Assessing the reliability of eBURST using simulated populations with known ancestry

BACKGROUND: The program eBURST uses multilocus sequence typing data to divide bacterial populations into groups of closely related strains (clonal complexes), predicts the founding genotype of each group, and displays the patterns of recent evolutionary descent of all other strains in the group from the founder. The reliability of eBURST was evaluated using populations simulated with different levels of recombination in which the ancestry of all strains was known. RESULTS: For strictly clonal simulations, where all allelic change is due to point mutation, the groups of related strains identified by eBURST were very similar to those expected from the true ancestry and most of the true ancestor-descendant relationships (90–98%) were identified by eBURST. Populations simulated with low or moderate levels of recombination showed similarly high performance but the reliability of eBURST declined with increasing recombination to mutation ratio. Populations simulated under a high recombination to mutation ratio were dominated by a single large straggly eBURST group, which resulted from the incorrect linking of unrelated groups of strains into the same eBURST group. The reliability of the ancestor-descendant links in eBURST diagrams was related to the proportion of strains in the largest eBURST group, which provides a useful guide to when eBURST is likely to be unreliable. CONCLUSION: Examination of eBURST groups within populations of a range of bacterial species showed that most were within the range in which eBURST is reliable, and only a small number (e.g. Burkholderia pseudomallei and Enterococcus faecium) appeared to have such high rates of recombination that eBURST is likely to be unreliable. The study also demonstrates how three simple tests in eBURST v3 can be used to detect unreliable eBURST performance and recognise populations in which there appears to be a high rate of recombination relative to mutation

Normalization factors for magnetic relaxation of small particle systems in non-zero magnetic field

We critically discuss relaxation experiments in magnetic systems that can be characterized in terms of an energy barrier distribution, showing that proper normalization of the relaxation data is needed whenever curves corresponding to different temperatures are to be compared. We show how these normalization factors can be obtained from experimental data by using the $T \ln(t/\tau_0)$ scaling method without making any assumptions about the nature of the energy barrier distribution. The validity of the procedure is tested using a ferrofluid of Fe_3O_4 particles.Comment: 5 pages, 6 eps figures added in April 22, to be published in Phys. Rev. B 55 (1 April 1997

Predictors of Hospitals with Endemic Community-Associated Methicillin-Resistant Staphylococcus aureus

OBJECTIVE: We sought to identify hospital characteristics associated with community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) carriage among inpatients. DESIGN: Prospective cohort study. SETTING: Orange County, California. PARTICIPANTS: Thirty hospitals in a single county. METHODS: We collected clinical MRSA isolates from inpatients in 30 of 31 hospitals in Orange County, California, from October 2008 through April 2010. We characterized isolates by spa typing to identify CA-MRSA strains. Using California’s mandatory hospitalization data set, we identified hospital-level predictors of CA-MRSA isolation. RESULTS: CA-MRSA strains represented 1,033 (46%) of 2,246 of MRSA isolates. By hospital, the median percentage of CA-MRSA isolates was 46% (range, 14%–81%). In multivariate models, CA-MRSA isolation was associated with smaller hospitals (odds ratio [OR], 0.97, or 3% decreased odds of CA-MRSA isolation per 1,000 annual admissions; P < .001), hospitals with more Medicaid-insured patients (OR, 1.2; P = .002), and hospitals with more patients with low comorbidity scores (OR, 1.3; P < .001). Results were similar when restricted to isolates from patients with hospital-onset infection. CONCLUSIONS: Among 30 hospitals, CA-MRSA comprised nearly half of MRSA isolates. There was substantial variability in CA-MRSA penetration across hospitals, with more CA-MRSA in smaller hospitals with healthier but socially disadvantaged patient populations. Additional research is needed to determine whether infection control strategies can be successful in targeting CA-MRSA influx

Late Miocene to early Pliocene biofacies of Wanganui and Taranaki Basins, New Zealand: Applications to paleoenvironmental and sequence stratigraphic analysis

The Matemateaonga Formation is late Miocene to early Pliocene (upper Tongaporutuan to lower Opoitian New Zealand Stages) in age. The formation comprises chiefly shellbeds, siliciclastic sandstone, and siltstone units and to a lesser extent non-marine and shallow marine conglomerate and rare paralic facies. The Matemateaonga Formation accumulated chiefly in shelf paleoenvironments during basement onlap and progradation of a late Miocene to early Pliocene continental margin wedge in the Wanganui and Taranaki Basins. The formation is strongly cyclothemic, being characterised by recurrent vertically stacked facies successions, bounded by sequence boundaries. These facies accumulated in a range of shoreface to mid-outer shelf paleoenvironments during conditions of successively oscillating sea level. This sequential repetition of facies and the biofacies they enclose are the result of sixth-order glacio-eustatic cyclicity. Macrofaunal associations have been identified from statistical analysis of macrofossil occurrences collected from multiple sequences. Each association is restricted to particular lithofacies and stratal positions and shows a consistent order and/or position within the sequences. This pattern of temporal paleoecologic change appears to be the result of lateral, facies-related shifting of broad biofacies belts, or habitat-tracking, in response to fluctuations of relative sea level, sediment flux, and other associated paleoenvironmental variables. The associations also show strong similarity in terms of their generic composition to biofacies identified in younger sedimentary strata and the modern marine benthic environment in New Zealand

TOP2A and EZH2 Provide Early Detection of an Aggressive Prostate Cancer Subgroup.

Purpose: Current clinical parameters do not stratify indolent from aggressive prostate cancer. Aggressive prostate cancer, defined by the progression from localized disease to metastasis, is responsible for the majority of prostate cancer–associated mortality. Recent gene expression profiling has proven successful in predicting the outcome of prostate cancer patients; however, they have yet to provide targeted therapy approaches that could inhibit a patient\u27s progression to metastatic disease. Experimental Design: We have interrogated a total of seven primary prostate cancer cohorts (n = 1,900), two metastatic castration-resistant prostate cancer datasets (n = 293), and one prospective cohort (n = 1,385) to assess the impact of TOP2A and EZH2 expression on prostate cancer cellular program and patient outcomes. We also performed IHC staining for TOP2A and EZH2 in a cohort of primary prostate cancer patients (n = 89) with known outcome. Finally, we explored the therapeutic potential of a combination therapy targeting both TOP2A and EZH2 using novel prostate cancer–derived murine cell lines. Results: We demonstrate by genome-wide analysis of independent primary and metastatic prostate cancer datasets that concurrent TOP2A and EZH2 mRNA and protein upregulation selected for a subgroup of primary and metastatic patients with more aggressive disease and notable overlap of genes involved in mitotic regulation. Importantly, TOP2A and EZH2 in prostate cancer cells act as key driving oncogenes, a fact highlighted by sensitivity to combination-targeted therapy. Conclusions: Overall, our data support further assessment of TOP2A and EZH2 as biomarkers for early identification of patients with increased metastatic potential that may benefit from adjuvant or neoadjuvant targeted therapy approaches. ©2017 AACR

Neuropsychological findings in childhood neglect and their relationships to pediatric PTSD

Although child neglect is the most prevalent form of child maltreatment, the neurocognitive effects of neglect is understudied

A random cell motility gradient downstream of FGF controls elongation of amniote embryos

Vertebrate embryos are characterized by an elongated antero-posterior (AP) body axis, which forms by progressive cell deposition from a posterior growth zone in the embryo. Here, we used tissue ablation in the chicken embryo to demonstrate that the caudal presomitic mesoderm (PSM) has a key role in axis elongation. Using time-lapse microscopy, we analysed the movements of fluorescently labelled cells in the PSM during embryo elongation, which revealed a clear posterior-to-anterior gradient of cell motility and directionality in the PSM. We tracked the movement of the PSM extracellular matrix in parallel with the labelled cells and subtracted the extracellular matrix movement from the global motion of cells. After subtraction, cell motility remained graded but lacked directionality, indicating that the posterior cell movements associated with axis elongation in the PSM are not intrinsic but reflect tissue deformation. The gradient of cell motion along the PSM parallels the fibroblast growth factor (FGF)/mitogen-activated protein kinase (MAPK) gradient1, which has been implicated in the control of cell motility in this tissue2. Both FGF signalling gain- and loss-of-function experiments lead to disruption of the motility gradient and a slowing down of axis elongation. Furthermore, embryos treated with cell movement inhibitors (blebbistatin or RhoK inhibitor), but not cell cycle inhibitors, show a slower axis elongation rate. We propose that the gradient of random cell motility downstream of FGF signalling in the PSM controls posterior elongation in the amniote embryo. Our data indicate that tissue elongation is an emergent property that arises from the collective regulation of graded, random cell motion rather than by the regulation of directionality of individual cellular movements

Remanent Magnetic Measurements on Perpendicular Recording Materials with Compensation for Demagnetizing Fields

Existing techniques for characterization of longitudinal recording media using remanence measurements are extended to perpendicular media, in particular to Alumite, and correction for demagnetizing fields is taken into account. It is found that these techniques have limited value because of the sensitivity of the analysis to the correction factor used. Measurement of the recoil lines is investigated as an alternative method of probing the reversal processes

Recovery of myocardial perfusion after percutaneous coronary intervention of chronic total occlusions is comparable to hemodynamically significant non-occlusive lesions.

BACKGROUND: The benefits of chronic coronary total occlusion (CTO) percutaneous coronary intervention (PCI) are being questioned. The aim of this study was to assess the effects of CTO PCI on absolute myocardial perfusion, as compared with PCI of hemodynamically significant non-CTO lesions. METHODS: Consecutive patients with a preserved left ventricular ejection fraction (≥50%) and a CTO or non-CTO lesion, in whom [15 O]H2 O positron emission tomography was performed prior and after successful PCI, were included. Change in quantitative (hyperemic) myocardial blood flow (MBF), coronary flow reserve (CFR) and perfusion defect size (in myocardial segments) were compared between CTOs and non-CTO lesions. RESULTS: In total 92 patients with a CTO and 31 patients with a non-CTO lesion were included. CTOs induced larger perfusion defect sizes (4.51 ± 1.69 vs. 3.23 ± 2.38 segments, P < 0.01) with lower hyperemic MBF (1.30 ± 0.37 vs. 1.58 ± 0.62 mL·min-1 ·g-1 , P < 0.01) and similarly impaired CFR (1.66 ± 0.75 vs. 1.89 ± 0.77, P = 0.17) compared with non-CTO lesions. After PCI both hyperemic MBF and CFR increased similarly between groups (P = 0.57 and 0.35) to normal ranges with higher hyperemic MBF values in non-CTO compared with CTO (2.89 ± 0.94 vs. 2.48 ± 0.73 mL·min-1 ·g-1 , P = 0.03). Perfusion defect sizes decreased similarly after CTO PCI and non-CTO PCI (P = 0.14), leading to small residual defect sizes in both groups (1.15 ± 1.44 vs. 0.61 ± 1.45 segments, P = 0.054). CONCLUSIONS: Myocardial perfusion findings are slightly more hampered in patients with a CTO before and after PCI. Percutaneous revascularization of CTOs, however, improves absolute myocardial perfusion similarly to PCI of hemodynamically significant non-CTO lesions, leading to satisfying results

Electrical lithosphere beneath the Kaapvaal craton, southern Africa

Author Posting. © American Geophysical Union, 2011. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 116 (2011): B04105, doi:10.1029/2010JB007883.A regional-scale magnetotelluric (MT) experiment across the southern African Kaapvaal craton and surrounding terranes, called the Southern African Magnetotelluric Experiment (SAMTEX), has revealed complex structure in the lithospheric mantle. Large variations in maximum resistivity at depths to 200–250 km relate directly to age and tectonic provenance of surface structures. Within the central portions of the Kaapvaal craton are regions of resistive lithosphere about 230 km thick, in agreement with estimates from xenolith thermobarometry and seismic surface wave tomography, but thinner than inferred from seismic body wave tomography. The MT data are unable to discriminate between a completely dry or slightly “damp” (a few hundred parts per million of water) structure within the transitional region at the base of the lithosphere. However, the structure of the uppermost ∼150 km of lithosphere is consistent with enhanced, but still low, conductivities reported for hydrous olivine and orthopyroxene at levels of water reported for Kaapvaal xenoliths. The electrical lithosphere around the Kimberley and Premier diamond mines is thinner than the maximum craton thickness found between Kimberley and Johannesburg/Pretoria. The mantle beneath the Bushveld Complex is highly conducting at depths around 60 km. Possible explanations for these high conductivities include graphite or sulphide and/or iron metals associated with the Bushveld magmatic event. We suggest that one of these conductive phases (most likely melt-related sulphides) could electrically connect iron-rich garnets in a garnet-rich eclogitic composition associated with a relict subduction slab.In addition to the funding and logistical support provided by SAMTEX consortium members, this work is also supported by research grants from the National Science Foundation (EAR‐0309584 and EAR‐0455242 through the Continental Dynamics Program), the Department of Science and Technology, South Africa, and Science Foundation of Ireland (grant 05/RFP/ GEO001)