Erratum: Azimuthal Anisotropy of K_{S}

This corrects the article DOI: 10.1103/PhysRevLett.89.132301.

Prediction of intramuscular fat in lamb by visible and near-infrared spectroscopy in an abattoir environment.

The study used visible and near-infrared spectroscopy (Vis-NIR) in a large commercial processing plant, to test a system for meat quality (intramuscular fat; IMF) data collection within a supply chain for UK lamb meat. Crossbred Texel x Scotch Mule lambs (n = 220), finished on grass on 4 farms and slaughtered across 2 months, were processed through the abattoir and cutting plant and recorded using electronic identification. Vis-NIR scanning of the cut surface of the M. longissimus lumborum produced spectral data that predicted laboratory-measured IMF% with moderate accuracy (R2 0.38-0.48). Validation of the Vis-NIR prediction equations on an independent sample of 30 lambs slaughtered later in the season, provided similar accuracy of IMF prediction (R2 0.54). Values of IMF from four different laboratory tests were highly correlated with each other (r 0.82-0.95) and with Vis-NIR predicted IMF (r 0.66-0.75). Results suggest scope to collect lamb loin IMF data from a commercial UK abattoir, to sort cuts for different customers or to feed back to breeding programmes to improve meat quality.

INCIDENCE OF TEENAGE PREGNANCY IN GEORGIA AND AUSTRALIA. PATTERNS OF SOCIAL ACCEPTANCE AND RELATED HEALTHCARE CONCERNS.

Teenage pregnancy has been a target for prevention in many countries. Teen motherhood may adversely influence social determinants of health, including education attainment, employment and reliance on welfare support. We compared socioeconomic factors and geographical influencers affecting teenage pregnancy and birth outcomes across Georgia and Australia. Georgia has a teenage pregnancy rate three times higher than Australia. However, there are similar proportions of contraceptive use between Georgian and Australian teenagers as well as increasing rates of sexual health literacy in both countries. Both countries, however, show a comparative deficiency in sexual health literacy for rural populations resulting in earlier sexual experiences in Georgia and higher teenage pregnancy rates in Australia with Indigenous teenage mothers over-represented. More age-appropriate sexual health and contraception education is required in both Georgia and Australia, especially for rural areas, Indigenous populations and ethnic minorities. Further research is needed to supply teenage pregnancy and birth data from Georgian population.

Addressing the pitfalls when designing intervention studies to discover and validate biomarkers of habitual dietary intake.

INTRODUCTION: Dietary exposure monitoring within populations is reliant on self-reported measures such as Food Frequency Questionnaires and diet diaries. These methods often contain inaccurate information due to participant misreporting, non-compliance and bias. Urinary metabolites derived from individual foods could provide additional objective indicators of dietary exposure. For biomarker approaches to have utility it is essential that they cover a wide-range of commonly consumed foods and the methodology works in a real-world environment. OBJECTIVES: To test that the methodology works in a real-world environment and to consider the impact of the major sources of likely variance; particularly complex meals, different food formulations, processing and cooking methods, as well as the dynamics of biomarker duration in the body. METHODS: We designed and tested a dietary exposure biomarker discovery and validation strategy based on a food intervention study involving free-living individuals preparing meals and collecting urine samples at home. Two experimental periods were built around three consecutive day menu plans where all foods and drinks were provided (n = 15 and n = 36). RESULTS: The experimental design was validated by confirming known consumption biomarkers in urinary samples after the first menu plan. We tested biomarker performance with different food formulations and processing methods involving meat, wholegrain, fruits and vegetables. CONCLUSION: It was demonstrated that spot urine samples, together with robust dietary biomarkers, despite major sources of variance, could be used successfully for dietary exposure monitoring in large epidemiological studies.

Quantifying intrinsic and extrinsic control of single-cell fates in cancer and stem/progenitor cell pedigrees with competing risks analysis.

The molecular control of cell fate and behaviour is a central theme in biology. Inherent heterogeneity within cell populations requires that control of cell fate is studied at the single-cell level. Time-lapse imaging and single-cell tracking are powerful technologies for acquiring cell lifetime data, allowing quantification of how cell-intrinsic and extrinsic factors control single-cell fates over time. However, cell lifetime data contain complex features. Competing cell fates, censoring, and the possible inter-dependence of competing fates, currently present challenges to modelling cell lifetime data. Thus far such features are largely ignored, resulting in loss of data and introducing a source of bias. Here we show that competing risks and concordance statistics, previously applied to clinical data and the study of genetic influences on life events in twins, respectively, can be used to quantify intrinsic and extrinsic control of single-cell fates. Using these statistics we demonstrate that 1) breast cancer cell fate after chemotherapy is dependent on p53 genotype; 2) granulocyte macrophage progenitors and their differentiated progeny have concordant fates; and 3) cytokines promote self-renewal of cardiac mesenchymal stem cells by symmetric divisions. Therefore, competing risks and concordance statistics provide a robust and unbiased approach for evaluating hypotheses at the single-cell level.

Merits of random forests emerge in evaluation of chemometric classifiers by external validation.

Real-world applications will inevitably entail divergence between samples on which chemometric classifiers are trained and the unknowns requiring classification. This has long been recognized, but there is a shortage of empirical studies on which classifiers perform best in 'external validation' (EV), where the unknown samples are subject to sources of variation relative to the population used to train the classifier. Survey of 286 classification studies in analytical chemistry found only 6.6% that stated elements of variance between training and test samples. Instead, most tested classifiers using hold-outs or resampling (usually cross-validation) from the same population used in training. The present study evaluated a wide range of classifiers on NMR and mass spectra of plant and food materials, from four projects with different data properties (e.g., different numbers and prevalence of classes) and classification objectives. Use of cross-validation was found to be optimistic relative to EV on samples of different provenance to the training set (e.g., different genotypes, different growth conditions, different seasons of crop harvest). For classifier evaluations across the diverse tasks, we used ranks-based non-parametric comparisons, and permutation-based significance tests. Although latent variable methods (e.g., PLSDA) were used in 64% of the surveyed papers, they were among the less successful classifiers in EV, and orthogonal signal correction was counterproductive. Instead, the best EV performances were obtained with machine learning schemes that coped with the high dimensionality (914-1898 features). Random forests confirmed their resilience to high dimensionality, as best overall performers on the full data, despite being used in only 4.5% of the surveyed papers. Most other machine learning classifiers were improved by a feature selection filter (ReliefF), but still did not out-perform random forests.

Measurement of dietary exposure: a challenging problem which may be overcome thanks to metabolomics?

The diet is an important environmental exposure, and its measurement is an essential component of much health-related research. However, conventional tools for measuring dietary exposure have significant limitations being subject to an unknown degree of misreporting and dependent upon food composition tables to allow estimation of intakes of energy, nutrients and non-nutrient food constituents. In addition, such tools may be inappropriate for use with certain groups of people. As an alternative approach, the recent techniques of metabolite profiling or fingerprinting, which allows simultaneous monitoring of multiple and dynamic components of biological fluids, may provide metabolic signals indicative of food intake. Samples can be analysed through numerous analytical platforms, followed by multivariate data analysis. In humans, metabolomics has been applied successfully in pharmacology, toxicology and medical screening, but nutritional metabolomics is still in its infancy. Biomarkers of a small number of specific foods and nutrients have been developed successfully but less targeted and more high-throughput methods, that do not need prior knowledge of which signals might be discriminatory, and which may allow a more global characterisation of dietary intake, remain to be tested. A proof a principle project (the MEDE Study) is currently underway in our laboratories to test the hypothesis that high-throughput, non-targeted metabolite fingerprinting using flow injection electrospray mass spectrometry can be applied to human biofluids (blood and urine) to characterise dietary exposure in humans.

Sci-Fri PM: Planning-11: Selection and optimization of angiographic roadmap images for magnetic resonance guided catheter tracking.

As endovascular magnetic resonance (MR) techniques for device tracking and guidance move closer to demonstrating clinical feasibility, more investigation in the generation and optimization of vascular roadmap images is need to achieve the full benefit of MR-guided procedure. MR angiographic roadmap imaging requires high signal-to-noise (SNR), good vascular-to-background contrast and short acquisition time. These requirements not only qualify the appropriate roadmaps for therapy, but also guide in the optimization of their acquisition parameters. We hypothesize that among the well established MR angiographic techniques, low-resolution phase-contrast (PC) images would prove satisfactory for vascular roadmap imaging. To verify this, four potential MR angiography techniques, specifically, time-of-flight, contrast-enhanced, phase-contrast and black-blood angiography, were explored for roadmap imaging using a canine model on a 3 T MR scanner. PC angiography was specifically performed to evaluate impact of key parameters on the SNR efficiency and vascular-to-background contrast efficiency in order to optimize the sequence for therapeutic use. Data were collected from five canines. Phase-contrast angiography was found to be most suitable for generating vascular roadmap for MR-guided endovascular therapy. It was also found that small acquisition matrix and large FOV produced satisfactory roadmap images provided that the size of the vessel of interest was more than a few times the in-plane pixel dimension. Also, reducing the phase encoding steps had minimal effect on vessel oriented parallel to the phase encode direction.

Improved embryonic stem cell technologies.

Murine embryonic stem (ES) cells have become an indispensable tool for investigating genetic function both in vitro and, importantly, in vivo. Recent advances, including tetraploid aggregation, new site-specific recombinases and RNAi, have enabled more sophisticated manipulation of the ES cell genome. For instance, it is now possible to control gene expression in both a temporally and spatially restricted manner. Such new technologies are answering complex questions surrounding the function and interaction of an increasing number of genes. This chapter will review both the history and recent technological progress that has been made in mouse ES cell derivation, genetic manipulation and the generation of ES cell-derived chimaeric animals.

Vestibular inputs elicit patterned changes in limb blood flow in conscious cats.

Previous experiments have demonstrated that the vestibular system contributes to regulating sympathetic nervous system activity, particularly the discharges of vasoconstrictor fibres. In the present study, we examined the physiological significance of vestibulosympathetic responses by comparing blood flow and vascular resistance in the forelimb and hindlimb during head-up tilt from the prone position before and after the removal of vestibular inputs through a bilateral vestibular neurectomy. Experiments were performed on conscious cats that were trained to remain sedentary on a tilt table during rotations up to 60 deg in amplitude. Blood flow through the femoral and brachial arteries was recorded during whole-body tilt using perivascular probes; blood pressure was recorded using a telemetry system and vascular resistance was calculated from blood pressure and blood flow measurements. In vestibular-intact animals, 60 deg head-up tilt produced approximately 20% decrease in femoral blood flow and approximately 37% increase in femoral vascular resistance relative to baseline levels before tilt; similar effects were also observed for the brachial artery ( approximately 25% decrease in blood flow and approximately 38% increase in resistance). Following the removal of vestibular inputs, brachial blood flow and vascular resistance during head-up tilt were almost unchanged. In contrast, femoral vascular resistance increased only approximately 6% from baseline during 60 deg head-up rotation delivered in the first week after elimination of vestibular signals and approximately 16% in the subsequent 3-week period (as opposed to the approximately 37% increase in resistance that occurred before lesion). These data demonstrate that vestibular inputs associated with postural alterations elicit regionally specific increases in vascular resistance that direct blood flow away from the region of the body where blood pooling may occur. Thus, the data support the hypothesis that vestibular influences on the cardiovascular system serve to protect against the occurrence of orthostatic hypotension.

Cytotrophoblast stem cell lines derived from human embryonic stem cells and their capacity to mimic invasive implantation events.

BACKGROUND: An effective embryonic-maternal interaction is crucial for successful human pregnancy. Failure of this process is a major cause of infertility and can lead to placental dysfunction resulting in recurrent miscarriage, fetal retardation and pre-eclampsia. Research is severely constrained by ethical and practical considerations; therefore, we aimed to generate cytotrophoblast stem (CTBS) cell lines from human embryonic stem cells (HESCs). METHOD: Beta-HCG was used as a marker of viable trophoblast cells. In defined culture, embryoid bodies were generated from HESCs and selected for trophoblast enrichment by rounds of cellular aggregation and disaggregation. Distinct CTBS cell lines were isolated and characterized. Spheroid cytotrophoblast bodies were generated and their interaction with luteal-phase endometrial stroma was analysed by real-time image analysis. RESULTS: Three CTBS cell lines were derived, which were maintained in the absence of residual HESCs, fibroblast feeder cells or extracellular matrix. CTBS cells displayed typical cytotrophoblast and syncytiotrophoblast characteristics and exhibited further differentiation to invasive endovascular cell phenotype. One cell line was generated with constitutive expression of enhanced green fluorescent protein (eGFP). Spheroid trophoblast bodies mimicked closely the early invasive stages of implantation when incubated with human endometrial stromal preparations in vitro. CONCLUSION: These human CTBS cell lines are a significant new model for investigating human placentation and may have considerable potential in cell therapy applications.

Effects of postural changes and removal of vestibular inputs on blood flow to the head of conscious felines.

Prior studies have shown that removal of vestibular inputs produces lability in blood pressure during orthostatic challenges (Holmes MJ, Cotter LA, Arendt HE, Cass SP, and Yates BJ. Brain Res 938: 62-72, 2002; Jian BJ, Cotter LA, Emanuel BA, Cass SP, and Yates BJ. J Appl Physiol 86: 1552-1560, 1999). Furthermore, these studies led to the prediction that the blood pressure instability results in susceptibility for orthostatic intolerance. The present experiments tested this hypothesis by recording common carotid blood flow (CCBF) in conscious cats during head-up tilts of 20, 40, and 60 degrees amplitudes, before and after the surgical elimination of labyrinthine inputs through a bilateral vestibular neurectomy. Before vestibular lesions in most animals, CCBF remained stable during head-up rotations. Unexpectedly, in five of six animals, the vestibular neurectomy resulted in a significant increase in baseline CCBF, particularly when the laboratory was illuminated; on average, basal blood flow measured when the animals were in the prone position was 41 +/- 17 (SE) % higher after the first week after the lesions. As a result, even when posturally related lability in CCBF occurred after removal of vestibular inputs, blood supply to the head was not lower than when labyrinthine inputs were present. These data suggest that vestibular influences on cardiovascular regulation are more complex than previously appreciated, because labyrinthine signals appear to participate in setting basal rates of blood flow to the head in addition to triggering dynamic changes in the circulation to compensate for orthostatic challenges.

Embryonic stem (ES) cells and embryonal carcinoma (EC) cells: opposite sides of the same coin.

Embryonal carcinoma (EC) cells are the stem cells of teratocarcinomas, and the malignant counterparts of embryonic stem (ES) cells derived from the inner cell mass of blastocyst-stage embryos, whether human or mouse. On prolonged culture in vitro, human ES cells acquire karyotypic changes that are also seen in human EC cells. They also 'adapt', proliferating faster and becoming easier to maintain with time in culture. Furthermore, when cells from such an 'adapted' culture were inoculated into a SCID (severe combined immunodeficient) mouse, we obtained a teratocarcinoma containing histologically recognizable stem cells, which grew out when the tumour was explanted into culture and exhibited properties of the starting ES cells. In these features, the 'adapted' ES cells resembled malignant EC cells. The results suggest that ES cells may develop in culture in ways that mimic changes occurring in EC cells during tumour progression.

Near-threshold production of the multistrange Xi- hyperon.

The yield for the multistrange Xi(-) hyperon has been measured in 6A GeV Au+Au collisions via reconstruction of its decay products pi(-) and Lambda, the latter also being reconstructed from its daughter tracks of pi(-) and p. The measurement is rather close to the threshold for Xi(-) production and therefore provides an important test of model predictions. The measured yield for Xi(-) and Lambda are compared for several centralities. In central collisions the Xi(-) yield is found to be in excellent agreement with statistical and transport model predictions, suggesting that multistrange hadron production approaches chemical equilibrium in high baryon density nuclear matter.

Comparison of source images for protons, pi-'s, and lambda's in 6A GeV Au+Au collisions.

Source images are extracted from two-particle correlations constructed from strange and nonstrange hadrons produced in 6A GeV Au+Au collisions. Very different source images result from pp vs p Lambda vs pi(-)pi(-) correlations. Scaling by transverse mass can describe the apparent source size ratio for p/pi(-) but not for Lambda/pi(-) or Lambda/p. These observations suggest important differences in the space-time emission histories for protons, pions, and neutral strange baryons produced in the same events.

Narrowing of the balance function with centrality in Au+Au collisions at the square root of SNN = 130 GeV.

The balance function is a new observable based on the principle that charge is locally conserved when particles are pair produced. Balance functions have been measured for charged particle pairs and identified charged pion pairs in Au+Au collisions at the square root of SNN = 130 GeV at the Relativistic Heavy Ion Collider using STAR. Balance functions for peripheral collisions have widths consistent with model predictions based on a superposition of nucleon-nucleon scattering. Widths in central collisions are smaller, consistent with trends predicted by models incorporating late hadronization.

Disappearance of back-to-back high-pT hadron correlations in central Au+Au collisions at sqrt[s NN ] =200 GeV.

Azimuthal correlations for large transverse momentum charged hadrons have been measured over a wide pseudorapidity range and full azimuth in Au+Au and p+p collisions at sqrt[s(NN)]=200 GeV. The small-angle correlations observed in p+p collisions and at all centralities of Au+Au collisions are characteristic of hard-scattering processes previously observed in high-energy collisions. A strong back-to-back correlation exists for p+p and peripheral Au+Au. In contrast, the back-to-back correlations are reduced considerably in the most central Au+Au collisions, indicating substantial interaction as the hard-scattered partons or their fragmentation products traverse the medium.

Azimuthal anisotropy and correlations in the hard scattering regime at RHIC.

Azimuthal anisotropy (v(2)) and two-particle angular correlations of high p(T) charged hadrons have been measured in Au+Au collisions at sqrt[s(NN)]=130 GeV for transverse momenta up to 6 GeV/c, where hard processes are expected to contribute significantly. The two-particle angular correlations exhibit elliptic flow and a structure suggestive of fragmentation of high p(T) partons. The monotonic rise of v(2)(p(T)) for p(T)<2 GeV/c is consistent with collective hydrodynamical flow calculations. At p(T)>3 GeV/c, a saturation of v(2) is observed which persists up to p(T)=6 GeV/c.

Centrality dependence of high-p(T) hadron suppression in Au+Au collisions at sqrt[s(NN)]=130 GeV.

Inclusive transverse momentum distributions of charged hadrons within 0.2