Expression of oncoproteins and the amount of eosinophilic and lymphocytic infiltrates can be used as prognostic factors in gastric cancer. Dutch Gastric Cancer Group (DGCG).

Preoperative staging of gastric cancer is difficult. Several molecular markers associated with initiation and progression of cancer seem promising for obtaining preoperative prognostic information. To investigate whether these markers are indicative especially for the presence of lymph node metastases in patients with gastric cancer, we have examined primary tumour specimens from 105 patients with primary adenocarcinoma of the stomach entered in a surgical trial. In this trial, lymph node status was determined by strictly quality-controlled lymph node dissection and examination. The selected markers were growth regulators (p53, Rb and myc), metastasis-suppressor gene product (nm23), adhesion molecules (Ep-CAM, E-cadherin, CD44v5 and CD44v6) and urokinase-type plasminogen activator (u-PA). Also, the amount of eosinophilic and lymphocytic infiltrates available post-operatively was analysed with respect to its prognostic value for lymph node status. Moreover, the association of these parameters with survival and disease-free period (DFP) was evaluated. Of all molecular markers investigated, only Rb expression had a significant association with the presence of lymph node metastasis in both univariate and multivariate analysis. For curative resectability, a significant association was found with Rb and E-cadherin expression, while in multivariate analysis Rb and myc were selected as the combination with additional independent prognostic value, and E-cadherin had no additional independent value. For overall survival in univariate analysis, the amount of both eosinophilic and lymphocytic infiltrates and Rb and myc expression were of significant prognostic value. Only the amount of lymphocytic infiltrate had a prognostic significance for DFP. In stepwise multivariate analysis, TNM stage (I + II) and marked lymphocytic infiltrate were associated with better overall survival and longer DFP. We conclude that, if these results are confirmed in a larger series of patients, molecular markers can provide useful prognostic information

The unusual ISM in blue and dusty gas-rich galaxies (BADGRS)

The Herschel-ATLAS unbiased survey of cold dust in the local Universe is dominated by a surprising population of very blue (FUV-K 0.5 fHI=MHI/(M∗+M+HI)>0.5 ). Dubbed ‘Blue and Dusty Gas-Rich Sources’ (BADGRS) they have cold diffuse dust temperatures, and the highest dust-to-stellar mass ratios of any galaxies in the local Universe. Here, we explore the molecular interstellar medium in a representative sample of BADGRS, using very deep CO(J up =1,2,3) CO(Jup=1,2,3) observations across the central and outer disc regions. We find very low CO brightnesses (Tp = 5–30 mK), despite the bright far-infrared emission and metallicities in the range 0.5 < Z/Z⊙ < 1.0. The CO line ratios indicate a range of conditions with R 21 =T 21 b /T 10 b =0.6−2.1 R21=Tb21/Tb10=0.6−2.1 and R 31 =T 32 b /T 10 b =0.2−1.2 R31=Tb32/Tb10=0.2−1.2 . Using a metallicity-dependent conversion from CO luminosity to molecular gas mass, we find M H 2 /M d ∼7−27 MH2/Md∼7−27 and Σ H 2 =0.5−6M ⊙ pc −2 ΣH2=0.5−6M⊙pc−2 , around an order of magnitude lower than expected. The BADGRS have lower molecular gas depletion time-scales (τd ∼ 0.5 Gyr) than other local spirals, lying offset from the Kennicutt–Schmidt relation by a similar factor to Blue Compact Dwarf galaxies. The cold diffuse dust temperature in BADGRS (13–16 K) requires an interstellar radiation field 10–20 times lower than that inferred from their observed surface brightness. We speculate that the dust in these sources has either a very clumpy geometry or a very different opacity in order to explain the cold temperatures and lack of CO emission. BADGRS also have low UV attenuation for their UV colour suggestive of an SMC-type dust attenuation curve, different star formation histories or different dust/star geometry. They lie in a similar part of the IRX-β space as z z ∼ 5 galaxies and may be useful as local analogues for high gas fraction galaxies in the early Universe

DustPedia: Multiwavelength photometry and imagery of 875 nearby galaxies in 42 ultraviolet-microwave bands

Aims. The DustPedia project is capitalising on the legacy of the Herschel Space Observatory, using cutting-edge modelling techniques to study dust in the 875 DustPedia galaxies – representing the vast majority of extended galaxies within 3000 km s-1 that were observed by Herschel. This work requires a database of multiwavelength imagery and photometry that greatly exceeds the scope (in terms of wavelength coverage and number of galaxies) of any previous local-Universe survey. Methods. We constructed a database containing our own custom Herschel reductions, along with standardised archival observations from GALEX, SDSS, DSS, 2MASS, WISE, Spitzer, and Planck. Using these data, we performed consistent aperture-matched photometry, which we combined with external supplementary photometry from IRAS and Planck. Results. We present our multiwavelength imagery and photometry across 42 UV-microwave bands for the 875 DustPedia galaxies. Our aperture-matched photometry, combined with the external supplementary photometry, represents a total of 21 857 photometric measurements. A typical DustPedia galaxy has multiwavelength photometry spanning 25 bands. We also present the Comprehensive & Adaptable Aperture Photometry Routine (CAAPR), the pipeline we developed to carry out our aperture-matched photometry. CAAPR is designed to produce consistent photometry for the enormous range of galaxy and observation types in our data. In particular, CAAPR is able to determine robust cross-compatible uncertainties, thanks to a novel method for reliably extrapolating the aperture noise for observations that cover a very limited amount of background. Our rich database of imagery and photometry is being made available to the community

Prednisone vs methotrexate in treatment naïve cardiac sarcoidosis

Background: Side effects limit the long-term use of glucocorticoids in cardiac sarcoidosis (CS), and methotrexate has gained attention as steroid sparing agent although the supporting evidence is poor. This study compared prednisone monotherapy, methotrexate monotherapy or a combination of both, in the reduction of myocardial Fluorine-18 fluorodeoxyglucose (FDG) uptake and clinical stabilization of CS patients. Methods and results: In this retrospective cohort study, 61 newly diagnosed and treatment naïve CS patients commenced treatment with prednisone (N = 21), methotrexate (N = 30) or prednisone and methotrexate (N = 10) between January 2010 and December 2017. Primary outcome was metabolic response on FDG PET/CT and secondary outcomes were treatment patterns, major adverse cardiovascular events, left ventricular ejection fraction, biomarkers and side effects. At a median treatment duration of 6.2 [5.7-7.2] months, 71.4% of patients were FDG PET/CT responders, and the overall myocardial maximum standardized uptake value decreased from 6.9 [5.0-10.1] to 3.4 [2.1-4.7] (P < 0.001), with no significant differences between treatment groups. During 24 months of follow-up, 7 patients (33.3%; prednisone), 6 patients (20.0%; methotrexate) and 1 patient (10.0%; combination group) experienced at least one major adverse cardiovascular event (P = 0.292). Left ventricular ejection fraction was preserved in all treatment groups. Conclusions: Significant suppression of cardiac FDG uptake occurred in CS patients after 6 months of prednisone, methotrexate or combination therapy. There were no significant differences in clinical outcomes during follow-up. These results warrant further investigation of methotrexate treatment in CS patients

Dependence of Intramyocardial Pressure and Coronary Flow on Ventricular Loading and Contractility: A Model Study

The phasic coronary arterial inflow during the normal cardiac cycle has been explained with simple (waterfall, intramyocardial pump) models, emphasizing the role of ventricular pressure. To explain changes in isovolumic and low afterload beats, these models were extended with the effect of three-dimensional wall stress, nonlinear characteristics of the coronary bed, and extravascular fluid exchange. With the associated increase in the number of model parameters, a detailed parameter sensitivity analysis has become difficult. Therefore we investigated the primary relations between ventricular pressure and volume, wall stress, intramyocardial pressure and coronary blood flow, with a mathematical model with a limited number of parameters. The model replicates several experimental observations: the phasic character of coronary inflow is virtually independent of maximum ventricular pressure, the amplitude of the coronary flow signal varies about proportionally with cardiac contractility, and intramyocardial pressure in the ventricular wall may exceed ventricular pressure. A parameter sensitivity analysis shows that the normalized amplitude of coronary inflow is mainly determined by contractility, reflected in ventricular pressure and, at low ventricular volumes, radial wall stress. Normalized flow amplitude is less sensitive to myocardial coronary compliance and resistance, and to the relation between active fiber stress, time, and sarcomere shortening velocity

JINGLE – IV. Dust, H I gas and metal scaling laws in the local Universe

Scaling laws of dust, Hi gas and metal mass with stellar mass, specific star formation rate and metallicity are crucial to our understanding of the buildup of galaxies through their enrichment with metals and dust. In this work, we analyse how the dust and metal content varies with specific gas mass (MHI/M?) across a diverse sample of 423 nearby galaxies. The observed trends are interpreted with a set of Dust and Element evolUtion modelS (DEUS) – including stellar dust production, grain growth, and dust destruction – within a Bayesian framework to enable a rigorous search of the multi-dimensional parameter space. We find that these scaling laws for galaxies with −1.0 . logMHI/M? . 0 can be reproduced using closed-box models with high fractions (37-89%) of supernova dust surviving a reverse shock, relatively low grain growth efficiencies (=30-40), and long dust lifetimes (1-2Gyr). The models have present-day dust masses with similar contributions from stellar sources (50-80%) and grain growth (20-50%). Over the entire lifetime of these galaxies, the contribution from stardust (>90%) outweighs the fraction of dust grown in the interstellar medium (<10%). Our results provide an alternative for the chemical evolution models that require extremely low supernova dust production efficiencies and short grain growth timescales to reproduce local scaling laws, and could help solving the conundrum on whether or not grains can grow efficiently in the interstellar medium

Risk factors for atherosclerotic and medial arterial calcification of the intracranial internal carotid artery

_Background and aims:_ Calcifications of the intracranial internal carotid artery (iICA) are an important risk factor for stroke. The calcifications can occur both in the intimal and medial layer of the vascular wall. The aim of this study is to assess whether medial calcification in the iICA is differently related to risk factors for cardiovascular disease, compared to intimal calcification. _Methods:_ Unenhanced thin slice computed tomography (CT) scans from 1132 patients from the Dutch acute stroke study cohort were assessed for dominant localization of calcification (medial or intimal) by one of three observers based on established methodology. Associations between known cardiovascular risk factors (age, gender, body mass index, pulse pressure, eGFR, smoking, hypertension, diabetes mellitus, hyperlipidemia, previous vascular disease, and family history) and the dominant localization of calcifications were assessed via logistic regression analysis. _Results:_ In the 1132 patients (57% males, mean age 67.4 years [SD 13.8]), dominant intimal calcification was present in 30.9% and dominant medial calcification in 46.9%. In 10.5%, no calcification was seen. Age, pulse pressure and family history were risk factors for both types of calcification. Multivariably adjusted risk factors for dominant intimal calcification only were smoking (OR 2.09 [CI 1.27–3.44]) and hypertension (OR 2.09 [CI 1.29–3.40]) and for dominant medial calcification diabetes mellitus (OR 2.39 [CI 1.11–5.14]) and previous vascular disease (OR 2.20 [CI 1.30–3.75]). _Conclusions:_ Risk factors are differently related to the dominant localizations of calcifications, a finding that supports the hypothesis that the intimal and medial calcification represents a distinct etiology

Development and Internal Validation of a Novel Nomogram Predicting the Outcome of Salvage Radiation Therapy for Biochemical Recurrence after Radical Prostatectomy in Patients without Metastases on Restaging Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography

BACKGROUND AND OBJECTIVE: Owing to the greater use of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) in patients with biochemical recurrence (BCR) of prostate cancer (PCa) after robot-assisted radical prostatectomy (RARP), patient selection for local salvage radiation therapy (sRT) has changed. Our objective was to determine the short-term efficacy of sRT in patients with BCR after RARP, and to develop a novel nomogram predicting BCR-free survival after sRT in a nationwide contemporary cohort of patients who underwent PSMA PET/CT before sRT for BCR of PCa, without evidence of metastatic disease.METHODS: All 302 eligible patients undergoing PCa sRT in four reference centers between September 2015 and August 2020 were included. We conducted multivariable logistic regression analysis using a backward elimination procedure to develop a nomogram for predicting biochemical progression of PCa, defined as prostate-specific antigen (PSA) ≥0.2 ng/ml above the post-sRT nadir within 1 yr after sRT.KEY FINDINGS AND LIMITATIONS: Biochemical progression of disease within 1 yr after sRT was observed for 56/302 (19%) of the study patients. The final predictive model included PSA at sRT initiation, pathological grade group, surgical margin status, PSA doubling time, presence of local recurrence on PSMA PET/CT, and the presence of biochemical persistence (first PSA result ≥0.1 ng/ml) after RARP. The area under the receiver operating characteristic curve for this model was 0.72 (95% confidence interval 0.64-0.79). Using our nomogram, patients with a predicted risk of &gt;20% had a 30.8% chance of developing biochemical progression within 1 yr after sRT.CONCLUSIONS: Our novel nomogram may facilitate better patient counseling regarding early oncological outcome after sRT. Patients with high risk of biochemical progression may be candidates for more extensive treatment.PATIENT SUMMARY: We developed a new tool for predicting cancer control outcomes of radiotherapy for patients with recurrence of prostate cancer after surgical removal of their prostate. This tool may help in better counseling of these patients with recurrent cancer regarding their early expected outcome after radiotherapy.</p

GAMA/H-ATLAS: the local dust mass function and cosmic density as a function of galaxy type - a benchmark for models of galaxy evolution

We present the dust mass function (DMF) of 15,750 galaxies with redshift z < 0:1, drawn from the overlapping area of the GAMA and H-ATLAS surveys. The DMF is derived using the density corrected Vmax method, where we estimate Vmax using: (i) the normal photometric selection limit (pVmax) and (ii) a bivariate brightness distribution (BBD) technique, which accounts for two selection effects. We fit the data with a Schechter function, and find M* = (4:65 ± 0.18) × 10^7 h^2/70 Mo, α = (-1.22 ± 0:01), Φ*= (6.26 ± 0.28) × 10^-3 h^3/70 Mpc^-3 dex^-1. The resulting dust mass density parameter integrated down to 10^4 M☉ is Ωd = (1.11 ± 0.02) × 10^-6 which implies the mass fraction of baryons in dust is fmb = (2.40 ± 0.04) × 10^-5; cosmic variance adds an extra 7-17 per cent uncertainty to the quoted statistical errors. Our measurements have fewer galaxies with high dust mass than predicted by semi-analytic models. This is because the models include too much dust in high stellar mass galaxies. Conversely, our measurements find more galaxies with high dust mass than predicted by hydrodynamical cosmological simulations. This is likely to be from the long timescales for grain growth assumed in the models. We calculate DMFs split by galaxy type and find dust mass densities of Ωd = (0.88 ± 0.03) × 10^-6 and Ωd = (0.060 ± 0.005) × 10^-6 for late-types and early-types respectively. Comparing to the equivalent galaxy stellar mass functions (GSMF) we find that the DMF for late-types is well matched by the GMSF scaled by (8.07 ± 0.35) × 10^-4

Development and Internal Validation of a Novel Nomogram Predicting the Outcome of Salvage Radiation Therapy for Biochemical Recurrence after Radical Prostatectomy in Patients without Metastases on Restaging Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography

BACKGROUND AND OBJECTIVE: Owing to the greater use of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) in patients with biochemical recurrence (BCR) of prostate cancer (PCa) after robot-assisted radical prostatectomy (RARP), patient selection for local salvage radiation therapy (sRT) has changed. Our objective was to determine the short-term efficacy of sRT in patients with BCR after RARP, and to develop a novel nomogram predicting BCR-free survival after sRT in a nationwide contemporary cohort of patients who underwent PSMA PET/CT before sRT for BCR of PCa, without evidence of metastatic disease.METHODS: All 302 eligible patients undergoing PCa sRT in four reference centers between September 2015 and August 2020 were included. We conducted multivariable logistic regression analysis using a backward elimination procedure to develop a nomogram for predicting biochemical progression of PCa, defined as prostate-specific antigen (PSA) ≥0.2 ng/ml above the post-sRT nadir within 1 yr after sRT.KEY FINDINGS AND LIMITATIONS: Biochemical progression of disease within 1 yr after sRT was observed for 56/302 (19%) of the study patients. The final predictive model included PSA at sRT initiation, pathological grade group, surgical margin status, PSA doubling time, presence of local recurrence on PSMA PET/CT, and the presence of biochemical persistence (first PSA result ≥0.1 ng/ml) after RARP. The area under the receiver operating characteristic curve for this model was 0.72 (95% confidence interval 0.64-0.79). Using our nomogram, patients with a predicted risk of &gt;20% had a 30.8% chance of developing biochemical progression within 1 yr after sRT.CONCLUSIONS: Our novel nomogram may facilitate better patient counseling regarding early oncological outcome after sRT. Patients with high risk of biochemical progression may be candidates for more extensive treatment.PATIENT SUMMARY: We developed a new tool for predicting cancer control outcomes of radiotherapy for patients with recurrence of prostate cancer after surgical removal of their prostate. This tool may help in better counseling of these patients with recurrent cancer regarding their early expected outcome after radiotherapy.</p