Les phlébotomes (Diptera-Psychodidae) de l'île de Chypre.II - Presence de Leishmania (Leishmania) infantum Nicolle, 1908 (zymodeme MON 1) chez Phlebotomus (Larroussius) tobbi Adler et Theodor, 1930

Dans le foyer leishmanien cypriote, les auteurs ont disseque 2910 femelles de phlebotomes appartenant a 11 especes : Phlebotomus papatasi, P. sergenti, P. jacusieli, P. alexandri, P. tobbi, P. galilaeus, P. mascittii, P. economidesi, Sergentomyia fallax, S. minuta et S. azizi . Les deux larroussius (P. galilaeus et P. tobbi ) sont les especes les plus abondantes. Elles representent plus de 60 % des captures realisees avec des pieges CDC. Des promastigotes ont ete observees chez un seul specimen appartenant a l'espece P. tobbi . Elles ont ete mises en culture puis identifiees selon la methode isoenzymatique. La souche de Leishmania isolee appartient a l'espece Leishmania infantum , zymodeme MON 1. Le meme zymodeme a ete aussi isole et identifie chez quatre chiens de l'ile. En l'absence des vecteurs habituels de L. infantum dans l'est mediterraneen (P. neglectus ef P. syriacus) et en raison de sa repartition a Chypre, P. tobbi constitue vraisemblablement un bon vecteur local. Sa faible anthropophilie expliquerait peut-etre le tres faible nombre de cas humains. Le role de P. galilaeus dans la transmission de la leishmaniose a Chypre reste a preciser

Evidence of pseudoprogression in patients treated with PD1/ PDL1 antibodies across tumor types

Background: PD(L)1 antibodies (anti-PD(L)-1) have been a major breakthrough in several types of cancer. Novel patterns of response and progression have been described with anti-PD(L)-1. We aimed at characterizing pseudoprogression (PSPD) among patients with various solid tumor types treated by anti-PD(L)-1. Methods: All consecutive patients (pts) enrolled in phase 1 trials with advanced solid tumors and lymphomas treated in phase I clinical trials evaluating monotherapy by anti-PD(L)-1 at Gustave Roussy were analyzed. We aimed to assess prevalence and outcome of PSPD across tumor types. We also intended to describe potential clinical and pathological factors associated with PSPD. Results: A total of 169 patients treated with anti-PD(L)-1 were included in the study. Most frequent tumor types included melanoma (n = 57) and non-small cell lung cancer (n = 19). At first tumor evaluation 77 patients (46%) presented with immune unconfirmed progressive disease. Six patients (8%) experienced PSPD: 2 patients with partial response; 4 patients with stable disease. Increase in target lesions in the first CT-scan was more frequently associated to PSPD (67% vs 33%; P = .04). Patients with a PSPD had a superior survival when compared to patients progressing (median OS: 10.7 months vs 8.7 months; P = .07). Conclusions: A small subset of PSPD patients may experience response after an initial progression. Assessment of the current strategy for immune-related response evaluations may require further attention

Performance status is the most powerful risk factor for early death among patients with advanced soft tissue sarcoma The European Organisation for Research and Treatment of Cancer – Soft Tissue and Bone Sarcoma Group (STBSG) and French Sarcoma Group (FSG) study

BACKGROUND: We investigated prognostic factors (PFs) for 90-day mortality in a large cohort of advanced/metastatic soft tissue sarcoma (STS) patients treated with first-line chemotherapy. METHODS: The PFs were identified by both logistic regression analysis and probability tree analysis in patients captured in the Soft Tissue and Bone Sarcoma Group (STBSG) database (3002 patients). Scores derived from the logistic regression analysis and algorithms derived from probability tree analysis were subsequently validated in an independent study cohort from the French Sarcoma Group (FSG) database (404 patients). RESULTS: The 90-day mortality rate was 8.6 and 4.5% in both cohorts. The logistic regression analysis retained performance status (PS; odds ratio (OR) = 3.83 if PS = 1, OR = 12.00 if PS >= 2), presence of liver metastasis (OR = 2.37) and rare site metastasis (OR = 2.00) as PFs for early death. The CHAID analysis retained PS as a major discriminator followed by histological grade (only for patients with PS >= 2). In both models, PS was the most powerful PF for 90-day mortality. CONCLUSION: Performance status has to be taken into account in the design of further clinical trials and is one of the most important parameters to guide patient management. For those patients with poor PS, expected benefits from therapy should be weighed up carefully against the anticipated toxicities. British Journal of Cancer (2011) 104, 1544-1550. doi: 10.1038/bjc.2011.136 www.bjcancer.com Published online 19 April 2011 (C) 2011 Cancer Research U

Characteristic mTOR activity in Hodgkin-lymphomas offers a potential therapeutic target in high risk disease – a combined tissue microarray, in vitro and in vivo study

BACKGROUND: Targeting signaling pathways is an attractive approach in many malignancies. The PI3K/Akt/mTOR pathway is activated in a number of human neoplasms, accompanied by lower overall and/or disease free survival. mTOR kinase inhibitors have been introduced in the therapy of renal cell carcinoma and mantle cell lymphoma, and several trials are currently underway. However, the pathological characterization of mTOR activity in lymphomas is still incomplete. METHODS: mTOR activity and the elements of mTOR complexes were investigated by immunohistochemistry on tissue microarrays representing different human non-Hodgkin-lymphomas (81 cases) and Hodgkin-lymphomas (87 cases). The expression of phospho-mTOR, phospho-4EBP1, phospho-p70S6K, phospho-S6, Rictor, Raptor and Bcl-2, Bcl-xL, Survivin and NF-kappaB-p50 were evaluated, and mTOR activity was statistically analyzed along with 5-year survival data. The in vitro and in vivo effect of the mTOR inhibitor rapamycin was also examined in human Hodgkin-lymphoma cell lines. RESULTS: The majority (>50%) of mantle cell lymphoma, Burkitt lymphoma, diffuse large B-cell lymphoma, anaplastic large-cell lymphoma and Hodgkin-lymphoma cases showed higher mTOR activity compared to normal lymphoid tissues. Hodgkin-lymphoma was characterized by high mTOR activity in 93% of the cases, and Bcl-xL and NF-kappaB expression correlated with this mTOR activity. High mTOR activity was observed in the case of both favorable and unfavorable clinical response. Low mTOR activity was accompanied by complete remission and at least 5-year disease free survival in Hodgkin-lymphoma patients. However, statistical analysis did not identify correlation beetween mTOR activity and different clinical data of HL patients, such as survival. We also found that Rictor (mTORC2) was not overexpressed in Hodgkin-lymphoma biopsies and cell lines. Rapamycin inhibited proliferation and induced apoptosis in Hodgkin-lymphoma cells both in vitro and in vivo, moreover, it increased the apoptotic effect of chemotherapeutic agents. CONCLUSIONS: Targeting mTOR activity may be a potential therapeutic tool in lymphomas. The presence of mTOR activity probably indicates that the inclusion of mTOR inhibition in the therapy of Hodgkin-lymphomas may be feasible and beneficial, especially when standard protocols are ineffective, and it may also allow dose reduction in order to decrease late treatment toxicity. Most likely, the combination of mTOR inhibitors with other agents will offer the highest efficiency for achieving the best clinical response

Consistent lensing and clustering in a low-S8 Universe with BOSS, DES Year 3, HSC Year 1, and KiDS-1000

We evaluate the consistency between lensing and clustering based on measurements from BOSS combined with galaxy-galaxy lensing from DES-Y3, HSC-Y1, KiDS-1000. We find good agreement between these lensing datasets. We model the observations using the Dark Emulator and fit the data at two fixed cosmologies: Planck (S 8 = 0.83), and a Lensing cosmology (S 8 = 0.76). For a joint analysis limited to large scales, we find that both cosmologies provide an acceptable fit to the data. Full utilisation of the higher signal-to-noise small-scale measurements is hindered by uncertainty in the impact of baryon feedback and assembly bias, which we account for with a reasoned theoretical error budget. We incorporate a systematic inconsistency parameter for each redshift bin, A, that decouples the lensing and clustering. With a wide range of scales, we find different results for the consistency between the two cosmologies. Limiting the analysis to the bins for which the impact of the lens sample selection is expected to be minimal, for the Lensing cosmology, the measurements are consistent with A=1; A = 0.91 ± 0.04 (A = 0.97 ± 0.06) using DES+KiDS (HSC). For the Planck case, we find a discrepancy: A = 0.79 ± 0.03 (A = 0.84 ± 0.05) using DES+KiDS (HSC). We demonstrate that a kSZ-based estimate for baryonic effects alleviates some of the discrepancy in the Planck cosmology. This analysis demonstrates the statistical power of small-scale measurements, but caution is still warranted given modelling uncertainties and foreground sample selection effects

Building an Efficient Cluster Cosmology Software Package for Modeling Cluster Counts and Lensing

We introduce a software suite developed for galaxy cluster cosmological analysis with the Dark Energy Survey Data. Cosmological analyses based on galaxy cluster number counts and weak-lensing measurements need efficient software infrastructure to explore an increasingly large parameter space, and account for various cosmological and astrophysical effects. Our software package is designed to model the cluster observables in a wide-field optical survey, including galaxy cluster counts, their averaged weak-lensing masses, or the cluster's averaged weak-lensing radial signals. To ensure maximum efficiency, this software package is developed in C++ in the CosmoSIS software framework, making use of the CUBA integration library. We also implement a testing and validation scheme to ensure the quality of the package. We demonstrate the effectiveness of this development by applying the software to the Dark Energy Survey Year 1 galaxy cluster cosmological data sets, and acquired cosmological constraints that are consistent with the fiducial Dark Energy Survey analysis

The effect of environment on Type Ia supernovae in the Dark Energy Survey three-year cosmological sample

Analyses of Type Ia supernovae (SNe Ia) have found puzzling correlations between their standardized luminosities and host galaxy properties: SNe Ia in high-mass, passive hosts appear brighter than those in lower mass, star-forming hosts. We examine the host galaxies of SNe Ia in the Dark Energy Survey 3-yr spectroscopically confirmed cosmological sample, obtaining photometry in a series of 'local' apertures centred on the SN, and for the global host galaxy. We study the differences in these host galaxy properties, such as stellar mass and rest-frame U - R colours, and their correlations with SN Ia parameters including Hubble residuals. We find all Hubble residual steps to be >3σ in significance, both for splitting at the traditional environmental property sample median and for the step of maximum significance. For stellar mass, we find a maximal local step of 0.098 ± 0.018 mag; ∼0.03 mag greater than the largest global stellar mass step in our sample (0.070 ± 0.017 mag). When splitting at the sample median, differences between local and global U - R steps are small, both ∼0.08 mag, but are more significant than the global stellar mass step (0.057 ± 0.017 mag). We split the data into sub-samples based on SN Ia light-curve parameters: stretch (x1) and colour (c), finding that redder objects (c > 0) have larger Hubble residual steps, for both stellar mass and U - R, for both local and global measurements, of ∼0.14 mag. Additionally, the bluer (star-forming) local environments host a more homogeneous SN Ia sample, with local U - R rms scatter as low as 0.084 ± 0.017 mag for blue (c < 0) SNe Ia in locally blue U - R environments

Measurement of the mean central optical depth of galaxy clusters via the pairwise kinematic Sunyaev-Zel'dovich effect with SPT-3G and des

We infer the mean optical depth of a sample of optically selected galaxy clusters from the Dark Energy Survey via the pairwise kinematic Sunyaev-Zel'dovich (KSZ) effect. The pairwise KSZ signal between pairs of clusters drawn from the Dark Energy Survey Year-3 cluster catalog is detected at 4.1σ in cosmic microwave background temperature maps from two years of observations with the SPT-3G camera on the South Pole Telescope. After cuts, there are 24,580 clusters in the ∼1,400 deg2 of the southern sky observed by both experiments. We infer the mean optical depth of the cluster sample with two techniques. The optical depth inferred from the pairwise KSZ signal is τ¯e=(2.97±0.73)×10-3, while that inferred from the thermal SZ signal is τ¯e=(2.51±0.55stat±0.15syst)×10-3. The two measures agree at 0.6σ. We perform a suite of systematic checks to test the robustness of the analysis