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PubMed1996

Multivariate determination of glucose concentrations from optimally filtered frequency-warped NIR spectra of human blood serum.

Glucose concentrations over the 39-160 mg dl-1 range have been determined from 357 NIR (near-infrared) spectra of human blood serum in the spectral region from 6766 cm-1 to 4003 cm-1. A frequency-warping procedure was applied to the NIR data to compress 511 spectral components into 102 in the 6766-4003 cm-1 spectral region. Before the data compression process was carried out, the NIR spectrum of deionized water was subtracted from each of the blood serum spectra to remove the intrinsic high background absorption due to the water. PLS (partial least-squares) regression was coupled with time-domain digital Butterworth bandpass filtering in an optimization procedure. The optimization procedure was carried out over a range of centre frequencies and bandwidths for first- (two-pole), second- (four-pole) and third- (six-pole) order bandpass filters, and over a range of PLS factors. The optimal PLS model and filter parameters were determined from a sequence of three-dimensional performance response maps for different numbers of PLS factors and filter orders. As a basis for comparison, the same optimization process was carried out for a Gaussian filter design approach (i.e., Fourier filtering). Using the optimally filtered frequency-warped NIR spectral data, an SEP (standard error of prediction) of 13.2 mg dl-1 was achieved fro the test (monitoring) data using 14 PLS factors and a simple first-order (two-pole) digital Butterworth bandpass filter.

Blood Glucose↗

PubMed2001

Generalized optimal current patterns and electrical safety in EIT.

There are a number of constraints which limit the current and voltages which can be applied on a multiple drive electrical imaging system. One obvious constraint is to limit the maximum ohmic power dissipated in the body. Current patterns optimizing distinguishability with respect to this constraint are singular functions of the difference of transconductance matrices with respect to the power norm (the optimal currents of Isaacson). If one constrains the total current (L1 norm) the optimal patterns are pair drives. On the other hand if one constrains the maximum current on each drive electrode (an L(infinity) norm), the optimal patterns have each drive channel set to the maximum source or sink current value. In this paper we consider appropriate safety constraints and discuss how to find the optimal current patterns with those constraints.

Electric Impedance↗

PubMed2004

1001 optimal PDB structure alignments: integer programming methods for finding the maximum contact map overlap.

Protein structure comparison is a fundamental problem for structural genomics, with applications to drug design, fold prediction, protein clustering, and evolutionary studies. Despite its importance, there are very few rigorous methods and widely accepted similarity measures known for this problem. In this paper we describe the last few years of developments on the study of an emerging measure, the contact map overlap (CMO), for protein structure comparison. A contact map is a list of pairs of residues which lie in three-dimensional proximity in the protein's native fold. Although this measure is in principle computationally hard to optimize, we show how it can in fact be computed with great accuracy for related proteins by integer linear programming techniques. These methods have the advantage of providing certificates of near-optimality by means of upper bounds to the optimal alignment value. We also illustrate effective heuristics, such as local search and genetic algorithms. We were able to obtain for the first time optimal alignments for large similar proteins (about 1,000 residues and 2,000 contacts) and used the CMO measure to cluster proteins in families. The clusters obtained were compared to SCOP classification in order to validate the measure. Extensive computational experiments showed that alignments which are off by at most 10% from the optimal value can be computed in a short time. Further experiments showed how this measure reacts to the choice of the threshold defining a contact and how to choose this threshold in a sensible way.

Algorithms↗

PubMedDate not supplied

The effect of depressive symptoms and optimism on the risk of spontaneous abortion among innercity women.

BACKGROUND: The role of depressive symptoms and optimism on the risk of spontaneous abortion has not been well examined. Prior studies have documented that emotional stress can affect immune and endocrine function, which may in turn influence fertilization, implantation, embryogenesis, and successful fetal growth. METHODS: We enrolled pregnant women coming to the emergency department at the Hospital of the University of Pennsylvania from January 1999 through August 2001 to examine the role of depressive symptoms and optimism on spontaneous abortion. Cases were women who experienced a spontaneous abortion during the follow-up period (n = 174), and controls were women who maintained their pregnancy through 22 weeks (n = 798). Baseline interviews collected measures of depressive symptoms, using the Center for Epidemiologic Studies Depression Scale (CES-D) and optimism using the Life Oriented Test-Revised (LOT-R). RESULTS: We did not find a significant, prospective relationship between depressive symptoms or optimism and the risk of spontaneous abortion in our specific study population. CONCLUSIONS: The impact of depressive symptoms and optimism on pregnancy outcomes should be examined further in other populations.

Abortion, Spontaneous↗

PubMed2006

Optimized predictions of absolute and relative amounts of body fat from weight, height, other anthropometric predictors, and age 1.

BACKGROUND: Body mass index (BMI) is the dominating weight-for-height index, but its validity as a body fat (BF) index has not been properly examined. OBJECTIVES: Our aims were to establish and validate optimal weight-for-height indexes for predicting absolute and relative (percentage) amounts of BF, to examine whether other commonly available anthropometric variables or age could add to the predictive power, and to explore the upper limit for percentage BF. DESIGN: One thousand one hundred twelve randomly selected subjects, and an additional 149 obese subjects, were included in the study. The subjects were randomly allocated to either a primary study group or a validation group. BF was measured with dual-energy X-ray absorptiometry. The relations between weight/heightx (W/Hx) and BF (absolute or percentage) were examined for values of the exponent x that ranged from 0.0 to 3.0. The predictive power of equations that were based on optimal weight-for-height indexes was compared with equations based on weight, height, other anthropometric variables, and age. RESULTS: Absolute BF was optimally and linearly predicted by W/H1, whereas the percentage BF was optimally and nonlinearly predicted by W/H2. The percentage BF asymptotically approached 52% in women and 56% in men. The percentage BF increased only marginally from BMI (in kg/m2) values of >35 in women and >60 in men. Predictions of absolute BF were associated with smaller errors (8.5% for men and 5.7% for women) than were predictions of percentage BF (8.7% for men and 7.9% for women). The addition of other anthropometric measurements for both men and women, and the addition of age for women only, in the regression analyses moderately reduced these errors. CONCLUSION: Our data suggest that W/H may be a more optimal weight-for-height index than is BMI, particularly at high body weights.

Absorptiometry, Photon↗

PubMed2025

Optimized phenotyping of complex morphological traits: enhancing discovery of common and rare genetic variants.

Genotype-phenotype (G-P) analyses for complex morphological traits typically utilize simple, predetermined anatomical measures or features derived via unsupervised dimension reduction techniques (e.g. principal component analysis (PCA) or eigen-shapes). Despite the popularity of these approaches, they do not necessarily reveal axes of phenotypic variation that are genetically relevant. Therefore, we introduce a framework to optimize phenotyping for G-P analyses, such as genome-wide association studies (GWAS) of common variants or rare variant association studies (RVAS) of rare variants. Our strategy is two-fold: (i) we construct a multidimensional feature space spanning a wide range of phenotypic variation, and (ii) within this feature space, we use an optimization algorithm to search for directions or feature combinations that are genetically enriched. To test our approach, we examine human facial shape in the context of GWAS and RVAS. In GWAS, we optimize for phenotypes exhibiting high heritability, estimated from either family data or genomic relatedness measured in unrelated individuals. In RVAS, we optimize for the skewness of phenotype distributions, aiming to detect commingled distributions that suggest single or few genomic loci with major effects. We compare our approach with eigen-shapes as baseline in GWAS involving 8246 individuals of European ancestry and in gene-based tests of rare variants with a subset of 1906 individuals. After applying linkage disequilibrium score regression to our GWAS results, heritability-enriched phenotypes yielded the highest SNP heritability, followed by eigen-shapes, while commingling-based traits displayed the lowest SNP heritability. Heritability-enriched phenotypes also exhibited higher discovery rates, identifying the same number of independent genomic loci as eigen-shapes with a smaller effective number of traits. For RVAS, commingling-based traits resulted in more genes passing the exome-wide significance threshold than eigen-shapes, while heritability-enriched phenotypes lead to only a few associations. Overall, our results demonstrate that optimized phenotyping allows for the extraction of genetically relevant traits that can specifically enhance discovery efforts of common and rare variants, as evidenced by their increased power in facial GWAS and RVAS.

Humans↗

PubMed2002

Optimal enhancement of immune response.

MOTIVATION: Therapeutic enhancement of innate immune response to microbial attack is addressed as the optimal control of a dynamic system. Interactions between an invading pathogen and the innate immune system are characterized by four non-linear, ordinary differential equations that describe rates of change of pathogen, plasma cell, and antibody concentrations, and of an indicator of organic health. Without therapy, the dynamic model evidences sub-clinical or clinical decay, chronic stabilization, or unrestrained lethal growth of the pathogen; the response pattern depends on the initial concentration of pathogens in the simulated attack. In the model, immune response can be augmented by therapeutic agents that kill the pathogen directly, that stimulate the production of plasma cells or antibodies, or that enhance organ health. A previous paper demonstrated open-loop optimal control solutions that defeat the pathogen and preserve organ health, given initial conditions that otherwise would be lethal (Stengel et al. (2002)). Therapies based on separate and combined application of the agents were derived by minimizing a quadratic cost function that weighted both system response and control usage, providing implicit control over harmful side effects. RESULTS: We demonstrate the ability of neighboring-optimal feedback control to account for a range of unknown initial conditions and persistent input of pathogens by adjusting the therapy to account for perturbations from the nominal-optimal response history. We examine therapies that combine open-loop control of one agent with closed-loop control of another. We show that optimal control theory points the way toward new protocols for treatment and cure of human diseases. CONTACT: stengel@princeton.edu; rghiglia@princeton.edu; nkulkarn@princeton.edu

Antibodies↗

PubMed2003

MaxSubSeq: an algorithm for segment-length optimization. The case study of the transmembrane spanning segments.

MOTIVATION: A problem in predicting the topography of transmembrane proteins is the optimal localization of the transmembrane segments along the protein sequences, provided that each residue is associated with a propensity of being or not being included in the transmembrane protein region. From previous work it is known that post-processing of propensity signals with suited algorithms can greatly improve the quality and the accuracy of the predictions. In this paper we describe a general dynamic programming-like algorithm (MaxSubSeq, Maximal SubSequence) specifically designed to optimize the number and length of segments with constrained length in a given protein sequence. Previous application of our algorithm, has proved its effectiveness in the optimization task of both neural network and hidden Markov models output, and in this paper we present the detailed description of MaxSubSeq. RESULTS: We describe the application of MaxSubSeq to the location of both helical and beta strand transmembrane segments, optimizing the outputs derived with different predictive algorithms. For all-alpha transmembrane proteins we use both the standard Kyte-Doolittle (KD) hydropathy scale and the TMHMM predictor (http://www.cbs.dtu.dk/). Using a set of 188 well characterized membrane proteins, MaxSubSeq nearly doubles the correct location of transmembrane segments as compared to the standard KD hydrophobicity plot, reaching 51% accuracy. If MaxSubSeq is used to optimize the TMHMM method the accuracy increases from 68 to 72%. When used to regularize the prediction of beta transmembrane strands, obtained using both a neural network and a HMM based predictors, MaxSubSeq increases the accuracy per protein up to 72 and 73% respectively. AVAILABILITY: The program is available upon request to the authors, or it is accessible through our web server (http://gpcr.biocomp.unibo.it/predictors/)

Algorithms↗

PubMed2006

Flow-related techniques for preoperative goal-directed fluid optimization.

BACKGROUND: Improved postoperative outcome has been demonstrated by perioperative maximization of cardiac stroke volume (SV) with fluid challenges, so-called goal-directed therapy. Oesophageal Doppler (OD) has been the most common technique for goal-directed therapy, but other flow-related techniques and parameters are available and they are potentially easier to apply in clinical practice. The objective of this investigation was therefore to use OD for preoperative SV maximization and compare the findings with a Modelflow determined SV, with an OD estimated corrected flow time (FTc), with central venous oxygenation ( Svo2 ) and with muscle and brain oxygenation assessed with near infrared spectroscopy (NIRS). METHODS: Twelve patients scheduled for radical prostatectomy were anaesthetized before optimization of SV estimated by OD. A fluid challenge of 200 ml colloid was provided and repeated if at least a 10% increment in OD SV was obtained. Values were compared with simultaneously measured values of Modelflow SV, FTc, Svo2 and muscle and cerebral oxygenation estimated by NIRS. RESULTS: Based upon OD assessment, optimization of SV was achieved after the administration of 400-800 ml (mean 483 ml) of colloid. The hypothetical volumes administered for optimization based upon Modelflow and Svo2 differed from OD in 10 and 11 patients, respectively. Changes in FTc and NIRS were inconsistent with OD guided optimization. CONCLUSION: Preoperative SV optimization guided by OD for goal-directed therapy is preferable compared with Modelflow SV, FTc, NIRS and Svo2 until outcome studies for the latter are available.

Aged↗

PubMed1989

Assessment of the optimal atrio-ventricular delay in DDD paced patients by impedance plethysmography.

The beneficial haemodynamic effects of sequential atrioventricular (AV) pacing have been clearly established and are dependent on the AV delay and pacing rate. However, the optimal AV delay is difficult to determine in each particular patient. We used a modified impedance plethysmographic method to assess variations in stroke volume for different AV delay and pacing rate settings. Impedance measurements showed a good correlation with CO2 rebreathing stroke volume measurements in VVI patients. Impedance variations were then used to set the optimal AV delay at different pacing rates in DDD patients. The inverse relationship between the optimal AV delay and the pacing rate has been accurately identified in most of the patients but is not predictable. In all cases, the cardiac output was higher in DDD mode at the optimal AV delay than in VVI mode. In some patients with a damaged myocardium, the stroke volume appeared to be highly sensitive to multiple AV delay settings. Impedance plethysmography can permit such repetitive non-invasive quick measurements, increasing the accuracy of optimal AV delay determination and is well suited for routine examination of patients with cardiac dual chamber pacemakers.

Atrioventricular Node↗

PubMed2002

High-risk sexual behaviour increases among London gay men between 1998 and 2001: what is the role of HIV optimism?

OBJECTIVE: To examine whether HIV optimism (i.e. optimism in the light of new HIV drug therapies) can account for the recent increase in high-risk sexual behaviour among London gay men. METHODS: Gay men (n = 2938) using London gyms were surveyed annually between 1998 and 2001. Information was collected on HIV status, unprotected anal intercourse (UAI) in the previous 3 months, and agreement with two statements concerning the severity of and susceptibility to HIV infection. Those who agreed were classified as 'optimistic'. RESULTS: Between 1998 and 2001, the percentage of men reporting high-risk UAI (i.e. UAI with a casual partner of unknown or discordant HIV status) increased: HIV-positive men 15.3-38.8%; HIV-negative men 6.8-12.1%; never-tested men 2.1-7.7%; (P < 0.01). Overall, less than a third were optimistic. In cross-sectional analysis, optimistic HIV-positive and -negative men were more likely to report high-risk UAI than other men (P < 0.05). However, the increase in high-risk UAI between 1998 and 2001 was seen in those who were optimistic and those who were not (P < 0.05). In multivariate analysis, the modelled increase in high-risk UAI over time remained significant after controlling for HIV optimism (P < 0.01), with no significant interaction between optimism and time. CONCLUSION: Among London gay men, no difference was detected between those who were optimistic and those who were not in the rate of increase in high-risk sexual behaviour between 1998 and 2001. Our findings suggest that HIV optimism is unlikely to explain the recent increase in high-risk sexual behaviour in these men.

Adult↗

PubMed1986

Computer-controlled optimization of positive end-expiratory pressure.

Positive end-expiratory pressure (PEEP) is a standard treatment for patients with refractory hypoxemia due to an acute restrictive pathology. The therapeutic range of PEEP can be quite narrow. PEEP therapy has been optimized using invasive variables such as oxygen transport and pulmonary shunt, and noninvasive variables such as compliance; however, the measurements are complex. We constructed a computerized PEEP-optimization system consisting of a Siemens 900C ventilator, Siemens prototype sulfur hexafluoride analyzer, Siemens 940 lung mechanics analyzer, and a DEC 11/23 microcomputer. The user may choose from three different noninvasive PEEP titration algorithms: maximizing static total respiratory system compliance (CTR), maximizing functional residual capacity(FRC)-based compliance (CFRC), and normalizing FRC. The device was tested in six dogs with pulmonary injury induced by oleic acid. The system was constrained to 3-cm H2O PEEP steps at 20-min intervals. The algorithm normalizing FRC reached optimal PEEP levels in 40 min, with a mean difference from the desired FRC of 15 +/- 48 (SEM) ml. This corresponds to a mean percent error of 1.0% +/- 2.63%. The CFRC and CTR algorithms reached optimal PEEP levels in 60 and 40 min, respectively, and maintained a maximal compliance for 85% of the time. This system provides fully automated noninvasive PEEP titration and is flexible enough to incorporate easily any other PEEP titration algorithms. It should improve patient care by guaranteeing that PEEP therapy is truly optimized throughout the patient's recovery.

Animals↗

PubMed1985

Theoretical considerations for optimizing intensity differences between primary musculoskeletal tumors and normal tissue with spin-echo magnetic resonance imaging.

In the radiographic assessment of primary musculoskeletal tumors, it is important for therapy planning to accurately define the extent of a tumor. Using a double spin-echo pulse sequence, the T1 and T2 relaxation times and relative hydrogen densities of several neoplastic tissues and of several normal tissues in four patients were measured. Neoplasms measured included one fibrosarcoma, two osteosarcomas, and one giant cell tumor. Normal tissues measured included normal muscle, fat, and bone marrow. Using a mathematical model of the double spin-echo pulse sequence, the intensity difference between each tumor and each normal tissue for multiple values of TR and TE was calculated. These calculated intensity differences were then used to plot isodifference contour curves for each tissue pair. These plots enabled us to pick combinations of TR and TE that optimized the signal difference between tumor and normal tissue. When comparing tumor with predominantly fatty tissue such as marrow or subcutaneous fat, optimal signal difference in our imager occurred at a TR of 600 to 800 msec and a very short TE. When comparing tumor with muscle, optimal signal difference occurred with very long TR times, and TE times ranging from 30 to 90 msec. These preliminary results suggest that an optimal scanning protocol for primary musculoskeletal tumors should contain at least two different pulse sequences with widely separated TR values (500 and 2000 msec in our instrument), and short to intermediate values of TE (28 and 56 msec in our instrument). It is believed that analysis of isodifference contour plots is a useful method for optimizing intensity differences between any two tissue types.

Bone Neoplasms↗

PubMed1994

Optimism, values, and commitment as forces in nursing leadership.

In a grounded theory study of nursing leadership undertaken in Western Australia, a substantive theory of optimizing as a leadership process was developed. In a context of repression and turbulence, optimizing meant "making the best of the situation, making optimal use of available and potential resources." The author discusses the aspects of the leaders' optimism, values, and commitment, and how these variables appeared to influence the level of optimizing attempted or achieved.

Attitude of Health Personnel↗

PubMedDate not supplied

Self-esteem and optimism in men and women infected with HIV.

BACKGROUND: Self-esteem and optimism have been associated with appraisal and outcomes in a variety of situations. The degree to which the contribution of self-esteem and optimism to outcomes over time is accounted for by the differences in threat (primary) or resource (secondary) appraisal has not been established in persons with human immunodeficiency virus (HIV). OBJECTIVES: To examine the longitudinal relationship of personality (self-esteem and optimism) on primary and secondary appraisal and outcomes of well-being, mood, CD4+ T-lymphocyte count, and selected activities. METHODS: Men (n = 56) and women (n = 42) infected with HIV completed eight self-report measures twice over 18 months. Hierarchical Multiple Regressions were used to examine the relationship of personality variables on appraisals and outcomes. The mediating effects of primary and secondary appraisals were explored. RESULTS: Self-esteem uniquely accounted for 6% of the variance in primary appraisal and 5% in secondary appraisal. Optimism accounted for 8% of the unique variance in secondary appraisal. Primary and secondary appraisal mediated differently between personality and outcome variables. A strong predictor of well-being, mood disturbance, and activity disruption at Time 2 was participants' initial level of these variables. Socioeconomic status was a strong predictor of mood. CONCLUSIONS: Self-esteem and optimism are important but different resources for adapting to HIV disease. Strategies for reducing threats and increasing resources associated with HIV may improve an individual's mood and sense of well-being.

Adaptation, Psychological↗

PubMed2005

Time required for equilibration of arterial oxygen pressure after setting optimal positive end-expiratory pressure in acute respiratory distress syndrome.

OBJECTIVE: To evaluate the time course of Pao2 change following the setting of optimal positive end-expiratory pressure (PEEP) in patients with acute respiratory distress syndrome (ARDS). DESIGN: Prospective clinical study. SETTING: Multidisciplinary intensive care unit of a university hospital. PATIENTS: Twenty-five consecutive patients with ARDS. INTERVENTIONS: ARDS was diagnosed during pressure-regulated volume control ventilation with tidal volume of 7 mL/kg actual body weight, respiratory rate of 12 breaths/min, inspiratory/expiratory ratio of 1:2, Fio2 of 1, and PEEP of 5 cm H2O. A critical care attending physician obtained pressure volume curves and determined the lower inflection point. Following a rest period of 30 mins with initial ventilation variables, PEEP was set at 2 cm H2O above the lower inflection point, and serial blood samples were collected during 1-hr ventilation with optimal PEEP. Arterial blood gas analyses were performed at 1, 3, 5, 7, 9, 11, 15, 20, 30, 45, and 60 mins. MEASUREMENTS AND MAIN RESULTS: Twenty-five patients were found eligible for the study. Three patients were excluded due to deterioration of oxygen saturation and hemodynamic instability following the initiation of optimal PEEP. Eight cases (36%) were considered to be of pulmonary origin and 14 cases (64%) of extrapulmonary origin. Optimal PEEP levels were 14 +/- 3 cm H2O and 14 +/- 4 cm H2O in pulmonary and extrapulmonary ARDS, respectively. Pao2 demonstrated a 130 +/- 101% increase at the end of 1-hr period in total study population. This improvement did not differ significantly between pulmonary and extrapulmonary forms of ARDS (135 +/- 118% vs. 127 +/- 95%, p = .8). Mean 90% oxygenation time was found to be 20 +/- 19 mins. In the subset of patients with ARDS of pulmonary origin, 90% oxygenation time was 25 +/- 26 mins, whereas it was 17 +/- 15 mins in patients with ARDS of extrapulmonary origin (p = .8). CONCLUSIONS: Our data showed that 20 mins would be adequate for obtaining a blood gas sample in ARDS patients with pulmonary and extrapulmonary origin after application of optimal PEEP 2 cm H2O above the lower inflection point.

Adolescent↗

PubMed2004

'Optimal' vortex rings and aquatic propulsion mechanisms.

Fishes swim by flapping their tail and other fins. Other sea creatures, such as squid and salps, eject fluid intermittently as a jet. We discuss the fluid mechanics behind these propulsion mechanisms and show that these animals produce optimal vortex rings, which give the maximum thrust for a given energy input. We show that fishes optimize both their steady swimming efficiency and their ability to accelerate and turn by producing an individual optimal ring with each flap of the tail or fin. Salps produce vortex rings directly by ejecting a volume of fluid through a rear orifice, and these are also optimal. An important implication of this paper is that the repetition of vortex production is not necessary for an individual vortex to have the 'optimal' characteristics.

Animals↗

PubMed2005

Design optimization methods for genomic DNA tiling arrays.

A recent development in microarray research entails the unbiased coverage, or tiling, of genomic DNA for the large-scale identification of transcribed sequences and regulatory elements. A central issue in designing tiling arrays is that of arriving at a single-copy tile path, as significant sequence cross-hybridization can result from the presence of non-unique probes on the array. Due to the fragmentation of genomic DNA caused by the widespread distribution of repetitive elements, the problem of obtaining adequate sequence coverage increases with the sizes of subsequence tiles that are to be included in the design. This becomes increasingly problematic when considering complex eukaryotic genomes that contain many thousands of interspersed repeats. The general problem of sequence tiling can be framed as finding an optimal partitioning of non-repetitive subsequences over a prescribed range of tile sizes, on a DNA sequence comprising repetitive and non-repetitive regions. Exact solutions to the tiling problem become computationally infeasible when applied to large genomes, but successive optimizations are developed that allow their practical implementation. These include an efficient method for determining the degree of similarity of many oligonucleotide sequences over large genomes, and two algorithms for finding an optimal tile path composed of longer sequence tiles. The first algorithm, a dynamic programming approach, finds an optimal tiling in linear time and space; the second applies a heuristic search to reduce the space complexity to a constant requirement. A Web resource has also been developed, accessible at http://tiling.gersteinlab.org, to generate optimal tile paths from user-provided DNA sequences.

Algorithms↗