Reference point insensitive molecular data analysis.

MOTIVATION: In biomedicine, every molecular measurement is relative to a reference point, like a fixed aliquot of RNA extracted from a tissue, a defined number of blood cells, or a defined volume of biofluid. Reference points are often chosen for practical reasons. For example, we might want to assess the metabolome of a diseased organ but can only measure metabolites in blood or urine. In this case, the observable data only indirectly reflects the disease state. The statistical implications of these discrepancies in reference points have not yet been discussed. RESULTS: Here, we show that reference point discrepancies compromise the performance of regression models like the LASSO. As an alternative, we suggest zero-sum regression for a reference point insensitive analysis. We show that zero-sum regression is superior to the LASSO in case of a poor choice of reference point both in simulations and in an application that integrates intestinal microbiome analysis with metabolomics. Moreover, we describe a novel coordinate descent based algorithm to fit zero-sum elastic nets. AVAILABILITY AND IMPLEMENTATION: The R-package "zeroSum" can be downloaded at https://github.com/rehbergT/zeroSum Moreover, we provide all R-scripts and data used to produce the results of this manuscript as Supplementary Material CONTACT: Michael.Altenbuchinger@ukr.de, Thorsten.Rehberg@ukr.de and Rainer.Spang@ukr.deSupplementary information: Supplementary material is available at Bioinformatics online.

Rifaximin preserves intestinal microbiota balance in patients undergoing allogeneic stem cell transplantation.

Intestinal dysbiosis has been associated with acute gastrointestinal GvHD and poor outcome following allogeneic stem cell transplantation (ASCT). To assess the effect of a switch in 2012 from ciprofloxacin/metronidazole to rifaximin for gut decontamination on intestinal microbiota composition and ASCT outcome, we retrospectively analyzed 394 patients receiving ASCT from September 2008 through June 2015. In 131 and 90 patients, respectively, urinary 3-indoxyl sulfate levels and intestinal enterococcal load were measured before conditioning and weekly within the first 28 days after ASCT. The use of rifaximin correlated with lower enterococcal positivity (6.9 vs 21.9%, P=0.05) and higher urinary 3-indoxyl sulfate concentrations (10.5 vs 4.6 µmoL/mmoL crea, P<0.001) after ASCT. Patients on rifaximin showed lower 1-year transplant-related mortality (P=0.04) and higher overall survival (P=0.008). Treatment of infectious complications with systemic antibiotics did not abrogate the beneficial effects of rifaximin on intestinal microbiota composition in the early course of ASCT and outcome. The data underscore the importance of maintaining a diverse population of symbiotic and mutualistic bacteria in the gut on ASCT outcome.

Nuclear magnetic resonance and mass spectrometry-based milk metabolomics in dairy cows during early and late lactation.

Milk production in dairy cows has dramatically increased over the past few decades. The selection for higher milk yield affects the partitioning of available nutrients, with more energy being allocated to milk synthesis and less to physiological processes essential to fertility and fitness. In this study, the abundance of numerous milk metabolites in early and late lactation was systematically investigated, with an emphasis on metabolites related to energy metabolism. The aim of the study was the identification and correlation of milk constituents to the metabolic status of the cows. To investigate the influence of lactation stage on physiological and metabolic variables, 2 breeds of different productivity were selected for investigation by high-resolution nuclear magnetic resonance spectroscopy and gas chromatography-mass spectrometry. We could reliably quantify 44 different milk metabolites. The results show that biomarkers such as acetone and beta-hydroxybutyrate are clearly correlated to the metabolic status of the individual cows during early lactation. Based on these data, the selection of cows that cope well with the metabolic stress of early lactation should become an option.

Autism and urinary exogenous neuropeptides: development of an on-line SPE-HPLC-tandem mass spectrometry method to test the opioid excess theory.

Autism is a complex neurodevelopmental disorder with unknown etiology. One hypothesis regarding etiology in autism is the "opioid peptide excess" theory that postulates that excessive amounts of exogenous opioid-like peptides derived from dietary proteins are detectable in urine and that these compounds may be pathophysiologically important in autism. A selective LC-MS/MS method was developed to analyze gliadinomorphin, beta-casomorphin, deltorphin 1, and deltorphin 2 in urine. The method is based on on-line SPE extraction of the neuropeptides from urine, column switching, and subsequent HPLC analysis. A limit of detection of 0.25 ng/mL was achieved for all analytes. Analyte recovery rates from urine ranged between 78% and 94%, with relative standard deviations of 0.2-6.8%. The method was used to screen 69 urine samples from children with and without autism spectrum disorders for the occurrence of neuropeptides. The target neuropeptides were not detected above the detection limit in either sample set.

Adsorbent materials commonly used in air analysis for adsorptive enrichment and thermal desorption of volatile organic compounds.

A review is given dealing with commonly used adsorbent materials in ambient air analysis of volatile organic compounds (VOCs). The adsorbents covered in the paper are selected in consideration of their compatibility with thermal desorption. Initially, we discuss the requirements that an adsorbent should fulfill, and useful parameters for the selection and evaluation of an appropriate material. Then, the most important materials are presented considering their properties, advantages, and drawbacks. A few applications are given, but a complete review of sampling techniques and applications dealing with adsorptive enrichment and thermal desorption is beyond the scope of this paper.

Family member knowledge of children's medical problems: the need for universal application of an emergency data set.

OBJECTIVE: Advances in medical care have led to a growing population of special needs children who are at risk for suboptimal care when they present to a physician with no previous knowledge of their medical history. This risk may be amplified in the emergency department setting when time-sensitive interventions must be initiated without immediate access to consultants or past records. Our purpose in this study was to evaluate caretakers' knowledge of their children's chronic medical problems and their ability to relate this knowledge to unfamiliar health care providers. METHODS: Caretaker/child pairs presenting for specialty visits were surveyed. Questions focused on knowledge of the child's illness, medicine regime, and how to contact the specialist. Chart review confirmed responses of caretakers and provided sociodemographic information. Descriptive statistics and chi2 were used in data analysis. RESULTS: Of the 49 caretakers interviewed, 85% were parents, 53% were African-American, and 43% were Caucasian. One-half of the group received medical assistance. The mean age of the children was 55 months. Responses showed that 53% of caretakers were unable to provide their children's specific diagnoses. Of these, one half could provide a lay diagnosis whereas the remaining one half could only identify the organ system involved or that there was a problem. For children on medications, 29% of caretakers could not provide an accurate list. Name of the subspecialist and phone number of the subspecialty clinic was unknown by 25% of caretakers. No child wore medical identification jewelry. CONCLUSIONS: Caretakers are not always able to accurately relay vital information on their child's essential medical needs, a problem that may be compounded in emergency situations. The use of some form of independent identification and information set is needed to assure proper treatment of children with special health care needs encountering an unfamiliar health care provider.

The determination of calcium, glucose, urea and uric acid using the Kodak EKTACHEM multilayer film technology: an evaluation.

Calcium, glucose, urea and uric acid determinations on the "'Kodak Ektachem Four Chemistry Analyzer" were tested for precision and an estimation of the accuracy was performed with our laboratory routine methods using patients' sera and proficiency fluids. Precision -- examined over a period of six weeks -- was very good. Even the very stringent claim of the College of American Pathologists (CAP) -- that analytical dispersion should be less than 1/16th of the normal range -- was fulfilled in almost all control samples. The results from patients' sera measured using both the Ektachem and the routine laboratory methods showed very good correlation. Proficiency fluids tested for calcium, glucose and uric acid all resulted in values well within the assigned interval. Some negative bias was noted for the urea determination however. This could not be completely eliminated even though the samples had been reconstituted with a bicarbonate solution according to the manufacturer's instructions. The linear range of the four determinations was checked: calcium is linear up to 4.2 mmol/l, glucose up to 33 mmol/l, urea up to 60 mmol/l and uric acid up to 1370 mumol/l. Our results confirmed the long-term stability of analyzer and slides to be so high that one calibration per week is sufficient.

[The determination of cystine aminopoptidase (oxytocinase) with a ENI fast analyzer (author's transl)]. / Die Bestimmung der Cystinaminopeptidase (Oxytocinase) mit einem ENI-Fast-Analyzer

A procedure for the determination of cystine aminopeptidase activity was adapted to a fast analyzer. The various reaction parameters were checked. The precision of the method was about 5%. Cystine aminopeptidase activity was stable for long storage periods at +4 degrees C and -20 degrees C. The normal range for the terminal weeks of pregnancy was determined on samples from female patients with normal pregnancies.

[Calculation of the parameters of the acid-base balance with the aid of a small computer]. / Berechnung der Parameter des Säure-Basen-Haushaltes mit Hilfe eines Kleincomputers

The application and modification of a program published by Hardt (1972), Clin. Chem. 18,658--661) for the calculation of the true pCO2, the standard bicarbonate and the base excess are reported. 217 Determinations of a random patient sample were evaluated graphically, with the aid of a nomogram of Siggaard-Andersen, and mathematically with a computer program. There was good agreement between the two evaluation methods.