Methods and reagent-lot comparisons by regression analysis: Sample size considerations.

Background: Parametric regression analysis is widely used in methods comparisons and more recently in checking the concordance of test results following receipt of new reagent lots. The greater frequency of reagent-lot evaluations increases pressure to detect bias with smallest possible sample sizes (i.e.

Predicting the Effect of Surface Waviness on Fatigue Life of a Wire + Arc Additive Manufactured Ti-6Al-4V Alloy.

This paper reports the effect of as-deposited surface conditions on the fatigue strength of an additively manufactured titanium alloy, Ti-6Al-4V (WAAM Ti64). First, the local stress concentration caused by the surface waviness was quantified using a metrology technique and computer modelling. Fatigue tests were conducted under bending loads at a cyclic load ratio of 0.

Calcium Channel Blocker Intoxication: A Critical Care Transport Perspective.

Calcium channel blockers (CCBs) have seen an increase in rate of non-therapeutic exposure that is both accidental and intentional in nature. Patients experiencing the toxic effects of a CCB overdose are resource intensive and can quickly outstrip the capabilities of local health systems, necessitating transfer to larger tertiary or quaternary care centers. We present a case of intentional non-dihydropyridine CCB overdose and toxicity in a 20-year-old patient requiring initial stabilization at a referring critical access emergency department with continuation of treatment and support during a 60-minute rotor wing transport from the referring hospital to an academic quaternary care center.

Negative values and variance functions: Implications for statistical analysis.

When reporting concentrations of substances in biological specimens it has been virtually universal practice to suppress negative results, initially by left-censoring negative results to zero and more recently by left-censoring to values such as limit of blank, limit of detection or even limit of quantification. Negative concentrations are obviously nonsensical and current reporting practices place proper emphasis on assisting the clinician. However, it is easily overlooked that negative concentrations are merely artefacts of data reduction and while adjusting them is sensible clinical practice there are potentially adverse consequences for statistical analysis, in particular for those parametric summaries and analyses which rely on reliable estimates of low-end uncertainty.

Using the variance function to generalize Bland-Altman analysis.

Background: Bland-Altman analysis is a popular and widely used method for assessing the level of agreement between two analytical methods. An important assumption is that paired method differences exhibit approximately constant (homogeneous) scatter when plotted against pair means. This allows estimation of limits of agreement which retain validity across the entire range of mean values.

Variance functions, detectability and bias: a re-evaluation.

Background A recent study used simulated internal quality control data (4 specimens × 40 replicates) to investigate the use of variance functions in estimating limit of blank and limit of detection, as per ISO definitions. Small systematic negative biases were found (typically <1%), but subsequent investigation has shown that these estimates had unacceptably large uncertainties because of an inadequate simulation size. Methods The previous data generation and variance function estimations were repeated 25 times using a different random number generator seed on each occasion.

Using the variance function to estimate limit of blank, limit of detection and their confidence intervals.

Background: Implementing International Organization for Standardization definitions of limit of blank and limit of detection requires precision estimates from specimens devoid of analyte (blank specimens) and also from specimens located close to zero. Calculations are straightforward if errors are constant over the relevant concentration range but estimation of the relationship between variability and concentration (variance function) is necessary in the general case when errors are not constant. This study investigated the efficacy of incorporating the variance function into estimation of limit of blank, limit of detection and their confidence intervals.

The gut microbiome modulates colon tumorigenesis.

Unlabelled: Recent studies have shown that individuals with colorectal cancer have an altered gut microbiome compared to healthy controls. It remains unclear whether these differences are a response to tumorigenesis or actively drive tumorigenesis. To determine the role of the gut microbiome in the development of colorectal cancer, we characterized the gut microbiome in a murine model of inflammation-associated colorectal cancer that mirrors what is seen in humans.

Gut microbiota protects against gastrointestinal tumorigenesis caused by epithelial injury.

Inflammation is a critical player in the development of both colitis-associated and sporadic colon cancers. Several studies suggest that the microbiota contribute to inflammation and tumorigenesis; however, studies to understand the role of the microbiota in colon tumor development in germ-free (GF) mice are limited. We therefore studied the effects of the microbiota on the development of inflammation and tumors in GF and conventionally raised specific pathogen-free (SPF) mice treated with azoxymethane (AOM) and dextran sulfate sodium (DSS).

Parathyroid hormone-related protein drives a CD11b+Gr1+ cell-mediated positive feedback loop to support prostate cancer growth.

In the tumor microenvironment, CD11b(+)Gr1(+) bone marrow-derived cells are a predominant source of protumorigenic factors such as matrix metalloproteinases (MMP), but how distal tumors regulate these cells in the bone marrow is unclear. Here we addressed the hypothesis that the parathyroid hormone-related protein (PTHrP) potentiates CD11b(+)Gr1(+) cells in the bone marrow of prostate tumor hosts. In two xenograft models of prostate cancer, levels of tumor-derived PTHrP correlated with CD11b(+)Gr1(+) cell recruitment and microvessel density in the tumor tissue, with evidence for mediation of CD11b(+)Gr1(+) cell-derived MMP-9 but not tumor-derived VEGF-A.

Drugs which inhibit osteoclast function suppress tumor growth through calcium reduction in bone.

Prostate carcinoma frequently metastasizes to bone where the microenvironment facilitates its growth. Inhibition of bone resorption is effective in reducing tumor burden and bone destruction in prostate cancer. However, whether drugs that inhibit osteoclast function inhibit tumor growth independent of inhibition of bone resorption is unclear.

Imprecision profiling.

* Imprecision profiles express precision characteristics of an assay over a range of concentration values. They can convert large quantities of potentially complex data into an easily interpreted graphical summary. * Imprecision profile estimation does not require precisely structured data.

Error models for immunoassays.

Background: For nearly 20 years, we and others have used a three-parameter power function as a direct estimation error model for immunoassays. The main application is imprecision profile plots (after translating from variance to coefficient of variation) but other uses include weighting functions for regression analysis and variance stabilizing transformations. Although generally successful, the intrinsic monotonicity of the function means that it fails to describe small but distinct increases in variance that occasionally occur near the assay detection limit.

Fiber digestibility by black lemurs (Eulemur macaco macaco).

Black lemurs, Eulemur macaco, are classified as generalist feeders, consuming a proportion of fruits and leaves that varies with seasonal availability. It is hypothesized that black lemurs are capable of using neutral detergent fiber (NDF) as a source of energy through fiber fermentation in the cecum and large intestine. In captivity, they are typically fed a diet of commercially available primate biscuits and readily available produce, both of which are limited in NDE Digestibility trials were conducted on 14 black lemurs; 12 were housed in groups (four, three, three, and two) and 2 were individually housed.

Fiber digestibility by the orangutan (Pongo abelii): in vitro and in vivo.

Limited nutritional information exists on diets of free-ranging orangutans, Pongo abelii and P. pygmaeus. Although they are classified as frugivores, the chemical composition of their diet and their gastrointestinal anatomy suggest that they rely on fiber fermentation for a substantial portion of energy.

Serum lipid concentrations in six canid and four ursid species in four zoos.

Serum lipid levels were measured in healthy captive wild canids and ursids, and the values were compared with previously published data. Serum lipid levels were evaluated in blood samples collected from eight African wild dogs (Lycaon pictus), three arctic foxes (Alopex lagopus), nine gray wolves (Canis lupus), four maned wolves (Chrysocyon brachyurus), two Mexican wolves (Canis lupus baleiyi), nine red wolves (Canis rufus), two brown bears (Ursus arctos), six polar bears (Ursus maritimus), six spectacled bears (Tremarctos ornatus), and five sun bears (Ursus malayanus). Samples were analyzed for total cholesterol, triacylglycerides, high-density lipoprotein-cholesterol, and low-density lipoprotein-cholesterol.

Serum concentrations of lipids, vitamin d metabolites, retinol, retinyl esters, tocopherols and selected carotenoids in twelve captive wild felid species at four zoos.

Serum concentrations of several nutrients were measured in 12 captive wild felid species including caracal (Felis caracal), cheetah (Acinonyx jubatus), cougar (Felis concolor), fishing cat (Felis viverrinus), leopard (Panthera pardus), lion (Panthera leo), ocelot (Felis pardalis), pallas cat (Felis manul), sand cat (Felis margarita), serval (Felis serval), snow leopard (Panthera uncia) and tiger (Panthera tigris). Diet information was collected for these animals from each participating zoo (Brookfield Zoo, Fort Worth Zoo, Lincoln Park Zoological Gardens and North Carolina Zoological Park). The nutritional composition of the diets at each institution met the probable dietary requirements for each species except for the pallas cat.

A new WIN32 computer program for estimating immunoassay variance functions.

A new WIN32 computer program for estimating immunoassay variance functions is described. It replaces and enhances an MS-DOS version written more than a decade ago. Input data can consist of either runs of raw replicated measurements (maximum: 40,000 observations) or sets of values of N, mean and SD (maximum: 20,000 sets).

Acquired aorta-pulmonary artery fistula: diagnosis by multiple imaging modalities.

Acquired communication between the aorta and the pulmonary artery is a rare phenomenon. We describe two patients with a thoracic aortic aneurysm in whom the diagnosis of a communication with the pulmonary artery was first made on transthoracic echocardiography and then more completely elucidated by means of multiple imaging modalities: transesophageal echocardiography, epiaortic ultrasound, computed tomography, and magnetic resonance imaging. Representative images from these complementary studies are presented.

Serum concentrations of vitamin D metabolites, vitamins A and E, and carotenoids in six canid and four ursid species at four zoos.

Nutritional status for six captive canid species (n=34) and four captive ursid species (n=18) were analyzed. The species analyzed included: African wild dog (Lycaon pictus), arctic fox (Alopex lagopus), gray wolf (Canis lupus), maned wolf (Chrysocyon brachyurus), Mexican wolf (Canis lupus baleiyi), red wolf (Canis rufus), brown bear (Ursus arctos), polar bear (Ursus maritimus), spectacled bear (Tremarctos ornatus), and sun bear (Ursus malayanus). Diet information was collected for these animals from each participating zoo (Brookfield Zoo, Fort Worth Zoo, Lincoln Park Zoological Gardens, and North Carolina Zoological Park).

A pragmatic approach to estimating total analytical error of immunoassays.

Several groups have recently commented on the need for more realistic information on analytical performance of laboratory tests. The term "total analytical error" is sometimes used in this context. However, differing opinions have been expressed on how best to obtain estimates of clinical assay error, as it would be perceived by clinicians.