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The empirical identification of insomnia subtypes: a cluster analytic approach.

Over the past 15 years, there has been considerable debate concerning the extent to which insomnia patients can be classified into diagnostic subtypes. Despite this debate, relatively little research has been conducted to empirically determine whether naturally occurring insomnia subtypes might be identified within populations of sleep clinic patients. In the current study we used a hierarchical cluster analysis to empirically identify subtypes among a mixed group of normal sleepers and the insomnia outpatients who presented to our sleep center over the past decade. Using factor-analytically derived composite variables that summarized data obtained from sleep history questionnaires and polysomnographic monitoring, this clustering procedure resulted in the identification of 14 subgroups that varied between four and 34 patients/subjects in size. Subsequently, subgroup mean scores for the composite variables used in the clustering procedure were used to construct profiles for each of the 14 clusters. A multivariate profile analysis, employed to elucidate subgroup differences, showed that these cluster profiles differed in terms of their configural shapes, average elevations, and degrees of interscale differences. Furthermore, both DSM-III-R (American Psychiatric Association) and International Classification of Sleep Disorders (ICSD) insomnia diagnoses, assigned independent of cluster findings, suggested that these subtypes differed significantly in regard to their diagnostic compositions. Nevertheless, a far-from-perfect concordance was observed between such clinically assigned diagnoses and cluster group membership. In fact, many of the empirically identified groups were composed of various DSM-III-R and/or ICSD diagnostic subtypes. These results provided only partial support for current DSM and ICSD insomnia categories. However, our results support the existence of multiple, clinically discrete insomnia subtypes and provide information that may be useful in future revisions of current insomnia nosologies.

Adult↗

Measurement of corticosterone metabolites in birds' droppings: an analytical approach.

Fecal steroid analyses are becoming increasingly popular among both field and laboratory scientists. The benefits associated with sampling procedures that do not require restraint, anesthesia, and blood collection include less risk to subject and investigator, as well as the potential to obtain endocrine profiles that are not influenced by the sampling procedure itself. In the feces, a species-specific pattern of metabolites is present, because glucocorticoids are extensively metabolized. Therefore, selection of adequate extraction procedures and immunoassays for measuring the relevant metabolites is a serious issue. In this review, emphasis is placed on the establishment and analytical validation of methods to measure glucocorticoid metabolites for a noninvasive evaluation of adrenocortical activity in droppings of birds.

Animals↗

[Governance in health: a conceptual and analytical approach to research].

In the Latin American region there is a notable absence of conceptual coherency in the use of the terms governability and governance. This is true for their application to both the social and political sciences and health. Researchers' understanding of governance varies, and the concept is used heterogeneously within academic circles, with ignorance of the term on the part of decision-makers and great confusion and ambiguity in the meanings used by researchers and decision-makers in the health sector. Instead of the prevailing normative use, promoted by most international agencies, a conceptual and analytical framework for governance is proposed here for health systems and services research. Advances in the design of this framework were used to evaluate the public health insurance program in Buenos Aires, Argentina, which allowed the use of the analytical framework to be assessed as a tool for systemizing the social, political, and institutional complexity of the health policy formulation and implementation processes.

Administrative Personnel↗

Oxidative stability and phenolic content of virgin olive oil: an analytical approach by traditional and high resolution techniques.

The characteristic resistance to oxidation of virgin olive oil is related to its unique fatty acid composition in addition to several minor components that have antioxidant properties. Among the latter, phenols are the most important. Several factors can influence the chemical or enzymatic oxidative processes that extend or shorten the shelf-life of olive oil. Furthermore, the amount of phenolic compounds extracted during production is fundamental for the oxidative and nutritional quality of the oil. In fact, it is well known that different steps used for preparation of virgin olive oil may determine differences in the quantities of phenol. At present, various analytical methods are available to analyze the hydrophilic components, including spectrophotometric assays (traditional) and high resolution chromatographic techniques (HRGC, HPLC, HPCE). In this review we summarize these different methodologies and demonstrate that the amount of phenolic compounds in virgin olive oil as determined by both traditional and high resolution techniques can be influenced by different factors including the olive cultivar and degree of ripeness, as well as by production and extraction technologies.

Chromatography, High Pressure Liquid↗

Analytic approach to the critical density in cellular automata for traffic flow.

The jamming transition in the stochastic traffic cellular automaton of Nagel and Schreckenberg [J. Phys. I 2, 2221 (1992)] is examined. We argue that most features of the transition found in the deterministic limit do not persist in the presence of noise, and suggest instead to define the transition to take place at that critical density rho(c) at which a large initial jam just fails to dissolve. We show that rho(c)=v(J)/(v(J)+v(F)), where v(F) is the velocity of noninteracting vehicles and v(J) is the speed of the dissolution wave moving into the jam. An approximate analytic calculation of v(J) in the framework of a simple renormalization scheme is presented, which explicitly displays the effect of the interaction between vehicles during the acceleration stage of the Nagel-Schreckenberg rules with maximum velocity v(max)>1. The analytic prediction is compared to numerical simulations. We find a remarkable correspondence between the analytic expression for v(J) and a phase diagram obtained numerically by Lübeck et al.

Journal Article↗

Analytical approach to sorting in periodic and random potentials.

There has been a recent revolution in the ability to manipulate micrometer-sized objects on surfaces patterned by traps or obstacles of controllable configurations and shapes. One application of this technology is to separate particles driven across such a surface by an external force according to some particle characteristic such as size or index of refraction. The surface features cause the trajectories of particles driven across the surface to deviate from the direction of the force by an amount that depends on the particular characteristic, thus leading to sorting. While models of this behavior have provided a good understanding of these observations, the solutions have so far been primarily numerical. In this paper we provide analytic predictions for the dependence of the angle between the direction of motion and the external force on a number of model parameters for periodic as well as random surfaces. We test these predictions against exact numerical simulations.

Journal Article↗

Analytical approach to determination of safety of milk ingredients from hyperimmunized cows.

Bovine milk-derived ingredients from cows hyperimmunized with a variety of antigens have been available experimentally or commercially for several decades. Although the safety of milk is rarely questioned, an assessment of ingredients derived from the milk of cows hyperimmunized with a proprietary bacterin (S100) was made to determine that these ingredients share the human food safety profile traditionally ascribed to regular milk. The critical elements in this determination are: (1) quantitative determination of the difference between S100 and regular dairy ingredients, (2) comparison of exposures resulting from proposed uses to background exposures already in the American diet, and (3) corroborative results of controlled clinical trials comparing safety outcomes from consumption of S100 with those of conventional dairy ingredients. Comparative analytical data reveal that the only difference between S100 and conventional dairy ingredients is significantly higher active (undenatured) immunoglobulin G (IgG) (61-79% vs. control Grade A fluid and powdered skim, respectively, p<0.005) with slightly altered specific antibody activity. Estimated daily intake projections show that use of S100 ingredients at maximum proposed levels results in exposures to active (undenatured) IgG below background in the present American diet in infants but above background in children and adults, whose intake of conventional dairy products is markedly lower. Safety of this consumption level is corroborated by clinical results showing no difference in safety outcomes between S100 ingredients, consumed at exaggerated levels, and conventional dairy products, in a variety of adult populations. There is no evidence that demonstrates a hazard to the public when S100 ingredients are used at levels that might reasonably be expected from the proposed applications.

Animals↗

The process of gas exchange in systemic circulation in a hyperbaric environment: an analytical approach.

A mathematical model is proposed to deal with the simultaneous transport of oxygen (O2) and carbon dioxide (CO2) in systemic capillaries and the surrounding tissue in a hyperbaric environment. The transport in the capillary region depends on molecular diffusion (radial as well as axial), the convective effect of the blood, and the saturation of haemoglobin with O2 and CO2. The corresponding equation in the tissue region describes the transport of the species due to radial and axial diffusion in the tissue and consumption of O2 in the metabolic process. The production of CO2 inside the tissue is incorporated through the respiratory quotient. The saturation of blood with O2 and CO2 have been approximated by linear functions to simulate the conditions of the hyperbaric environment. The resulting system of governing equations with the physiologically relevant boundary conditions is solved analytically. The concentration of O2 is shown to decrease from the core of the capillary to the tissue periphery, whereas the concentration of CO2 increases. It is shown that very little of the CO2 is transported radially. The location of the vulnerable point from the point of view of CO2 accumulation is found to be the corner (x = R2, z = L) situated at the periphery of the tissue near the venous end of the capillary. The accumulation of O2 and CO2 in the tissue is discussed in terms of various dimensionless parameters. It is found that the accumulation of CO2 increases whereas that of O2 decreases in the hyperbaric environment. Finally, it is surmised that one of the major causes of discomfort among divers could be excessive accumulation of CO2 in the tissue.

Blood Circulation↗

Comparative effects of short-term psychodynamic psychotherapy and cognitive-behavioral therapy in depression: a meta-analytic approach.

UNLABELLED: This article reviews the efficacy of short-term psychodynamic psychotherapy (STPP) in depression compared to cognitive-behavioral therapy (CBT) or behavioral therapy (BT). In this review, only studies in which at least 13 therapy sessions were performed have been included, and a sufficient number of patients per group were treated (N > or = 20). With regard to outcome criteria, the results were reviewed for improvements in depressive symptoms, general psychiatric symptoms, and social functioning. Six studies met the inclusion criteria. RESULTS: In 58 of the 60 comparisons (97%) performed in the six studies and their follow-ups, no significant difference could be detected between STPP and CBT/BT concerning the effects in depressive symptoms, general psychiatric symptomatology, and social functioning. Furthermore, STPP and CBT/BT did not differ significantly with regard to the patients that were judged as remitted or improved. According to a meta-analytic procedure described by R. Rosenthal (1991) the studies do not differ significantly with regard to the patients that were judged as remitted or improved after treatment with STPP or CBT/BT. The mean difference between STPP and CBT/BT concerning the number of patients that were judged as remitted or improved corresponds to a small effect size (post-assessment: phi = 0.08, follow-up assessment: phi = 0.12). Thus, STPP and CBT/BT seem to be equally effective methods in the treatment of depression. However, because of the small number of studies which met the inclusion criteria, this result can only be preliminary. Furthermore, it applies only to the specific forms of STPP that were examined in the selected studies and cannot be generalized to other forms of STPP. Further studies are needed to examine the effects of specific forms of STPP in both controlled and naturalistic settings. Furthermore, there are findings indicating that 16-20 sessions of both STPP and CBT/BT are insufficient for most patients to achieve lasting remission. Future studies should address the effects of longer treatments of depression.

Adult↗

Decision making in nosocomial pneumonia. An analytic approach to the interpretation of quantitative bronchoscopic cultures.

Quantitative cultures of specimens obtained at fiberoptic bronchoscopy have been used to diagnose nosocomial pneumonia in research settings, but their clinical role remains controversial. We reviewed the literature comparing these culture techniques with other accepted methods to diagnose pneumonia in mechanically ventilated patients and extracted data to describe the receiver operator characteristics (ROC) of quantitative cultures of protected specimen brush (PSB) and bronchoalveolar lavage (BAL) samples. Analysis of ROCs reveals that these tests have a discriminating power comparable or superior to that of many widely accepted routinely used tests. Current data do not suggest that either culture technique offers an advantage over the other. Since benefits of antibiotic therapy of pneumonia and risks of treatment of noninfected critically ill patients are not well quantified, universally applicable recommendations for appropriate values to define an abnormal test result cannot logically be made. Multiple decision analytic tools show that values lower than those previously recommended are more appropriate in patients suspected of having pneumonia unless the risk of antibiotic therapy is judged to be extreme. On the basis of these findings, we suggest guidelines for clinicians' interpretation of PSB and BAL quantitative culture results.

Bacteria↗

Electric and magnetic fields of the brain computed by way of a discrete systems analytical approach: theory and validation.

It is shown how the stationary volume conduction phenomena in the brain, namely the electric and magnetic fields can be described in discrete terms. The volume conductor is sampled in space by introducing a sampling distance corresponding to the uncertainty in the measurements. In this way, a three-dimensional lattice is needed with equidistantly spaced nodes. The electric and magnetic properties of such a lattice are assumed to be equivalent to that of brain and other tissues. The electric and magnetic potential fields are calculated for each node as the output of a linear feedback system which has the impressed currents as the input. By way of the feedback loop the reflection phenomena at the boundaries between media of different conductivity can be taken into account. This discrete formalism has been implemented in a software system. To demonstrate the validity and accuracy of this system a number of analytically tractable problem in volume conduction has been evaluated.

Animals↗

An analytical approach to quantify uniformity artifacts for circular and noncircular detector motion in single photon emission computed tomography imaging.

Uniformity artifacts in rotating gamma camera tomography will result if there are errors in the correction factors which are routinely calculated from a static uniformity flood image. The accuracy of the correction factors is a function of the statistics in the collected flood image. Since the factors are applied to each projection view, an error in a correction factor will propagate as a projection error at the same pixel location for each view. For circular detector motion, the error in each projection is reconstructed as a ring whose maximum amplitude varies approximately inversely proportional to the square root of the distance of the projection error from the center of rotation. For noncircular detector motion the artifacts are not rings but are more complicated geometric curves. Simulations show that statistical fluctuations in the reconstructed image will mask the uniformity artifacts provided the correction flood satisfies minimum count requirements. An analytical expression is derived for the percent root-mean-square (% rms) error in the reconstruction and is compared with the percent relative amplitude error (% RAE) of the reconstructed artifacts in order to obtain expressions for uniformity flood counting statistics. For an elliptical source distribution with total counts equal to CT, the uniformity statistics required to reconstruct elliptical disks is inversely proportional to the square root of the area: U greater than or equal to KCT/area 1/2. The constant K depends on the filter function and type of detector motion.

Biophysical Phenomena↗

Analytical approaches to improved characterization of substitution in hydroxypropyl cellulose.

Chemical characterization of cellulose derivatives is of high importance as it provides information about the often inhomogeneous substitution that may seriously affect the properties of these polymers in various applications. A detailed mapping of the chemical structure of these derivatives requires several advanced techniques to be employed. In this study, the average substitution and the substitution heterogeneity in two hydroxypropyl cellulose (HPC) samples from different suppliers were studied by means of NMR spectroscopy, MALDI-TOF MS, and HPAEC-PAD. (1)H and (13)C NMR provided information on the molar substitution, a parameter that could be analyzed by MALDI-TOF MS as well. In addition, the latter technique was used for determination of the distribution of the number of hydroxypropyl groups per glucose unit present in the two polymers. The heterogeneity of the substitution was studied by determining the amount of unsubstituted glucose units in the HPC samples, which was accomplished by HPAEC-PAD analysis. The results obtained suggest that the two HPC samples differ in both hydroxypropoxy content and distribution of the hydroxypropyl groups. Further, the benefits and importance of employing several analytical methods when investigating the cellulose ether substitution are demonstrated, as each method provides different kinds of information on the chemical content.

Carbohydrate Sequence↗

The analytical approach to polydimethylsiloxane microfluidic technology and its biological applications.

This review article discusses PDMS (polydimethylsiloxane) microfluidic devices and their biological applications. First, the already developed devices are classified from the viewpoints of underlying technology within a common logical framework comprising single-layer, multilayer, and integrated devices, as well as surface chemistry modifications of PDMS. Combinatorial techniques are applied to re-derive existing devices within this framework. Next, the relevant scales of both microfluidics and biology are compared, obtaining the promise and limitations of PDMS microfluidics. Finally, the body of work is reclassified in terms of addressed biological applications and compared to the standard methods in cellular and molecular biology, to offer insights for future devices and applications.

Animals↗

Need for common internal controls when assessing the relative efficacy of pharmacologic agents using a meta-analytic approach: case study of cyclooxygenase 2-selective inhibitors for the treatment of osteoarthritis.

OBJECTIVE: To evaluate the role of common internal controls in a meta-analysis of the relative efficacy of cyclooxygenase 2-selective inhibitors (coxibs) in the treatment of osteoarthritis (OA). METHODS: A systematic search of Medline and US Food and Drug Administration electronic databases was performed to identify randomized, placebo-controlled clinical trials of coxibs (etoricoxib, celecoxib, rofecoxib, valdecoxib) in patients with hip and/or knee OA. The effect size for coxibs and common active internal controls (nonsteroidal antiinflammatory drugs [NSAIDs], naproxen) were determined by the mean changes from baseline in Western Ontario and McMaster Universities Osteoarthritis Index pain subscores as compared with placebo. RESULTS: The effect size for all coxib groups combined (0.44) indicated greater efficacy as compared with placebo, but significant heterogeneity (P < 0.0001) was observed. Rofecoxib at dosages of 12.5 mg/day and 25 mg/day and etoricoxib at a dosage of 60 mg/day had similar effect sizes (0.68 and 0.73, respectively), but these effect sizes were comparatively greater than those for both celecoxib at dosages of 200 mg/day and 100 mg twice daily or valdecoxib at a dosage of 10 mg/day (0.26 and 0.16, respectively). The effect sizes for NSAIDs or naproxen versus placebo, as determined using data from rofecoxib/etoricoxib trials, were consistently higher than the effect sizes derived from trials of celecoxib/valdecoxib. Significant heterogeneity was present in the overall effect size for NSAIDs (P = 0.007) and naproxen (P = 0.04) groups based on data available from all coxib trials. CONCLUSION: Coxibs and common active internal controls showed larger effect sizes versus placebo in the rofecoxib/etoricoxib trials than in the celecoxib/valdecoxib trials. These findings suggest systematic differences among published coxib trials and emphasize the need for direct-comparison trials. In the absence of such trials, common internal controls should be assessed when performing indirect meta-analytic comparisons.

Anti-Inflammatory Agents, Non-Steroidal↗

Analytical approach for monitoring endocrine-disrupting compounds in urban waste water treatment plants.

The presence of endocrine-disrupting compounds in influent and effluent water samples from four waste water treatment plants located in Italy was studied. The estrogen-like activity of the water samples was measured using a chemiluminescent recombinant yeast assay which is based on genetically engineered yeast cells that express the human estrogen receptor. This receptor, once activated, elicits the expression of the reporter gene lac-Z and, consequently, the production of beta-galactosidase, which is then measured by chemiluminescence. To control and minimize sample matrix effects, an external control based on a modified yeast strain stably expressing beta-galactosidase was developed and also used in the assay. Rapid and sensitive chemiluminescent enzyme immunoassays were also developed and validated for the quantification of 17beta-estradiol, estrone, and estriol in waste water samples. Results from both methods were compared with a reference high-performance liquid chromatography and electrospray ionization tandem mass spectrometry (HPLC ESI-MS-MS) method developed for the quantification of natural estrogens. The recombinant yeast assay revealed a significant estrogenic activity in the influent samples, ranging from 80 to 400 pmol/L 17beta-estradiol equivalents (EEQ), which was reduced by 70-95% in the effluent samples. The yeast assay also showed a systematic 20-30% overestimation of estrogenic activity relative to the HPLC ESI-MS-MS method, suggesting the presence of other compounds in the samples with estrogenic activity. The chemiluminescent enzyme immunoassays showed the presence of estrogens in the influent samples (mean concentrations: 350-450 pmol/L for estrone, 5-100 pmol/L for 17beta-estradiol, 25-300 pmol/L for estriol), with significantly lower concentrations detected in the respective effluent samples. The waste water treatment was able to reduce natural estrogen concentrations by 40-95%, although a high variability was observed. The enzyme immunoassay data correlated well with data obtained by the HPLC ESI-MS-MS method. Although the recombinant yeast assay represents a useful tool for a first-level screening of estrogenic activity due to its simplicity and high analytical throughput, sample matrix effects observed in waste water of industrial origin were found to strongly affect the yeast cells response, even when properly corrected for using the external control, thereby limiting its use to urban waste water. Its integration with chemiluminescent enzyme immunoassays would improve its performance by reducing false negative results, thereby enabling its use in extensive studies monitoring for the presence of endocrine-disrupting compounds in urban treatment plant effluents.

Chromatography, High Pressure Liquid↗

Analytical approaches to the determination of phosphorus partitioning patterns in sediments.

Three methods for phosphorus fractionation in sediments based on chemical extractions have been applied to fourteen aquatic sediment samples of different origin and characteristics. Two of the methods used different approaches to obtain the inorganic fractions. The Hieltjes and Lijklema procedure (HL) uses strong acids or bases, whereas the Golterman procedure (G) uses chelating reagents. The third one, the Standards, Measurements and Testing (SMT) protocol, was proposed in the frame of the SMT Programme (European Commission) which aimed to provide harmonisation and the validation of such methodologies. This harmonised procedure was also used for the certification of the extractable phosphorus contents in a sediment certified reference material (CRM BCR 684). Principal component analysis (PCA) was used to group sediments according to their composition and the three extraction methods were applied to the samples including CRM BCR 684. The data obtained show that there is some correlation between the results from the three methods when considering the organic and the residual fractions together. The SMT and the HL methods are the most comparable, whereas the G method, using a different type of reagent, yields different distribution patterns depending on sample composition. In relation to the inorganic phosphorus, the three methods give similar information, although the distribution between non-apatite and apatite fractions can be different.

Certification↗

An analytical approach to the measurement of equilibrium binding constants: application to EGF binding to EGF receptors in intact cells measured by flow cytometry.

In ligand binding studies, ligand depletion often limits the accuracy of the results obtained. This problem is approached by employing the simple observation that as the concentration of receptor in the assay is reduced, ligand depletion is also reduced. Measuring apparent K(D)'s of a ligand at multiple concentrations of receptor with extrapolation to infinitely low receptor concentration takes ligand depletion into account and, depending on the binding model employed, yields a K(D) within the defined limits of accuracy. We apply this analysis to the binding of epidermal growth factor (EGF) to the EGF receptor expressed in intact 32D cells, using a homogeneous fluorescein-labeled preparation of EGF and measuring binding by flow cytometry. Binding isotherms were carried out at varying cell densities with each isotherm fit to the generally applied model with two independent binding sites. Examination of the variation in the K(D)'s versus cell density yields a high-affinity site that accounts for 18% of the sites and a lower affinity site that accounts for the remainder. However, further examination of these data suggests that while consistent with each individual isotherm, the simple model of two independent binding sites that is generally applied to EGF binding to the EGF receptor is inconsistent with the changes in the apparent K(D)'s seen across varying cell densities.

Animals↗