CT-based radiomic signature predicts distant metastasis in lung adenocarcinoma

BACKGROUND AND PURPOSE: Radiomics provides opportunities to quantify the tumor phenotype non-invasively by applying a large number of quantitative imaging features. This study evaluates computed-tomography (CT) radiomic features for their capability to predict distant metastasis (DM) for lung adenocarcinoma patients. MATERIAL AND METHODS: We included two datasets: 98 patients for discovery and 84 for validation. The phenotype of the primary tumor was quantified on pre-treatment CT-scans using 635 radiomic features. Univariate and multivariate analysis was performed to evaluate radiomics performance using the concordance index (CI). RESULTS: Thirty-five radiomic features were found to be prognostic (CI > 0.60, FDR < 5%) for DM and twelve for survival. It is noteworthy that tumor volume was only moderately prognostic for DM (CI=0.55, p-value=2.77 × 10(−5)) in the discovery cohort. A radiomic-signature had strong power for predicting DM in the independent validation dataset (CI=0.61, p-value=1.79 ×10(−17)). Adding this radiomic-signature to a clinical model resulted in a significant improvement of predicting DM in the validation dataset (p-value=1.56 × 10(−11)). CONCLUSIONS: Although only basic metrics are routinely quantified, this study shows that radiomic features capturing detailed information of the tumor phenotype can be used as a prognostic biomarker for clinically-relevant factors such as DM. Moreover, the radiomic-signature provided additional information to clinical data

CT-based radiomic signature predicts distant metastasis in lung adenocarcinoma

Background and Purpose: Radiomics provides opportunities to quantify the tumor phenotype non-invasively by applying a large number of quantitative imaging features. This study evaluates computed-tomography (CT) radiomic features for their capability to predict distant metastasis (DM) for lung adenocarcinoma patients. Material and Methods: We included two datasets: 98 patients for discovery and 84 for validation. The phenotype of the primary tumor was quantified on pre-treatment CT-scans using 635 radiomic features. Univariate and multivariate analysis was performed to evaluate radiomics performance using the concordance index (CI). Results: Thirty-five radiomic features were found to be prognostic (CI > 0.60, FDR < 5%) for DM and twelve for survival. It is noteworthy that tumor volume was only moderately prognostic for DM (CI=0.55, p-value=2.77 × 10−5) in the discovery cohort. A radiomic-signature had strong power for predicting DM in the independent validation dataset (CI=0.61, p-value=1.79 ×10−17). Adding this radiomic-signature to a clinical model resulted in a significant improvement of predicting DM in the validation dataset (p-value=1.56 × 10−11). Conclusions: Although only basic metrics are routinely quantified, this study shows that radiomic features capturing detailed information of the tumor phenotype can be used as a prognostic biomarker for clinically-relevant factors such as DM. Moreover, the radiomic-signature provided additional information to clinical data

Pairing in nuclear systems: from neutron stars to finite nuclei

We discuss several pairing-related phenomena in nuclear systems, ranging from superfluidity in neutron stars to the gradual breaking of pairs in finite nuclei. We focus on the links between many-body pairing as it evolves from the underlying nucleon-nucleon interaction and the eventual experimental and theoretical manifestations of superfluidity in infinite nuclear matter and of pairing in finite nuclei. We analyse the nature of pair correlations in nuclei and their potential impact on nuclear structure experiments. We also describe recent experimental evidence that points to a relation between pairing and phase transitions (or transformations) in finite nuclear systems. Finally, we discuss recent investigations of ground-state properties of random two-body interactions where pairing plays little role although the interactions yield interesting nuclear properties such as 0+ ground states in even-even nuclei.Comment: 74 pages, 33 figs, uses revtex4. Submitted to Reviews of Modern Physic

Time to culture positivity and sputum smear microscopy during tuberculosis therapy.

Sputum smear microscopy is widely used for tuberculosis diagnosis and treatment monitoring. We evaluated the correlation between smear microscopy and time to liquid culture positivity during early tuberculosis treatment. The study included patients with smear-positive pulmonary tuberculosis hospitalized at a tuberculosis reference centre in Germany between 01/2012 and 05/2013. Patient records were reviewed and clinical, radiological and microbiological data were analysed. Sputum samples were collected before treatment initiation and weekly thereafter. A number of 310 sputum samples from 30 patients were analysed. Time to liquid culture positivity inversely correlated with smear grade (Spearman's rho -0.439, p<0.001). There was a better correlation within the first two months vs. after two months of therapy (-0.519 vs. -0.416) with a trend to a more rapid increase in time to positivity between baseline and week 2 in patients who culture-converted within the first two months (5.9 days vs. 9.4 days, p = 0.3). In conclusion, the numbers of acid-fast bacilli in sputum smears of patients with pulmonary tuberculosis and time to culture positivity for M. tuberculosis cultures from sputum are correlated before and during tuberculosis treatment. A considerable proportion of patients with culture conversion after two months of therapy continued to have detectable acid-fast bacilli on sputum smears

Profit enhancing competitive pressure in vertically related industries

Coevolution of viruses and their hosts represents a dynamic molecular battle between the immune system and viral factors that mediate immune evasion. After the abandonment of smallpox vaccination, cowpox virus infections are an emerging zoonotic health threat, especially for immunocompromised patients. Here we delineate the mechanistic basis of how cowpox viral CPXV012 interferes with MHC class I antigen processing. This type II membrane protein inhibits the coreTAP complex at the step after peptide binding and peptide-induced conformational change, in blocking ATP binding and hydrolysis. Distinct from other immune evasion mechanisms, TAP inhibition is mediated by a short ER-lumenal fragment of CPXV012, which results from a frameshift in the cowpox virus genome. Tethered to the ER membrane, this fragment mimics a high ER-lumenal peptide concentration, thus provoking a trans-inhibition of antigen translocation as supply for MHC I loading. These findings illuminate the evolution of viral immune modulators and the basis of a fine-balanced regulation of antigen processing

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Decoding the land, modeling the landscape. Robert Smithson, the Nonsites and the Geosciences : a model for the relationship between Art and Science in resonance with the works of Giuseppe Penone and Olafur Eliasson.

Construite sur une analyse approfondie des archives de Robert Smithson, cette thèse réévalue la série des Nonsites (1967-1969) dans sa relation d'inspiration avec les Géosciences. Elle rappelle le contexte culturel des années soixante comme toile de fond pour l’inspiration de l’artiste et détermine l’envergure de son expertise dans le domaine des sciences. Des documents préparatoires inédits viennent éclairer son processus de création et la manière dont il formule ses œuvres complexes, à partir des sources géologiques, de l'information scientifique et de la muséographie. La relation entre arts et sciences apparaît centrale dans l’élaboration des Nonsites. Chaque œuvre de la série est ainsi rattachée à ses sources artistiques et scientifiques et révèle le moment historique de l’émergence de la sculpture post-minimale. Le jeu de l’espace muséal avec la tridimensionnalité est alors enrichi par le déploiement de strates d’informations contextuelles et crée les prémices d’une interaction nouvelle entre œuvre et spectateur.De plus, deux perspectives ouvertes sur un choix d'œuvres de Giuseppe Penone et Olafur Eliasson démontrent comment leurs démarches artistiques sont en résonance avec les préoccupations créatives de Smithson. Il est ainsi possible de problématiser l’expédition scientifique de terrain (et la manière de penser le territoire qui lui préexiste), ainsi que les agencements muséographiques en art comme en sciences comme sources déterminantes dans la confluence de l’art et des sciences.Based on a thorough analysis of Robert Smithson's archives, this dissertation re-evaluates the Nonsites series (1967-1969) in its inspirational relationship with the Geosciences. It recalls the cultural context of the sixties as a backdrop for the artist's inspiration and determines the scope of his expertise in the field of science. Unpublished preparatory documents enlighten his creative process and the way he formulates his complex works from geological sources, scientific information and museography. The relationship between arts and sciences is central to the development of the Nonsites. Each work in the series is thus linked to its artistic and scientific sources and reveals the spectacular historical moment of the emergence of post-minimalist sculpture. The play between the museum space and three-dimensionality is then enriched by the deployment of layers of contextual information and provides the basis for a new interaction between viewer and artwork.In addition, two perspectives are drawn towards the work of Giuseppe Penone and Olafur Eliasson and demonstrate how their artistic approaches resonate with Smithson's creative concerns. It is thus possible to problematize the scientific field expedition (and the analysis of the territory, its prerequisite), as well as the museographic arrangements, as determining sources in the confluence of art and science

Insights into Social Inequality. A Quantitative Study of Neolithic to Early Medieval Societies in Southwest Germany

Social inequality is a subject of contemporary concerns. Life capabilities and the access to resources vary significantly in rich and poor countries, between elites and others. Furthermore, inequalities based on bio-anthropological and non-bio-anthropological causes are almost universal. Accordingly, inequality was also inherent in past societies and archaeologists have continually examined and interpreted social inequalities in sources such as burial grounds. This book continues such analyses with a new multi-proxy approach. It reveals social inequalities in selected past burial grounds from Southwestern Germany. The burial grounds date to the Early Neolithic (Schwetzingen), the Final Neolithic (Lauda-Königshofen), the Early Bronze Age (Singen), the Early Iron Age (Magdalenenbergle), and the Early Medieval period (Horb-Altheim). The challenge was to identify hierarchical and heterarchical differences and inequalities within the burial grounds based on a multitude of different proxies. The examination encompasses variations in the distribution of grave goods, burial pit sizes, as well as bio-anthropological and isotope data. Furthermore, spatial analyses of burial grounds and, in particular, on the distances between the graves play an essential role in this examination. The results reveal social inequalities among and within genders and age cohorts that are differently pronounced in the respective cemeteries. Furthermore, the results of multi-proxy analyses lead to the interpretation that the sites differ concerning the respective degrees of inequality and power strategy modes. In detail, it can be observed that the Early Iron Age and the Early Bronze Age sites demonstrate a relatively high degree of inequality as compared to the other sites. More specifically, the investigation of sites from the Early Iron Age and the Final Neolithic rather reveal a network-based power strategy, whereas sites from the Early Neolithic, the Early Bronze Age and the Early Medieval period tend to show a corporate-based power strategy