Second international collaborative study evaluating performance characteristics of methods measuring the von Willebrand factor cleaving protease (ADAMTS-13)

BACKGROUND: Over the last 4 years ADAMTS-13 measurement underwent dramatic progress with newer and simpler methods. AIMS: Blind evaluation of newer methods for their performance characteristics. DESIGN: The literature was searched for new methods and the authors invited to join the evaluation. Participants were provided with a set of 60 coded frozen plasmas that were prepared centrally by dilutions of one ADAMTS-13-deficient plasma (arbitrarily set at 0%) into one normal-pooled plasma (set at 100%). There were six different test plasmas ranging from 100% to 0%. Each plasma was tested 'blind' 10 times by each method and results expressed as percentage vs. the local and the common standard provided by the organizer. RESULTS: There were eight functional and three antigen assays. Linearity of observed-vs.-expected ADAMTS-13 levels assessed as r2 ranged from 0.931 to 0.998. Between-run reproducibility expressed as the (mean) CV for repeated measurements was below 10% for three methods, 10-15% for five methods and up to 20% for the remaining three. F-values (analysis of variance) calculated to assess the capacity to distinguish between ADAMTS-13 levels (the higher the F-value, the better the capacity) ranged from 3965 to 137. Between-method variability (CV) amounted to 24.8% when calculated vs. the local and to 20.5% when calculated vs. the common standard. Comparative analysis showed that functional assays employing modified von Willebrand factor peptides as substrate for ADAMTS-13 offer the best performance characteristics. CONCLUSIONS: New assays for ADAMTS-13 have the potential to make the investigation/management of patients with thrombotic microangiopathies much easier than in the past.

An empirical comparison of methods for meta-analysis of diagnostic accuracy showed hierarchical models are necessary

OBJECTIVE: Meta-analysis of studies of the accuracy of diagnostic tests currently uses a variety of methods. Statistically rigorous hierarchical models require expertise and sophisticated software. We assessed whether any of the simpler methods can in practice give adequately accurate and reliable results. STUDY DESIGN AND SETTING: We reviewed six methods for meta-analysis of diagnostic accuracy: four simple commonly used methods (simple pooling, separate random-effects meta-analyses of sensitivity and specificity, separate meta-analyses of positive and negative likelihood ratios, and the Littenberg-Moses summary receiver operating characteristic [ROC] curve) and two more statistically rigorous approaches using hierarchical models (bivariate random-effects meta-analysis and hierarchical summary ROC curve analysis). We applied the methods to data from a sample of eight systematic reviews chosen to illustrate a variety of patterns of results. RESULTS: In each meta-analysis, there was substantial heterogeneity between the results of different studies. Simple pooling of results gave misleading summary estimates of sensitivity and specificity in some meta-analyses, and the Littenberg-Moses method produced summary ROC curves that diverged from those produced by more rigorous methods in some situations. CONCLUSION: The closely related hierarchical summary ROC curve or bivariate models should be used as the standard method for meta-analysis of diagnostic accuracy.

What do case-control studies estimate? Survey of methods and assumptions in published case-control research

To evaluate strategies used to select cases and controls and how reported odds ratios are interpreted, the authors examined 150 case-control studies published in leading general medicine, epidemiology, and clinical specialist journals from 2001 to 2007. Most of the studies (125/150; 83%) were based on incident cases; among these, the source population was mostly dynamic (102/125; 82%). A minority (23/125; 18%) sampled from a fixed cohort. Among studies with incident cases, 105 (84%) could interpret the odds ratio as a rate ratio. Fifty-seven (46% of 125) required the source population to be stable for such interpretation, while the remaining 48 (38% of 125) did not need any assumptions because of matching on time or concurrent sampling. Another 17 (14% of 125) studies with incident cases could interpret the odds ratio as a risk ratio, with 16 of them requiring the rare disease assumption for this interpretation. The rare disease assumption was discussed in 4 studies but was not relevant to any of them. No investigators mentioned the need for a stable population. The authors conclude that in current case-control research, a stable exposure distribution is much more frequently needed to interpret odds ratios than the rare disease assumption. At present, investigators conducting case-control studies rarely discuss what their odds ratios estimate.

The lifestyle of our kids (LOOK) project: outline of methods

This methods paper outlines the overall design of a community-based multidisciplinary longitudinal study with the intent to stimulate interest and communication from scientists and practitioners studying the role of physical activity in preventive medicine. In adults, lack of regular exercise is a major risk factor in the development of chronic degenerative diseases and is a major contributor to obesity, and now we have evidence that many of our children are not sufficiently active to prevent early symptoms of chronic disease. The lifestyle of our kids (LOOK) study investigates how early physical activity contributes to health and development, utilizing a longitudinal design and a cohort of eight hundred and thirty 7-8-year-old (grade 2) school children followed to age 11-12 years (grade 6), their average family income being very close to that of Australia. We will test two hypotheses, that (a) the quantity and quality of physical activity undertaken by primary school children will influence their psychological and physical health and development; (b) compared with existing practices in primary schools, a physical education program administered by visiting specialists will enhance health and development, and lead to a more positive perception of physical activity. To test the first hypothesis we will monitor all children longitudinally over the 4 years. To test the second we will involve an intervention group of 430 children who receive two 50min physical education classes every week from visiting specialists and a control group of 400 who continue with their usual primary school physical education with their class-room teachers. At the end of grades 2, 4, and 6 we will measure several areas of health and development including blood risk factors for chronic disease, cardiovascular structure and function, physical fitness, psychological characteristics and perceptions of physical activity, bone structure and strength, motor control, body composition, nutritional intake, influence of teachers and family, and academic performance.

The role of psychological stress in inflammatory bowel disease: quality assessment of methods of 18 prospective studies and suggestions for future research

BACKGROUND: Enquiries among patients on the one hand and experimental and observational studies on the other suggest an influence of stress on inflammatory bowel diseases (IBD). However, since this influence remains hypothetical, further research is essential. We aimed to devise recommendations for future investigations in IBD by means of scrutinizing previously applied methodology. METHODS: We critically reviewed prospective clinical studies on the effect of psychological stress on IBD. Eligible studies were searched by means of the PubMed electronic library and through checking the bibliographies of located sources. RESULTS: We identified 20 publications resulting from 18 different studies. Sample sizes ranged between 10 and 155 participants. Study designs in terms of patient assessment, control variables, and applied psychometric instruments varied substantially across studies. Methodological strengths and weaknesses were irregularly dispersed. Thirteen studies reported significant relationships between stress and adverse outcomes. CONCLUSIONS: Study designs, including accuracy of outcome assessment and repeated sampling of outcomes (i.e. symptoms, clinical, and endoscopic), depended upon conditions like sample size, participants' compliance, and available resources. Meeting additional criteria of sound methodology, like taking into account covariates of the disease and its course, is strongly recommended to possibly improve study designs in future IBD research.

Strengthening the food systems governance evidence base: Supporting commensurability of research through a systematic review of methods

Governance of food systems is a poorly understood determinant of food security. Much scholarship on food systems governance is non-empirical, while existing research is often case study-based and theoretically and methodologically incommensurable. This frustrates aggregation of evidence and generalisation. We undertook a systematic review of methods used in food systems governance research with a view to identifying a core set of indicators for future research. We gathered literature through a structured consultation and sampling from recent reviews. Indicators were identified and classified according to the levels and sectors they investigate. We found a concentration of indicators in food production at local to national levels and a sparseness in distribution and consumption. Unsurprisingly, many indicators of institutional structure were found, while agency-related indicators are moderately represented. We call for piloting and validation of these indicators and for methodological development to fill gaps identified. These efforts are expected to support a more consolidated future evidence base and eventual meta-analysis.

Comparison of methods for assessing in home night time crying in healthy infants

Background. Infant colic is a common condition that is thought to put infants at risk for Shaken Baby Syndrome, a particularly devastating form of child abuse. However, little research has been done on techniques parents can use to deal with infant colic. This pilot study was conducted to assess the equipment that will be used in a randomized control trial that will compare the results for two different techniques that parents can use to reduce crying in infants with colic. ^ Methods. A total of 11 healthy infants, between one and five months of age, were recruited into this pilot study. All infants had a dosimeter, actiwatch and maternal log placed into the home and a subset of infants (N=3) were also recorded by a video camera. The equipment recorded between 6pm and 6am for at least two and up to five nights. The maternal log and video log were compared with one another to determine if the maternal log provides an accurate representation of the infant's night-time activities (i.e. sleep, awake, crying, feeding). The maternal log was then compared to the dosimeter and actiwatch data to determine if the dosimeter/actiwatch accurately reproduce the maternal log. ^ Results. Data from 10 infants were included in the analyses. The maternal log and video log were in full or partial agreement 90% of the time. When comparing events noted by the mother, the maternal log and dosimeter data were in agreement 84% of the time, and the maternal log and actiwatch data were in agreement 87% of the time. In combination, the dosimeter and/or actiwatch data agreed with the maternal log 90% of the time. ^ Conclusions. Our preliminary analyses of these data suggest the dosimeter and actiwatch will be useful tool for defining infant sleep patterns relative to the maternal log. However further analysis will be required to develop threshold values that can be used to objectively define events in the proposed RCT. Such analyses will need to integrate data from multiple dosimeters and deal with the shifting baselines observed for both the dosimeter and actiwatch.^

(Table T1) Mineralogy of ODP Leg 199 and DSDP Hole 16-162 sediments - comparison of methods

During Ocean Drilling Program Leg 199 in the equatorial Pacific, visible and near-infrared spectroscopy (VNIS) was used to measure the reflectance spectra (350-2500 nm) of 1343 sediment samples. Reflectance spectra were also measured for a suite of 60 samples of known mineralogy, thereby providing a local ground-truth calibration of spectral features to percentages of calcite, opal, smectite, and illite. The associated algorithm was used to calculate mineral percentages from the 1343 spectra. Using multiple regression and VNIS mineralogy, multisensor track physical properties and light spectroscopy data were then converted into continuous high-resolution mineralogy logs.

Comparison of methods for downscaling runoff from regional climate models in Spanish basins

At present there is much literature that refers to the advantages and disadvantages of different methods of statistical and dynamical downscaling of climate variables projected by climate models. Less attention has been paid to other indirect variables, like runoff, which play a significant role in evaluating the impact of climate change on hydrological systems. Runoff presents a much greater bias in climate models than other climate variables, like temperature or precipitation. It is very important to identify the methods that minimize bias while downscaling runoff from the gridded results of climate models to the basin scale

A comparative study of methods for automatic compile-time parallelization of logic programs

This paper presents a study of the effectiveness of three different algorithms for the parallelization of logic programs based on compile-time detection of independence among goals. The algorithms are embedded in a complete parallelizing compiler, which incorporates different abstract interpretation-based program analyses. The complete system shows the task of automatic program parallelization to be practical. The trade-offs involved in using each of the algorithms in this task are studied experimentally, weaknesses of these identified, and possible improvements discussed.