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The impact of optimal stenting techniques on cardiac catheterization laboratory resource utilization and costs.

Coronary stenting has been shown to reduce angiographic restenosis and improve clinical outcomes compared with conventional balloon angioplasty, but at greater in-lab cost. Recent studies have suggested that "optimal" stent deployment can eliminate the need for intensive oral anticoagulation after stenting, with the potential to reduce vascular complications, length of stay, and hospital cost. Between January and June 1995, we performed elective 1-vessel coronary stenting in 78 patients with a single, discrete (< 15 mm) coronary stenosis (optimal single-lesion group) and in 30 patients with either a single, long stenosis or serial discrete lesions (optimal multilesion group). Compared with stent patients from the Stent Restenosis Study (STRESS) economic substudy, optimal single-lesion stenting required more stents (1.3 +/- 0.6 vs 1.1 +/- 0.4, p <0.01) and more adjunctive angioplasty balloons per patient (2.5 +/- 1.0 vs 2.0 +/- 0.9, p <0.01). As a result, catheterization laboratory costs for single-lesion stenting increased by nearly $600 between 1993 and 1995 ($4,619 +/- $1,120 [median $4,435] to $5,209 +/- $1,697 [median $4,6731, p <0.01). Compared with the STRESS angioplasty group, optimal coronary stenting increased catheterization laboratory costs by nearly $2,200 ($3,012 +/- $1,382 [median $2,548] vs $5,209 +/- $1,697 [median $4,673], p <0.01). Optimal stenting of long lesions or multiple discrete stenoses increased catheterization laboratory costs by an additional $2,000 compared with optimal single-lesion stenting ($7,201 +/- $2,428 [median $6,887] vs $5,209 +/- $1,697 [median $4,673], p <0.01). These findings demonstrate that optimal coronary stenting increases in-lab procedural resource utilization and costs compared with historical stenting techniques. Based on the downstream cost savings seen in the STRESS trial ($1,400/patient), it is unlikely that current optimal stenting techniques will result in an overall cost savings compared with balloon angioplasty.

Aged↗

The role of optimism in the process of schema-focused cognitive therapy of personality problems.

The aim of this study was to examine the determinants and effects of optimism in the process of schema-focused cognitive therapy of personality problems. The sample consisted of 35 patients with panic disorder and/or agoraphobia and DSM-IV Cluster C personality traits who participated in an 11-week residential program with one symptom-focused and one personality-focused phase. This study examines the role played by optimism during the individual sessions of the second phase, using a time series approach. Decreased patient's belief in his/her primary Early Maladaptive Schema and increased patient-experienced empathy from the therapist in a session predicted increased patient-rated optimism before the subsequent session. Increased patient-rated optimism in turn predicted decreased schema belief and distress and increased insight, empathy, and therapist-rated optimism. The slope of optimism across sessions was related to change in most of the overall outcome measures. There appears to be a positive feedback in the process of schema-focused cognitive therapy between decreased schema belief and increased optimism. In addition, optimism appears to mediate the effects of schema belief and therapist empathy on overall improvement, and to serve as an antecedent to decreased distress and to increased empathy, insight, and therapist's optimism.

Adult↗

Optimistic explanatory style and dispositional optimism in HIV-infected men.

OBJECTIVE: This study examined associations of two types of optimism (Peterson and Seligman's optimistic explanatory style and Scheier and Carver's dispositional optimism) with each other as well as with symptoms and immune status among human immunodeficiency virus (HIV)-infected men. METHOD: We related both types of optimism to HIV symptoms and to CD4 counts in a cross-sectional study of 78 men, and to change in CD4 counts in a 2-year prospective study of a subsample of these men. RESULTS: Analyses controlled for age, education, employment status, duration since diagnosis, and azidothymidine (AZT) use. The two types of optimism were only minimally related to each other (r=.25). Cross-sectionally, higher levels of both types of optimism were associated with having fewer HIV symptoms, but a more optimistic explanatory style was related to having poorer immune status (lower CD4). Prospectively, an optimistic explanatory style was a substantial predictor of greater decline in CD4 counts after 2 years, after controlling for baseline CD4. Dispositional optimism was unrelated to CD4 counts. Neither health behaviors nor coping strategies mediated these relationships, and the relationships of optimistic explanatory style (and to a lesser extent, dispositional optimism) were independent of negative affectivity. CONCLUSIONS: These optimism measures tap different types of optimism, and although both are related to better subjective health in HIV-infected men, an optimistic explanatory style predicts greater decline in immune status over time. This latter relationship may be related to the unique stress and life experiences associated with having HIV.

Adult↗

Geometric optical optimization of the corneal lens of Notonecta glauca.

The optimal shape of the corneal lens of the water bug backswimmer (Notonecta glauca) and the optimal shape and position of the thin transition layer between the distal and proximal units of its cornea are theoretically determined. Using a geometric optical method, first the shape of a geometric interface between the lens units is determined, which eliminates the longitudinal spherical aberration. This interface is investigated for differently formed thick lenses when the medium in contact with the entrance surface of the lens is water or air. The optimal transition layer for the amphibious backswimmer is that, the boundaries of which are the theoretical interfaces for water and air, and the refractive index varies continuously in it. The optimal shape of the corneal lens is determined, with the disadvantageous lenses, with respect to the possible minimal spherical aberration and amount of reflected light from the transition layer, being rejected. The optimal position of the transition layer in the cornea can be obtained from the minimization of the amount of diffracted light on the marginal connection of the layers. The optimal corneal lens for backswimmer has ellipsoid boundary surfaces; the optimal transition layer in it is thin bell-shaped, at the marginal connection of which there is no dimple, the maximum of the layer is on the margin of the cornea. The shape of the theoretically optimal corneal lens, the shape and position of the theoretically optimal transition layer agree well with those of Notonecta glauca. The question posed, the geometric optical method used and the results presented are of general importance, and not only with respect to vision in the bug Notonecta, but also in the fossil trilobites, or in the wave guide theories which have been employed in similar modelling problems, in design of system of lenses without spherical aberration, for example.

Amphibians↗

Optimizing radiation treatment plans for lung cancer using lung perfusion information.

PURPOSE: To study the impact of incorporation of lung perfusion information in the optimization of radical radiotherapy (RT) treatment plans for patients with medically inoperable non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: The treatment plans for a virtual phantom and for five NSCLC patients with typical defects of pre-RT lung perfusion were optimized to minimize geometrically determined parameters as the mean lung dose (MLD), the lung volume receiving more than 20 Gy (V20), and the functional equivalent of the MLD, using perfusion-weighted dose-volume histograms. For the patients the (perfusion-weighted) optimized plans were compared to the clinically applied treatment plans. RESULTS: The feasibility of perfusion-weighted optimization was demonstrated in the phantom. Using perfusion information resulted in an increase of the weights of those beams that were directed through the hypo-perfused lung regions both for the phantom and for the studied patients. The automatically optimized dose distributions were improved with respect to lung toxicity compared with the clinical treatment plans. For patients with one hypo-perfused hemi-thorax, the estimated gain in post-RT lung perfusion was 6% of the prescribed dose compared to the geometrically optimized plan. For patients with smaller perfusion defects, perfusion-weighted optimization resulted in the same plan as the geometrically optimized plan. CONCLUSION: Perfusion-weighted optimization resulted in clinically well applicable treatment plans, which cause less radiation damage to functioning lung for patients with large perfusion defects.

Carcinoma, Non-Small-Cell Lung↗

Inverse and forward optimization of one- and two-dimensional intensity-modulated radiation therapy-based treatment of concave-shaped planning target volumes: the case of prostate cancer.

BACKGROUND: Intensity-modulated radiation therapy (IMRT) was suggested as a suitable technique to protect the rectal wall, while maintaining a satisfactory planning target volume (PTV) irradiation in the case of high-dose radiotherapy of prostate cancer. However, up to now, few investigations tried to estimate the expected benefit with respect to conventional three-dimensional (3D) conformal radiotherapy (CRT). PURPOSE: Estimating the expected clinical gain coming from both 1D and 2D IMRT against 3DCRT, in the case of prostate cancer by mean of radiobiological models. In order to enhance the impact of IMRT, the case of concave-shaped PTV including prostate and seminal vesicles (P+SV) was considered. MATERIALS AND METHODS: Five patients with concave-shaped PTV including P+SV were selected. Two different sets of constraints were applied during planning: in the first one a quite large inhomogeneity of the dose distribution within the PTV was accepted (set (a)); in the other set (set (b)) a greater homogeneity was required. Tumor control probability (TCP) and normal tissue control probability (NTCP) indices were calculated through the Webb-Nahum and the Lyman-Kutcher models, respectively. Considering a dose interval from 64.8 to 100.8 Gy, the value giving a 5% NTCP for the rectum was found (D(NTCP(rectum)=5%)) using two different methods, and the corresponding TCP(NTCP(rectum)=5%) and NTCP(NTCP(rectum)=5%) for the other critical structures were derived. With the first method, the inverse optimization of the plans was performed just at a fixed 75.6 Gy ICRU dose; with the second method (applied to 2/5 patients) inverse treatment plannings were re-optimized at many dose levels (from 64.8 to 108 Gy with 3.6 Gy intervals). In this case, three different values of alpha/beta (10, 3, 1.5)were used for TCP calculation. The 3DCRT plan consisted of a 3-fields technique; in the IMRT plans, five equi-spaced beams were applied. The Helios Inverse Planning software from Varian was used for both the 2D IMRT and the 1D IMRT inverse optimization, the last one being performed fixing only one available pair of leaves for modulation. A previously proposed forward 1D IMRT 'class solution' technique was also considered, keeping the same irradiation geometry of the inversely optimized IMRT techniques. RESULTS: With the first method, the average gains in TCP(NTCP(rectum)=5%) of the 2D IMRT technique, with respect 3DCRT, were 10.3 and 7.8%, depending on the choice of the DVHs constraints during the inverse optimization procedure (set (a) and set (b), respectively). The average gain (DeltaTCP(NTCP(rectum)=5%)) coming from the inverse 1D IMRT optimization was 5.0%, when fixing the set (b) DVHs constraints. Concerning the forward 1D IMRT optimization, the average gain in TCP(NTCP(rectum)=5%) was 4.5%. The gain was found to be correlated with the degree of overlapping between rectum and PTV. When comparing 2D IMRT and 1D IMRT, in the case of the more realistic set (b) constraints, DeltaTCP(NTCP(rectum)=5%) was always less than 3%, excepting one patient with a very large overlap region. Basing our choice on this result, the second method was applied to this patient and one of the remaining. Through the inverse re-optimization of the treatment plans at each dose level, the gain in TCP(NTCP(rectum)=5%) of the inverse 2D technique was significantly higher than the ones obtained by applying the first method (concerning the two patients: +6.1% and +2.4%), while no significant benefit was found for inverse 1D. The impact of changing the alpha/beta ratio was less evident in the patient with the lower gain in TCP(NTCP(rectum)=5%). CONCLUSIONS: The expected benefit due to IMRT with respect to 3DCRT seems to be relevant when the overlap between PTV and rectum is high. Moreover, the difference between the inverse 2D and the simpler inverse or forward 1D IMRT techniques resulted in being relatively modest, with the exception of one patient, having a very large overlap between rectum and PTV. Optimizing the inverse planning at each dose level to find TCP(NTCP(rectum)=5%)e level to find TCP(NTCP(rectum)=5%) can improve the performances of inverse 2D IMRT, against a significant increase of the time for planning. These results suggest the importance of selecting the patients that could have significant benefit from the application of IMRT.

Dose-Response Relationship, Radiation↗

On the design of optimal dynamic experiments for parameter estimation of a Ratkowsky-type growth kinetics at suboptimal temperatures.

It is generally known that accurate model building, i.e., proper model structure selection and reliable parameter estimation, constitutes an essential matter in the field of predictive microbiology, in particular, when integrating these predictive models in food safety systems. In this context, Versyck et al. (1999) have introduced the methodology of optimal experimental design techniques for parameter estimation within the field. Optimal experimental design focuses on the development of optimal input profiles such that the resulting rich (i.e., highly informative) experimental data enable unique model parameter estimation. As a case study, Versyck et al. (1999) [Versyck, K., Bernaerts, K., Geeraerd, A.H., Van Impe, J.F., 1999. Introducing optimal experimental design in predictive modeling: a motivating example. Int. J. Food Microbiol., 51(1), 39-51] have elaborated the estimation of Bigelow inactivation kinetics parameters (in a numerical way). Opposed to the classic (static) experimental approach in predictive modelling, an optimal dynamic experimental setup is presented. In this paper, the methodology of optimal experimental design or parameter estimation is applied to obtain uncorrelated estimates of the square root model parameters [Ratkowsky, D.A., Olley, J., McMeekin, T.A., Ball, A., 1982. Relationship between temperature and growth rate of bacterial cultures. J. Bacteriol. 149, 1-5] describing the effect of suboptimal growth temperatures on the maximum specific growth rate of microorganisms. These estimates are the direct result of fitting a primary growth model to cell density measurements as a function of time. Apart from the design of an optimal time-varying temperature profile based on a sensitivity study of the model output, an important contribution of this publication is a first experimental validation of this innovative dynamic experimental approach for uncorrelated parameter identification. An optimal step temperature profile, within the range of model validity and practical feasibility, is developed for Escherichia coli K12 and successfully applied in practice. The presented experimental validation result illustrates the large potential of the dynamic experimental approach in the context of uncorrelated parameter estimation. Based on the experimental validation result, additional remarks are formulated related to future research in the field of optimal experimental design.

Escherichia coli↗

A new method for evaluation and dietary therapy of congenital: deficiencies of amino acid metabolic enzymes. Linear system analysis and optimization of feedback inputs for the metabolic pathways of lysine, methionine and isoleucine.

We intended to elucidate an integrated mathematical model of amino acid metabolism and we propose a system for optimization treatment of disturbed metabolic states caused by congenital enzyme deficiencies. Our analysis focused on the metabolic pathway starting at asparaginic acid proceeding to isoleucine, methionine and lysine. The rate of change in the concentration of the biochemical species was expressed as 21 linear rate equations. We obtained the rate constants and the magnitude of feedback from reported experimental data. Linear systems analysis revealed that the metabolic system under study was stable but uncontrollable. These properties were insensitive to changes in the magnitude of feedback. To show the effect of optimizing the feedback so that it minimizes the square of the concentration of the species and the control input, we analyzed the impulse response of the species, transient response and the singular value of the system for four cases; (1) at the physiological state without optimizing the feedback, (2) at the physiological state attained after optimizing the feedback, (3) at the pathophysiological state attained with enzyme deficiency states for lysine and methionine metabolism without optimizing the feedback, and (4) at the pathophysiological state attained after optimizing the feedback for enzyme deficiencies. In the enzyme deficient model, the impulse response oscillated and lasted longer than that in the physiological state. These changes appeared even in the species on other branched pathways. The singular value was elevated in the enzyme deficient state. By optimizing the feedback, all the impulse responses in the enzyme deficient state recovered to nearly those in the normal physiological state. Similarly, the transient response and the singular value in the enzyme deficient state recovered to nearly the normal physiological values. We elucidated the numerical value of the feedback gain for this optimization. The present analysis is useful for the evaluation of the integrated properties of amino acid metabolism and the optimization technique is potentially of use for determining a treatment course for congenital metabolic enzyme deficiencies.

Amino Acid Metabolism, Inborn Errors↗

Optimized beam planning for linear accelerator-based stereotactic radiosurgery.

PURPOSE: Current treatment planning for linear accelerator-based stereotactic radiosurgery and radiotherapy is a lengthy and iterative procedure. The planner has to manually select the beam arcs and carefully consider many different selections to ensure target volume coverage while sparing dose to critical organs. In this article we report an optimization procedure that can automatically select the beam arcs based on geometric and dosimetric analysis of the treatment parameters. METHODS AND MATERIALS: The optimization problem is introduced by using a Beam's Eye View (BEV) map where a pattern of lines represents a beam arc combination for a treatment plan. The collection of all possible treatment plans is described by using the concept of phase space where each point corresponds to a particular configuration of the system under consideration, and in this case, a particular beam arc combination. A geometric reduction of the phase space is performed by excluding static beam ports that irradiate too much critical organs and too little target volume. The phase space is further reduced by excluding beam arc combinations that do not comply with treatment convenience considerations and established planning experiences. These reductions significantly reduces the number of beam arc combinations to be considered and thus dramatically simplifies the computational complexity. The method of simulated annealing is then used to the reduced phase space to select the set of beam arcs that provides the best surface dose distribution for the target volume. The optimization procedure is applied to a radiosurgery case to compare the optimized beam arcs with the previously manually planned beam arcs. The procedure is also applied to 10 randomly selected cases for a comparison in terms of tissue-volume ratio calculations. RESULTS: The system is a highly automated beam arc planning tool for stereotactic radiosurgery and stereotactic radiotherapy. Its interactive nature allows the planner to rapidly consider many treatment plans to search for the best option. For the case presented, it is shown that the optimized beams substantially reduce the dose to the postrema. The tissue-volume ratio calculations demonstrate that the optimization often produces clinically superior treatment plans than the manual beam planning method. CONCLUSIONS: Our method of phase space reduction proves to be very useful in approaching the complex problem of treatment planning optimization. Not only does it substantially reduce the number of beam arcs that need to be considered, but it also simplifies the evaluation of the beam arc options. Both of these greatly reduce the computational complexity of the optimization and make the procedure fast and efficient. Moreover, the reduction of phase space adds another layer of interaction between the user and the beam selection procedure, so that the optimization process is well controlled and thus very effective.

Brain Neoplasms↗

Optimal L(1)-L(2) primary tone level separation remains independent of test frequency in humans.

Previous studies described a systematic asymmetry of the level of the 2f(1)-f(2) distortion product otoacoustic emission (DP) in the space of the primary tones levels L(1) and L(2) in normal-hearing humans. Optimal primary tone level separations L(1)-L(2), which result in maximum DP levels, were close to L(1)=L(2) at high levels, but continuously increased with decreasing stimulus level towards L(1)>L(2) (Gaskill and Brown, 1990, J. Acoust. Soc. Am. 88, 821-839). At these optimal L(1)-L(2), however, not only DP levels in normal hearing were maximal, but also trauma-induced DP reductions. A linear equation that approximates optimal L(1)-L(2) level separations thus was suggested to be optimum for use in clinical applications (Whitehead et al., 1995, J. Acoust. Soc. Am. 97, 2359-2377). It was the aim of this study to extend the generality of optimal L(1)-L(2) separations to the typical human test frequency range for f(2) frequencies between 1 and 8 kHz. DPs were measured in 22 normal-hearing human ears at 61 primary tone level combinations, with L(2) between 5 and 65 dB SPL and L(1) between 30 and 70 dB SPL (f(2)/f(1)=1.2). It was found that the systematic dependence of the maximum DP level on the L(1)-L(2) separation is independent on frequency. Optimal L(1)-L(2) level separations may well be approximated by a linear equation L(1)=a L(2)+(1-a) b (after Whitehead et al., 1995) with parameters a=0.4 and b=70 dB SPL at f(2) frequencies between 1 and 8 kHz and L(2) levels between 20 and 65 dB SPL. Below L(2)=20 dB SPL, the optimal L(1) was found to be almost constant. Following previous notions (Gaskill and Brown, 1990), an analysis of basilar membrane response data in experimental animals (after Ruggero and Rich, 1991, Hear. Res. 51, 215-230) is further presented that relates optimal L(1)-L(2) separations to frequency-selective compression of the basilar membrane. Based on the assumption that optimal conditions for the DP generation are equal primary tone responses at the f(2) place, a linear increase of the optimal L(1)-L(2) level separation is graphically demonstrated, similar to our results in human ears.

Acoustic Stimulation↗

Optimal multiple trait selection for multiple linked quantitative trait loci.

A method was developed to optimize selection on multiple traits with multiple quantitative trait loci (QTLs) over multiple generations. The basis of the method was to replace in the objective function the genotypic value of a single trait with an aggregate genotypic value of multiple traits weighted by their corresponding economic weight, and to maximize the weighted sum of the selection response in the planning horizon. The optimization was formulated as a multiple stage optimal control problem and solved by a forward and backward iteration cycle. The practical utility of this method was illustrated in an example of pig breeding population, in which the number born alive (NBA) and days to 100 kg (D100) were used as parameters. The selection response of this method was compared with standard QTL selection and regular best linear unbiased prediction (BLUP) selection. Results showed that optimal selection achieved greater selection response than either standard QTL or regular BLUP selections. The influence of economic weight to optimal selection was significant, and the optimization was better as the economic weight of D100 increased. Optimal selection increased the total selection response by two ways: 1) it sacrificed some QTL responses during early generations and 2) it put more emphasis on D100. Optimal cumulative discounted selection gave more weight to D100 than optimal terminal selection in the longer generations.

Algorithms↗

Modeling retrovirus production for gene therapy. 2. Integrated optimization of bioreaction and downstream processing.

In this work a model envisaging the integrated optimization of bioreaction and downstream processing is presented. This model extends the work presented in part 1 of this pair of papers by adding ultrafiltration to process optimization. The new operational parameters include ultrafiltration time, pressure, and stirring rate. For global optimization, the model uses as constraints the final product titer and quality to be achieved after downstream processing. This extended model was validated with the same system used in part 1, i.e., PA317 cells producing a recombinant retrovirus containing the LacZ gene as a marker in stirred tanks using porous supports. Optimization of the extended model led to the conclusion that bioreaction should have two steps, batch and perfusion, similar to what was found in part 1. Ultrafiltration in a stirred cell should be performed at low pressures and stirring rates to reduce the losses of infective retroviruses. Sensitivity analysis performed on the results of the integrated optimization showed that under optimal conditions the productivity is less sensitive to the parameters related to ultrafiltration than to those associated with bioreaction. These results were interpreted as reflecting the high yield of ultrafiltration (90%). The relevance of the model extension to perform integrated optimization was also demonstrated since a restriction in the specific ultrafiltration area in downstream processing conditioned perfusion duration and perfusion rate in bioreaction. This clearly indicates that overall process optimization cannot be achieved without integrated optimization.

Bioreactors↗

Facile and statistical optimization of transfection conditions for secretion of foreign proteins from insect Drosophila S2 cells using green fluorescent protein reporter.

Insect Drosophila melanogaster S2 cells were developed as a plasmid-based and therefore nonlytic expression system for functional foreign proteins. Transfection is an important step to introduce foreign target DNA into cells and should be properly optimized to obtain maximum production yield. Single factor search (SFS) methodology is still generally used to determine optimal condition in a biological system. Although this method is relatively simple to perform, it has many disadvantages such as not considering interactions between several factors and not covering the entire region of the solution pool. Therefore, we approached this optimization problem statistically with response surface (RSM) and evolutionary operation (EVOP) methodologies and compared the transfection efficiencies with the traditional SFS method. We employed secreted green fluorescent protein (GFP) as a reporter for determination of optimal transfection condition and secreted human erythropoietin (hEPO) as a confirming foreign model protein. Consequently, we arrived at the best optimal transient transfection condition (1 microg of plasmid DNA, 5 microg of lipofectin, 2 x 10(6) cells of initial cell number, and 18 h of transfection duration time) through a systematic access in a series of SFS, RSM, and EVOP. The secreted hEPO yield using optimal transient transfection condition by EVOP methodology was enhanced by about 1.8-fold compared to that of traditional SFS. This optimized transient transfection condition can be used as a basis for optimal stable transfections. A linear relationship between secreted GFP fluorescence intensity and secreted hEPO concentration indicated that facile and noninvasive determination of optimal transfection conditions for expression and secretion of foreign proteins in S2 cell cultures was made possible by simple measurement of GFP fluorescence.

Animals↗

Optimal risk factors in the population: prognosis, prevalence, and secular trends; data from Göteborg population studies.

AIMS: To assess the prognosis and prevalence of optimal risk factors in the population. METHODS AND RESULTS: Data from several Göteborg population studies were used. Optimal risk factors were defined as serum cholesterol <5 mmol x l(-1), blood pressure <140/90 without treatment and being a non-smoker. In a 20-year follow-up of 7130 men aged 47 to 55 at baseline a group of 117 men who were optimal with respect to cholesterol, blood pressure and smoking were identified. In this group there was only one death from coronary disease, corresponding to 0.4 deaths per 1000 years, whereas the overall risk of coronary death in the study was 4.8 per 1000 years. Among men and women aged 25 to 34 in the Göteborg MONICA study 1995, less than half were optimal on all three scores, and in men and women aged 55 to 64, only 7% and 6%, respectively, were optimal. If body mass index below 25 was included only 34% and 37%, respectively, of men and women aged 25 to 34 were optimal, and 11% and 22% among men and women aged 35 to 44. In an analysis of secular trends over 30 years in four successive cohorts of men aged 50 the prevalence of optimal risk factors with respect to cholesterol, blood pressure and smoking increased from 1963 to 1993 but was still only 11% in 1993. CONCLUSIONS: As expected, optimal risk factors with respect to serum cholesterol, blood pressure and smoking confers a very low risk of coronary death. However, the prevalence of optimal risk factor status in the Swedish population is still low.

Adult↗

Reduced optimality as an indicator of developmental status at 18 months and school achievement at 8 years.

Birth records of 97 children assessed at 18 months and found to be developmentally delayed were scored according to the optimality concept developed by Prechtl. These children were compared to a control series of 81 children. In order to evaluate the predictive validity of the parental developmental assessments performed at 18 months the children had been screened for school achievement problems at the age of eight years, yielding a distribution of true and false positives and true and false negatives. Rates of reduced optimality were compared to investigate firstly, the relationship between reduced optimality and developmental delay at 18 months and secondly, whether the follow-up distribution of true and false positives at eight years could be related to reduced optimality. The overall relationship between reduced optimality and developmental delay at 18 months and reduced optimality and school achievement problems at eight years was also investigated. The 15 low scoring cases registered as mentally retarded differed significantly from controls on total mean reduced optimality. Retarded and non-retarded low-scorers differed significantly on post partum sub-scores only. When the eight-year follow-up groups were compared both retarded and non-retarded true positives differed significantly from true negatives on total mean reduced optimality. The difference in post-partum reduced optimality between retarded and all other follow-up groups but non-retarded true positives reached statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗

Reduced optimality in pre- and perinatal conditions in dyskinetic cerebral palsy--distribution and comparison to controls.

The optimality concept developed by Prechtl was adopted to investigate a series of 108 dyskinetic cerebral palsy (CP) cases. The results were compared to those from a control series of 229 newborns. The dyskinetic cases, as compared to the controls, had significantly more reduced optimality scores. Reduced optimality was especially pronounced in the partum and postpartum periods, but was to a highly significant degree also found in the prepartum period. Dystonics and choreoathetotics differed in their pattern of reduced optimality. Dystonics had more reduced optimality in items related to deficient intrauterine growth, intra- and extrauterine asphyxia-choreoathetotics in items related to preterm birth, postpartal hypoxia and hyperbilirubinemia. Term cases had more reduced optimality scores (median 7 vs 1) compared to term controls than preterm cases compared to preterm controls (median 9 vs 4.5). The pattern of reduced optimality in term cases corresponded primarily to that among the dystonics, and the pattern in preterm cases mainly to that of the choreoathetotics. Prepartum warning signals for further partum and postpartum reduced optimality related to the brain cell damage, were maternal disorder, blood group incompatibility and leanness at birth (weight for length less than or equal to -1.0 SD). The latter condition was found to discriminate for reduced optimality in the partum period.

Athetosis↗

Segment-based dose optimization using a genetic algorithm.

Intensity modulated radiation therapy (IMRT) inverse planning is conventionally done in two steps. Firstly, the intensity maps of the treatment beams are optimized using a dose optimization algorithm. Each of them is then decomposed into a number of segments using a leaf-sequencing algorithm for delivery. An alternative approach is to pre-assign a fixed number of field apertures and optimize directly the shapes and weights of the apertures. While the latter approach has the advantage of eliminating the leaf-sequencing step, the optimization of aperture shapes is less straightforward than that of beamlet-based optimization because of the complex dependence of the dose on the field shapes, and their weights. In this work we report a genetic algorithm for segment-based optimization. Different from a gradient iterative approach or simulated annealing, the algorithm finds the optimum solution from a population of candidate plans. In this technique, each solution is encoded using three chromosomes: one for the position of the left-bank leaves of each segment, the second for the position of the right-bank and the third for the weights of the segments defined by the first two chromosomes. The convergence towards the optimum is realized by crossover and mutation operators that ensure proper exchange of information between the three chromosomes of all the solutions in the population. The algorithm is applied to a phantom and a prostate case and the results are compared with those obtained using beamlet-based optimization. The main conclusion drawn from this study is that the genetic optimization of segment shapes and weights can produce highly conformal dose distribution. In addition, our study also confirms previous findings that fewer segments are generally needed to generate plans that are comparable with the plans obtained using beamlet-based optimization. Thus the technique may have useful applications in facilitating IMRT treatment planning.

Algorithms↗

Algorithm and performance of a clinical IMRT beam-angle optimization system.

This paper describes the algorithm and examines the performance of an intensity-modulated radiation therapy (IMRT) beam-angle optimization (BAO) system. In this algorithm successive sets of beam angles are selected from a set of predefined directions using a fast simulated annealing (FSA) algorithm. An IMRT beam-profile optimization is performed on each generated set of beams. The IMRT optimization is accelerated by using a fast dose calculation method that utilizes a precomputed dose kernel. A compact kernel is constructed for each of the predefined beams prior to starting the FSA algorithm. The IMRT optimizations during the BAO are then performed using these kernels in a fast dose calculation engine. This technique allows the IMRT optimization to be performed more than two orders of magnitude faster than a similar optimization that uses a convolution dose calculation engine. Any type of optimization criterion present in the IMRT system can be used in this BAO system. An objective function based on clinically-relevant dose-volume (DV) criteria is used in this study. This facilitates the comparison between a BAO plan and the corresponding plan produced by a planner since the latter is usually optimized using a DV-based objective function. A simple prostate case and a complex head-and-neck (HN) case were used to evaluate the usefulness and performance of this BAO method. For the prostate case we compared the BAO results for three, five and seven coplanar beams with those of the same number of equispaced coplanar beams. For the HN case we compare the BAO results for seven and nine non-coplanar beams with that for nine equispaced coplanar beams. In each case the BAO algorithm was allowed to search up to 1000 different sets of beams. The BAO for the prostate cases were finished in about 1-2 h on a moderate 400 MHz workstation while that for the head-and-neck cases were completed in 13-17 h on a 750 MHz machine. No a priori beam-selection criteria have been used in achieving this performance. In both the prostate and the head-and-neck cases, BAO is shown to provide improvements in plan quality over that of the equispaced beams. The use of DV-based objective function also allows us to study the dependence of the improvement of plan quality offered by BAO on the DV criteria used in the optimization. We found that BAO is especially useful for cases that require strong DV criteria. The main advantages of this BAO system are its speed and its direct link to a clinical IMRT system.

Algorithms↗