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Comparative analysis of heroin and cocaine seizures.

In this brief review the analytical techniques mainly used for comparative analysis of both cocaine and heroin seizures are reported. The characterization of illicit samples is carried out by means of a variety of techniques including thin-layer chromatography, high-performance liquid chromatography, gas chromatography and capillary electrophoresis. By means of these technique it is possible to resolve some component in illicit drugs and their application for comparative analyses is described in this review. Owing to the complexity and the variability of the mixture related to the origin and manufacturing impurities a unique analytical approach based on the application of a single technique it is not sufficient to achieve the requested global characterization of the sample for comparative purposes. Generally a complete characterization is obtained focusing on the identification of minor and major components, origin and manufacturing impurities other than trace compounds such as solvent residues. Nevertheless the application of a single robust methods able to resolve any possible significant marker compounds, is still not described and there is a need for a standardized general procedure suitable for a complete cross-examination of analytical data related to comparative analyses that can be carried out at an international level.

Chromatography↗

Conceptual and empirical approaches to developing family-based assessment procedures: resolving the case of the Family Environment Scale.

This article focuses on the reliability and validity of the Family Environment Scale (FES). The FES subscales generally show adequate internal consistency reliability and stability over time when applied in samples that are diverse; the items also have good content and face validity. An extensive body of research supports the construct, concurrent, and predictive validity of the FES. More generally, reliability and validity are a joint function of scale items and response formats and of the characteristics and diversity of specific samples. To contribute to further advances in family assessment, researchers need to use both conceptual and psychometric criteria rather than rely too heavily on the pursuit of internal consistency reliability and factor analytic approaches to scale construction and validation.

Adult↗

Analysis of fructans from higher plants by matrix-assisted laser desorption/ionization mass spectrometry.

In this communication both matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) and high-performance anion-exchange chromatography (HPAEC) have been applied to analyze fructans from higher plants. Size distribution of a commercially available fructan preparation from Dahlia variabilis L. was determined by MALDI-MS. Molecular masses ranged from 2,000 up to 6,000 Da with a peak value of distribution at 2,635 Da. Essentially the same pattern was obtained using HPAEC. Low-molecular-weight fructans from onion bulbs (Allium cepa L.) were studied in more detail. Tissue extracts were analyzed by MALDI-MS without any analyte purification. Mass-spectra of both proteins and oligosaccharides were obtained. For identification, metastable ion scanning was performed. Neither deproteinization nor deionization of the samples affected the oligosaccharide pattern. Using HPAEC, a more complex oligosaccharide pattern was obtained because isomeric glycans were differentiated. However, the overall size distribution was similar to that obtained by MALDI-MS. In further experiments epidermal or parenchyma cell layers of the onion bulb were placed into matrix solution and were then subjected to MALDI-MS and metastable ion scanning as well. By taking this approach, analyte desorption was achieved immediately from plant tissue. Oligosaccharide mass spectra were essentially the same as those of the extracts. To our knowledge, this is the first time that MALDI-MS has been applied as a microprobe to plant tissue. Finally MALDI-MS analysis was performed using single-cell extracts from onion tissues without any purification of the analyte.

Allium↗

Combined static and dynamic analysis for determining the quality of time-series expression profiles.

Expression profiling of time-series experiments is widely used to study biological systems. However, determining the quality of the resulting profiles remains a fundamental problem. Because of inadequate sampling rates, the effect of arrest-and-release methods and loss of synchronization, the measurements obtained from a series of time points may not accurately represent the underlying expression profiles. To solve this, we propose an approach that combines time-series and static (average) expression data analysis--for each gene, we determine whether its temporal expression profile can be reconciled with its static expression levels. We show that by combining synchronized and unsynchronized human cell cycle data, we can identify many cycling genes that are missed when using only time-series data. The algorithm also correctly distinguishes cycling genes from genes that specifically react to an environmental stimulus even if they share similar temporal expression profiles. Experimental validation of these results shows the utility of this analytical approach for determining the accuracy of gene expression patterns.

Algorithms↗

A simplified method for measuring critical pressures during sleep in the clinical setting.

Upper airway critical pressure measurements correlate with the degree of upper airway obstruction during sleep and may have a role in the diagnosis and treatment of obstructive sleep apnea. Nevertheless, the utility of the critical pressure has not yet been realized in the clinical setting because significant technical expertise is still required for the acquisition and analysis of pressure-flow data. Using segmented regression, we developed and validated a simplified approach to analyze the pressure-flow relationship and to determine the effects of protocol-related factors in 44 subjects with sleep apnea. When compared with expert visual analysis, segmented regression method was found to accurately determine the critical pressure (-0.98 +/- 2.47 cm H(2)O vs. -1.07 +/- 2.47 cm H(2)O, respectively; p = 0.46). Furthermore, it was found that two series of measurements acquired at varying nasal pressure levels with two or more breaths per level were sufficient to determine the critical pressure with a minimum of variability. Therefore, this analytic approach has the potential for standardizing and simplifying the ascertainment of the critical pressure for studies examining the effect of therapeutic devices and agents on upper airway collapsibility during sleep.

Airway Resistance↗

Kin-cohort evaluation of relative risks of genetic variants.

The kin-cohort study, an embedded retrospective cohort of first-degree relatives of probands, has been used frequently in conjunction with case-control studies to evaluate penetrance of high-risk genotypes. However, in principle, the kin-cohort approach can be used in conjunction with a case-control study in which family history data are carefully recorded to examine and validate the observed association of any candidate genotype with disease. Its utility for this purpose is governed by the relative efficiency of the kin-cohort analysis to test hypotheses about the relevant genotype-disease odds ratios, which in turn depends strongly on various factors, notably the magnitude of the disease incidence rate and the prevalence of the aberrant genotype. In this study, we compare the efficiencies of the two analytic approaches, case-control vs. kin-cohort, and illustrate the results in the context of cancer epidemiology. The kin-cohort analysis can provide substantial, important supplementary information for relatively common cancers such as breast, lung, colorectal, and prostate, and is also relatively efficient in general for the evaluation of the stronger and more rare genetic risk factors. Genet Epidemiol 24:220-229, 2003.

Case-Control Studies↗

Sample size for multiple regression: obtaining regression coefficients that are accurate, not simply significant.

An approach to sample size planning for multiple regression is presented that emphasizes accuracy in parameter estimation (AIPE). The AIPE approach yields precise estimates of population parameters by providing necessary sample sizes in order for the likely widths of confidence intervals to be sufficiently narrow. One AIPE method yields a sample size such that the expected width of the confidence interval around the standardized population regression coefficient is equal to the width specified. An enhanced formulation ensures, with some stipulated probability, that the width of the confidence interval will be no larger than the width specified. Issues involving standardized regression coefficients and random predictors are discussed, as are the philosophical differences between AIPE and the power analytic approaches to sample size planning.

Humans↗

Randomized, controlled trials using the Metro Firm System.

The Firm System at MetroHealth Medical Center was begun almost two decades ago to foster improved continuity of patient care and teaching of medical students and residents in Internal Medicine. For the past 8 years, these parallel teams of providers and patients also have been used to conduct clinical, educational, and health care delivery research. Randomized, controlled trials are made possible by ongoing random assignment of patients and providers to the three teams, or small group practices. Each group practice has equivalent inpatient and outpatient areas supported by nonrotating nursing, paramedical, and clerical staff. The system's current relationships were established after a controlled trial established both decreased costs and increased effectiveness of the "group practice model" as compared to more traditional approaches to patient care by residents in an academic medical center. Other trials, both on the inpatient and outpatient settings, have been used to guide ongoing institutional change. The unique advantages of the randomized controlled trial are high-lighted by contrasting the results of within-group changes during an intervention with results that incorporate control group changes. A variety of methodologic and logistical issues must be addressed when conducting controlled trials that use ongoing randomization within a single institution. These include determination that the groups are equivalent for all important parameters preintervention, choosing an analytic approach that accounts for potential differences among providers and patients, and, in trials designed to affect behavior, assurance that a "steady state" exists prior to initiating another trial designed to affect similar behavior. Consideration also must be given to the possibilities of cross-team contamination, the Hawthorne effect, the "dominant attending effect," and ethical issues related to informed consent. Clinical trials in a single institution may be performed for common problems and those with well defined stages of severity. Since the costs of maintaining the ongoing randomization are relatively small, the incremental costs of conducting randomized controlled trials are low by comparison to traditional approaches. The establishment of analogous systems at other institutions will permit multisite trials for less common clinical problems, enhance the generalizability of findings, and permit new types of health services research, including the rigorous evaluation of practice guidelines.

Health Services Research↗

An entropic characterization of protein interaction networks and cellular robustness.

The structure of molecular networks is believed to determine important aspects of their cellular function, such as the organismal resilience against random perturbations. Ultimately, however, cellular behaviour is determined by the dynamical processes, which are constrained by network topology. The present work is based on a fundamental relation from dynamical systems theory, which states that the macroscopic resilience of a steady state is correlated with the uncertainty in the underlying microscopic processes, a property that can be measured by entropy. Here, we use recent network data from large-scale protein interaction screens to characterize the diversity of possible pathways in terms of network entropy. This measure has its origin in statistical mechanics and amounts to a global characterization of both structural and dynamical resilience in terms of microscopic elements. We demonstrate how this approach can be used to rank network elements according to their contribution to network entropy and also investigate how this suggested ranking reflects on the functional data provided by gene knockouts and RNAi experiments in yeast and Caenorhabditis elegans. Our analysis shows that knockouts of proteins with large contribution to network entropy are preferentially lethal. This observation is robust with respect to several possible errors and biases in the experimental data. It underscores the significance of entropy as a fundamental invariant of the dynamical system, and as a measure of structural and dynamical properties of networks. Our analytical approach goes beyond the phenomenological studies of cellular robustness based on local network observables, such as connectivity. One of its principal achievements is to provide a rationale to study proxies of cellular resilience and rank proteins according to their importance within the global network context.

Computer Simulation↗

Application of the general Jacobi diagonalization method to the optical properties of a medium perturbed by an external field.

An analytical approach is presented for studying the convergence of the general Jacobi method applied to diagonalizing the second-rank tensors that describe the optical properties of a medium subjected to an external field. This approach utilizes the fact that the components of such tensors are usually given in field-free principal axes as power series in the field strength, neglecting terms beyond a chosen power of the field. It is shown that for a biaxial or uniaxial medium, the finite number of iterations, which guarantees exact reduction of all the initial terms up to the required power in the series expansions of all off-diagonal elements, can always be found. Moreover, a fixed sequence of rotations in the Jacobi algorithm can be predicted. These findings allow one to derive analytical formulas in noniterative form for a given highest order of the effects being considered and also to optimize numerical iterative diagonalization procedures. Formulas for eigenvalues and eigenvectors applicable to biaxial and uniaxial mediums perturbed by the linear and quadratic effects are presented. Illustrations are given of the electro-optic and piezo-optic effects for the point group 3m. Conditions for biaxial and uniaxial perturbation of a uniaxial crystal are discussed.

Journal Article↗

Meta-analysis in evidence-based orthodontics.

OBJECTIVE: In the last 10 years, health sciences literature has seen a significant increase in papers that report findings of meta-analyses. Meta-analysis overcomes the weakness of conventional narrative literature review. Moreover, it has established itself as a significant tool in clinical research and evidence-based medicine. But despite its station in the field, it is not without controversy. The aim of this paper is to present the main controversies that surround meta-analyses and to discuss the most important issues of conduct and reporting of results derived from these studies. RESULTS: Controversial issues include the ability of the investigators to combine studies that differ in important aspects; such as study populations, experimental designs and quality controls, and the like. It has been argued that selection bias could exist. Thus, it is common for the results of metaanalyses to be contradictory. As any other statistical procedure or analytical approach, meta-analyses too can be misused or abused. Misleading results could be avoided if certain basic principles are followed in the conduct of a meta-analysis. In particular, attention should be given to: (a) the methods of literature search for the studies to be included in the analysis, (b) the measures taken to reduce or eliminate bias, (c) the inclusion and exclusion criteria of the individual studies from the analysis, (d) how the data will be extracted from the literature, and (e) how the data will be analyzed statistically. CONCLUSION: Reports of meta-analytical studies carried out with the above parameters in mind yield a more objective appraisal of the evidence, and a more precise estimate of the treatment effect.

Dental Research↗

Distance and risk measures for the analysis of spatial data: a study of childhood cancers.

Three statistical approaches, used to detect spatial clusters of disease associated with a point source exposure, are applied to childhood cancer data for the city of San Francisco (1973-88). The distributions of incident cases of leukemia (51 cases), brain cancer (35 cases), and lymphatic cancer (37 cases) among individuals less than 21 years of age are described using three measures of clustering: distance on a geopolitical map, distance on a density equalized transformed map, and relative risk. The point source of exposure investigated is a large microwave tower located southwest of the center of the city (Sutro Tower). The three analytic approaches indicate that the patterns of the major childhood cancers are essentially random with respect to the point source. These results and a statistical model for spatial clustering are used to explore distance and risk measures in the analysis of spatial data. Both types of measures of spatial clustering are shown to perform similarly when a specific area of exposure can be defined.

Adolescent↗

Performing coolness: smoking refusal and adolescent identities.

The implications of smoking refusal for personal identity style were studied through conversations in six small focus groups or dyads of 13- and 14-year-old non-smokers from an urban New Zealand secondary school. The approach to analyzing their talk was informed by notions of 'performativity' and 'social space' to focus on the connections between identity and social relations. Smoking emerged as a key signifier of power and status. It was salient at both top and bottom ends of the social hierarchy depending upon the competence displayed in smoking as part of a larger ensemble of personal deportment and behavior. Being a non-smoker therefore inevitably carried connotations of being 'average' or 'in the middle', presenting non-smoking adolescents with the problem of accrediting themselves against superior 'smoker cool' groups. A discourse analytic approach was used to examine the resources and strategies participants brought to bear on this 'problem', which was then seen to be solved differently by boys and girls. Boys could establish alternatives to 'smoker cool' through physical activity, girls had little recourse but to accept their inferior status. The implications of this for health education and promotion are discussed.

Adolescent↗

Rapid liquid chromatography with tandem mass spectrometry-based screening procedures for studies on the biotransformation of drug candidates.

The accelerated pace of contemporary drug discovery and development in the pharmaceutical industry has generated increasing demands for early information on the metabolic fate of candidate drugs to guide the selection of new compounds for clinical evaluation. In response to these demands, we have developed a procedure for the rapid analysis of complex biological mixtures for the presence of drug-related materials and have embarked on the development of novel computer-based approaches whereby such procedures can be automated. The goal of this work was to rapidly identify drug metabolites (derived either from a single substrate or from a mixture of substrates) formed in vivo or in vitro. The approach that we have developed relies on the use of generic chromatographic and mass spectrometric methods for analysis of mixtures of drugs and metabolites and on correlation analysis of tandem mass spectrometry spectra to distinguish drug-related components from endogenous materials. Cross-correlation of the spectra also is used to identify the relationship between each metabolite and its respective parent drug in the mixture. In this manner, metabolites of a mixture of several drugs may be analyzed in the time it normally would take to analyze the products from a single substrate. We show that this rapid analytical approach can, with only minor sacrifices in the completeness of the data, significantly increase the number of compounds whose metabolic fate can be elucidated in a given time.

Biotransformation↗

Expanded polytetrafluoroethylene patch versus braided polyester tape for the repair of incompetent cervix.

BACKGROUND: This study was done to evaluate pregnant patients with cervical incompetence using an expanded polytetrafluoroethylene (ePTFE) patch versus the commonly used braided polyester tape, comparing the rate of local tissue reaction or onset of contractions, or both. STUDY DESIGN: This study was a prospective clinical trial on 20 patients divided into two groups. Patients having tissue reactions or contractions were identified and each material was analyzed using a new approach by means of scanning electron microscopy (SEM) and roentgenogram diffraction studies. RESULTS: In the group of pregnant patients sutured with polyester tape there were four failures because of infection and contractions. There were no direct or indirect complications encountered in the ePTFE group. Bacteriologic evaluations of the failures revealed Escherichia coli, Gardnerella vaginalis, Bacteroides species, and Trichomonas vaginalis in various combinations, in addition to crystal structure degradation and layers of phagocytes. CONCLUSIONS: Our results provide a rationale for understanding the differences in morphologic integrity and the superiority of the ePTFE patch over the polyester tape using a new analytic approach of SEM and roentgenographic diffraction studies. Because of the small number of patients and because the procedure was performed in a select patient population, we recommend that further trials be undertaken with a larger number of patients in more advanced gestational age and in patients presenting with emergent cervical incompetence.

Abortion, Spontaneous↗

Using half-normal probability plot and regression analysis to differentiate complex traits: differentiating disease response of multigenic resistance and susceptibility in tomatoes to multiple pathogen isolates.

The need for a new analytical approach was encountered in the course of characterizing newly developed tomato lines resistant to late blight. Late blight resistant tomato lines were created in independent breeding programs using the accession Solanum pimpinellifolium L. (formerly Lycopersicon pimpinellifolium (L.) Miller) L3708 as the source of the resistance. However, initial field observation suggested that the late blight resistance in the lines produced by two independent breeding programs differed. Possible causes included a partial transfer of the late blight resistance derived from S. pimpinellifolium L3708 or the possibility of race specificity of this resistance. A crucial issue was determining the most appropriate and robust analytical method to use with data from laboratory analyses of the responses of nine tomato lines against five P. infestans isolates. Prior analysis by standard ANOVA revealed significant differences across tomato lines but could not determine whether the disease responses in the CLN-R lines were different from those of the heterozygous F(1) hybrids, created by crossing susceptible tomatoes with the fixed CU-R lines. A different analytical method was needed. Therefore, sporangia numbers/leaflet and diseased area data were analyzed using a half-normal probability plot and regression analysis. The results of this analysis show its utility for genetic or pathology studies. Considering only populations of the uniform tomato lines, this method confirms the results obtained by using a standard ANOVA, but provides a clearer demonstration of the distributions of the individuals within the populations and how this distribution impacts variance and the difference among the populations. This method also allows a joint analysis of the uniform lines with an additional population that is less uniform, because it is segregating. Such an analysis would be invalid using a standard ANOVA. The results of this joint analysis determined that the additional population was divergent from the fixed CU-R lines, and, against some isolates, against the CLN-R lines as well. Half-normal probability plot analysis method would be applicable more broadly beyond analysis of disease resistance data. It could be useful for data from populations that are not normally distributed, for traits which are affected by epistatic gene action, and could be useful for selection of extremes.

Genotype↗

Evolution of density- and patch-size-dependent dispersal rates.

Based on a marginal value approach, we derive a nonlinear expression for evolutionarily stable (ES) dispersal rates in a metapopulation with global dispersal. For the general case of density-dependent population growth, our analysis shows that individual dispersal rates should decrease with patch capacity and-beyond a certain threshold-increase with population density. We performed a number of spatially explicit, individual-based simulation experiments to test these predictions and to explore further the relevance of variation in the rate of population increase, density dependence, environmental fluctuations and dispersal mortality on the evolution of dispersal rates. They confirm the predictions of our analytical approach. In addition, they show that dispersal rates in metapopulations mostly depend on dispersal mortality and inter-patch variation in population density. The latter is dominantly driven by environmental fluctuations and the rate of population increase. These conclusions are not altered by the introduction of neighbourhood dispersal. With patch capacities in the order of 100 individuals, kin competition seems to be of negligible importance for ES dispersal rates except when overall dispersal rates are low.

Adaptation, Biological↗

Interpretive management: what general managers can learn from design.

The past two decades have seen a dramatic acceleration in the pace of marketplace change. Companies have abandoned the old hierarchical model, with its clean functional divisions and clear lines of authority, and adopted flatter, less bureaucratic structures. But if most organizations have begun to adapt to the uncertainty of rapid change, most managers have not. They remain locked into the mechanical mind-set of the industrial age--that is, they assume that any management challenge can be translated into a clearly defined problem for which an optimal solution can be found. That approach works in stable markets and even in markets that change in predictable ways. Today's markets, however, are increasingly unstable and unpredictable. Managers can never know precisely what they're trying to achieve or how best to achieve it. They can't even define the problem, much less engineer a solution. The challenges facing the general manager in these circumstances, the authors argue, resemble those typically confronted by design managers. In the unpredictable world of research and design, neither the flow of the development process nor its end point can be defined at the outset. Rather than the traditional analytical approach to management, the design world requires an interpretive one. And that approach is equally well suited to rapidly changing, unpredictable markets. The authors describe how companies such as Levi Strauss & Company and Chiron Corporation have stayed at the top of their industries by adopting just such an interpretive approach to management.

Administrative Personnel↗