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PubMed1999

Optimization of separation of a complex mixture of natural and synthetic corticoids by micellar liquid chromatography using sodium dodecyl sulphate. Application to urine samples.

A systematic optimization of the separation of a mixture of corticoids by micellar liquid chromatography, using sodium dodecyl sulphate as surfactant, a Hypersil (250 mm x 3.2 mm I.D.) C18 column, a flow-rate of 0.5 ml min(-1), and UV absorbance detection at 245 nm has been carried out. Several mobile phases consisting of sodium dodecyl sulphate and different organic modifiers were tested of which tetrahydrofuran, PrOH and BuOH were finally selected. On the basis of analysis time, resolution and number of compounds separated, a mobile phase containing 36 mM sodium dodecyl sulphate and 1.91% butanol allowed the separation of thirteen corticoids out of sixteen in about 27 min. Under these conditions the optimal concentration of sodium dodecyl sulphate was found to be 36 mM. A bivariant optimization method for the mobile phase BuOH-sodium dodecyl sulphate corrobored these results. The effects of temperature, ionic strength and flow-rate effect have also been studied. The most important analytical figures of merit were assessed and compared with those obtained using conventional mobile phases. The optimized method was applied to human urine samples of subjects administered with Dezacor (tablets containing 30 mg of the active ingredient deflazacort) with and without sample preparation.

Adrenal Cortex Hormones↗

PubMed2002

Optimization of a self-nanoemulsified tablet dosage form of Ubiquinone using response surface methodology: effect of formulation ingredients.

The objectives of the present study were (1) to evaluate the effect of formulation ingredients on the release rate of Ubiquinone from its adsorbing solid compact; and (2) to prepare and evaluate an optimized self-nanoemulsified tablet formulation. A three factor, three-level Box-Behnken design was used for the optimization procedure, with the amounts of copolyvidone (X(1)), maltodextrin (X(2)) and microcrystalline cellulose (X(3)) as the independent variables. The response variable was cumulative percent of Ubiquinone emulsified in 45 min with constraints on weight, flowability index, tensile strength, friability and disintegration time of the dry powdered emulsion and the resultant compact. Based on the experimental design, different Ubiquinone release rates and profiles were obtained. Mathematical equations and response surface plots were used to relate the dependent and independent variables. The regression equation generated for the cumulative percent emulsified in 45 min was Y(6)=64.10-12.32X(1)-4.36X(2)-25.53X(3)+6.99X(1)X(2)+3.97X(1)X(3)+9.70X(2)X(3)-8.98X(1)(2)16.22X(2)(2)+17.10X(3)(2). The optimization model predicted an 85.4% release with X(1), X(2) and X(3) levels of 66.6, 560.1 and 100, respectively. A new formulation was prepared according to these levels. The observed responses were in close agreement with the predicted values of the optimized formulation.

Cellulose↗

PubMed1998

Optimization of the ultrafast Look-Locker echo-planar imaging T1 mapping sequence.

The Look-Locker echo-planar imaging (LL-EPI) sequence has been numerically optimized in terms of the signal-to-noise ratio in the measured value of T1, for both single-shot (repetition time (TR) = infinity), and dynamically repeated T1 measurements. The sequence is optimized for the normal biologic range of T1 (0.2 s to 2.0 s) and for a range of sequence parameters found on most magnetic resonance (MR) scanners. Both linearly and geometrically spaced magnetization sample pulse intervals were considered. For single-shot measurements, the sequence with 24 linearly spaced sample pulses, an inversion time of 0.01 s, an inter-sample pulse delay of 0.10 s, and a sample radiofrequency (RF) pulse flip angle of 25 degrees was found to be optimum. When the number of sample pulses was limited due to hardware limitations, different pulse sequence parameters were indicated. The optimization procedures used are appropriate for any single-shot T1 mapping sequence variant and for any rapid T1 mapping application. The use of an optimized Look-Locker echo-planar imaging sequence is demonstrated by an example of dynamic contrast-enhanced scanning in the brain using fast T1 mapping.

Brain↗

PubMed1999

Development of flexible and efficient strategies for optimizing chromatographic separations.

The intensive research in chemometrics is resulting in continuous development of new concepts and optimization methods. The practical chromatographic optimization examples described in this paper highlight the importance of developing efficient and flexible optimization strategies, which are adapted to the (complex) separation problems encountered in the real chromatographic world. The availability of efficient and user-friendly software should contribute to a more systematic use of chemometrical approaches. Two primordial aspects are discussed in more details: (1) the selection of adequate optimization criteria and (2) the optimum robustness.

Chromatography↗

PubMed2000

High levels of plasma brain natriuretic peptide and interleukin-6 after optimized treatment for heart failure are independent risk factors for morbidity and mortality in patients with congestive heart failure.

OBJECTIVES: The aim of this study was to evaluate whether repetitive measurements of plasma levels of neurohumoral factors and cytokines before and after additional treatment are useful for predicting mortality in patients with congestive heart failure (CHF). BACKGROUND: Neurohumoral and immune activation play an important role in the pathophysiology of CHF. However, the effects of serial changes in these factors on the prognostic value remain unknown. METHODS: We measured plasma levels of neurohumoral factors and cytokines and left ventricular ejection fraction (LVEF) before and three months after optimized treatment for CHF in 102 consecutive patients with severe CHF (New York Heart Association class III to IV) on admission to our hospital. Physicians who were blind to the plasma neurohumoral factors until study completion treated patients using standard drugs. Patients were monitored for a mean follow-up period of 807 days. RESULTS: Plasma levels of neurohumoral factors, cytokines and LVEF were significantly improved three months after optimized treatment. Cardiac death occurred in 26 patients. Among 19 variables including LVEF, only a high level of brain natriuretic peptide (BNP) and interleukin-6 (IL-6) at three months after optimized treatment showed significant independent relationships by Cox proportional hazard analysis with a high mortality for patients with CHF. CONCLUSIONS: These findings indicate that high plasma BNP and IL-6 levels three months after optimized treatment are independent risk factors for mortality in patients with CHF, suggesting that sustained high plasma levels of BNP and IL-6 after additional standard treatment were independent risk factors for mortality in patients with CHF despite improvements in LVEF and symptoms.

Aged↗

PubMed2001

Achieving optimal results with standard balloon angioplasty: can baseline and angiographic variables predict stent-like outcomes?

OBJECTIVES: To predict which patients might not require stent implantation, we identified clinical and angiographic characteristics associated with repeat revascularization after standard balloon angioplasty. BACKGROUND: Stents reduce the risk of repeat revascularization but are costly and may lead to in-stent restenosis, which remains difficult to treat. Identification of patients at low risk for repeat revascularization may allow clinicians to reserve stents for patients most likely to benefit. METHODS: Data from five interventional trials (5,146 patients) were pooled for analysis. We identified patients with optimal angiographic results (final diameter stenosis < or =30% and no dissection) after balloon angioplasty and determined the multivariable predictors of repeat revascularization. RESULTS: Optimal angiographic results were achieved in 18% of patients after angioplasty. The repeat revascularization rate at six months was lower for patients with optimal results (20% vs. 26%, p < 0.001) but still higher than observed in stent trials. Independent predictors of repeat revascularization were female gender (odds ratio [OR] 1.67, p = 0.01), lesion length > or =10 mm (OR 1.62, p = 0.03) and proximal left anterior descending coronary artery lesions (OR 1.62, p = 0.03). For the 8% of patients with optimal angiographic results and none of these risk factors, the repeat revascularization and target vessel revascularization rates were 14% and 8% respectively, similar to rates after stent implantation. Cost analysis estimated that $78 million per year might be saved in the U.S. with a provisional stenting strategy using these criteria compared with elective stenting. CONCLUSIONS: A combination of baseline characteristics and angiographic results can be used to identify a small group of patients at very low risk for repeat revascularization after balloon angioplasty. Provisional stenting for these low risk patients could substantially reduce costs without compromising clinical outcomes.

Angioplasty, Balloon↗

PubMed2003

Optimization of ultrasound parameters for cardiac gene delivery of adenoviral or plasmid deoxyribonucleic acid by ultrasound-targeted microbubble destruction.

OBJECTIVES: This study was undertaken to optimize echocardiographic parameters for successful gene delivery to the heart and to extend the method from adenoviral to plasmid deoxyribonucleic acid (DNA). BACKGROUND: We have previously shown that ultrasound-targeted microbubble destruction can direct tissue expression of adenoviral transgenes to the heart. The optimal echocardiographic parameters for this technique have not been reported. METHODS: Adenoviral or plasmid DNA encoding the luciferase reporter gene was incorporated into liposome microbubbles and infused intravenously into anesthetized rats. We systematically evaluated the effects of ultrasound parameters known to influence microbubble destruction, including electrocardiogram (ECG) triggering, ultrasound frequency, mode of ultrasound, and mechanical index, on gene expression in rat myocardium four days after treatment. In addition, gene expression in heart, liver, and skeletal muscle were compared between adenoviral and plasmid DNA. RESULTS: Optimal ultrasound parameters for this technique include low-transmission frequency (1.3 MHz), maximal mechanical index, and ECG triggering to allow complete filling of the myocardial capillary bed by microbubbles. No difference was seen between ultraharmonics and power Doppler mode. Using adenoviral DNA, optimal ultrasound parameters yielded myocardial luciferase activity on the order of 104 relative light units/mg protein/min but with even higher liver activity. Plasmid DNA was expressed in rat myocardium at similar levels but without detectable liver expression. CONCLUSIONS: Ultrasound-targeted microbubble destruction can be used to deliver adenoviral or plasmid DNA to the myocardium. This technique holds great promise in applying the rapidly expanding repertoire of gene therapies being developed for cardiac disease.

Adenoviridae↗

PubMed1999

Effects of adjunctive balloon angioplasty after intravascular ultrasound-guided optimal directional coronary atherectomy: the result of Adjunctive Balloon Angioplasty After Coronary Atherectomy Study (ABACAS).

OBJECTIVES: This study was conducted to evaluate: 1) the effect of adjunctive percutaneous transluminal coronary angioplasty (PTCA) after directional coronary atherectomy (DCA) compared with stand-alone DCA, and 2) the outcome of intravascular ultrasound (IVUS)-guided aggressive DCA. BACKGROUND: It has been shown that optimal angiographic results after coronary interventions are associated with a lower incidence ofrestenosis. Adjunctive PTCA after DCA improves the acute angiographic outcome; however, long-term benefits of adjunctive PTCA have not been established. METHODS: Out of 225 patients who underwent IVUS-guided DCA, angiographically optimal debulking was achieved in 214 patients, then theywere randomized to either no further treatment or to added PTCA. RESULTS: Postprocedural quantitative angiographic analysis demonstrated an improved minimum luminal diameter (2.88 +/- 0.48 vs. 2.6 +/- 0.51 mm; p = 0.006) and a less residual stenosis (10.8% vs.15%; p = 0.009) in the adjunctive PTCA group. Quantitative ultrasound analysis showed a larger minimum luminal diameter (3.26 +/- 0.48 vs. 3.04 +/- 0.5 mm; p < 0.001) and lower residual plaque mass in the adjunctive PTCA group (42.6% vs. 45.6%; p < 0.001). Despite the improved acute findings in the adjunctive PTCA group, six-month angiographic and clinical results were not different. The restenosis rate (adjunctive PTCA 23.6%, DCA alone 19.6%; p = ns) and target lesion revascularization rate (20.6% vs. 15.2%; p = ns) did not differ between the groups. CONCLUSIONS: With IVUS guidance, aggressive DCA can safely achieve optimal angiographic results with low residual plaque mass, and this was associated with a low restenosis rate. Although adjunctive PTCA after optimal DCA improved the acute quantitative coronary angiography and quantitative coronary ultrasonography outcomes, its benefit was not maintained at six months.

Aged↗

PubMed1998

Optimal glottal configuration for ease of phonation.

Recent experimental studies have shown the existence of optimal values of the glottal width and convergence angle, at which the phonation threshold pressure is minimum. These results indicate the existence of an optimal glottal configuration for ease of phonation, not predicted by the previous theory. In this paper, the origin of the optimal configuration is investigated using a low dimensional mathematical model of the vocal fold. Two phenomena of glottal aerodynamics are examined: pressure losses due to air viscosity, and air flow separation from a divergent glottis. The optimal glottal configuration seems to be a consequence of the combined effect of both factors. The results agree with the experimental data, showing that the phonation threshold pressure is minimum when the vocal folds are slightly separated in a near rectangular glottis.

Glottis↗

PubMedDate not supplied

Proper orthogonal decomposition based optimal neurocontrol synthesis of a chemical reactor process using approximate dynamic programming.

The concept of approximate dynamic programming and adaptive critic neural network based optimal controller is extended in this study to include systems governed by partial differential equations. An optimal controller is synthesized for a dispersion type tubular chemical reactor, which is governed by two coupled nonlinear partial differential equations. It consists of three steps: First, empirical basis functions are designed using the 'Proper Orthogonal Decomposition' technique and a low-order lumped parameter system to represent the infinite-dimensional system is obtained by carrying out a Galerkin projection. Second, approximate dynamic programming technique is applied in a discrete time framework, followed by the use of a dual neural network structure called adaptive critics, to obtain optimal neurocontrollers for this system. In this structure, one set of neural networks captures the relationship between the state variables and the control, whereas the other set captures the relationship between the state and the costate variables. Third, the lumped parameter control is then mapped back to the spatial dimension using the same basis functions to result in a feedback control. Numerical results are presented that illustrate the potential of this approach. It should be noted that the procedure presented in this study can be used in synthesizing optimal controllers for a fairly general class of nonlinear distributed parameter systems.

Models, Chemical↗

PubMed1999

Analysis and optimal design of continuous neural networks with applications to associative memory.

The asymptotic stability of a continuous neural network is analyzed for associative memory. An optimal design method is proposed which ensures the highest associative memory speed and guarantees the storage of each desired memory with attractivity. The network asymptotic stability is analyzed by means of a new energy function, and four theorems are obtained. By comparing these theorems with existing ones, it can be shown that in some cases they are consistent, while in others they are not equivalent but complementary to each other. Further study results in two more generalized conclusions, of which the existing conclusions are special cases. The network optimal design method is proposed in terms of an optimal associative memory theorem. Two application examples are presented to demonstrate the defeffectiveness of the optimal design method, which can be used to design the network for many applications.

Journal Article↗

PubMedDate not supplied

A multiscale optimization approach for the dynamic contour-based boundary detection issue.

We present a new multiscale approach for deformable contour optimization. The method relies on a multigrid minimization method and a coarse-to-fine relaxation algorithm. This approach consists in minimizing a cascade of optimization problems of reduced and increasing complexity instead of considering the minimization problem on the full and original configuration space. Contrary to classical multiresolution algorithms, no reduction of image is applied. The family of defined energy functions are derived from the original (full resolution) objective function, ensuring that the same function is handled at each scale and that the energy decreases at each step of the deformable contour minimization process. The efficiency and the speed of this multiscale optimization strategy is demonstrated in the difficult context of the minimization of a region-based contour energy function ensuring the boundary detection of anatomical structures in ultrasound medical imagery. In this context, the proposed multiscale segmentation method is compared to other classical region-based segmentation approaches such as Maximum Likelihood or Markov Random Field-based segmentation techniques. We also extend this multiscale segmentation strategy to active contour models using a classical edge-based likelihood approach. Finally, time and performance analysis of this approach, compared to the (commonly used) dynamic programming-based optimization procedure, is given and allows to attest the accuracy and the speed of the proposed method.

Algorithms↗

PubMed2002

Wiring optimization in cortical circuits.

Wiring a brain presents a formidable problem because neural circuits require an enormous number of fast and durable connections. We propose that evolution was likely to have optimized neural circuits to minimize conduction delays in axons, passive cable attenuation in dendrites, and the length of "wire" used to construct circuits, and to have maximized the density of synapses. Here we ask the question: "What fraction of the volume should be taken up by axons and dendrites (i.e., wire) when these variables are at their optimal values?" The biophysical properties of axons and dendrites dictate that wire should occupy 3/5 of the volume in an optimally wired gray matter. We have measured the fraction of the volume occupied by each cellular component and find that the volume of wire is close to the predicted optimal value.

Animals↗

PubMed2002

[Design of an inverse planning system for radiotherapy using linear optimization].

Our approach shows that inverse planning for intensity-modulated beams in radiotherapy can be solved efficiently by the mathematical method of linear optimization. The completeness property of this method guarantees that calculated treatment plans fulfill the dose constraints given by the oncologist. Techniques developed by our group can also avoid the possible infeasibility caused by a physically impossible dose distribution. In contrast to other optimization methods, the simplex algorithm used for linear optimization allows a very high optimization speed, i.e., very short planning cycles. These preconditions were integrated in the development of the software system MIPART ("Munich Inverse Planning And Radiotherapy Treatment"). The object-oriented software architecture of MIPART achieves a maximum of extensibility and flexibility. Our clinical tests show that MIPART can be easily integrated in the clinical routine in spite of the complexity of data in the field of intensity-modulated radiotherapy. Moreover, qualitatively better treatment plans can be generated than in conventional treatment planning, especially in complicated cases.

Humans↗

PubMed2000

Optimal conduit size for extracardiac Fontan operation.

BACKGROUND: Lack of conduit growth potential and thrombogenicity are the main drawbacks of the extracardiac Fontan operation (ECFO). Optimal size of the conduit according to the patients age and inferior vena cava diameter has not been established. OBJECTIVES: We set out to ascertain whether the optimal dimensions of the conduit could be determined before an ECFO. METHODS: Actual and expected age-related inferior vena cava diameters were compared with the extracardiac conduit diameter in 20 patients after ECFO. In 50 other pediatric and adult patients, the distance between intrapericardial part of the inferior vena cava and the undersurface of the right pulmonary artery (IVC-RPA) was measured. Cases of conduit thrombosis were analyzed. RESULTS: The actual diameter of the inferior vena cava was variable and has a weak correlation with anthropometric data and expected diameter (R=0.07-0.23, P=0.32-0.76). The IVC-RPA distance correlated with height (R=0.87, P=0.0001), but was also variable. At the age of 2-4 years and body weight 12-15 kg IVC diameter and IVC-RPA distance are equal to 60-80% of adult values. Conduit thrombosis developed in two patients with unfavorable Fontan hemodynamics and oversized conduits. CONCLUSIONS: Considering the inferior vena cava size, ECFO may be performed at the age of 2-3 years and at a body weight 12-15 kg, when a hemodynamically optimal almost adult sized conduit can be implanted. Optimization of the conduit is necessary on the basis of the actual inferior vena cava diameter and IVC-RPA distance. Anticoagulation postoperatively should be considered to prevent conduit thrombosis in patients with suboptimal Fontan circulation

Adolescent↗

PubMed2001

Optimization of venous return tubing diameter for cardiopulmonary bypass.

OBJECTIVE: To determine the optimal venous tubing diameter for adult cardiopulmonary bypass (CPB) to improve gravity drainage and to reduce priming volume. METHODS: (A) Maximum bovine blood flow rates by gravity drainage were assessed in vitro for four different tubing diameters (1/2, 3/8, 5/16,1/4 inch) with three different lengths and various pre- and afterloads. Based on the results of (A) and multiple regression analyses, we developed equations to predict tubing sizes as a function of target flows. (C) The equations obtained in (B) were validated by ex vivo bovine experiments. (D) The clinically required maximal flows were determined retrospectively by reviewing 119 perfusion records at Zurich University. (E) Based on our model (B), the clinical patient and hardware requirements, the optimal venous tubing diameter was calculated. (F) The optimized venous tubing was evaluated in a prospective clinical trial involving 312 patients in Hangzhou. RESULTS: For a mean body surface area of 1.83+/-0.2 m(2), the maximal perfusion flow rate (D) achieved with 1/2-inch (=1.27 cm(2)) venous tubing was 4.62+/-0.57 l/min (range: 2.50-6.24 l/min). Our validated model (B,C) predicted 1.0 cm(2) as optimal cross-sectional area for the venous line. New tubing packs developed accordingly were used routinely thereafter. The maximal flow rate was 4.93+/-0.58 l/min (range: 3.9-7.0) in patients with a mean body surface area of 1.62+/-0.21 m(2). CONCLUSION: The new venous tubing with 1.0-cm(2) cross-sectional area improves the drainage in the vast majority of adult patients undergoing CPB and reduces the priming volume (-27 ml/m). Reduced hemodilution can prevent homologous transfusions if a predefined transfusion trigger level is not reached.

Adult↗

PubMed2001

Preoperative modeling of an optimal left ventricle volume for surgical treatment of ventricular aneurysms.

OBJECTIVE: We evaluated the results of surgical treatment postinfarction ventricular aneurysms, with preoperative modeling of an optimal left ventricle volume. METHODS: From January 1998 to December 2000, 41 patients underwent left ventricular (LV) aneurysm repair. There were 39 men and two women, with a mean age 45.6+/-6.2 years. With echocardiography study, an optimal end-diastolic volume of LV was modeled on the basis of the proper stroke index and the contractile ejection fraction (EF). A permissible area of aneurysm resection was calculated by using a difference between the initial and the projected surface area of LV. The patch position and sizes were measured preoperatively. Ventricular reconstruction was performed by using linear plasty in eight patients, septal plasty of the Stoney et al. technique in 14 patients, and endoventriculoplasty of the Dor et al. technique in 19 patients. RESULTS: The mean NYHA functional class decreased from 2.9+/-0.6 to 1.6+/-0.7 postoperatively. The improvement of LV contracting function made itself evident in a decreased end-diastolic volume from 216+/-98 to 158+/-35 ml, and end-systolic volume from 133+/-85 to 80+/-34 ml postoperatively. The mean EF increased from 38+/-11 to 49+/-9% after operation. We noted that preoperative contractile EF corresponded with postoperative EF (49.8+/-11% and 49.3+/-9%, respectively). The projected optimal end-diastolic volume of LV estimated before operation agreed with postoperative data (152+/-33 ml and 158+/-35 ml, respectively). The hospital mortality rate was 7.3%. CONCLUSIONS: Preoperative modeling of an optimal LV volume allows for the estimation of a permissible area of aneurysm resection, the position and sizes of the patch, as well as for the prevention of an excessive reduction of the LV cavity after aneurysm repair.

Adult↗

PubMed1999

Optimized radiation therapy based on radiobiological objectives.

In the broad field of radiation therapy optimization, both simple and complex problems have their origins in the interaction of the radiation beams with the biological structures of normal and malignant tissues of the human body. Therefore, it is no great surprise that many treatment optimization problems are best handled by the use of well-designed radiobiological models. The classic way of quantifying dose-response relations for tumors and normal tissues as well as their cross-correlation with each other and their dependence on the underlying genetic and molecular biology of the cell are first briefly reviewed. Radiobiological objective functions, such as the probability of achieving complication-free cure and its expectation value under influence of stochastic processes during the course of treatment, are defined and shown to solve many of the problems of radiation therapy planning. Finally, it is shown through the use of these quantifiers that, simply by introducing biologically optimal intensity modulated dose delivery, the treatment outcome can be improved by about 20% or more in cases with a complex spread of the disease. Once radiobiological optimal plans have been developed, they can be approximated by ordinary physical planning, but the biological objective functions are still needed to have a figure of merit for the quality of the treatment.

Dose-Response Relationship, Radiation↗