EMMPRIN is associated with S100A4 and predicts patient outcome in colorectal cancer

BACKGROUND: Proteolytic enzymes and their regulators have important biological roles in colorectal cancer by stimulating invasion and metastasis, which makes these factors attractive as potential prognostic biomarkers. METHODS: The expression of extracellular matrix metalloproteinase inducer (EMMPRIN) was characterised using immunohistochemistry in primary tumours from a cohort of 277 prospectively recruited colorectal cancer patients, and associations with expression of S100A4, clinicopathological parameters and patient outcome were investigated. RESULTS: One hundred and ninety-eight samples (72%) displayed positive membrane staining of the tumour cells, whereas 10 cases (4%) were borderline positive. EMMPRIN expression was associated with shorter metastasis-free, disease-specific and overall survival in both univariate and multivariate analyses. The prognostic impact was largely confined to TNM stage III, and EMMPRIN-negative stage III patients had an excellent prognosis. Furthermore, EMMPRIN was significantly associated with expression of S100A4, and the combined expression of these biomarkers conferred an even poorer prognosis. However, there was no evidence of direct regulation between the two proteins in the colorectal cancer cell lines HCT116 and SW620 in siRNA knockdown experiments. CONCLUSION: EMMPRIN is a promising prognostic biomarker in colorectal cancer, and our findings suggest that it could be used in the selection of stage III patients for adjuvant therapy

Cosmology of the selfaccelerating third order Galileon

In this paper we start from the original formulation of the galileon model with the original choice for couplings to gravity. Within this framework we find that there is still a subset of possible Lagrangians that give selfaccelerating solutions with stable spherically symmetric solutions. This is a certain constrained subset of the third order galileon which has not been explored before. We develop and explore the background cosmological evolution of this model drawing intuition from other even more restricted galileon models. The numerical results confirm the presence of selfacceleration, but also reveals a possible instability with respect to galileon perturbations.Comment: 30 pages, 24 figure

Accelerated expansion from ghost-free bigravity: a statistical analysis with improved generality

We study the background cosmology of the ghost-free, bimetric theory of gravity. We perform an extensive statistical analysis of the model using both frequentist and Bayesian frameworks and employ the constraints on the expansion history of the Universe from the observations of supernovae, the cosmic microwave background and the large scale structure to estimate the model's parameters and test the goodness of the fits. We explore the parameter space of the model with nested sampling to find the best-fit chi-square, obtain the Bayesian evidence, and compute the marginalized posteriors and mean likelihoods. We mainly focus on a class of sub-models with no explicit cosmological constant (or vacuum energy) term to assess the ability of the theory to dynamically cause a late-time accelerated expansion. The model behaves as standard gravity without a cosmological constant at early times, with an emergent extra contribution to the energy density that converges to a cosmological constant in the far future. The model can in most cases yield very good fits and is in perfect agreement with the data. This is because many points in the parameter space of the model exist that give rise to time-evolution equations that are effectively very similar to those of the $\Lambda$CDM. This similarity makes the model compatible with observations as in the $\Lambda$CDM case, at least at the background level. Even though our results indicate a slightly better fit for the $\Lambda$CDM concordance model in terms of the $p$-value and evidence, none of the models is statistically preferred to the other. However, the parameters of the bigravity model are in general degenerate. A similar but perturbative analysis of the model as well as more data will be required to break the degeneracies and constrain the parameters, in case the model will still be viable compared to the $\Lambda$CDM.Comment: 42 pages, 9 figures; typos corrected in equations (2.12), (2.13), (3.7), (3.8) and (3.9); more discussions added (footnotes 5, 8, 10 and 13) and abstract, sections 4.2, 4.3 and 5 (conclusions) modified in response to referee's comments; references added; acknowledgements modified; all results completely unchanged; matches version accepted for publication in JHE

Reduced Complexity Model Intercomparison Project Phase 1: introduction and evaluation of global-mean temperature response

Reduced-complexity climate models (RCMs) are critical in the policy and decision making space, and are directly used within multiple Intergovernmental Panel on Climate Change (IPCC) reports to complement the results of more comprehensive Earth system models. To date, evaluation of RCMs has been limited to a few independent studies. Here we introduce a systematic evaluation of RCMs in the form of the Reduced Complexity Model Intercomparison Project (RCMIP). We expect RCMIP will extend over multiple phases, with Phase 1 being the first. In Phase 1, we focus on the RCMs' global-mean temperature responses, comparing them to observations, exploring the extent to which they emulate more complex models and considering how the relationship between temperature and cumulative emissions of CO2 varies across the RCMs. Our work uses experiments which mirror those found in the Coupled Model Intercomparison Project (CMIP), which focuses on complex Earth system and atmosphere–ocean general circulation models. Using both scenario-based and idealised experiments, we examine RCMs' global-mean temperature response under a range of forcings. We find that the RCMs can all reproduce the approximately 1 ∘C of warming since pre-industrial times, with varying representations of natural variability, volcanic eruptions and aerosols. We also find that RCMs can emulate the global-mean temperature response of CMIP models to within a root-mean-square error of 0.2 ∘C over a range of experiments. Furthermore, we find that, for the Representative Concentration Pathway (RCP) and Shared Socioeconomic Pathway (SSP)-based scenario pairs that share the same IPCC Fifth Assessment Report (AR5)-consistent stratospheric-adjusted radiative forcing, the RCMs indicate higher effective radiative forcings for the SSP-based scenarios and correspondingly higher temperatures when run with the same climate settings. In our idealised setup of RCMs with a climate sensitivity of 3 ∘C, the difference for the ssp585–rcp85 pair by 2100 is around 0.23∘C(±0.12 ∘C) due to a difference in effective radiative forcings between the two scenarios. Phase 1 demonstrates the utility of RCMIP's open-source infrastructure, paving the way for further phases of RCMIP to build on the research presented here and deepen our understanding of RCMs

Scientific data from precipitation driver response model intercomparison project

This data descriptor reports the main scientific values from General Circulation Models (GCMs) in the Precipitation Driver and Response Model Intercomparison Project (PDRMIP). The purpose of the GCM simulations has been to enhance the scientific understanding of how changes in greenhouse gases, aerosols, and incoming solar radiation perturb the Earth's radiation balance and its climate response in terms of changes in temperature and precipitation. Here we provide global and annual mean results for a large set of coupled atmospheric-ocean GCM simulations and a description of how to easily extract files from the dataset. The simulations consist of single idealized perturbations to the climate system and have been shown to achieve important insight in complex climate simulations. We therefore expect this data set to be valuable and highly used to understand simulations from complex GCMs and Earth System Models for various phases of the Coupled Model Intercomparison Project

Updated global warming potentials and radiative efficiencies of halocarbons and other weak atmospheric absorbers

Human activity has led to increased atmospheric concentrations of many gases, including halocarbons, and may lead to emissions of many more gases. Many of these gases are, on a per molecule basis, powerful greenhouse gases, although at present‐day concentrations their climate effect is in the so‐called weak limit (i.e. their effect scales linearly with concentration). We published a comprehensive review of the radiative efficiencies (RE) and global warming potentials (GWP) for around 200 such compounds in 2013 (Hodnebrog et al., 2013). Here we present updated RE and GWP values for compounds where experimental infrared absorption spectra are available. Updated numbers are based on a revised “Pinnock curve”, which gives RE as a function of wavenumber, and now also accounts for stratospheric temperature adjustment (Shine and Myhre, 2020). Further updates include the implementation of around 500 absorption spectra additional to those in the 2013 review, and new atmospheric lifetimes from the literature (mainly from WMO (2019)). In total, values for 60 of the compounds previously assessed are based on additional absorption spectra, and 42 compounds have REs which differ by >10% from our previous assessment. New RE calculations are presented for more than 400 compounds in addition to the previously assessed compounds, and GWP calculations are presented for a total of around 250 compounds. Present‐day radiative forcing due to halocarbons and other weak absorbers is 0.38 [0.33‐0.43] W m‐2, compared to 0.36 [0.32‐0.40] W m‐2 in IPCC AR5 (Myhre et al., 2013), which is about 18% of the current CO2 forcing

EGFR, CD10 and proliferation marker Ki67 expression in ameloblastoma: possible role in local recurrence

<p>Abstract</p> <p>Background</p> <p>Ameloblastoma is an odontogenic neoplasm characterized by local invasiveness and tendency towards recurrence.</p> <p>Aims</p> <p>Studying the role played by EGFR, CD10 and Ki67 in the recurrence of ameloblastoma.</p> <p>Methods</p> <p>This study was carried out on 22 retrospective cases of mandibular ameloblastoma from the period from Jan 2002 to Jan 2008 with follow up period until Jan 2011 (3 to 8 years follow up peroid). Archival materials were obtained from pathology department, Mansoura university. Paraffin sections of tumor tissue from all cases were submitted for routine H&E stains and immunohistochemistry using EGFR, CD10 and Ki67 monoclonal antibodies. Statistical analysis using of clinical data for all patients, tumor type, EGFR, CD10 and Ki67 expression in relation to recurrence were evaluated.</p> <p>Results</p> <p>Among the 22 cases, 10 cases were males and 12 were females with sex ratio 1:1.2. Age ranged from 34 to 59 years old with a mean age 44.18 year. Five cases showed local recurrence within studied period and proved by biopsy. No statistically significant relation was found between local recurrence and patient age, tumor size, tumor type, EGFR expression. There was a significant relation between CD10 expression as well as Ki67 labelling index and recurrence (P value = 0.003, 0.000 respectively).</p> <p>Conclusion</p> <p>Evaluation of CD10 and Ki67 status together with conventional histological evaluation can help in providing more information about the biologic behavior of the tumor, while EGFR could be a target of an expanding class of anticancer therapies.</p> <p>Since ameloblastomas are EGFR-positive tumors, anti-EGFR agents could be considered to reduce the size of large tumors and to treat unresectable tumors that are in close proximity to vital structures.</p> <p>Virtual Slides</p> <p>The virtual slide(s) for this article can be found here:</p> <p><url>http://www.diagnosticpathology.diagnomx.eu/vs/1902106905645651</url></p

The impact of ADHD and conduct disorder in childhood on adult delinquency: A 30 years follow-up study using official crime records

<p>Abstract</p> <p>Background</p> <p>Few longitudinal studies have explored lifetime criminality in adults with a childhood history of severe mental disorders. In the present study, we wanted to explore the association between adult delinquency and several different childhood diagnoses in an in-patient population. Of special interest was the impact of disturbance of activity and attention (ADHD) and mixed disorder of conduct and emotions on later delinquency, as these disorders have been variously associated with delinquent development.</p> <p>Methods</p> <p>Former Norwegian child psychiatric in-patients (n = 541) were followed up 19-41 years after hospitalization by record linkage to the National Register of Criminality. On the basis of the hospital records, the patients were re-diagnosed according to ICD-10. The association between diagnoses and other baseline factors and later delinquency were investigated using univariate and multivariate Cox regression analyses.</p> <p>Results</p> <p>At follow-up, 24% of the participants had been convicted of criminal activity.</p> <p>In the multivariate Cox regression analysis, conduct disorder (RR = 2.0, 95%CI = 1.2-3.4) and hyperkinetic conduct disorder (RR = 2.7, 95% CI = 1.6-4.4) significantly increased the risk of future criminal behaviour. Pervasive developmental disorder (RR = 0.4, 95%CI = 0.2-0.9) and mental retardation (RR = 0.4, 95%CI = 0.3-0.8) reduced the risk for a criminal act. Male gender (RR = 3.6, 95%CI = 2.1-6.1) and chronic family difficulties (RR = 1.3, 95% CI = 1.1-1.5) both predicted future criminality.</p> <p>Conclusions</p> <p>Conduct disorder in childhood was highly associated with later delinquency both alone or in combination with hyperactivity, but less associated when combined with an emotional disorder. ADHD in childhood was no more associated with later delinquency than the rest of the disorders in the study population. Our finding strengthens the assumption that there is no direct association between ADHD and criminality.</p