Comparison of the prognostic value of measures of the tumor inflammatory cell infiltrate and tumor-associated stroma in patients with primary operable colorectal cancer

The aim of the present study was to compare the clinical utility of two measures of the inflammatory cell infiltrate - a H&E-based assessment of the generalised inflammatory cell infiltrate (the Klintrup-Mäkinen (KM) grade), and an immunohistochemistry-based assessment of combined CD3+ and CD8+ T-cell density (the “Immunoscore”), in conjunction with assessment of the tumor stroma percentage (TSP) in patients undergoing resection of stage I-III colorectal cancer (CRC). 246 patients were identified from a prospectively maintained database of CRC resections in a single surgical unit. Assessment of KM grade and TSP was performed using full H&E sections. CD3+ and CD8+ T-cell density was assessed on full sections and the Immunoscore calculated. KM grade and Immunoscore were strongly associated (P<0.001). KM grade stratified cancer-specific survival (CSS) from 88% to 66% (P=0.002) and Immunoscore from 93% to 61% (P<0.001). Immunoscore further stratified survival of patients independent of KM grade from 94% (high KM, Im4) to 60% (low KM, Im0/1). Furthermore, TSP stratified survival of patients with a weak inflammatory cell infiltrate (low KM: from 75% to 47%; Im0/1: from 71% to 38%, both P<0.001) but not those with a strong inflammatory infiltrate. On multivariate analysis, only Immunoscore (HR 0.44, P<0.001) and TSP (HR 2.04, P<0.001) were independently associated with CSS. These results suggest that the prognostic value of an immunohistochemistry-based assessment of the inflammatory cell infiltrate is superior to H&E-based assessment in patients undergoing resection of stage I-III CRC. Furthermore, assessment of the tumor-associated stroma, using TSP, further improves prediction of outcome

The Relation between Physical and Gravitational Geometry

The appearance of two geometries in one and the same gravitational theory is familiar. Usually, as in the Brans-Dicke theory or in string theory, these are conformally related Riemannian geometries. Is this the most general relation between the two geometries allowed by physics ? We study this question by supposing that the physical geometry on which matter dynamics take place could be Finslerian rather than just Riemannian. An appeal to the weak equivalence principle and causality then leads us the conclusion that the Finsler geometry has to reduce to a Riemann geometry whose metric - the physical metric - is related to the gravitational metric by a generalization of the conformal transformation.Comment: 15 pages, Te

Global asteroseismic properties of solar-like oscillations observed by Kepler : A comparison of complementary analysis methods

We present the asteroseismic analysis of 1948 F-, G- and K-type main-sequence and subgiant stars observed by the NASA {\em Kepler Mission}. We detect and characterise solar-like oscillations in 642 of these stars. This represents the largest cohort of main-sequence and subgiant solar-like oscillators observed to date. The photometric observations are analysed using the methods developed by nine independent research teams. The results are combined to validate the determined global asteroseismic parameters and calculate the relative precision by which the parameters can be obtained. We correlate the relative number of detected solar-like oscillators with stellar parameters from the {\em Kepler Input Catalog} and find a deficiency for stars with effective temperatures in the range $5300 \lesssim T_\mathrm{eff} \lesssim 5700$\,K and a drop-off in detected oscillations in stars approaching the red edge of the classical instability strip. We compare the power-law relationships between the frequency of peak power, $\nu_\mathrm{max}$, the mean large frequency separation, $\Delta\nu$, and the maximum mode amplitude, $A_\mathrm{max}$, and show that there are significant method-dependent differences in the results obtained. This illustrates the need for multiple complementary analysis methods to be used to assess the robustness and reproducibility of results derived from global asteroseismic parameters.Comment: 14 pages, 9 figures, accepted for publication in Monthly Notices of the Royal Astronomical Societ

Comment on ‘Tumour-infiltrating inflammation and prognosis in colorectal cancer: systematic review and meta-analysis’

No abstract available

Mode identification in rapidly rotating stars

Context: Recent calculations of pulsation modes in rapidly rotating polytropic models and models based on the Self-Consistent Field method have shown that the frequency spectrum of low degree pulsation modes can be described by an empirical formula similar to Tassoul's asymptotic formula, provided that the underlying rotation profile is not too differential. Aims: Given the simplicity of this asymptotic formula, we investigate whether it can provide a means by which to identify pulsation modes in rapidly rotating stars. Methods: We develop a new mode identification scheme which consists in scanning a multidimensional parameter space for the formula coefficients which yield the best-fitting asymptotic spectra. This mode identification scheme is then tested on artificial spectra based on the asymptotic formula, on random frequencies and on spectra based on full numerical eigenmode calculations for which the mode identification is known beforehand. We also investigate the effects of adding random frequencies to mimic the effects of chaotic modes which are also expected to show up in such stars. Results: In the absence of chaotic modes, it is possible to accurately find a correct mode identification for most of the observed frequencies provided these frequencies are sufficiently close to their asymptotic values. The addition of random frequencies can very quickly become problematic and hinder correct mode identification. Modifying the mode identification scheme to reject the worst fitting modes can bring some improvement but the results still remain poorer than in the case without chaotic modes

Cancer and systemic inflammation: treat the tumour and treat the host

Determinants of cancer progression and survival are multifactorial and host responses are increasingly appreciated to have a major role. Indeed, the development and maintenance of a systemic inflammatory response has been consistently observed to confer poorer outcome, in both early and advanced stage disease. For patients, cancer-associated symptoms are of particular importance resulting in a marked impact on day-to-day quality of life and are also associated with poorer outcome. These symptoms are now recognised to cluster with one another with anorexia, weight loss and physical function forming a recognised cluster whereas fatigue, pain and depression forming another. Importantly, it has become apparent that these symptom clusters are associated with presence of a systemic inflammatory response in the patient with cancer. Given the understanding of the above, there is now a need to intervene to moderate systemic inflammatory responses, where present. In this context the rationale for therapeutic intervention using nonselective anti-inflammatory agents is clear and compelling and likely to become a part of routine clinical practice in the near future. The published literature on therapeutic intervention using anti-inflammatory agents for cancer-associated symptoms was reviewed. There are important parallels with the development of useful treatments for the systemic inflammatory response in patients with rheumatological disease and cardiovascular disease

Characterising climate change discourse on social media during extreme weather events

When extreme weather events occur, people often turn to social media platforms to share information, opinions and experiences. One of the topics commonly discussed is the role climate change may or may not have played in influencing an event. Here, we examine Twitter posts that mentioned climate change in the context of three high-magnitude extreme weather events – Hurricane Irene, Hurricane Sandy and Snowstorm Jonas – in order to assess how the framing of the topic and the attention paid to it can vary between events. We also examine the role that contextual factors can play in shaping climate change coverage on the platform. We find that criticism of climate change denial dominated during Irene, while political and ideological struggle frames dominated during Sandy. Discourse during Jonas was, in contrast, more divided between posts about the scientific links between climate change and the events, and posts contesting climate science in general. The focus on political and ideological struggle frames during Sandy reflects the event’s occurrence at a time when the Occupy movement was active and the 2012 US Presidential Election was nearing. These factors, we suggest, could also contribute to climate change being a more prominent discussion point during Sandy than during Irene or Jonas. The Jonas frames, meanwhile, hint at lesser public understanding of how climate change may influence cold weather events when compared with tropical storms. Overall, our findings demonstrate how event characteristics and short-term socio-political context can play a critical role in determining the lenses through which climate change is viewed

On the interpretation of echelle diagrams for solar-like oscillations. Effect of centrifugal distortion

This work aims at determining the impact of slow to moderate rotation on the regular patterns often present in solar-like oscillation spectra. We focus on the well-known asteroseismic diagnostic echelle diagrams, examining how rotation may modify the estimates of the large and small spacings, as well as the identification of modes. We illustrate the work with a real case: the solar-like star $\eta$ Bootis. The modeling takes into account rotation effects on the equilibrium models through an effective gravity and on the oscillation frequencies through both perturbative and non-perturbative calculations. We compare the results of both type of calculations in the context of the regular spacings (like the small spacings and the scaled small spacings) and echelle diagrams. We show that for echelle diagrams the perturbative approach remains valid for rotational velocities up to 40-50 km/s. We show that for the rotational velocities measured in solar-like stars, theoretical oscillation frequencies must be corrected up to the second-order in terms of rotation rate, including near degeneracy effects. For rotational velocities of about 16 km/S and higher, diagnostics on large spacings and on modal identification through echelle diagrams can be significantly altered by the presence of the $m\neq0$ components of the rotationally split modes. We found these effects to be detectable in the observed frequency range. Analysis of the effects of rotation on small spacings and scaled small spacings reveals that these can be of the order of, or even larger than surface effects, typically turbulence, microscopic diffusion, etc. Furthermore, we show that scaled spacings are significantly affected by stellar distortion even for small stellar rotational velocities (from 10-15 km/s) and therefore some care must be taken when using them as indicators for probing deep stellar interiors.Comment: 10 pages,5 figures, accepted for publication in ApJ; http://iopscience.iop.org/0004-637X/721/1/537

Effects of Large-Scale Convection on p-mode Frequencies

We describe an approach for finding the eigenfrequencies of solar acoustic modes (p modes) in a convective envelope in the WKB limit. This approximation restricts us to examining the effects of fluid motions which are large compared to the mode wavelength, but allows us to treat the three-dimensional mode as a localized ray. The method of adiabatic switching is then used to investigate the frequency shifts resulting from simple perturbations to a polytropic model of the convection zone as well as from two basic models of a convective cell. We find that although solely depth-dependent perturbations can give frequency shifts which are first order in the strength of the perturbation, models of convective cells generate downward frequency shifts which are second order in the perturbation strength. These results may have implications for resolving the differences between eigenfrequencies derived from solar models and those found from helioseismic observations.Comment: 27 pages + 6 figures; accepted for publication in Ap

Prospects for asteroseismology

The observational basis for asteroseismology is being dramatically strengthened, through more than two years of data from the CoRoT satellite, the flood of data coming from the Kepler mission and, in the slightly longer term, from dedicated ground-based facilities. Our ability to utilize these data depends on further development of techniques for basic data analysis, as well as on an improved understanding of the relation between the observed frequencies and the underlying properties of the stars. Also, stellar modelling must be further developed, to match the increasing diagnostic potential of the data. Here we discuss some aspects of data interpretation and modelling, focussing on the important case of stars with solar-like oscillations.Comment: Proc. HELAS Workshop on 'Synergies between solar and stellar modelling', eds M. Marconi, D. Cardini & M. P. Di Mauro, Astrophys. Space Sci., in the press Revision: correcting abscissa labels on Figs 1 and