Integrated stratigraphy of the Kimmeridge Clay Formation (Upper Jurassic) based on exposures and boreholes in south Dorset, UK

For the purposes of a high-resolution multi-disciplinary study of the Upper Jurassic Kimmeridge Clay Formation, two boreholes were drilled at Swanworth Quarry and one at Metherhills, south Dorset, UK. Together, the cores represent the first complete section through the entire formation close to the type section. We present graphic logs that record the stratigraphy of the cores, and outline the complementary geophysical and analytical data sets (gamma ray, magnetic susceptibility, total organic carbon, carbonate, [delta]13Corg). Of particular note are the new borehole data from the lowermost part of the formation which does not crop out in the type area. Detailed logs are available for download from the Kimmeridge Drilling Project web-site at http://kimmeridge.earth.ox.ac.uk/. Of further interest is a mid-eudoxus Zone positive shift in the [delta]13Corg record, a feature that is also registered in Tethyan carbonate successions, suggesting that it is a regional event and may therefore be useful for correlation. The lithostratigraphy of the cores has been precisely correlated with the nearby cliff section, which has also been examined and re-described. Magnetic-susceptibility and spectral gamma-ray measurements were made at a regular spacing through the succession, and facilitate core-to-exposure correlation. The strata of the exposure and core have been subdivided into four main mudrock lithological types: (a) medium-dark–dark-grey marl; (b) medium-dark–dark grey–greenish black shale; (c) dark-grey–olive-black laminated shale; (d) greyish-black–brownish-black mudstone. The sections also contain subordinate amounts of siltstone, limestone and dolostone. Comparison of the type section with the cores reveals slight lithological variation and notable thickness differences between the coeval strata. The proximity of the boreholes and different parts of the type section to the Purbeck–Isle of Wight Disturbance is proposed as a likely control on the thickness changes

Pengaruh Perceived Service Quality Terhadap Unibrand Performance Melalui Satisfaction Pada Universitas Swasta

This study refers to an earlier study that has been done by Sultan & Wong (2014). The purpose of this study was to determine the influence of Perceived Service Quality on the UniBrand Performance through Satisfaction in Private Universities. The design of this research is hypothesis testing using primary data obtained by distributing questionnaires directly to the 200 respondents who were active students of Private Universities in Jakarta. The analytical method used is Structure Equation Model (SEM). The result of this research conclude that there is a significant and positive relation between Perceived Service Quality and Satisfaction. There is a significant and positive relation between Satisfaction and UniBrand Performance. There is a significant and positive relation between Perceived Service Quality and UniBrand Performance

Loss of chromosome 3q is a prognostic marker in fusion-negative rhabdomyosarcoma

PURPOSE: Soft tissue sarcomas (STS) are rare mesenchymal neoplasms that frequently show complex chromosomal aberrations such as amplifications or deletions of DNA sequences or even whole chromosomes. We recently found that gain of chromosome (chr) 8 is associated with worse overall survival (OS) in STS as a group. We therefore aimed to investigate the overall copy number profile of rhabdomyosarcoma (RMS) to evaluate for prognostic signatures. METHODS: Fluorescence in situ hybridization (FISH) testing was performed on a cohort of STS to assess for chr8 gain. Copy number variation (CNV) data from the National Cancer Institute were analyzed to assess for prognostically significant CNV aberrations in RESULTS: Chr8 gain is a highly prevalent CNV in embryonal RMS and shows slightly improved prognosis. Meanwhile, loss of chr3q was associated with worse outcome in FN-RMS compared with FP-RMS. CONCLUSION: The pathogenesis of STS including FN-RMS remains poorly understood, emphasizing the need for new therapeutic advances and adequate risk stratification. Our data demonstrate that loss of chr3q is associated with poor OS in FN-RMS, supporting it as an important tool for risk stratification

A Cosmological Framework for the Co-Evolution of Quasars, Supermassive Black Holes, and Elliptical Galaxies: I. Galaxy Mergers & Quasar Activity

(Abridged) We develop a model for the cosmological role of mergers in the evolution of starbursts, quasars, and spheroidal galaxies. Combining halo mass functions (MFs) with empirical halo occupation models, we calculate where major galaxy-galaxy mergers occur and what kinds of galaxies merge, at all redshifts. We compare with observed merger MFs, clustering, fractions, and small-scale environments, and show that this yields robust estimates in good agreement with observations. Making the simple ansatz that major, gas-rich mergers cause quasar activity, we demonstrate that this naturally reproduces the observed rise and fall of the quasar luminosity density from z=0-6, as well as quasar LFs, fractions, host galaxy colors, and clustering as a function of redshift and luminosity. The observed excess of quasar clustering on small scales is a natural prediction of the model, as mergers preferentially occur in regions with excess small-scale galaxy overdensities. We show that quasar environments at all observed redshifts correspond closely to the empirically determined small group scale, where mergers of gas-rich galaxies are most efficient. We contrast with a secular model in which quasar activity is driven by bars/disk instabilities, and show that while these modes probably dominate at Seyfert luminosities, the constraints from clustering (large and small-scale), pseudobulge populations, disk MFs, luminosity density evolution, and host galaxy colors argue that they must be a small contributor to the z>1 quasar luminosity density.Comment: 34 pages, 27 figures, submitted to ApJ. Fixed appearance of Figure

Integrative Acoustic Mapping Reveals Hudson River Sediment Processes and Habitats

Rivers and estuaries around the world are the focus of human settlements and activities. Needs for clean water, ecosystem preservation, commercial navigation, industrial development, and recreational access compete for the use of estuaries, and management of these resources requires a detailed understanding of estuarine morphology and sediment dynamics. This article presents an overview of the first estuary-wide study of a heavily used estuary, the Hudson River, based on high-resolution acoustic mapping of the river bottom. The integration of three high-resolution acoustic methods with extensive sampling reveals an unexpected complexity of bottom features and allows detailed classification of the benthic environment in terms of riverbed morphology, sediment type, and sedimentary processes

Microstructural characterisation of resistance artery remodelling in diabetes mellitus

Introduction: Microvascular remodelling is a symptom of cardiovascular disease. Despite the mechanical environment being recognized as a major contributor to the remodelling process, it is currently only understood in a rudimentary way. Objective: A morphological and mechanical evaluation of the resistance vasculature in health and diabetes mellitus. Methods: The cells and extracellular matrix of human subcutaneous resistance arteries from abdominal fat biopsies were imaged using two-photon fluorescence and second harmonic generation at varying transmural pressure. The results informed a two-layer mechanical model. Results: Diabetic resistance arteries reduced in wall area as pressure was increased. This was attributed to the presence of thick, straight collagen fibre bundles that braced the outer wall. The abnormal mechanical environment caused the internal elastic lamina and endothelial and vascular smooth muscle cell arrangements to twist. Conclusions: Our results suggest diabetic microvascular remodelling is likely to be stress-driven, comprising at least 2 stages: (1) Laying down of adventitial bracing fibres that limit outward distension, and (2) Deposition of additional collagen in the media, likely due to the significantly altered mechanical environment. This work represents a step towards elucidating the local stress environment of cells, which is crucial to build accurate models of mechanotransduction in disease

Inflammation and acute traffic-related air pollution exposures among a cohort of youth with type 1 diabetes

Background: Evidence remains equivocal regarding the association of inflammation, a precursor to cardiovascular disease, and acute exposures to ambient air pollution from traffic-related particulate matter. Though youth with type 1 diabetes are at higher risk for cardiovascular disease, the relationship of inflammation and ambient air pollution exposures in this population has received little attention. Objectives: Using five geographically diverse US sites from the racially- and ethnically-diverse SEARCH for Diabetes in Youth Cohort, we examined the relationship of acute exposures to PM2.5 mass, Atmospheric Dispersion Modeling System (ADMS)-Roads traffic-related PM concentrations near roadways, and elemental carbon (EC) with biomarkers of inflammation including interleukin-6 (IL-6), c-reactive protein (hs-CRP) and fibrinogen. Methods: Baseline questionnaires and blood were obtained at a study visit. Using a spatio-temporal modeling approach, pollutant exposures for 7 days prior to blood draw were assigned to residential addresses. Linear mixed models for each outcome and exposure were adjusted for demographic and lifestyle factors identified a priori. Results: Among the 2566 participants with complete data, fully-adjusted models showed positive associations of EC average week exposures with IL-6 and hs-CRP, and PM2.5 mass exposures on lag day 3 with IL-6 levels. Comparing the 25th and 75th percentiles of average week EC exposures resulted in 8.3% higher IL-6 (95%CI: 2.7%,14.3%) and 9.8% higher hs-CRP (95%CI: 2.4%,17.7%). We observed some evidence of effect modification for the relationships of PM2.5 mass exposures with hs-CRP by gender and with IL-6 by race/ethnicity. Conclusions: Indicators of inflammation were associated with estimated traffic-related air pollutant exposures in this study population of youth with type 1 diabetes. Thus youth with type 1 diabetes may be at increased risk of air pollution-related inflammation. These findings and the racial/ethnic and gender differences observed deserve further exploration

Roles for Treg expansion and HMGB1 signaling through the TLR1-2-6 axis in determining the magnitude of the antigen-specific immune response to MVA85A

© 2013 Matsumiya et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedA better understanding of the relationships between vaccine, immunogenicity and protection from disease would greatly facilitate vaccine development. Modified vaccinia virus Ankara expressing antigen 85A (MVA85A) is a novel tuberculosis vaccine candidate designed to enhance responses induced by BCG. Antigen-specific interferon-γ (IFN-γ) production is greatly enhanced by MVA85A, however the variability between healthy individuals is extensive. In this study we have sought to characterize the early changes in gene expression in humans following vaccination with MVA85A and relate these to long-term immunogenicity. Two days post-vaccination, MVA85A induces a strong interferon and inflammatory response. Separating volunteers into high and low responders on the basis of T cell responses to 85A peptides measured during the trial, an expansion of circulating CD4+ CD25+ Foxp3+ cells is seen in low but not high responders. Additionally, high levels of Toll-like Receptor (TLR) 1 on day of vaccination are associated with an increased response to antigen 85A. In a classification model, combined expression levels of TLR1, TICAM2 and CD14 on day of vaccination and CTLA4 and IL2Rα two days post-vaccination can classify high and low responders with over 80% accuracy. Furthermore, administering MVA85A in mice with anti-TLR2 antibodies may abrogate high responses, and neutralising antibodies to TLRs 1, 2 or 6 or HMGB1 decrease CXCL2 production during in vitro stimulation with MVA85A. HMGB1 is released into the supernatant following atimulation with MVA85A and we propose this signal may be the trigger activating the TLR pathway. This study suggests an important role for an endogenous ligand in innate sensing of MVA and demonstrates the importance of pattern recognition receptors and regulatory T cell responses in determining the magnitude of the antigen specific immune response to vaccination with MVA85A in humans.This work was funded by the Wellcome Trust. MM has a Wellcome Trust PhD studentship and HM is a Wellcome Trust Senior Fello

Cell-free DNA ultra-low-pass whole genome sequencing to distinguish malignant peripheral nerve sheath tumor (MPNST) from its benign precursor lesion: A cross-sectional study

BACKGROUND: The leading cause of mortality for patients with the neurofibromatosis type 1 (NF1) cancer predisposition syndrome is the development of malignant peripheral nerve sheath tumor (MPNST), an aggressive soft tissue sarcoma. In the setting of NF1, this cancer type frequently arises from within its common and benign precursor, plexiform neurofibroma (PN). Transformation from PN to MPNST is challenging to diagnose due to difficulties in distinguishing cross-sectional imaging results and intralesional heterogeneity resulting in biopsy sampling errors. METHODS AND FINDINGS: This multi-institutional study from the National Cancer Institute and Washington University in St. Louis used fragment size analysis and ultra-low-pass whole genome sequencing (ULP-WGS) of plasma cell-free DNA (cfDNA) to distinguish between MPNST and PN in patients with NF1. Following in silico enrichment for short cfDNA fragments and copy number analysis to estimate the fraction of plasma cfDNA originating from tumor (tumor fraction), we developed a noninvasive classifier that differentiates MPNST from PN with 86% pretreatment accuracy (91% specificity, 75% sensitivity) and 89% accuracy on serial analysis (91% specificity, 83% sensitivity). Healthy controls without NF1 (participants = 16, plasma samples = 16), PN (participants = 23, plasma samples = 23), and MPNST (participants = 14, plasma samples = 46) cohorts showed significant differences in tumor fraction in plasma (P = 0.001) as well as cfDNA fragment length (P \u3c 0.001) with MPNST samples harboring shorter fragments and being enriched for tumor-derived cfDNA relative to PN and healthy controls. No other covariates were significant on multivariate logistic regression. Mutational analysis demonstrated focal NF1 copy number loss in PN and MPNST patient plasma but not in healthy controls. Greater genomic instability including alterations associated with malignant transformation (focal copy number gains in chromosome arms 1q, 7p, 8q, 9q, and 17q; focal copy number losses in SUZ12, SMARCA2, CDKN2A/B, and chromosome arms 6p and 9p) was more prominently observed in MPNST plasma. Furthermore, the sum of longest tumor diameters (SLD) visualized by cross-sectional imaging correlated significantly with paired tumor fractions in plasma from MPNST patients (r = 0.39, P = 0.024). On serial analysis, tumor fraction levels in plasma dynamically correlated with treatment response to therapy and minimal residual disease (MRD) detection before relapse. Study limitations include a modest MPNST sample size despite accrual from 2 major referral centers for this rare malignancy, and lack of uniform treatment and imaging protocols representing a real-world cohort. CONCLUSIONS: Tumor fraction levels derived from cfDNA fragment size and copy number alteration analysis of plasma cfDNA using ULP-WGS significantly correlated with MPNST tumor burden, accurately distinguished MPNST from its benign PN precursor, and dynamically correlated with treatment response. In the future, our findings could form the basis for improved early cancer detection and monitoring in high-risk cancer-predisposed populations

Effect of a behavioural intervention in obese pregnant women (the UPBEAT study):a multicentre, randomised controlled trial

BACKGROUND: Behavioural interventions might improve clinical outcomes in pregnant women who are obese. We aimed to investigate whether a complex intervention addressing diet and physical activity could reduce the incidence of gestational diabetes and large-for-gestational-age infants.METHODS: The UK Pregnancies Better Eating and Activity Trial (UPBEAT) is a randomised controlled trial done at antenatal clinics in eight hospitals in multi-ethnic, inner-city locations in the UK. We recruited pregnant women (15-18 weeks plus 6 days of gestation) older than 16 years who were obese (BMI ?30 kg/m(2)). We randomly assigned participants to either a behavioural intervention or standard antenatal care with an internet-based, computer-generated, randomisation procedure, minimising by age, ethnic origin, centre, BMI, and parity. The intervention was delivered once a week through eight health trainer-led sessions. Primary outcomes were gestational diabetes (diagnosed with an oral glucose tolerance test and by criteria from the International Association of Diabetes in Pregnancy Study Groups) and large-for-gestational-age infants (?90th customised birthweight centile). Analysis was by intention to treat. This trial is registered with Current Controlled Trials, ISCRTN89971375. Recruitment and pregnancy outcomes are complete but childhood follow-up is ongoing.FINDINGS: Between March 31, 2009, and June 2, 2014, we assessed 8820 women for eligibility and recruited 1555, with a mean BMI of 36·3 kg/m(2) (SD 4·8). 772 were randomly assigned to standard antenatal care and 783 were allocated the behavioural intervention, of which 651 and 629 women, respectively, completed an oral glucose tolerance test. Gestational diabetes was reported in 172 (26%) women in the standard care group compared with 160 (25%) in the intervention group (risk ratio 0·96, 95% CI 0·79-1·16; p=0·68). 61 (8%) of 751 babies in the standard care group were large for gestational age compared with 71 (9%) of 761 in the intervention group (1·15, 0·83-1·59; p=0·40). Thus, the primary outcomes did not differ between groups, despite improvements in some maternal secondary outcomes in the intervention group, including reduced dietary glycaemic load, gestational weight gain, and maternal sum-of-skinfold thicknesses, and increased physical activity. Adverse events included neonatal death (two in the standard care group and three in the intervention group) and fetal death in utero (ten in the standard care group and six in the intervention group). No maternal deaths were reported. Incidence of miscarriage (2% in the standard care group vs 2% in the intervention group), major obstetric haemorrhage (1% vs 3%), and small-for-gestational-age infants (?5th customised birthweight centile; 6% vs 5%) did not differ between groups.INTERPRETATION: A behavioural intervention addressing diet and physical activity in women with obesity during pregnancy is not adequate to prevent gestational diabetes, or to reduce the incidence of large-for-gestational-age infants.<br/