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Phosphate measurement in natural waters: two examples of analytical problems associated with silica interference using phosphomolybdic acid methodologies

Assessment of phosphate species for bicarbonate-bearing lowland rivers of the Thames valley, England and acidic Welsh upland streams (the Plynlimon area, mid-Wales) reveal problems of silica interference when employing standard automated 'phosphomolybdic acid' colorimetric methodologies. The interference occurs under a combination of two conditions: (1) when the reagents and samples are heated to speed up the rate of formation of phosphomolybdic acid; and (2) when the strength of a sulfuric acid reagent is too low. While this paper alerts researchers to potential analytical problems with silica interference within phosphomolybdic acid methodologies to determine soluble reactive phosphorus (SRP) concentrations, it cannot detail whether or not there is a general problem. This lack of specificity occurs because there are a variety of phosphomolybdic acid methodologies available which vary in their reagent recipes and it is not clear which methods will or will not suffer from silica interference. Changing the sulfuric acid reagent strength by a factor of two overcame the problem, in this case, with regards to the determination of soluble reactive phosphorus. However, even here, the method may not be applicable to very high alkalinity waters owing to their potential for reducing the acidity of the analyte. With regard to total dissolved phosphorus (TDP) and total phosphorus (TP) measurements, the importance of undertaking the analysis under ambient conditions is clearly shown. There are many small variants on standard phosphomolybdate methods for determining SRP, TDP and TP in use and it is not always clear which methods will or will not show silica interference for particular water types. It is therefore recommended that individual laboratories check their methodologies for silica interference using phosphate-free solutions with similar silica and alkalinity ranges for the waters being assayed.

Journal Article↗

The methodologic quality of clinical trials on regional anesthesia for cataract surgery.

OBJECTIVE: To assess the methodologic quality of published randomized trials of regional anesthesia management strategies for cataract surgery. DESIGN: Literature review and analysis. METHOD: We performed a systematic search of the literature to identify all articles pertaining to regional anesthesia for cataract surgery on adults. Overall quality scores and scores for individual methodologic domains were based on the evaluations of two investigators experienced in methodologic research who independently reviewed all relevant articles using a quality abstraction form. MAIN OUTCOME MEASURES: Study quality in each of five domains: representativeness, bias and confounding, intervention description, outcomes and follow-up, and statistical quality and interpretation. RESULTS: Eighty-two randomized clinical trials were identified with a mean overall quality score of 44%. The mean domain scores ranged from 37% for representativeness to 58% for outcomes and follow-up. Forty percent or fewer studies received the maximum score for reporting the setting, the population, and the start and end dates; describing the inclusion and exclusion criteria; adequately randomizing subjects; and adequately masking individuals participating in the study. Key outcomes were often inadequately reported, including the distribution of patient-reported pain scores and the mean surgical time. CONCLUSIONS: Greater attention to methodologic quality and detailed reporting of study results will improve the ability of readers to interpret the results of clinical trials assessing regional anesthesia for cataract surgery.

Adult↗

Methodologic rigor of clinical trials on surgical management of eyes with coexisting cataract and glaucoma.

OBJECTIVE: To assess the methodologic quality of published studies of the surgical management of coexisting cataract and glaucoma. DESIGN: Literature review and analysis. METHOD: We performed a systematic search of the literature to identify all English language articles pertaining to the surgical management of coexisting cataract and glaucoma in adults. Quality assessment was performed on all randomized controlled trials, nonrandomized controlled trials, and cohort studies. Overall quality scores and scores for individual methodologic domains were based on the evaluations of two experienced investigators who independently reviewed articles using an objective quality assessment form. MAIN OUTCOME MEASURES: Quality in each of five domains (representativeness, bias and confounding, intervention description, outcomes and follow-up, and statistical quality and interpretation) measured as the percentage of methodologic criteria met by each study. RESULTS: Thirty-six randomized controlled trials and 45 other studies were evaluated. The mean quality score for the randomized, controlled clinical trials was 63% (range, 11%-88%), and for the other studies the score was 45% (range, 3%-83%). The mean domain scores were 65% for description of therapy (range, 0%-100%), 62% for statistical analysis (range, 0%-100%), 58% for representativeness (range, 0%-94%), 49% for outcomes assessment (range, 0%-83%), and 30% for bias and confounding (range, 0%-83%). Twenty-five of the studies (31%) received a score of 0% in the bias and confounding domain for not randomizing patients, not masking the observers to treatment group, and not having equivalent groups at baseline. CONCLUSIONS: Greater methodologic rigor and more detailed reporting of study results, particularly in the area of bias and confounding, could improve the quality of published clinical studies assessing the surgical management of coexisting cataract and glaucoma.

Cataract↗

Analytical methodologies for atomic spectrometric determination of metallic oxides in UV sunscreen creams.

In this study, methodologies for determining titanium oxide, zinc oxide and iron oxide are proposed and assayed in commercial sunscreen products. The proposed methodology for TiO2, determination in sunscreens is based on a microwave-assisted treatment for digesting the organic components in a closed teflon reactor in presence of HNO3 and HCl. Titanium is determined by inductive coupled plasma emission spectrometry (ICP-AES). The proposed methodologies for measuring ZnO and Fe2O3 are based on a sample emulsification in water with a non ionic tensioactive and IBMK, followed by Zn and Fe determination by flame atomic absorption spectrometry (FAAS). The methodologies allow a precise and accurate determination of metallic oxides in UV sunscreen creams, where the sample treatment is less time-consuming than in the classic methods. To our knowledge this is the first study focused to the determination of metallic oxides in commercial sunscreen products.

Ferric Compounds↗

Origins of an epidemic: the methodological and political emergence of rapid assessment.

The recent emergence of rapid assessment as a public health tool in the drug and alcohol field has been a relatively ahistorical process. The lack of such an explicit historical biography is understandable - the findings and impact of rapid assessment have rarely made their way into mainstream journals. However, its continued absence presents the manifest danger of an inward-looking field. This paper describes the development of rapid assessment during the past two decades, with a detailed focus on the emergence of rapid assessment in the drug and alcohol field. This focuses on the central role played by international agencies during the 1980s and 1990s, and the development of rapid methodologies by the World Health Organization to prevent epidemics of HIV among injecting drug users, and the use of rapid methodologies by the United Nations International Drug Control Programme to instruct drug policy reform. The paper also describes key events in other fields including: the emergence of the first formal rapid methodologies in the late 1970s, and the production of the first formal guidelines on conducting rapid assessment during the mid-1980s. The paper concludes by highlighting common challenges that rapid methodologies have faced throughout their history.

Journal Article↗

Waste ecocompatibility in storage and reuse scenarios: global methodology and detailed presentation of the impact study on the recipient environments.

In 1995, the ADEME launched a research program called "Waste Ecocompatibility" in order to define a reliable methodology for measuring the impact of waste in storage or reuse scenarios. The French concept of "Ecocompatibility" is defined as the situation where the pollutant flux from waste disposed of or used in specified conditions is compatible with the environmental acceptance of the receiving environments. The chief feature of this definition is to integrate the evaluation of the three following terms: pollutants emission from the waste, transport of the pollutants from the waste to the receptor cells and the environmental acceptance of the receiving environments. The "Waste Ecocompatibility" program consisted of a literature survey and an experimental part. The literature study aimed to determine factors and waste characteristics to be considered for a reliable ecocompatility assessment, to provide an overview of the available tools for measuring those factors and characteristics and to propose a first approach of the methodology. In the framework of the experimental program, this approach was then applied to three theoretical scenarios to validate the laboratory tools (comparative study of laboratory and field results) and to calibrate the global methodology. This paper deals with the results of the experimental program concerning the impact study on receiving environments: impact on plants and microorganisms living in soil, impacts on soil fauna and aquatic fauna. In other papers we intend to present the operational methodology for the assessment of waste ecocompatibility. It includes bio-assays at laboratory scale (microcosms), pilot scale (mesocosms) and in situ experiments (experimental prairie). To limit the use of in situ experiments other research works are necessary to validate bio-assays at laboratory or pilot scale.

Animals↗

A methodology for the quantitative assessment of articular cartilage histomorphometry.

OBJECTIVE: Traditionally, histological analysis of cartilage and cartilage repair has been performed qualitatively. While new techniques and grading systems have attempted to improve the quantitative nature of histological assessment, the advent of computer-based analysis systems have enabled development of more quantitative methodologies for cartilage repair. The objective of this study was to develop such a methodology for a more quantitative assessment of cartilage repair using a color-based image analysis system. DESIGN: Repair parameters were defined to describe the degree of cartilage restoration: repair dimensions, degree of attachment, surface roughness and repair location. This technique was experimentally applied to a cartilage repair study using cultured perichondrial cells implanted in a polylactic acid matrix in the rabbit femoral condyle. Specimens were examined and compared with the contralateral normal knee. RESULTS: Results showed increases in cartilage height, repair area, and surface roughness over controls for both 6 and 12 weeks. Surface elevation was significantly decreased at 6 weeks over 12 weeks. The percentage of repair improved between 6 and 12 weeks. Results were compared with a traditional grading system and demonstrated close correlation. Intraobserver and interobserver precision analysis were performed and demonstrated the reproducibility of the quantitative results by and between individuals. CONCLUSIONS: The methodology was deemed successful for a more objective analysis of cartilage with the added advantage of providing measured parameters that can assist in making comparisons between different studies using the same methodology.

Animals↗

Looking for an insulin pill? Use the BRET methodology!

Insulin exerts its biological effects through a plasma membrane receptor that possesses a tyrosine-kinase activity. This tyrosine-kinase activity depends on the autophosphorylation of the receptor on tyrosine residues and on its dephosphorylation by protein tyrosine-phosphatases. The discovery of pharmacological agents that specifically stimulate the autophosphorylation of the insulin receptor or inhibit its dephosphorylation will be of great importance for the treatment of insulin resistant or insulin deficient patients. Bioluminescence Resonance Energy Transfer (BRET) has developed in recent years as a new technique to study protein-protein interactions. In the BRET technique, one partner is fused to Renilla luciferase, whereas the other partner is fused to a fluorescent protein (e.g. YFP, Yellow Fluorescent Protein). The luciferase is excited by addition of its substrate, coelenterazine. If the two partners interact, resonance energy transfer occurs between the luciferase and the YFP, and a fluorescent signal, emitted by the YFP, can be detected. Our work indicates that this methodology could be an important tool for the search of molecules that activate insulin receptor autophosphorylation or that inhibit its dephosphorylation. Indeed, we first showed that the activation of the insulin receptor by different ligands can be monitored using a chimeric receptor with one B-subunit fused to Renilla luciferase and the other B-subunit fused to YFP. The conformational changes induced by different ligands could be detected as an energy transfer (BRET signal) between the luciferase and the YFP, that reflects the activation state of the receptor. This methodology allows for rapid analysis of the effects of agonists on insulin receptor activity and may therefore be used in high-throughput screening for the discovery of molecules with insulin-like properties. More recently, we demonstrated that the BRET methodology could also be used to monitor the interaction of the insulin receptor with protein tyrosine-phosphatase 1B, one of the main tyrosine-phosphatase that controls its activity. HEK cells were co-transfected with the insulin receptor fused to Renilla luciferase and a substrate-trapping mutant of PTP1B (PTP1B-D181A) fused to YFP. Insulin-induced BRET signal could be followed in real time for more than 30 min. Therefore, this methodology can also be used in high-throughput screening for the search of molecules that will specifically disrupt the interaction between the insulin receptor and PTP1B.

Administration, Oral↗

Measuring clinical pain in chronic widespread pain: selected methodological issues.

Assessing clinical pain is an important task in clinical practice and research. A large empirical literature has documented that patients' pain reports can be systematically biased by a number of methodological factors. This chapter reviews a selection of methodological issues that can affect pain ratings, including: the impact of recall bias, the use of paper and electronic diaries to assess pain experiences, ecological momentary assessment methods as a way of capturing real-time pain data in the real world, and pain scaling and data analysis considerations. Data from a recent study that implemented an electronic diary for capturing real-time pain data are presented and reviewed in the context of the methodological factors reviewed above. It is concluded that methodological factors can greatly affect our understanding of patients' pain experiences.

Area Under Curve↗

Getting quality in qualitative research: a short introduction to feminist methodology and methods.

The present paper reflects a practical activity undertaken by the Nutrition Society's qualitative research network in October 2005. It reflects the structure of that exercise. First, there is an introduction to feminist methodology and methods. The informing premise is that feminist methodology is of particular interest to practitioners (professional and/or academic) engaged in occupations numerically dominated by women, such as nutritionists. A critical argument is made for a place for feminist methodology in related areas of social research. The discussion points to the differences that exist between various feminist commentators, although the central aims of feminist research are broadly shared. The paper comprises an overview of organizing concepts, discussion and questions posed to stimulate discussion on the design and process of research informed by feminist methodology. Issues arising from that discussion are summarized.

Female↗

Measuring the impact of medicines information services on patient care: methodological considerations.

INTRODUCTION: Medicines information services (MISs) aim to promote the safe, effective and economic use of medicines. Results from published studies suggest that they provide effective information, which in many cases results in improved patient outcome. However, there are several methodological issues that are important in the interpretation of such studies. AIM: To address methodological issues in the evaluation of MISs. OBJECTIVES: To carry out a critical appraisal of papers assessing the impact on patient outcome of passive information given to health care professionals, to identify the key methodological issues and to make recommendations for future research in Europe. METHODS: Literature search to identify relevant papers meeting the inclusion criteria, critical evaluation of the methods used. RESULTS: Most studies have been conducted in the United States. Various methodological considerations were identified: study design, sampling, data collection, choice of outcome measures, and validity. The results of each study are interpreted in view of the methods used. In addition, the implications of the methods selected on the validity, reliability and generalisability of the results are discussed. Finally, suggestions for future studies are provided, in order to maximise validity and reliability.

Drug Information Services↗

Methodological issues in the social cost of gambling studies.

The appropriate way to classify and measure the "social costs" of gambling is a very important, unresolved methodological issue that has been addressed by Collins and Lapsley (2000); Thompson, Gazel, and Rickman (1999); and Walker and Barnett (1999), among others. What should be included and excluded from social cost studies continues to be a controversial issue, as illustrated in the literature and recent conferences. This paper is an attempt to explain the "economics" conception of social costs in accessible language. By using a simple economic model and everyday examples, it shows that the economics methodology is better than the other methodologies currently available. There are four specific goals of the paper: (1) Discuss the importance of the social cost methodological debate and the state of research in the area; (2) Explain the Walker-Barnett definition of social cost in the context of a simple production possibilities frontier and indifference curve model; (3) Use simple illustrative examples to show why many of the alleged social costs should not be classified as such; and (4) Suggest a new method for analyzing the social costs and effects attributable to pathological gambling.

Behavior, Addictive↗

A methodology for describing and decomposing complex psychosocial and behavioral interventions.

This article presents a comprehensive conceptual framework and methodology for characterizing multidimensional psychosocial and behavioral interventions for family caregivers of people with Alzheimer's disease. The methodology involved conducting a detailed task analysis of the interventions, and the application of the analytical hierarchy process. The authors were able to achieve high levels of consistency and reliability using this methodology to decompose and describe the interventions according to a complex conceptual framework comprising 3 dimensions: target domain, functional domain, and delivery system characteristics. Application of this methodology will enhance the ability to describe and measure interventions consistently, make comparisons across studies, isolate causal factors that achieve desired outcomes, and more generally elevate the science of psychosocial intervention research.

Aged↗

Prognosis of idiopathic membranous nephropathy: a methodologic meta-analysis.

Results in studies on prognosis and treatment of membranous nephropathy are conflicting. The aim of this investigation was to analyze the methodology of the existing research and to identify sources of these conflicting results. Studies published on prognosis of membranous nephropathy from 1970 to 1995 were identified using a Medline database literature search. The criteria for inclusion in the methodologic analysis were: (1) original article; (2) cohort study or clinical trial with > or = 50 adults; (3) zero time near the diagnostic renal biopsy; and (4) follow-up > or = six months. Ten well-accepted methodologic standards for prognostic research were applied to each study and the compliance was evaluated. Among the 26 studies that met the inclusion criteria, the median number of standards fulfilled was 4 and the highest was 7. The proportion of studies adhering to the individual standards was: (1) adequate diagnostic criteria, 35%; (2) definite end point, 46%; (3) adequate analysis of a surrogate end point, 52%; (4) analysis of baseline severity, 0%; (5) indication of baseline frequency for candidate predictors, 35%; (6) reproducible classification of predictors, 85%; (7) multivariable analysis, 50%; (8) identification of the variables' importance in multivariable analysis, 38%; (9) evaluation of the effect of treatment on predictors, 19%; and (10) adequate analysis of censored patients, 58%. We conclude that basic methodologic principles have frequently been disregarded. The consideration of these standards in future research can improve the interpretability and applicability of results and help reconcile conflict when results are compared among different studies.

Adult↗

High-throughput screening methodology for the directed evolution of glycosyltransferases.

Engineering of glycosyltransferases (GTs) with desired substrate specificity for the synthesis of new oligosaccharides holds great potential for the development of the field of glycobiology. However, engineering of GTs by directed evolution methodologies is hampered by the lack of efficient screening systems for sugar-transfer activity. We report here the development of a new fluorescence-based high-throughput screening (HTS) methodology for the directed evolution of sialyltransferases (STs). Using this methodology, we detected the formation of sialosides in intact Escherichia coli cells by selectively trapping the fluorescently labeled transfer products in the cell and analyzing and sorting the resulting cell population using a fluorescence-activated cell sorter (FACS). We screened a library of >10(6) ST mutants using this methodology and found a variant with up to 400-fold higher catalytic efficiency for transfer to a variety of fluorescently labeled acceptor sugars, including a thiosugar, yielding a metabolically stable product.

Amino Acid Sequence↗

Towards evidence-based drug treatment research on premature ejaculation: a critical evaluation of methodology.

In the last decade, an increasing number of drug studies on premature ejaculation have been published. The methodology used in these studies differed widely. In this review, it is therefore questioned as to how far the differences in methodology could have influenced clinical outcomes. The aim of the present review was to compare the different methodologies that were used in drug studies on premature ejaculation. The majority of these studies were conducted between 1973 and 2003 and were strikingly different in study design and in the quantification of clinical outcomes. It appeared that in some of these studies, placebo and active drug effects were neglected due to an erroneous methodology. The few studies that were using stopwatch assessment at each intercourse at baseline and during treatment and in which the intravaginal ejaculation latency time (IELT) was included appeared to be comparable in their results. The use of a well-defined definition of premature ejaculation, for example, an IELT of less than 1 min revealed reproducible results. Finally, the retrospective use of a questionnaire or a subjective report on ejaculation time induced higher effects with regard to placebo effects and an underestimation of active drug effects. In conclusion, for drug treatment research of premature ejaculation it is recommended to use a randomized double-blind prospective design, the use of the IELT, the use of a stopwatch at each coitus both during a baseline period and during drug treatment and a definition of premature ejaculation as an ejaculation that occurs within 1 min after vaginal penetration.

Evidence-Based Medicine↗

Groundwater monitoring plans at small-scale sites--an innovative spatial and temporal methodology.

An innovative methodology for improving existing groundwater monitoring plans at small-scale sites is presented. The methodology consists of three stand-alone methods: a spatial redundancy reduction method, a well-siting method for adding new sampling locations, and a sampling frequency determination method. The spatial redundancy reduction method eliminates redundant wells through an optimization process that minimizes the errors in plume delineation and the average plume concentration estimation. The well-siting method locates possible new sampling points for an inadequately delineated plume via regression analysis of plume centerline concentrations and estimation of plume dispersivity values. The sampling frequency determination method recommends the future frequency of sampling for each sampling location based on the direction, magnitude, and uncertainty of the concentration trend derived from representative historical concentration data. Although the methodology is designed for small-scale sites, it can be easily adopted for large-scale site applications. The proposed methodology is applied to a small petroleum hydrocarbon-contaminated site with a network of 12 monitoring wells to demonstrate its effectiveness and validity.

Environmental Monitoring↗

Methodology and reporting in studies of local recurrence after curative excision of the rectum for cancer.

BACKGROUND: Widely varying rates have been reported in the extensive literature published in the English language on local recurrence after curative excision of rectal carcinoma. These variations may be attributable to differences in the case mix of pathological factors influencing recurrence, differences in surgical technique or expertise, differences in the administration of adjuvant therapy and various combinations of these. They may also arise from methodological differences among studies. METHODS: This paper reviews the adequacy of methodology and reporting in 21 recent studies of local recurrence after curative resection of rectal cancer. RESULTS: Many flaws in reporting and apparent inadequacies in methodology were identified. On an index of 26 criteria examined, eight studies scored no more than 8 and only three studies scored more than 11. CONCLUSION: To date, the value of reports of local recurrence rates following curative excision of rectal cancer has been limited by inadequacies in documentation and methodology. Suggestions are made for preferred procedures to be followed in the reporting of future studies.

Clinical Trials as Topic↗