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PubMed2001

The Data Protection Act (1998): implications for health researchers.

AIMS: This paper reports on the methods used in two studies to obtain access to subjects to comply with the common law duty of confidence laid out in the Data Protection Act (1998) and discusses the researchers' problems in interpreting the procedures. RATIONALE: The amendments to the United Kingdom (UK) Data Protection Act (1998) are causing confusion within the health service and academic institutions. There is a need to balance patient confidentiality with the requirement to conduct vital, unbiased research in which health service professionals are not subject to ethical dilemmas. This paper examines the recruitment methods used in two studies in which the researchers' attempts to adhere to the requirements lengthened the study costs and may have produced less reliable results. METHODS: The methodological difficulties in two studies are presented. In Study 1, the difficulties encountered when the Multicentre Research Ethics Committee refused permission for researchers to recruit patients directly to a multicentre randomized controlled trial are discussed. In Study 2, the method used to compile a sampling frame for a national questionnaire survey following the eight principles of the Act are described. FINDINGS: Our experience has shown that health care professionals are increasingly required to recruit patients to intervention trials, and that researchers are not allowed access to the names of patients or other subjects to ask them for consent to participate in a study. The requirement for researchers to use "intermediaries" to obtain consent from and recruit subjects to studies increases the risk of selection bias, may expose the practitioner to ethical difficulties and may compromise the external validity of trial results. There is also a danger that research costs will soar when the Data Protection Act (1998) is fully realized. CONCLUSION: The Data Protection Act (1998) is currently being interpreted in a number of different ways. We conclude there is an urgent need for consensus within the health service and academic communities.

Clinical Trials as Topic↗
PubMed2001

A review of ethnicity, health and nutrition-related diseases in relation to migration in the United Kingdom.

OBJECTIVES: To identify lessons from and gaps in research on diet-disease links among former migrants in the United Kingdom (UK). RESULTS: Migrant status and self-identified ethnicity do not match so these terms mask differences in social, nutritional and health status within and between population groups. Some former migrants differ in causes of death from the general population, e.g.: fewer coronary heart disease deaths among Caribbean-born; fewer cancer deaths among Caribbean, South Asian- and East African-born adults. Irish- and Scottish-born have higher mortality from all causes. Experience of risk factors differ also, e.g.: higher prevalences of hypertension and diabetes in Caribbean- and South Asian-born adults than representative samples of the general population; obesity and raised waist-hip circumference ratios in South Asian, African-Caribbean and some Irish-born adults. Former migrants experience long-term disadvantage, associated with more self-defined illness and lower reported physical activity. Nutrient intake data from the few, recent, small-scale studies must be interpreted with caution due to methodological diversity. However, second generation offspring of former migrants appear to adopt British dietary patterns, increasing fat and reducing vegetable, fruit and pulse consumption compared with first generation migrants. CONCLUSIONS: There is insufficient evidence on why some former migrants but not others experience lower specific mortality than the general population. Dietary intake variations provide important clues particularly when examined by age and migration status. Majority ethnic and younger migrant groups could raise and sustain high fruit and vegetable intakes but lower proportions of fat, by adopting many dietary practices from older migrants. Objective measures of physical activity and longitudinal studies of diets among different ethnic groups are needed to explain diversity in health outcomes and provide for evidence-based action.

Africa↗
PubMed1976

Quantity conceptions in university students: another look.

One hundred and thirty-eight post-graduate students enrolled in a Diploma in Education course were tested for their ability to converse weight and volume. A methodological criticism of the earlier work or Elkind (1962) and Towler & Wheatley (1971) is offered which casts doubt on the extremely high proportion of non-conservers of volume reported in those studies. Nevertheless, using a modified version of Elkind's methodology, 18 per cent of our sample were non-conservers of volume, a result providing some support for the generaltiy of Elkind's findings. The results are discussed under the four headings of horizontal decalage, sex differences, possible effects of pre-graduate courses of study and educational implications. The importance of the individual as constructor and interpreter of his own experience is emphasized.

Adult↗
PubMed2005

Phase-constrained parallel MR image reconstruction.

A generalized method for phase-constrained parallel MR image reconstruction is presented that combines and extends the concepts of partial-Fourier reconstruction and parallel imaging. It provides a framework for reconstructing images employing either or both techniques and for comparing image quality achieved by varying k-space sampling schemes. The method can be used as a parallel image reconstruction with a partial-Fourier reconstruction built in. It can also be used with trajectories not readily handled by straightforward combinations of partial-Fourier and SENSE-like parallel reconstructions, including variable-density, and non-Cartesian trajectories. The phase constraint specifies a better-conditioned inverse problem compared to unconstrained parallel MR reconstruction alone. This phase-constrained parallel MRI reconstruction offers a one-step alternative to the standard combination of homodyne and SENSE reconstructions with the added benefit of flexibility of sampling trajectory. The theory of the phase-constrained approach is outlined, and its calibration requirements and limitations are discussed. Simulations, phantom experiments, and in vivo experiments are presented.

Algorithms↗
PubMed2005

Global and site-specific detection of human integrin alpha 5 beta 1 glycosylation using tandem mass spectrometry and the StrOligo algorithm.

Glycans are oligosaccharides associated with proteins, and are known to confer specific functions and conformations on glycoproteins. As protein tridimensional structures are related to function, the study of glycans and their impact on protein folding can provide important information to the field of proteomics. The subdiscipline of glycomics (or glycoproteomics) is rapidly growing in importance as glycans in proteins have shown to be involved in protein-protein or protein-(drug, virus, antibody) interactions. Glycomics studies most often aim at identifying glycosylation sites, and thus are performed on deglycosylated proteins resulting in loss of site-specific details concerning the glycosylation. In order to obtain such details by mass spectrometry (MS), either whole glycoproteins must be digested and analyzed as mixtures of peptides and glycopeptides, or glycans must be isolated from glycopeptide fractions and analyzed as pools. This article describes parallel experiments involving both approaches, designed to take advantage of the StrOligo algorithm functionalities with the aim of characterizing glycosylation microheterogeneity on a specific site. A hybrid quadrupole-quadrupole-time-of-flight (QqTOF) instrument equipped with a matrix-assisted laser desorption/ionization (MALDI) source was used. Glycosylation of alpha 5 beta 1 subunits of human integrin was studied to test the methodology. The sample was divided in two aliquots, and glycans from the first aliquot were released enzymatically, labelled with 2-aminobenzamide, and identified using tandem mass spectrometry (MS/MS) and the StrOligo program. The other aliquot was digested with trypsin and the resulting peptides separated by reversed-phase high-performance liquid chromatography (HPLC). A specific collected fraction was then analyzed by MS before and after glycan release. These spectra allowed, by comparison, detection of a glycopeptide (several glycoforms) and elucidation of peptide sequence. Compositions of glycans present were proposed, and identification of possible glycan structures was conducted using MS/MS and StrOligo.

Algorithms↗
PubMed2006

Hydro-mechanical behavior of municipal solid waste subject to leachate recirculation in a large-scale compression reactor cell.

The paper presents the results of a laboratory experiment on Municipal Solid Waste (MSW) subjected to one-dimensional compression in a 1 m3 instrumented cell. The focus was on the hydro-mechanical behavior of the material under conditions of confinement and leachate percolation that replicate those found in real-scale landfills. The operation of the apparatus is detailed together with the testing methodology and the monitoring program. Two samples of waste were tested: the first extended over a period of 10 months ('Control Test') and the second for 22 months ('Enhanced Test' with leachate recirculation). Consolidation data is reported with regard to both short-term (stress-dependent) and long-term (time-dependent) settlements. A discussion follows based on the derived values of primary and secondary compression ratios. Correlations between compression parameters and the biodegradation process are presented. In particular, results clearly highlight the effect of leachate recirculation on waste settlement: 24% secondary deformation reached after slightly less than 2 years (equivalent to a 5-fold increase in compressibility) and 17.9% loss of dry matter. Comparisons are proposed considering the results derived from the few monitoring programs conducted on experimental bioreactors worldwide. Finally, the hydraulic characterization of waste is discussed with regard to the evaluation of effective porosity and permeability.

Cities↗
PubMed1981

Hemolytic transfusion reaction due to anti-Kell undetectable in low-ionic-strength solutions.

Low-ionic-strength solution (LISS) reagents and methodologies have become popular in recent years in hospital transfusion service laboratories for alloantibody detection and compatibility testing of blood recipients. It has been the experience with all other hemagglutination technics that some examples of alloantibodies unpredictably fail to react. Such is the case with this patient's alloantibody with respect to LISS. The patient had a significant hemolytic transfusion reaction due to Kell incompatibility of one unit of packed human erythrocytes. Using various LISS reagents and methodologies, the anti-Kell was undetectable in pretransfusion and posttransfusion samples through the fifth day. The anti-Kell was of immunoglobulin class IgG, and it was detected in saline solution or albumin at room temperature, at 37 C and by the antiglobulin technic.

Aged↗
PubMed1996

Flow-cytometric characterization of hematopoietic cells in non-pregnant human endometrium.

PROBLEM: Immunologic evaluation and quantitation of hematopoietic cells in human endometrium has been difficult to perform, particularly in nonpregnant subjects. In this study, we describe a method for the flow-cytometric characterization of hematopoietic cells present in the endometrium of non-pregnant women. METHOD: Endometrial biopsy samples from normal donors were first mechanically disrupted and filtered to generate a single-cell suspension of leukocyte-enriched endometrial cells. Cells were labeled with a panel of monoclonal antibodies, stained with propidium iodide (PI), and one- or two-color flow-cytometric analysis performed on cells excluding PI. RESULTS: The methodology described in this study was highly reproducible in experiments evaluating the interrun and intrarun variability. We then determined the immunophenotypic profile of endometrial leukocytes from 12 normal females. The majority of leukocytes were T cells (CD3: 47%; CD4: 24%; CD8: 28%) with an important contingent of NK cells (CD56: 32%), the majority of which harbored the unusual CD16-CD56 bright phenotype, and a minority of B cells (CD20: 6%) and monocytes (CD14: 7%). CONCLUSIONS: Flow cytometry can be used to assess antigen expression on the surface of endometrial leukocytes from nonpregnant women. In future studies, it will be possible to use this approach to investigate the role of immune cell populations in the endometrium of patients experiencing reproductive failure.

Cell Separation↗
PubMed2005

Tree measures and the number of segregating sites in time-structured population samples.

BACKGROUND: Time-structured genetic samples are a valuable source of information in population genetics because they provide several correlated observations of the underlying evolutionary processes. In this paper we study basic properties of the genetic variation in time-structured samples as reflected in the genealogies relating individuals and the number of segregating sites observed. Our emphasis is on "measurably evolving populations" i.e. populations from which it is possible to obtain time-structured samples that span a significant interval of evolutionary time. RESULTS: We use results from the coalescent process to derive properties of time-structured samples. In the first section we extend existing results to attain measures on coalescent trees relating time-structured samples. These include the expected time to a most recent common ancestor, the expected total branch length and the expected length of branches subtending only ancient individuals. The effect of different sampling schemes on the latter measure is studied. In the second section we study the special case where the full sample consists of a group of contemporary extant samples and a group of contemporary ancient samples. As regards this case, we present results and applications concerning the probability distribution of the number of segregating sites where a mutation is unique to the ancient individuals and the number of segregating sites where a mutation is shared between ancient and extant individuals. CONCLUSION: The methodology and results presented here is of use to the design and interpretation of ancient DNA experiments. Furthermore, the results may be useful in further development of statistical tests of e.g. population dynamics and selection, which include temporal information.

Animals↗
PubMed1981

Analysis of micro-encapsulated d-limonene dimercaptan, a possible herbicide marker for Cannabis sprayed with paraquat, using gas chromatography.

A method for the determination of encapsulated d-limonene dimercaptan (d-LDM), a possible marker for Cannabis sativa L. sprayed with herbicide, has been developed. The methodology includes a single-step extraction, followed by gas chromatography with flame photometric detector (FDP) using n-octadecyl mercaptan (n-octadecylthiol) as an internal standard. A liner relationship was obtained from spiked samples with an average coefficient of variation of 9.0 per cent. The method has been used to determine part-per-million levels of LDM in actual field experiments in Mexico. The FDP limit was found to be 7 ng for d-LDM.

Cannabis↗
PubMed2006

A supervised hidden markov model framework for efficiently segmenting tiling array data in transcriptional and chIP-chip experiments: systematically incorporating validated biological knowledge.

MOTIVATION: Large-scale tiling array experiments are becoming increasingly common in genomics. In particular, the ENCODE project requires the consistent segmentation of many different tiling array datasets into 'active regions' (e.g. finding transfrags from transcriptional data and putative binding sites from ChIP-chip experiments). Previously, such segmentation was done in an unsupervised fashion mainly based on characteristics of the signal distribution in the tiling array data itself. Here we propose a supervised framework for doing this. It has the advantage of explicitly incorporating validated biological knowledge into the model and allowing for formal training and testing. METHODOLOGY: In particular, we use a hidden Markov model (HMM) framework, which is capable of explicitly modeling the dependency between neighboring probes and whose extended version (the generalized HMM) also allows explicit description of state duration density. We introduce a formal definition of the tiling-array analysis problem, and explain how we can use this to describe sampling small genomic regions for experimental validation to build up a gold-standard set for training and testing. We then describe various ideal and practical sampling strategies (e.g. maximizing signal entropy within a selected region versus using gene annotation or known promoters as positives for transcription or ChIP-chip data, respectively). RESULTS: For the practical sampling and training strategies, we show how the size and noise in the validated training data affects the performance of an HMM applied to the ENCODE transcriptional and ChIP-chip experiments. In particular, we show that the HMM framework is able to efficiently process tiling array data as well as or better than previous approaches. For the idealized sampling strategies, we show how we can assess their performance in a simulation framework and how a maximum entropy approach, which samples sub-regions with very different signal intensities, gives the maximally performing gold-standard. This latter result has strong implications for the optimum way medium-scale validation experiments should be carried out to verify the results of the genome-scale tiling array experiments.

Artificial Intelligence↗
PubMedDate not supplied

Insulinoma: diagnostic strategies and surgical treatment. A 22-year experience.

BACKGROUND/AIMS: The efficacy of preoperative localization methods and the results of the surgical treatment of insulinoma were studied. METHODOLOGY: Fifty-nine patients referred for surgical treatment were studied and the results of the diagnostic tools for tumor localization were compared with findings at surgical intervention. The influence of the type of surgical procedure in the immediate and late postoperative course was also studied. RESULTS: Ultrasonography had a sensitivity of 30%, computed tomography 25%, angiography 54%, portal vein sampling 94%, endoscopic ultrasonography 27% and magnetic resonance 17%. Intraoperative palpation localized 98.2% of the tumors and by the addition of intraoperative echography, all lesions were identified. In 55 patients with benign lesions, 22 enucleations, 25 distal pancreatectomies, 7 pancreatectomies plus enucleation and one duodenopancreatectomy were performed. Malignant tumors were treated by pancreatic resection, postoperative hepatic artery embolization and systemic chemotherapy. There was no postoperative mortality. Pancreatic fistula was the most common complication. Three patients who underwent distal pancreatectomy developed late diabetes (9.3%). CONCLUSIONS: Extensive preoperative investigation, mainly with invasive methods, is not indicated and by combining intraoperative palpation and echography most of the cases can be adequately dealt with. Preservation of pancreatic tissue with enucleation and preservation of the spleen are the best choice for treatment of benign insulinomas.

Adolescent↗
PubMed1976

Methodological simplifications in radioimmunoassay of urinary aldosterone.

Simplification of radioimmunoassay procedures of urinary aldosterone-18-glucuronide was attempted, taking into consideration the aspects implied by the hydrolysis of urine and the assay itself. The procedure standardized for the hydrolysis step (samples diluted with a two-fold volume of 0.2 N HCl and incubated at 30 degrees C for 16-24 h) proved suitable in terms of practicability and accuracy. Aldosterone antisera, raised in the rabbit against an aldosterone-3-bovine albumin conjugate, were selected according to their specificity towards competing steroids. Depending on the characteristics of the antisera used, an assay of extracts, or even direct measurements of hydrolyzed urines excluding any extraction, were found to yield reliable results. In the case of a high-quality antiserum, evidence for the adequacy of assay on non-hydrolyzed urine extracts for the measurement of the excretion of unconjugated aldosterone was provided by some preliminary data. The results of the experiments, directed at the methodological and clinical validation of the simplified procedures, are reported and discussed in this paper.

Aldosterone↗
PubMed2004

Therapists' perceptions of the link between stress and the urge to drink among alcoholics.

The present study examined the ability of therapists who have clinical experience in treating alcoholism to perceive the specific way alcoholics function cognitively when confronted with potentially stressful events and to conceive of the link between stress and the urge to drink in an alcoholic population. The methodological framework used was an application of Anderson's functional theory of cognition (FTC) [Anderson, N. H. (1996). A functional theory of cognition. Mahwah, NJ: Erlbaum]. The total sample was composed of 226 participants (76 therapists and 150 alcoholic inpatients). The results revealed that therapists were (a) highly capable of assessing the cognitive processes of patients, both their judgments of stress and urge to drink and (b) well aware of the particular relationship between stress and alcohol that characterizes the alcoholic population. However, the results also indicated a propensity on the part of therapists to overestimate the extent of the urge to drink generated by different situations. Despite several limitations, this study is one of the first to demonstrate therapists' understanding of the cognitive functioning of alcoholic patients.

Adaptation, Psychological↗
PubMed2001

Harmonisation and quality assurance in pre-analytical steps of soil contamination studies--conclusions and recommendations of the CEEM Soil project.

The paper summarises the project's results and consequences including expert's statements. Based on sampling strategies and methodological details which have been recognised to be critical for the comparability of the results of soil contamination studies, recommendations are given towards harmonisation of soil sampling guidelines, improvement of quality assurance of pre-analytical steps and inclusion of soil sampling into accreditation systems. Recommended approaches to improve QA and QC in soil sampling are: harmonised guidelines; specified SOPs; written sampling (strategy) plans; defined qualification and experience of sampling personnel; sampling records; regular interlaboratory comparisons (proficency tests) for sampling; and inclusion of sampling and sample preparation into accreditation procedures. Needs for further research in the field of pre-analytical phases of soil contamination studies are outlined and further R&D projects are encouraged.

Accreditation↗
PubMedDate not supplied

Screening of protein-ligand interactions by affinity chromatography.

This paper examines affinity chromatography (AC) as an alternative tool for the determination of protein-ligand interactions for the particular case in which the ligand is the same protein. The methodology is less labor-intensive and more sample-efficient than traditional methods used to measure the second virial coefficient (B(22)), a parameter commonly used to evaluate protein-protein interactions. The chromatographic capacity factor (k') was studied for lysozyme and equine serum albumin for a wide range of experimental solution conditions such as crystallizing agent concentration, protein concentration and pH. Parallel experiments using AC to determine k' and static light scattering (SLS) to determine B(22) showed that the two parameters were highly correlated. Two different column volumes ( approximately 1 and approximately 0.1 mL) were tested and gave essentially the same values for k', showing the feasibility of miniaturization.

Chromatography, Affinity↗
PubMed2006

Mayisha II: pilot of a community-based survey of sexual attitudes and lifestyles and anonymous HIV testing within African communities in London.

The pilot aim was to assess the feasibility and acceptability of undertaking anonymous HIV testing using oral fluid samples as part of a community-based survey of sexual attitudes and lifestyles of black African communities in London. The three components of the study were administered in various venues across London: (1) a cross-sectional self-completion anonymous questionnaire survey, (2) an optional oral fluid sample for anonymous HIV testing and (3) a nested in-depth interview study in a sub-set of respondents. A total of 114 black African men and women were recruited. A large number of African countries were represented among respondents from newly-migrant and well-established communities. The response rate to the oral fluid sample was high at 82% and all samples collected were of sufficient quality to be tested for HIV. In-depth interviews with respondents revealed positive views and experiences about participating in the study whilst understanding of the questionnaire was good. We therefore conclude that anonymous HIV testing as part of a community-based survey is feasible and acceptable, whilst a set of recommendations was produced to refine the survey methodology and questionnaire. Participatory research methods are essential for achieving successful community-based surveys among black Africans in Britain.

Adult↗