Treatment of Batch in the Detection, Calibration, and Quantification of Immunoassays in Large-scale Epidemiologic Studies

Many laboratory assays measure biomarkers via a 2-stage process. Direct measurement yields relative measures that are subsequently transformed to the unit of interest by using a calibration experiment. The calibration experiment is performed within the main experiment and uses a validation set for which true values are known and relative values are measured by assays to estimate the relation between relative and absolute values. Immunoassays, polymerase chain reaction, and chromatographic approaches are among assays performed in this manner. METHODS: For studies with multiple batches, data from more than a single calibration experiment are available. Conventionally, calibration of assays based on the standard curve is performed specific to each batch; the calibration experiment from each batch is used to calibrate each batch independently. This batch-specific approach incorporates batch variability but, due to the small number of calibration measurements in each batch, may not be best suited for this purpose. RESULTS: Mixed-effects models have been described to address interassay variability and to provide a measure of quality assurance. Conversely, when interbatch variability is negligible, a model that does not incorporate batch effect may be used to estimate an overall calibration curve. CONCLUSION: We explore approaches for use of calibration data in studies with many batches. Using a real data example with biomarker and outcome information, we show that risk estimates may vary depending on the calibration approach used. We demonstrate the potential for bias when using simulations. Under minimal interbatch variability, as seen in our data, conventional batch-specific calibration does not best use information available in the data and results in attenuated risk estimates

Maps of active layer thickness in northern Alaska by upscaling P-band polarimetric synthetic aperture radar retrievals

Extensive, detailed information on the spatial distribution of active layer thickness (ALT) in northern Alaska and how it evolves over time could greatly aid efforts to assess the effects of climate change on the region and also help to quantify greenhouse gas emissions generated due to permafrost thaw. For this reason, we have been developing high-resolution maps of ALT throughout northern Alaska. The maps are produced by upscaling from high-resolution swaths of estimated ALT retrieved from airborne P-band synthetic aperture radar (SAR) images collected for three different years. The upscaling was accomplished by using hundreds of thousands of randomly selected samples from the SAR-derived swaths of ALT to train a machine learning regression algorithm supported by numerous spatial data layers. In order to validate the maps, thousands of randomly selected samples of SAR-derived ALT were excluded from the training in order to serve as validation pixels; error performance calculations relative to these samples yielded root-mean-square errors (RMSEs) of 7.5–9.1 cm, with bias errors of magnitude under 0.1 cm. The maps were also compared to ALT measurements collected at a number of in situ test sites; error performance relative to the site measurements yielded RMSEs of approximately 11–12 cm and bias of 2.7–6.5 cm. These data are being used to investigate regional patterns and underlying physical controls affecting permafrost degradation in the tundra biome

Fecal pancreatic elastase-1 levels in older individuals without known gastrointestinal diseases or diabetes mellitus

Background - Structural changes occur in the pancreas as a part of the natural aging process. With aging, also the incidence of maldigestive symptoms and malnutrition increases, raising the possibility that these might be caused at least in part by inadequate pancreatic enzyme secretion due to degenerative processes and damage of the gland. Fecal elastase-1 is a good marker of pancreatic exocrine secretion. The aim of this study was to investigate the fecal elastase-1 levels among over 60 years old Finnish and Polish healthy individuals without any special diet, known gastrointestinal disease, surgery or diabetes mellitus. Methods - A total of 159 patients participated in this cross-sectional study. 106 older individuals (aged 60-92 years) were recruited from outpatient clinics and elderly homes. They were divided to three age groups: 60-69 years old (n = 31); 70-79 years old (n = 38) and over 80 years old (n = 37). 53 young subjects (20-28 years old) were investigated as controls. Inclusion criteria were age over 60 years, normal status and competence. Exclusion criteria were any special diet, diabetes mellitus, any known gastrointestinal disease or prior gastrointestinal surgery. Fecal elastase-1 concentration was measured from stool samples with an ELISA that uses two monoclonal antibodies against different epitopes of human elastase-1. Results - Fecal elastase-1 concentrations correlated negatively with age (Pearson r = -0,3531, P < 0.001) and were significantly lower among subjects over 70 years old compared to controls (controls vs. 70-79 years old and controls vs. over 80 years old, both P < 0.001). Among the over 60 years old subjects, the fecal elastase-1 concentrations were below the cut off level of 200 μg/g in 23 of 106 (21.7%) individuals [mean 112 (86-138) μg/g] indicating pancreatic exocrine insufficiency. Of those, 9 subjects had fecal elastase-1 level below 100 μg/g as a marker of severe pancreatic insufficiency. Conclusion - In our study one fifth of healthy older individuals without any gastrointestinal disorder, surgery or diabetes mellitus suffer from pancreatic exocrine insufficiency and might benefit from enzyme supplementation therapy.peerReviewe

Formal Public Health Education and Career Outcomes of Medical School Graduates

Few data are available evaluating the associations of formal public health education with long-term career choice and professional outcomes among medical school graduates. The objective of this study was to determine if formal public health education via completion of a masters of public health (MPH) degree among US medical school graduates was associated with early and long-term career choice, professional satisfaction, or research productivity.We conducted a retrospective cohort study in 1108 physicians (17.1% completed a MPH degree) who had 10–20 years of follow-up post medical school graduation. Multivariable logistic regression analyses were conducted.Compared to their counterparts with no MPH, medical school graduates with a MPH were more likely to have completed a generalist primary care residency only [relative risk (RR) 1.79, 95% confidence interval (CI) 1.35–2.29], obtain employment in an academic institution (RR 1.81; 95% CI 1.33–2.37) or government agency (RR 3.26; 95% CI 1.89–5.38), and practice public health (RR 39.84; 95% CI 12.13–107.38) or primary care (RR 1.59; 95% CI 1.18–2.05). Furthermore, medical school graduates with a MPH were more likely to conduct public health research (RR 8.79; 95% CI: 5.20–13.82), receive NIH or other federal funding (RR 3.11, 95% CI 1.74–5.33), have four or more peer-reviewed publications (RR 2.07; 95% CI 1.56–2.60), and have five or more scientific presentations (RR 2.31, 95% CI 1.70–2.98).Formal public health education via a MPH was associated with career choice and professional outcomes among physicians

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference