or remained with permanent, severe neurological deficits. Of these, none had epidural hemorrhages, 4 had subdural hemorrhages, 5 had subarachnoid hemorrhages, and 4 had intracerebral hemorrhages. The linear regression tree constructed with C.A.R.T. revealed that the most important predictor of outcome was the GCS score of the patient on arrival at the neurosurgical center. Specifically, 71.43% of individuals arriving with a GCS score less than or equal to 7 died or remained with a severe neurological deficit, whereas only 5.66% of individuals arriving with a GCS score greater than or equal to 8 had such an outcome (P<.11). The regression tree constructed using C.H.A.I.D. revealed a similar result. Patients with a GCS score less than or equal to 5 on arrival at the neurosurgical center had a 70% chance of dying or remaining with a severe neurological deficit, whereas those with a GCS score greater than or equal to 13 had a 0% chance of having such an outcome (P <.0001). Furthermore, 100% of patients with post-transfer GCS scores less than or equal to 5 and an absent gag reflex died or remained with a severe neurological deficit compared with only 25% of those with a GCS score less than or equal to 5 with an intact gag reflex (P =.0005). This study also revealed a number of incidental findings. The presence of bilateral unreactive pupils, absent corneal reflex or absent vestibulo-ocular reflex (dolls-eye) independently predicted mortality in 100% of patients (not statistically significant). No patient with any of the following characteristics: any pupillary abnormality or age > 62 with a GCS < 5, achieved a normal functional outcome. Within the population of patients referred from community hospitals to a neurosurgical center for evaluation of intracranial hemorrhage, specific clinical findings are powerful predictors of mortality and poor functional outcome. Patients with a post-transfer GCS score <= 5 and an absent gag reflex had a 100% incidence of death or severe, permanent neurological dysfunction compared with only 25% of those arriving with GCS scores <= 5 with an intact gag reflex (P =.0005). Additionally, The presence of bilateral unreactive pupils, absent corneal reflex and absent vestibulo-ocular reflex independently predicted mortality in 100% of patients (not statistically significant). Other clinical findings including any pupillary abnormality and GCS <=5 combined with age => 62 negated the possibility of normal functional outcome (not statistically significant). These findings may have wide-ranging implications regarding the transfer and treatment of patients with intracranial hemorrhages, use of resources and counseling of families.

Adult↗
PubMed2004

LocalSCF method for semiempirical quantum-chemical calculation of ultralarge biomolecules.

A linear-scaling semiempirical method, LocalSCF, has been proposed for the quantum-chemical calculations of ultralarge molecular systems by treating the large-scale molecular task as a variational problem. The method resolves the self-consistent field task through the finite atomic expansion of weakly nonorthogonal localized molecular orbitals. The inverse overlap matrix arising from the nonorthogonality of the localized orbitals is approximated by preserving the first-order perturbation term and applying the second-order correction by means of a penalty function. This allows for the separation of the orbital expansion procedure from the self-consistent field optimization of linear coefficients, thereby maintaining the localized molecular orbital size unchanged during the refinement of linear coefficients. Orbital normalization is preserved analytically by the variation of virtual degrees of freedom, which are orthogonal to the initial orbitals. Optimization of linear coefficients of localized orbitals is performed by a gradient procedure. The computer program running on a commodity personal computer was applied to the GroEL-GroES chaperonin complex containing 119,273 atoms.

Algorithms↗
PubMed2004

CisModule: de novo discovery of cis-regulatory modules by hierarchical mixture modeling.

The regulatory information for a eukaryotic gene is encoded in cis-regulatory modules. The binding sites for a set of interacting transcription factors have the tendency to colocalize to the same modules. Current de novo motif discovery methods do not take advantage of this knowledge. We propose a hierarchical mixture approach to model the cis-regulatory module structure. Based on the model, a new de novo motif-module discovery algorithm, CisModule, is developed for the Bayesian inference of module locations and within-module motif sites. Dynamic programming-like recursions are developed to reduce the computational complexity from exponential to linear in sequence length. By using both simulated and real data sets, we demonstrate that CisModule is not only accurate in predicting modules but also more sensitive in detecting motif patterns and binding sites than standard motif discovery methods are.

Algorithms↗
PubMed2002

Comparative ab initio prediction of gene structures using pair HMMs.

We present a novel comparative method for the ab initio prediction of protein coding genes in eukaryotic genomes. The method simultaneously predicts the gene structures of two un-annotated input DNA sequences which are homologous to each other and retrieves the subsequences which are conserved between the two DNA sequences. It is capable of predicting partial, complete and multiple genes and can align pairs of genes which differ by events of exon-fusion or exon-splitting. The method employs a probabilistic pair hidden Markov model. We generate annotations using our model with two different algorithms: the Viterbi algorithm in its linear memory implementation and a new heuristic algorithm, called the stepping stone, for which both memory and time requirements scale linearly with the sequence length. We have implemented the model in a computer program called DOUBLESCAN. In this article, we introduce the method and confirm the validity of the approach on a test set of 80 pairs of orthologous DNA sequences from mouse and human. More information can be found at: http://www.sanger.ac.uk/Software/analysis/doublescan/

Algorithms↗
PubMed1991

Statistical analysis in dBASE-compatible databases.

Database management in clinical and experimental research often requires statistical analysis of the data in addition to the usual functions for storing, organizing, manipulating and reporting. With most database systems, transfer of data to a dedicated statistics package is a relatively simple task. However, many statistics programs lack the powerful features found in database management software. dBASE IV and compatible programs are currently among the most widely used database management programs. d4STAT is a utility program for dBASE, containing a collection of statistical functions and tests for data stored in the dBASE file format. By using d4STAT, statistical calculations may be performed directly on the data stored in the database without having to exit dBASE IV or export data. Record selection and variable transformations are performed in memory, thus obviating the need for creating new variables or data files. The current version of the program contains routines for descriptive statistics, paired and unpaired t-tests, correlation, linear regression, frequency tables, Mann-Whitney U-test, Wilcoxon signed rank test, a time-saving procedure for counting observations according to user specified selection criteria, survival analysis (product limit estimate analysis, log-rank test, and graphics), and normal t and chi-squared distribution functions.

Database Management Systems↗
PubMedDate not supplied

HPLC separations with micro-bore columns using high-temperature water and flame ionization detection.

Previous work demonstrates that a flame ionization detector (FID) may be used as a detector for high-temperature water separation. However, the relatively high flow rate of the eluent required by standard high-performance liquid chromatography columns causes instability of the FID. In this work, micro-bore columns are packed with poly(styrene-divinylbenzene) (PRP-1) or Daiso gel octadecylsilane-bonded phase particles. Because micro columns require low volume flow rates, the eluent used in high-temperature water chromatography does not cause instability of the FID. Separation of carbohydrates, amino acids, and other organic acids and bases is performed on two micro-bore columns using a homemade high-temperature water chromatograph with FID. Both isothermal and programmed temperatures are used in this work. The limit of detection and the linear range are also determined for amino acids tested.

Journal Article↗
PubMed2001

Population pharmacokinetics of panipenem in neonates and retrospective evaluation of dosage.

The population pharmacokinetics of panipenem was studied in 23 neonates. Their postconceptional age (PCA) was 24.7-42.6 weeks and their body weight was 530-4455 g at initiation of therapy. Panipenem was infused over a period of 60 min in a dose of 10.2-34.7 mg/kg bd in 21 patients, tid in one patient and four times daily in one patient for a mean of 10.7 days. Blood samples were obtained just before the infusion and 1-2 h after and again 6 h after the infusion. All the data for the 108 serum panipenem concentrations were evaluated with a non-linear mixed-effect model (NONMEM with first-order method), a computer program designed for population pharmacokinetic analysis. One- and two-compartment population pharmacokinetic parameters were measured. The two-compartment parameters were as follows: panipenem clearance CL = 0.150 L/h, central volume of distribution = 0.54 L, intercompartmental clearance = 0.014 L/h and peripheral volume of distribution = 0.28 L. The one-compartment parameters were CL = 0.175 L/h and volume of distribution = 0.55 L. In the fitting process using the one-compartment model, significantly fixed effects related to CL were PCA, postnatal age (PNA), gestational age (GA), body weight (BW) and serum creatinine, and that for the distribution volume (V) was BW. CL showed a logarithmic rise with PCA (CL = 0.00176 x exp(0.14 x PCA)). The CL levels in the patients with PCA < 33 weeks (0.098 L/h) were significantly lower (P < 0.001) than those with PCA > or = 33 weeks (0.25 L/h). The final formulae for the population pharmacokinetic parameters are as follows: CL = 0.0832 (PCA < 33 weeks), CL = 0.179 x BW (PCA > or = 33 weeks), V = 0.53 x BW (coefficient of variation; 23.9% for CL, 28.5% for V). Based on these data, a simulated time-concentration curve was compared with that for adult data in a clinical Phase I study. Our findings suggest that the panipenem dosage regimen of 10-20 mg/kg every 12 h should yield concentrations within the accepted therapeutic range.

Anti-Bacterial Agents↗
PubMed2006

In vivo mechanical behavior of intra-abdominal organs.

For realistic surgical simulation in a virtual environment, in vivo material properties of biological tissues are required for simulating the deformations and the reaction forces from the tool-tissue interactions. In this paper, the in vivo static and dynamic mechanical behavior of the liver and lower esophagus of pigs were presented both in linear and nonlinear regions under compressive and shear indentations. A robotic device was programmed to function as a mechanical stimulator with a 2-mm flat-tipped cylindrical probe attached to its tip. A series of ramp and hold stimuli, as well as sinusoidal indentation stimuli, were delivered to the organs and reaction forces were measured. The conditions for these indentation stimuli were designed such that they were similar to conditions in an operating room. Experiments were also carried out on the organs for ex vivo and in vitro conditions. Results show that the breathing and pulse rate significantly affect the measured force responses of the organs. From the obtained force-displacement relationships, steady-state impedances as well as dynamic impedances of both organs were calculated. The results also show that in vivo steady-state impedance of the lower esophagus is significantly higher than that of the liver. The in vivo steady-state response of the liver, however, exhibits a greater degree of nonlinearity than that of the lower esophagus. The in vivo steady-state response of the lower esophagus in the three orthogonal directions also indicates that the lower esophagus is not significantly anisotropic. The impedance of both organs under sinusoidal indentations (0-5 Hz) are fairly similar each other. Magnitudes of the impedance over the stimulus frequencies are fairly constant. The impedance phase angles decrease over the range of stimulus frequencies applied. Comparison of the measurements obtained from the in vivo, ex vivo, and in vitro experiments shows that the mechanical properties of the biological tissues change significantly after the death of the animal. The tissues generally become stiffer and exhibit greater nonlinearity. The degree of change in their mechanical properties is dependent on the amount of time after the death of the animal. These data can be further utilized in the computing of the material parameters of tissue models for laparoscopic surgery simulators as well as open surgery simulators.

Abdomen↗
PubMed2006

Sebum output as a factor contributing to the size of facial pores.

BACKGROUND: Many endogenous and exogenous factors are known to cause enlarged pilosebaceous pores. Such factors include sex, genetic predisposition, ageing, chronic ultraviolet light exposure, comedogenic xenobiotics, acne and seborrhoea. This study was an attempt to determine the factors related to enlarged pores. OBJECTIVES: To assess the relationship of sebum output, age, sex, hormonal factors and severity of acne with pore size. METHODS: A prospective, randomized, controlled study was designed. A total of 60 volunteers, 30 males and 30 females, were recruited for this study. Magnified images of pores were taken using a dermoscopic video camera and measured using an image analysis program. The sebum output level was measured with a Sebumeter. RESULTS: Using multiple linear regression analysis, increased pore size was significantly associated with increased sebum output level, sex and age. Among the variables, sebum output level correlated most with the pore size followed by male sex. In comparing male and female participants, males had higher correlation between the sebum output level and the pore size (male: r = 0.47, female: r = 0.38). Thus, additional factors seem to influence pore size in females. Pore size was significantly increased during the ovulation phase (P = 0.008), but severity of acne was not significantly associated with the pore size. CONCLUSIONS: Enlarged pore sizes are associated with increased sebum output level, age and male sex. In female patients, additional hormonal factors, such as those of the menstrual cycle, affect the pore size.

Acne Vulgaris↗
PubMed2004

Prostate-specific antigen doubling time among Japanese men in an annual health screening program.

BACKGROUND: Prostate-specific antigen doubling time (PSA-DT) has been studied as a parameter reflecting the biological doubling rate of clinically localized prostate cancer treated expectantly. With the use of PSA-DT, we studied the natural history of PSA changes among Japanese men in a health screening program. METHODS: Between July 1994 and December 2002, a cohort of 1995 men aged 40-79 years underwent a total of 5700 PSA measurements in an annual multiphasic health screening program. Prostate-specific antigen doubling time was calculated using a log-linear regression model for 994 (49.8%) men who had three or more serial PSA measurements with a mean follow-up of 46.2 months. RESULTS: Of the 994 men, 192 (19.3%) had a PSA-DT of less than 10 years and 12 (1.2%) had a PSA-DT of less than 2 years. Median PSA-DT in 14 men with a subsequent diagnosis of prostate cancer was 41.6 months (range, 12.2 to stable). A log-linear model statistically fitted 65 of 180 non-cancer patients with a PSA-DT of less than 10 years. The percentages of statistically fit cases increased with higher baseline PSA (5.3%, 7.7% and 8.7% among men with <1.0, 1.0-1.99 and 2.0-3.99 ng/mL, respectively) and older baseline age (3.7%, 8.5% and 6.9% among ages 40-49, 50-59 and 60 or older, respectively). CONCLUSION: In a small but significant portion of men, PSA increases exponentially when it is still less than 4.0 ng/mL, with a PSA-DT of less than 10 years. The clinical significance of this finding should be evaluated by a prospective screening including biopsy.

Adult↗
PubMed2005

Quantification of the magnification and distortion effects of a pediatric flexible video-bronchoscope.

BACKGROUND: Flexible video bronchoscopes, in particular the Olympus BF Type 3C160, are commonly used in pediatric respiratory medicine. There is no data on the magnification and distortion effects of these bronchoscopes yet important clinical decisions are made from the images. The aim of this study was to systematically describe the magnification and distortion of flexible bronchoscope images taken at various distances from the object. METHODS: Using images of known objects and processing these by digital video and computer programs both magnification and distortion scales were derived. RESULTS: Magnification changes as a linear function between 100 mm (x1) and 10 mm (x9.55) and then as an exponential function between 10 mm and 3 mm (x40) from the object. Magnification depends on the axis of orientation of the object to the optic axis or geometrical axis of the bronchoscope. Magnification also varies across the field of view with the central magnification being 39% greater than at the periphery of the field of view at 15 mm from the object. However, in the paediatric situation the diameter of the orifices is usually less than 10 mm and thus this limits the exposure to these peripheral limits of magnification reduction. Intraclass correlations for measurements and repeatability studies between instruments are very high, r = 0.96. Distortion occurs as both barrel and geometric types but both types are heterogeneous across the field of view. Distortion of geometric type ranges up to 30% at 3 mm from the object but may be as low as 5% depending on the position of the object in relation to the optic axis. CONCLUSION: We conclude that the optimal working distance range is between 40 and 10 mm from the object. However the clinician should be cognisant of both variations in magnification and distortion in clinical judgements.

Artifacts↗
PubMed1989

Time constants of the vestibular thermal reaction.

For the thermal test, adaptation time constants of about 100 s are described in the literature. By automatically alternating hot-cold irrigation, as designed by us, precision of stimulus application of different temperatures was considerably improved. Furthermore, temperature was registered with a thermocouple device. The actually effective thermal stimulus on the horizontal canal was calculated by a mathematical model. Nystagmus analysis was carried out automatically with the Kiel-program. With 15 radical cavities (where stimulus intensity is very strong) non-linearities were especially distinct. After switching to the 44 degrees C stimulus, there was an extremely steep rise in the reaction in the form of a so-called "on-effect" or "post-inhibitory overshoot". After reaching maxima of up to 150 degrees/s, the reaction decreased quickly with time constants of 22-45 s.

Adaptation, Physiological↗
PubMed1997

Multiple memory hearing aid. Consistency of program-usage in real-world listening situations.

The aim of this study was to assess the repeatability of the program-usage in everyday listening situations. A blind field test was used. The Widex Quattro (WQ) system served as a model for multiple memory hearing aids (linear amplification) Eleven experienced WQ wearers (41-73 years) with mild to moderate, recruiting, cochlear hearing losses participated. Eight of them regularly used all four available programs (all used at least three programs). The participants stated in duplicate the best hearing aid program in 15 real-world listening situations. The percentage of subjects who selected identical programs (repeatability) surpassed the level corresponding to pure guess under almost all listening conditions (14). Maximum repeatability (100%) was achieved by the five subjects who visited an industrial environment twice. Interestingly, the repeatability exceeded 70% in demanding listening situations such as: party, conversation in group, etc. Support for this high repeatability was given by a distinct improvement in the mean aided speech-to-noise threshold (3.7 dB, p < 0.005).

Adult↗
PubMedDate not supplied

Modelling the arterial wall by finite elements.

The mechanical behaviour of the arterial wall was determined theoretically utilizing some parameters of blood flow measured in vivo. Continuous experimental measurements of pressure and diameter were recorded in anesthetized dogs on the thoracic ascending and midabdominal aorta. The pressure was measured by using a catheter, and the diameter firstly, at the same site, by a plethysmograph with mercury gauge and secondly, by a sonomicrometer with ferroelectric ceramic transducers. The unstressed radius and thickness were measured at the end of each experiment in situ. Considering that the viscous component is not important relatively to the nonlinear component of the elasticity and utilizing several equations for Young modulus calculation (thick and thin wall circular cylindrical tube formulas and Bergel's equation) the following values were obtained for this parameter: 0.6 MPa-2 MPa in midabdominal aorta and 2 MPa-6.5 MPa in thoracic ascending aorta. The behaviour of the aorta wall was modelled considering an elastic law and using the finite element program "Lagamine" working in large deformations. The discretized equilibrium equations are non-linear and a unique axi-symmetric, iso-parametric element of 1 cm in length with 8 knots was used for this bi-dimensional problem. The theoretical estimation of radius vessel, utilizing a constant 5 MPa Young modulus and also a variable one, are in good agreement with the experimental results, showing that this finite element model can be applied to study mechanical properties of the arteries in physiological and pathological conditions.

Animals↗
PubMed2006

[Simultaneous quantitative analysis of three kinds of phenols by Elman recurrent neural network].

Elman recurrent neural network ( ERNN) was applied to study the simultaneous quantitative analysis of seriously overlapped spectra of a p-nitrophenol, o-nitrophenol and 2,4-dinitrophenol system. The multivariate linear regression (MLR) method was also applied in this study for comparison. Two programs (PERNN and PMLR) were designed to perform the calculations. By optimization, the structure and parameters of Elman recurrent neural network were defined. The relative standard errors of prediction (RSEP) for all components with ERNN and MLR were 3.1% and 2 027.3%, respectively. Experimental results showed the method to be successful even where there was a severe overlap of spectra. The ERNN method is a valuable tool in solving the minimum problem and improving the convergence rate, and can be used to analyze the whole spectra rather than just picking out a few characteristic values. The method provides a new way of simultaneous determination of severely overlapped molecular spectra without prior separation.

English Abstract↗
PubMed2006

[Clinical pharmacokinetic trial of intravenous injection of recombinant human lymphotoxin-alpha derivative].

BACKGROUND & OBJECTIVE: Animal experiment showed that recombinant human lymphotoxin-alpha derivate (rhLTalpha-Da) could inhibit tumor growth,activate immunity, sensitize tumors to chemotherapy, and has low toxicity in vivo. rhLTalpha-Da won't accumulate after multiple administrations. This study was to investigate pharmacokinetic profile of rhLTalpha-Da in tumor patients to provide reference for phase II clinical trail. METHODS: The dosage of rhLTalpha-Da was 10, 20, and 33 microg x m(-2) x d(-1) according to phase I clinical endurance trial. rhLTalpha-Da was mixed with 100 ml 5% glucose solution, and then infused over 30 min on each of 5 consecutive days. Blood samples and urine samples were collected before and after infusion at different time points. Enzyme-linked immunosorbent assay (ELISA) and fluorescent bead immunoassay (FBI) were used to detect the concentration of rhLTalpha-Da in blood and urine. The main pharmacokinetic parameters were calculated by 3p97 pharmacokinetic program. RESULTS: From Feb. 2003 to Dec. 2003, 19 patients were enrolled. The linear range, specificity, precision, accuracy, and stability of ELISA method were satisfied. The lower limit of quantification (LLOQ) was 39 pg/ml. The linear range, sensitivity, specificity, intra-assay precision, and accuracy of FBI method were satisfied, but coefficient of variation of inter-assay precision was over 20%. rhLTalpha-Da in pharmacokinetics conformed to be a one-compartment open model:it had been eliminated quickly from serum and could not be detected 2 h after the cessation of infusion. The half lives (t1/2) of 33 microg x m(-2) x d(-1) and 20 microg x m(-2) x d(-1) of rhLTalpha-Da were (0.24+/-0.09) h and (0.25+/-0.10) h; the abundant volumes of distribution (Vd) were (35.8+/-1.6) L/m(2) and (43.3+/-26.0) L/m(2); the clearance (CL) were (343.36+/-63.23) ng x m(-2) x h(-1) and (269.60+/-24.52)ng x m(-2) x h(-1); the areas under concentration-time curve (AUC) were (74.6+/-18.4) ng x h x L(-1) and (99.0+/-17.8) ng x h x L(-1), respectively. CONCLUSIONS: The pharmacokinetics of rhLTalpha-Da after infusion is fitted to one compartment model and its elimination is linear. There is no rhLTalpha-Da accumulation after multiple administrations.

Adult↗
PubMed1984

A densitometer based on a microcomputer and TV camera, for use in the clinical laboratory.

We describe a microcomputer-based densitometer that includes a television camera for the analysis of one- and two-dimensional electrophoresis gels. The hardware configuration is a modification of that described by Mariash et al. (Anal Biochem 212: 388-394, 1982). The video signal is digitized by a commercially available interface, yielding 1 of 64 greyscale values for each pixel examined. The operator controls the region being analyzed through the use of a joystick and video monitor. We have optimized the linear response range (0-1.5 A) and have written a relatively simple control program ("GELSCAN 5.0"). For analyses of one-dimensional gels, the required operator decisions include the start and finish points of the gel, the width of the scan (analogous to slit size), and the level of background correction. The digital information may be stored on disk, displayed by one of several graphic routines, and analyzed for total scan and individual peak absorbance values. Similar analyses may be done with two-dimensional gel spots.

Computers↗