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At least 721 records · Page 40Linked to original sources
PubMed2003

Analysis of multiple pesticide residues in tobacco using pressurized liquid extraction, automated solid-phase extraction clean-up and gas chromatography-tandem mass spectrometry.

A new method was developed for the analysis of pesticide residues in tobacco. The objective was to significantly increase the number of samples that can be processed by the laboratory and to enable the extension of the current coverage to additional pesticides. A new analytical approach was therefore defined based on two main axes, the automation of the sample preparation and the selectivity of the analyte detection using tandem mass spectrometry. This latter aspect reduces the stringency of the requirements placed on the clean-up of the extracts and on the chromatographic resolution when less selective detectors are used. The extraction of the analytes from the matrix is performed using the pressurized liquid extraction technique. Tobacco samples are extracted at elevated temperature and pressure (100 C and 100 atm; 1 atm = 101,325 Pa) using acetone as an extraction solvent. The resulting extract is then concentrated using a Vortex evaporator. Three different solid-phase extraction (SPE) procedures, adjusted to the chemical properties of the different active ingredients to be measured, are applied to the concentrated extract, thus leading to three extract fractions. The first fraction contains such main classes of active ingredients as organohalogenated and 2,6-dinitroaniline compounds while the second one collects the organophosphorus and acylalanines residues; these two fractions are analyzed by capillary gas chromatography coupled to tandem mass spectrometry using negative chemical ionization and electron impact ionization in the positive mode, respectively. The third extract fraction gathers the N-methylcarbamates residues which are analyzed by HPLC with post-column derivatization and fluorescence detection. The different sample preparation stages from extraction to SPE clean-up have been automated through the use of recent analytical technologies. In combination with the analysis by tandem mass spectrometry, this provided a potential for a high sample throughput.

Automation↗
PubMed2003

Genetic analysis of multiple sclerosis.

Multiple sclerosis (MS) is a complex disease with a significant genetic contribution. Similar to other complex diseases, the genetic risk for MS results from a combination of many genetic variants which individually confer only modest effects. Here we review the results of the complementary genetic approaches of linkage and association in MS, highlighting the challenges of identifying loci of modest effect. We describe meta-analytical approaches that provide additional statistical power necessary for detecting such loci and further apply this approach to evaluate the association of a CTLA-4 variant with MS. Lastly, we review recent important advances in our understanding of the patterns of genetic variation in the human genome and speculate about how these advances will aid in future studies of the genetic causes of MS.

Genetic Linkage↗
PubMed2003

Genomics, proteomics and bioinformatics of human heart failure.

Unraveling the molecular complexities of human heart failure, particularly end-stage failure, can be achieved by combining multiple investigative approaches. There are several parts to the problem. Each patient is the product of a complex set of genetic variations, different degrees of influence of diets and lifestyles, and usually heart transplantation patients are treated with multiple drugs. The genomic status of the myocardium of any one transplant patient can be analysed using gene arrays (cDNA- or oligonucleotide-based) each with its own strengths and weaknesses. The proteins expressed by these failing hearts (myocardial proteomics) were first investigated over a decade ago using two-dimensional polyacrylamide gel electrophoresis (2DGE) which promised to resolve several thousand proteins in a single sample of failing heart. However, while 2DGE is very successful for the abundant and moderately expressed proteins, it struggles to identify proteins expressed at low levels. Highly focused first dimension separations combined with recent advances in mass spectrometry now provide new hope for solving this difficulty. Protein arrays are a more recent form of proteomics that hold great promise but, like the above methods, they have their own drawbacks. Our approach to solving the problems inherent in the genomics and proteomics of heart failure is to provide experts in each analytical method with a sample from the same human failing heart. This requires a sufficiently large number of samples from a sufficiently large pool of heart transplant patients as well as a large pool of non-diseased, non-failing human hearts. We have collected more than 200 hearts from patients undergoing heart transplantations and a further 50 non-failing hearts. By combining our expertise we expect to reduce and possibly eliminate the inherent difficulties of each analytical approach. Finally, we recognise the need for bioinformatics to make sense of the large quantities of data that will flow from our laboratories. Thus, we plan to provide meaningful molecular descriptions of a number of different conditions that result in terminal heart failure.

Animals↗
PubMed2004

Stem cell bioengineering for regenerative medicine.

Stem cells can be used to treat a variety of diseases and several recent studies in animal models demonstrate the potential of bioengineering strategies targeting adult and embryonic stem cells. In order to obtain the desired cells for transplantation, stem cell bioengineering approaches entail the manipulation of environmental signals influencing cell survival, proliferation, self-renewal and differentiation. In that regard, multivariate analytical approaches have been used with success to optimise different stem cell culture processes. The genetic or molecular enhancement of stem cells is also a powerful means to control their proliferation or differentiation or to correct genetic defects in recipients. In the future, systems-level approaches have the potential to revolutionise the field of stem cell bioengineering by improving our understanding of regulatory networks controlling cellular behaviour. This advance in basic biology will be instrumental for the implementation of many stem cell-based regenerative therapies at the clinical level, as treatment accessibility will depend on the development of robust technologies to produce sufficient cell numbers.

Animals↗
PubMed1989

[Systems analysis in hospital management].

Organization is one of the most important concepts for contemporary society. Whereas in recent years industry and the private services field have adopted management criteria to establish aims and methods, and to manage their organizations, the same is not true for public services. So in this area, particularly in health services, the need for a managerial type of organization is particularly evident. The basic change in the approach to the solution of organization problems, in accordance with a management type criterion, is the substitution of the traditional analytical approach with an assessment of systemic type that examines relations and interactions between the various components of an organization. Of the various methods proposed, one conceptual instrument that permits a management-type analysis of an organization is the "7S" method. An approach of this type may be particularly useful for the evaluation of an extremely complex structure like that of a hospital. According to this method, the interactions between strategy, structure, systems, staff, style, skills, and system of prevalent values of the hospital's organization structure are analysed with the purpose of improving their management.

Hospital Administration↗
PubMed1994

Mass spectrometry of trace elements in biological samples.

Mass spectrometry is a powerful analytical tool for determining the isotope ratios and concentrations of trace elements in various samples at levels ranging from major constituents to subparts per billion. Because isotope dilution is free from matrix effects, it has the potential of being incorporated into a definitive analytical approach that can provide reference values for concentrations in physiological and pathological conditions. In addition, isotope dilution mass spectrometry results are free from the constraints of quantitative recovery of the analyte, an essential requirement in other analytical techniques that is difficult to achieve with complex biological samples. A variety of mass spectrometric approaches have been used for determining the concentration of trace elements in biological samples. The more commonly used are thermal ionization mass spectrometry, inductively coupled plasma mass spectrometry, fast atom bombardment mass spectrometry, and gas chromatography mass spectrometry. This article reviews the work on trace element determination in biological samples using different mass spectrometric techniques and highlights the experiments performed by the authors in establishing gas chromatography mass spectrometry.

Animals↗
PubMed2003

Assessing and interpreting treatment effects in longitudinal clinical trials with missing data.

Treatment effects are often evaluated by comparing change over time in outcome measures; however, valid analyses of longitudinal data can be problematic, particularly if some data are missing. For decades, the last observation carried forward (LOCF) approach has been a common method of handling missing data. Considerable advances in statistical methodology and our ability to implement those methods have been made in recent years. Thus, it is appropriate to reconsider analytic approaches for longitudinal data. This review examines the following from a clinical perspective: 1) the characteristics of missing data that influence analytic choices; 2) the attributes of common methods of handling missing data; and 3) the use of the data characteristics and the attributes of the various methods, along with empirical evidence, to develop a robust approach for the analysis and interpretation of data from longitudinal clinical trials. We propose that, in many settings, the primary efficacy analysis should use a repeated measures, likelihood-based, mixed-effects modeling approach, with LOCF used as a secondary, composite measure of efficacy, safety, and tolerability. We illustrate how repeated-measures analyses can be used to enhance decision-making, and we review the caveats that remain regarding the use of LOCF as a composite measure.

Analysis of Variance↗
PubMed1999

A comparison of traditional approaches to hierarchical linear modeling when analyzing longitudinal data.

Longitudinal designs typically involve repeated time-ordered observations for each individual (or unit). Such designs are uniquely suited to studying changes over time within individuals, and relating these to individual characteristics to identify processes and causes of intra- individual changes and interindividual differences in physiologic and psychological development. The purpose of this paper is to compare and contrast univariate and multivariate ANOVA with repeated measures to hierarchical linear modeling as approaches to analyzing such longitudinal data. This will enable researchers to choose the approach that best meets their research needs, and it will enable them to compare research results that are reported using one analytical approach with results that are reported using the other approach.

Analysis of Variance↗
PubMed1999

Measurement of PM10/2.5 fractionated respirable particles in urban Toronto by INAA, PIXE, ICP-AES, and LAMS. A comparison.

The chemical analysis of urban Toronto airborne particulate matter (PM), size segregated into respirable PM10/2.5, is presented. The characterization of PM by use of proton-induced X-ray emission analysis (PIXE), and inductively coupled plasma-atomic emission spectrometry revealed elemental information; a newer laser ablation-ionization mass spectrometry approach has the potential to expand the chemical information from PM by analyzing both the inorganic and organic species. These PM analytical approaches will be continued in the future for studying (1) emission source identification, (2) inhalation health hazards, and (3) urban smog chemistry.

Air Pollutants↗
PubMed1995

Case-cohort analysis of case-coverage studies of vaccine effectiveness.

Evaluation of vaccine field effectiveness may be performed by combining surveillance data on incident cases with an immunization coverage survey. Although many methods have been used for the analysis of studies of similar design, they are not always desirable or optimal. The authors discuss these approaches and propose use of a case-cohort analysis for such a study design when appropriate. The case-cohort analytic approach is illustrated with data from studies of a vaccine for Haemophilus influenzae type b (Hib) disease in children living on a southwestern Native American reservation during 1988-1993.

Bacterial Outer Membrane Proteins↗
PubMed2005

The role of behavioral data in HIV surveillance.

This paper reviews the ways in which data on sexual behavior can contribute to the understanding of HIV prevalence trends based on sentinel surveillance, building on work presented at a meeting on new strategies for HIV/AIDS surveillance in resource-constrained countries, held in Addis Ababa in January 2004. A key component of second-generation surveillance is the collection of data on the behaviors and background characteristics that may influence the course of the HIV epidemic in a population. However, the most appropriate methods for the collection and analysis of these data for various types of epidemic have yet to be established. A conceptual framework is presented outlining the relationships between background characteristics, behaviors and HIV infection. The different methods used to collect data on HIV infection, risk behaviors and background characteristics in generalized and concentrated epidemics are reviewed, including population-based surveys, and surveillance in high- and low-risk groups. The various biases inherent in different approaches are discussed. The implications of linking data at the individual and community levels are explored and recommendations made concerning appropriate analytical approaches, drawing on an example of a pilot study that linked biological and behavioral surveillance in Tanzanian antenatal clinics. The paper concludes with recommendations for the methods and frequency with which to collect the data required for second-generation HIV surveillance.

Data Interpretation, Statistical↗
PubMed2005

Phylogenetics of modern birds in the era of genomics.

In the 14 years since the first higher-level bird phylogenies based on DNA sequence data, avian phylogenetics has witnessed the advent and maturation of the genomics era, the completion of the chicken genome and a suite of technologies that promise to add considerably to the agenda of avian phylogenetics. In this review, we summarize current approaches and data characteristics of recent higher-level bird studies and suggest a number of as yet untested molecular and analytical approaches for the unfolding tree of life for birds. A variety of comparative genomics strategies, including adoption of objective quality scores for sequence data, analysis of contiguous DNA sequences provided by large-insert genomic libraries, and the systematic use of retroposon insertions and other rare genomic changes all promise an integrated phylogenetics that is solidly grounded in genome evolution. The avian genome is an excellent testing ground for such approaches because of the more balanced representation of single-copy and repetitive DNA regions than in mammals. Although comparative genomics has a number of obvious uses in avian phylogenetics, its application to large numbers of taxa poses a number of methodological and infrastructural challenges, and can be greatly facilitated by a 'community genomics' approach in which the modest sequencing throughputs of single PI laboratories are pooled to produce larger, complementary datasets. Although the polymerase chain reaction era of avian phylogenetics is far from complete, the comparative genomics era-with its ability to vastly increase the number and type of molecular characters and to provide a genomic context for these characters-will usher in a host of new perspectives and opportunities for integrating genome evolution and avian phylogenetics.

Animals↗
PubMed2005

Evidence of hunting and hafting during the Middle Stone Age at Sibidu Cave, KwaZulu-Natal, South Africa: a multianalytical approach.

Points and point fragments from Middle Stone Age layers (dated to between 50,000 and 60,000 years ago) from Sibudu Cave, KwaZulu-Natal, South Africa, were examined to establish whether they were used as hafted spearheads for hunting. A multi-analytical approach was followed, using macrofracture analysis, use-wear analysis, and residue analysis. In addition to the analytical processes, an experimental project tested the results of the macrofracture analysis on local raw materials. The study shows that points from Sibudu Cave were indeed hafted and used as hunting tools. It was further established that plant twine was probably the preferred binding material to attach the points to wooden hafts. Resin may have been used as an adhesive in combination with the binding material. A detailed examination of the ochre distribution on the points confirmed that ochre was also part of the hafting arrangement. The need to use a dependable methodology for the recognition of hunting and hafting traces on stone points from the southern African Middle Stone Age context is briefly discussed.

Animals↗
PubMed1981

Three-dimensional approach to analysis and treatment of hemifacial microsomia.

Based on our experience with 40 patients with hemifacial microsomia (first and second branchial arch deformity), we have developed a three-dimensional analytic approach to the skeletal deformity. The sagittal plane x-ray views (lateral cephalogram and panorex) demonstrate the anatomy of the temporomandibular joint as well as the shape and height of the mandibular rami. The frontal plane is demonstrated by the anterio-posterior (A-P) cephalogram, which shows the discrepancy in ramus height and the abnormal arc of mandibular rotation toward the affected side. The transverse plane is evaluated with a submental vertex radiograph, which shows the shape of the mandibular body and medial displacement of the temporomandibular joint. Three-plane radiographic analysis demonstrates the total anatomic distortion and the abnormal growth vectors. We hypothesize that abnormal mandibular growth is of primary importance in this deformity. Application of this analysis has influenced the timing of intervention and the design of corrective procedures.

Adult↗
PubMed2003

Quantifying the information in auditory-nerve responses for level discrimination.

An analytical approach for quantifying the information in auditory-nerve (AN) fiber responses for the task of level discrimination is described. A simple analytical model for ANT responses is extended to include temporal response properties, including the nonlinear-phase effects of the cochlear amplifier. Use of simple analytical models for AN discharge patterns allows quantification of the contributions of level-dependent aspects of the patterns to level discrimination. Specifically, the individual and combined contributions of the information contained in discharge rate, synchrony, and relative phase cues are explicitly examined for level discrimination of tonal stimuli. It is shown that the rate information provided by individual AN fibers is more constrained by increases in variance with increases in rate than by saturation. As noted in previous studies, there is sufficient average-rate information within a narrow-CF region to account for robust behavioral performance over a wide dynamic range; however, there is no model based on a simple limitation or use of AN information consistent with parametric variations in performance. This issue is explored in the current study through analysis of performance based on different aspects of AN patterns. For example, we show that performance predicted from use of all rate information degrades significantly as level increases above low-medium levels, inconsistent with Weber's Law. At low frequencies, synchrony information extends the range over which behavioral performance can be explained by 10-15 dB, but only at low levels. In contrast to rate and synchrony, nonlinear-phase cues are shown to provide robust information at medium and high levels in near-CF fibers for low-frequency stimuli. The level dependence of the discharge rate and phase properties of AN fibers are influenced by the compressive nonlinearity of the inner ear. Evaluating the role of the compressive nonlinearity in level coding is important for understanding neural encoding mechanisms and because of its association with the cochlear amplifier, which is a fragile aspect of the ear believed to be affected in common forms of hearing impairment.

Animals↗
PubMed2005

Design and analysis in genetic studies of human ageing and longevity.

With the success of the Human Genome Project and taking advantage of the recent developments in high-throughput genotyping techniques as well as in functional genomics, it is now feasible to collect vast quantities of genetic data with the aim of deciphering the genetics of human complex traits. As a result, the amount of research on human ageing and longevity has been growing rapidly in recent years. The situation raises questions concerning efficient choice of study population, sampling schemes, and methods of data analysis. In this article, we summarize the key issues in genetic studies of human ageing and longevity ranging from research design to statistical analyses. We discuss the virtues and drawbacks of the multidisciplinary approaches including the population-based cross-sectional and cohort studies, family-based linkage analysis, and functional genomics studies. Different analytical approaches are illustrated with their performances compared. In addition, important research topics are highlighted together with experiment design and data analyzing issues to serve as references for future studies.

Aging↗
PubMedDate not supplied

Evaluation of shotgun sequencing for proteomic analysis of human plasma using HPLC coupled with either ion trap or Fourier transform mass spectrometry.

This paper reports on studies directed to the characterization of the proteome of human plasma by the shotgun sequencing approach, namely the use of HPLC coupled to mass spectrometry (MS). The report will present data from two laboratories that allows the comparison of peptide and protein identifications by either accurate mass measurement on a Fourier transform mass spectrometry or MS/MS fragmentation on an ion trap mass spectrometer. Because the dynamic range of the protein components of plasma is one of the largest for a biological sample, the analysis of such a challenging sample was aided by the use of these two MS approaches. The major classes of proteins observed were transport proteins, enzymes, and enzyme inhibitors, blood-clotting factors, membrane-associated proteins including soluble forms of receptors, hormones, immunoglobulins, and other glycoproteins. The protein identifications were also highly consistent with results obtained from 2D gel studies, although a larger number of additional proteins were observed with the shotgun sequencing approach. The quantitation of low to medium level proteins was explored in the ion trap with an add-back of a known amount of human growth hormone (hGH) at a clinically relevant level (5 ug/L). The isotope coded affinity tag (ICAT) approach was used to quantitate successfully different levels of hGH in replicate analysis via the disulfide linked tryptic peptide (T6-T16). These studies suggest that the shotgun sequencing approach can be used to characterize part of the plasma proteome and serve as a starting point for the use of multidimensional analytical approaches for the analysis of complex biological samples.

Algorithms↗
PubMed2006

The limitations due to exposure detection limits for regression models.

Biomarker use in exposure assessment is increasingly common, and consideration of related issues is of growing importance. Exposure quantification may be compromised when measurement is subject to a lower threshold. Statistical modeling of such data requires a decision regarding the handling of such readings. Various authors have considered this problem. In the context of linear regression analysis, Richardson and Ciampi (Am J Epidemiol 2003;157:355-63) proposed replacement of data below a threshold by a constant equal to the expectation for such data to yield unbiased estimates. Use of such an imputation has some limitations; distributional assumptions are required, and bias reduction in estimation of regression parameters is asymptotic, thereby presenting concerns about small studies. In this paper, the authors propose distribution-free methods for managing values below detection limits and evaluate the biases that may result when exposure measurement is constrained by a lower threshold. The authors utilize an analytical approach and a simulation study to assess the effects of the proposed replacement method on estimates. These results may inform decisions regarding analytical plans for future studies and provide a possible explanation for some amount of the discordance seen in extant literature.

Bias↗