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PubMed1985

Optimizing stimulating and recording parameters in somatosensory evoked potential studies.

Methods to increase the signal:noise ratio of evoked potentials are reviewed, dividing them into three groups: (1) increasing the number of stimuli averaged; (2) decreasing the noise (muscle relaxation, filters, intermittent artifact reject methods); and (3) increasing the amplitude of the signal (stimulus intensity, nerves stimulated, bilateral versus unilateral stimulation, stimulus modality, and montage). Examples of these different methods applied to recording of somatosensory evoked potentials are given, and it is concluded that, for optimal recording of somatosensory evoked potentials, a combination of all these methods should be used.

Electric Stimulation↗

PubMed1994

Optimal sampling theory: effect of error in a nominal parameter value on bias and precision of parameter estimation.

The authors examined the robustness of optimal sampling theory in estimating the parameter values of two different populations of patients receiving a constant rate, half-hour intravenous infusion of theophylline. One population consisted of smokers; the other included nonsmokers. The smoking population was predicted to have a serum clearance approximately 50% greater than the nonsmokers because of an induction of the cytochrome P450 system. After an initial study to provide both patient-specific and population mean parameter values, optimal sampling strategies that were derived from each population (seven sample split designs) and the patient's seven sample and four sample design were determined. A second study was performed with an overall sampling strategy that was superset of all the above strategies. The analysis of all samples served as the reference for the parameter values. Bias and precision of the values determined with each of the optimal sampling sets (seven sample sets based on the "correct" and "wrong" populations, the patient's seven and four sample sets) were determined relative to these reference values. Irrespective of the sample set used for analysis, unbiased and precise parameter estimates, particularly of hybrid parameters were provided. With the patient's four sample set, Vss was significantly biased, but the value of (2.2%) was clinically insignificant. The authors conclude that optimal sampling theory, as implemented in this study, provides robust estimates of important pharmacokinetic parameter values, even when errors of 50% are present in the clearance of the population used to calculate the optimal sampling design.

Adolescent↗

PubMedDate not supplied

In-vivo particle mediated delivery of mRNA to mammalian tissues: ballistic and biologic effects.

Biolistic transmission of mRNA provides transient gene therapy to in vivo organs. This study documents particle mediated mRNA transmission to a solid organ and wound healing model using the mRNA of Green Fluorescent Protein to determine optimal delivery parameters. Renal function, bullet penetration, cellular injury, and Green Fluorescent Protein synthesis were quantified. Chimeric human epidermal growth factor-FLAG epitope cDNA or mRNA was transmitted to wounds in normal or steroid treated animals. Wound bursting strength, human epidermal growth factor-FLAG, and collagen synthesis were determined. Injury and bullet penetration correlated with the delivery velocity and bullet size. Optimal delivery parameters were established which provided widespread Green Fluorescent Protein synthesis. Human epidermal growth factor-FLAG treatment significantly increased collagen content and wound breaking strength in normal and steroid treated animals. FLAG protein synthesis was evident in mRNA treated fascia following treatment. We found the gene gun provides a novel method for efficient, in vivo delivery of mRNA-based therapeutic strategies to mammalian organs with minimal histologic damage allowing transient expression of protein in in vivo target tissues. Co-delivery of Green Fluorescent Protein mRNA may provide a useful positive control to determine effective transmission. Biolistic transmission of human epidermal growth factor-FLAG mRNA provides increased tissue epidermal growth factor levels and accelerates wound healing in normal and steroid exposed animals.

Animals↗

PubMed2006

Vestibular evoked myogenic potentials in young children: test parameters and normative data.

OBJECTIVE: The vestibular evoked myogenic potential (VEMP) is a test of the vestibulocollic reflex that has been extensively studied in adults. Much is known about the normal values in adults as well as their changes with age. In children, the expected test values and their possible changes in development have not yet been described nor has the feasibility of reliable testing in this group. The aim of this prospective study is to accumulate normative data and to verify the viability of testing in young children. The study focused on optimal test parameters, reproducibility, and subject compliance in a pediatric population. METHODS: Thirty normal-hearing children (60 ears) ages 3 to 11 completed VEMP testing and audiograms for analysis. VEMP testing was performed with alternating clicks at three intensities (80-, 85-, and 90-dB normalized hearing level) using averaged, unrectified electromyograms recorded by surface electrode on the sternocleidomastoid muscle ipsilateral to the stimulus. VEMP latencies, amplitude, compliance, and length of testing were recorded for each patient, as well as their feedback on the testing session. The subjects were divided into four age groups for analysis. RESULTS: All but one of the subjects attempting VEMP testing was able to finish. Of 30 children completing VEMP tests, bilateral reflexes were recorded for all subjects with symmetric responses in 28 of 30 subjects (93%). The mean peak latencies (+/- standard deviation [SD]) of pI and nII were 11.3 msec (1.3 ms) and 17.6 msec (1.4 ms), respectively. The mean pI-nII amplitude (+/- SD) was 122 muV (68 muV). There was a significantly shorter nII mean peak latency of group I (ages 3-5) left ear in comparison to other groups, with an absolute shorter mean latency nII in the right ear of group I (not significant). Average test time was 15 minutes with two researchers testing, and subjects were highly compliant. CONCLUSIONS: VEMP is a well-tolerated test for screening vestibular function in young children, performed with minimal test time and reproducible results. Mean latencies in this study suggested a shorter initial negative peak (nII) than in adult studies, consistent with prolongation seen in previous research on the effects of age. Ninety-decibel normalized hearing level clicks were adequate for uniform response rates. Expected latency and amplitude values in single-channel VEMP-unrectified electromyograms were established. This is the first study describing expected latencies and optimal testing parameters in children.

Child↗

PubMed1985

A microcomputer method for designing optimal experiments for estimating enzyme kinetic parameters.

A computer program, written in BASIC, for designing optimal experiments with the aim of evaluating estimates of the parameters for any enzyme kinetic model is given. This computer program can be run on any microcomputer with less than 32 Kbytes of random access memory. The program uses the termed D-optimization design criterion, which minimizes the determinant of the variance-covariance matrix. The user only supplies the rate equation, the maximum and minimum concentrations of substrates and inhibitors, the weighting pattern, and the best possible values of the parameters. The computer supplies the optimal substrate and inhibitor concentrations (one for each parameter), for estimating the parameter values, and the determinant of the variance-covariance matrix. Likewise, the microcomputer supplies the eigenvalues and eigenvectors of information and redundancy matrices, the sensitivity and the global redundancy.

Biometry↗

PubMed2004

Pulsatile motion effects on 3D magnetic resonance angiography: implications for evaluating carotid artery stenoses.

In-plane carotid artery motion during a 3D MR angiography (MRA) scan can significantly degrade the resulting image resolution. This study characterizes the effect of cardiac pulsatility on 3D contrast-enhanced (CE) MRA with elliptical centric acquisitions using a point-spread function (PSF) analysis. Internal carotid artery (ICA) motion was collected from volunteers and patients using both MR and ultrasound (US) scans. After measuring the carotid artery motion displacement, a simulation was performed which calculated the blurring effects for three different protocols: nongated and two different cardiac gating schemes. The motion sensitivity of each protocol was evaluated for different spatial resolutions. The selection of optimal imaging parameters for a given scan time was investigated. The final results showed that cardiac-gated acquisitions only over a limited region of k-space high spatial frequencies are more time-efficient than cardiac gating for the entire k-space, as it allows for higher resolutions to be achieved and for capturing the arterial phase with low spatial frequencies. Selecting the optimal gating parameters depends directly on the motion characteristics of each individual. Our initial clinical experience is presented, and the need for a real-time tool that characterizes motion behavior for each individual as a prescan protocol is discussed.

Carotid Arteries↗

PubMedDate not supplied

[Optimization of artificial respiration parameters in patients with acute pulmonary parenchymal damage syndrome].

The relationship between the mean pressure in the trachea, generated in mechanical ventilation of the lungs (Ptr.m), and normal arterial oxygenation is linear in ventilated patients with severe bilateral acute parenchymatous damage to the lungs. Under conditions of mechanical ventilation of the lungs (MVL) with regulated volume, constant end-expiratory pressure (PEEP) and inspiratory pause (eIP) are effective methods for regulating Ptr.m. However, the efficacy of regulating Ptr.m by PEEP and IF for each clinical case is different. The algorithm of using PEEP and IF for optimizing the respiratory pattern in this category of patients is not clear, too. The results indicate that optimization of MVL with controlled volume should be started with selecting the optimal level of PEEP for each patient. The level of Ptr.m should not be increased immediately at by of prolonging eIP, because the probability of compromising the hemodynamics is higher in such a case than the probability of improving blood oxygenation. Only after selecting the optimal PEEP is it permissible to try to improve arterial oxygenation by prolonging xx, because under such conditions the efficacy of prolonged inspiration is notably increased. Our data indicate that eIP no higher than 30% of the respiratory cycle (inspiration/expiration = 1.5/1) is the optimal. A further increase of eIP gives rise to a tendency towards decrease of arterial oxygenation and oxygen transport to tissues.

Acute Disease↗

PubMed2002

Optimization of sorghum transformation parameters using genes for green fluorescent protein and beta-glucuronidase as visual markers.

Early and reliable detection of plant transformation events is essential for establishing efficient transformation protocols. We have compared the effectiveness of using the gene encoding a green fluorescent protein (GFP) and a beta-glucuronidase (gus) as reporter genes for early detection of transgene expression in explants subjected to biolistic bombardment and Agrobacterium-mediated transformation. The results indicate that gfp gene is superior to gus gene in following transgene expression in transiently transformed materials in both methods of transformation. Using GFP as the screenable marker, we have optimized sorghum transformation with respect to the conditions for transformation, type of explants, promoters, and inbreds. These optimized conditions have been used to obtain stably transformed explants for subsequent regeneration.

Biolistics↗

PubMed2004

Intraoperative identification and neurophysiologic parameters to verify pelvic autonomic nerve function during total mesorectal excision for rectal cancer.

BACKGROUND: Preservation of parasympathetic and sympathetic nerves is required to avoid urogenital function disturbances after total mesorectal excision (TME) for rectal carcinoma. This study sought to determine whether intraoperative stimulation of parasympathetic nerves with monitoring of bladder contraction is useful in meeting this demand. STUDY DESIGN: In a prospective pilot study, 17 patients, 11 men and 6 women, underwent TME with pelvic autonomic nerve preservation performed by an experienced surgeon. The parasympathetic nerves were stimulated by an electrostimulation device (Screener 3625, Medronic), and the resulting bladder contraction was measured manometrically in all patients. Variations in pulse rate and voltage were measured to determine optimal stimulation parameters. A standardized questionnaire was used to record urogenital function disturbances. Residual urine volume was measured by ultrasound pre- and postoperatively. Shortterm outcomes data were evaluated to establish a possible association between intraoperative test results and postoperative bladder function. RESULTS: In 15 of 17 patients undergoing TME with pelvic autonomic nerve preservation for rectal carcinoma, the parasympathetic nerves were identified based on nerve stimulation-induced bladder contraction. Two patients with negative results on intraoperative nerve stimulation had persisting bladder dysfunction requiring an indwelling catheter after discharge from hospital. In spite of a short median followup of 2 months (range 1 to 4 months), in 7 of 10 men with intact erectile function prior to surgery, postoperative erectile dysfunction could be excluded. The study showed a pulse rate of 35 Hz and an electric potential of 12 V to be optimal stimulation parameters, associated with a mean intravesical pressure rise of 12.7 cm H(2)O (range 2.8 to 18.0 cm H(2)O). CONCLUSIONS: Intraoperative nerve stimulation with monitoring of intravesical pressure represents a technically simple procedure for the identification and verification of function of pelvic parasympathetic nerves during TME for rectal carcinoma.

Electric Stimulation↗

PubMed2005

Error estimation and global fitting in transverse-relaxation dispersion experiments to determine chemical-exchange parameters.

Off-resonance effects can introduce significant systematic errors in R2 measurements in constant-time Carr-Purcell-Meiboom-Gill (CPMG) transverse relaxation dispersion experiments. For an off-resonance chemical shift of 500 Hz, 15N relaxation dispersion profiles obtained from experiment and computer simulation indicated a systematic error of ca. 3%. This error is three- to five-fold larger than the random error in R2 caused by noise. Good estimates of total R2 uncertainty are critical in order to obtain accurate estimates in optimized chemical exchange parameters and their uncertainties derived from chi2 minimization of a target function. Here, we present a simple empirical approach that provides a good estimate of the total error (systematic + random) in 15N R2 values measured for the HIV protease. The advantage of this empirical error estimate is that it is applicable even when some of the factors that contribute to the off-resonance error are not known. These errors are incorporated into a chi2 minimization protocol, in which the Carver-Richards equation is used fit the observed R2 dispersion profiles, that yields optimized chemical exchange parameters and their confidence limits. Optimized parameters are also derived, using the same protein sample and data-fitting protocol, from 1H R2 measurements in which systematic errors are negligible. Although 1H and 15N relaxation profiles of individual residues were well fit, the optimized exchange parameters had large uncertainties (confidence limits). In contrast, when a single pair of exchange parameters (the exchange lifetime, tau(ex), and the fractional population, p(a)), were constrained to globally fit all R2 profiles for residues in the dimer interface of the protein, confidence limits were less than 8% for all optimized exchange parameters. In addition, F-tests showed that quality of the fits obtained using tau(ex), p(a) as global parameters were not improved when these parameters were free to fit the R2 profiles of individual residues. Finally, nearly the same optimized global tau(ex), p(a) values were obtained, when the 1H and 15N data sets for residues in the dimer interface, were fit independently; the difference in optimized global parameters, ca. 10%, was of marginal significance according to the F-test.

Data Interpretation, Statistical↗

PubMed2005

Optimization of the Lactococcus lactis nisin-controlled gene expression system NICE for industrial applications.

BACKGROUND: The nisin-controlled gene expression system NICE of Lactococcus lactis is one of the most widely used expression systems in Gram-positive bacteria. Despite its widespread use, no optimization of the culture conditions and nisin induction has been carried out to obtain maximum yields. As a model system induced production of lysostaphin, an antibacterial protein (mainly against Staphylococcus aureus) produced by S. simulans biovar. Staphylolyticus, was used. Three main areas need optimization for maximum yields: cell density, nisin-controlled induction and protein production, and parameters specific for the target-protein. RESULTS: In a series of pH-controlled fermentations the following parameters were optimized: pH of the culture, use of NaOH or NH4OH as neutralizing agent, the addition of zinc and phosphate, the fermentation temperature, the time point of induction (cell density of the culture), the amount of nisin added for induction and the amount of three basic medium components, i.e. yeast extract, peptone and lactose. For each culture growth and lysostaphin production was followed. Lysostaphin production yields depended on all parameters that were varied. In the course of the optimization a three-fold increase in lysostaphin yield was achieved from 100 mg/l to 300 mg/l. CONCLUSION: Protein production with the NICE gene expression system in L. lactis strongly depends on the medium composition, the fermentation parameters and the amount of nisin added for induction. Careful optimization of key parameters lead to a significant increase in the yield of the target protein.

Journal Article↗

PubMed2006

Optimizing experiment and analysis parameters for spotted microarrays.

This chapter outlines considerations and methods of experimental design for spotted microarray studies that contribute to the robustness of the acquired data. The chapter is divided into two principal sections: (1) a summary of factors that affect the quality of individual array results; and (2) a discussion of experimental design features and replication criteria that enable researchers to gain confidence in their findings. The goal of section (2) is to promote the careful design of microarray studies, with downstream statistical analysis in mind, such that a minimal amount of biological and/or technical replication is required to achieve reproducible results. Topics addressed include choosing appropriate samples to be compared, determining the optimal amount of sample to use, flagging uninformative data, establishing confidence limits in normalized data and the application of statistical tests to identify differentially expressed genes.

Animals↗

PubMedDate not supplied

Treatment of irritable bowel syndrome with colonic pacing: evaluation of pacing parameters required for correction of the "tachyarrhythmia" of the IBS.

BACKGROUND/AIMS: A recent study of the electromyographic (EMG) activity of irritable bowel syndrome (IBS) has shown that the frequency, amplitude and conduction velocity of the slow waves (SWs) of the sigmoid colon (SC) were significantly higher in IBS patients than in the healthy volunteers. The SW rhythm was irregular. A "tachyarrhythmic pattern" was characteristic of the IBS. The SC pressure in the IBS was also significantly higher than that of the healthy controls. We suggested that the cause of IBS is related to an aberrant focus in one or more of the colonic pacemakers which possibly triggers abnormal impulses to the colon. We hypothesized that stimulation of the pacemaker which delivers electric waves to the SC, may correct the abnormal electric waves and eliminate the IBS symptoms. In this communication we tried to define the adequate pacing parameters necessary for normalization of the tachyarrhythmic pattern of the electric waves in IBS. METHODOLOGY: Nineteen subjects with IBS were divided into a study group (age 48.6+/-9.8 years; 7 women, 4 men) and a control group (age 47.6+/-9.2 years; 5 women, 3 men). The study also included 8 healthy volunteers (47.9+/-9.7 years; 5 women). Three 28-gauge cardiac pacing electrodes were used: one for pacing applied to the pacemaker at the colosigmoid junction (CSJ) and 2 for recording applied to the SC mucosa. In the study group, the CSJ electrode was stimulated using an electrical stimulator which delivered a constant current. The optimal pacing parameters had been determined after repeated trials with different variables. In the control group, recording was done without pacemaker activation. The SC pressure was measured by a 10-F saline-perfused tube. RESULTS: In the healthy volunteers, the basal SWs were regular and followed or superimposed by action potentials (APs). Pacing produced a significant increase in the SW variables and SC pressure; the latency was 20.3+/-3.6 s. The study and the control group exhibited a basal tachyarrhythmic pattern and a significantly higher SC pressure than the healthy volunteers. Pacing of the study group effected lowering of the SW variables and SC pressure which did not show a significant difference against those of the healthy volunteers at rest. The optimal pacing parameters comprised an amplitude of 6 mA, a pulse width of 150 ms and a 25% higher frequency than that of the already recorded basal colonic waves. The control group showed no change in the tachyarrhythmic pattern. CONCLUSIONS: CS pacing parameters were identified and succeeded in normalizing the tachyarrhythmic pattern of the IBS. We suggest that this method be used for the treatment of patients with IBS when other measures have failed to cure the condition.

Adult↗

PubMed1997

Effects of radiofrequency glow discharge on impression material surface wettability.

STATEMENT OF PROBLEM: Argon radiofrequency glow discharge (RGD) may simultaneously sterilize and improve surface wettability of impression materials. PURPOSE: The purpose of this study was to define RGD technical parameters that influence the surface wettability of impression material (optimization phase). Definition of RGD was followed by an assessment of these optimized RGD parameters on the wettability of four impression materials either uncontaminated or contaminated with saliva, compared with conventional liquid disinfection (application phase). MATERIAL AND METHODS: For the optimization phase, addition silicone samples were cast against glass with 10 samples per group/parameter (n = 210). Parameters evaluated were duration of exposure, sample shape and angle, position within the RGD chamber, and argon gas delivery pressure. Changes in surface wettability were determined with contact angle measurements. For the application phase, standardized RGD parameters (90 degrees to the plasma flow, flat, 60 seconds, 5 psi) were used on four groups of impression materials with (n = 120 samples, 30 per material) or without (n = 120 samples, 30 per material) prior saliva contamination. RESULTS: RGD treatment of a polyvinyl siloxane impression material significantly (p < 0.0001) reduced contact angle measurements from 63 +/- 1 to 13 +/- 4 degrees, regardless of the parameter evaluated. For the application phase, results indicated different responses to RGD relative to nontreated controls. With all materials treated with RGD or disinfectant exposure, the finest 20 microns standard line was reproduced at x10 magnification with the American National Standards Institute/American Dental Association Specification 19 test die (Sabri Enterprise, Downers Grove, Ill.; n = 80, 10 samples per group). CONCLUSION: These results suggest RGD selectively alters impression material surface wettability.

Analysis of Variance↗

PubMed2006

Optimal intervention for an epidemic model under parameter uncertainty.

We will be concerned with optimal intervention policies for a continuous-time stochastic SIR (susceptible-->infective-->removed) model for the spread of infection through a closed population. In previous work on such optimal policies, it is common to assume that model parameter values are known; in reality, uncertainty over parameter values exists. We shall consider the effect upon the optimal policy of changes in parameter estimates, and of explicitly taking into account parameter uncertainty via a Bayesian decision-theoretic framework. We consider policies allowing for (i) the isolation of any number of infectives, or (ii) the immunisation of all susceptibles (total immunisation). Numerical examples are given to illustrate our results.

Algorithms↗

PubMed2004

Postmortem MR imaging of formalin-fixed human brain.

High-resolution postmortem neuroimaging of the brain can play a role in research programs by providing archival and reslicable images of brain specimens before permanent sectioning. These images can supplement evidence attained from both traditional neuropathological observations and in vivo neuroimaging. Differential brain tissue conspicuity, detectable with MRI, is determined by the density and mobility of water protons. Water content is about 70% in white matter, 80% in gray matter, and 99% in cerebrospinal fluid (CSF). To the extent that brain tissue contrast is determined by the number and microenvironment of water protons, timing parameters of MR image acquisition can interrogate this environment. Because the chemical environment of protons is different in living from dead tissue, optimal temporal imaging parameters, for example, for spin-echo imaging, commonly used for in vivo clinical and research study are different from those best for postmortem imaging. Here, we present a series of observations to identify relaxation times and optimal parameters for high-resolution structural imaging of formalin-fixed postmortem brain tissue using commercially available clinical scanners and protocols. Examples of high-resolution images and results from attempts at diffusion imaging are presented.

Aged↗

PubMed2000

Ultrasound imaging-guided noninvasive ultrasound thrombolysis: preclinical results.

BACKGROUND: Catheter-based therapeutic ultrasound thrombolysis was recently shown to be effective and safe. The purpose of this work was to study the safety and efficacy of external high-intensity focused ultrasound thrombolysis guided by ultrasound imaging in experimental settings. METHODS AND RESULTS: A therapeutic transducer was constructed from an acoustic lens and integrated with an ultrasound imaging transducer. In vitro clots were inserted into bovine arterial segments and sonicated under real-time ultrasound imaging guidance in a water tank. With pulsed-wave (PW) ultrasound, the total sonication time correlated with thrombolysis efficiency (r(2)=0.7666). A thrombolysis efficiency of 91% was achieved with optimal PW parameters (1:25 duty cycle, 200-micros pulse length) at an intensity (I(spta)) of >35+/-5 W/cm(2). Ultrasound imaging during sonication showed the cavitation field as a spherical cloud of echo-dense material. Within <2 minutes, the vessel lumen evidenced neither residual clot nor damage to the arterial wall. On serial filtration, 93+/-1% of the lysed clot became subcapillary in size (<8 microm). In vitro safety studies, however, showed arterial damage when an I(spta) of 45 W/cm(2) was used for periods of >/=300 seconds. CONCLUSIONS: External high-intensity focused ultrasound thrombolysis using optimal PW parameters for periods of </=300 seconds appears to be a safe and effective method to induce thrombolysis. The procedure can be guided by ultrasound imaging, thereby allowing the monitoring of therapy.

Animals↗

PubMed1994

[The nuclear magnetic tomographic diagnosis of focal lesions of the red bone marrow. The optimization of the acquisition parameters for GE and SE sequences].

Gradient-echo (GE) imaging with repetition times equivalent to those of T1-weighted spin-echo (SE) sequences and echo times for antiphase (opposed) transverse magnetisation have proved to be sensitive for high contrast imaging of focal lesions of red bone marrow. The sensitivity of antiphase GE sequences is due to the chemical shift between water-bound and fat-bound protons which introduces a tissue parameter that is not accessible by SE sequences. Main advantage of these GE sequences is the low signal intensity of intact red marrow and the high signal intensity of tumours and inflammatory lesions which allows, similar to T2-weighted SE sequences, for positive contrast imaging of lesions. In order to evaluate and to optimise the contrast-to-noise ratio (CNR) for red bone marrow and tumour 200 GE and 40 SE sequences with repetition times (TR) between 100 and 900 ms, echo times (TE) between 14 and 21 ms and flip angles (alpha) between 10 and 90 degrees were studied. CNR was measured and optimized regarding TR, TE, and alpha. The results indicate that opposed GE sequences, relatively independent from TR and alpha, are characterized by a high contrast-to-noise ratio. According to their high sensitivity for lesion detection they are suited to replace T2-weighted SE sequences.

Artifacts↗