Gonadal function in males after chemotherapy for early-stage Hodgkin's lymphoma treated in four subsequent trials by the European Organisation for Research and Treatment of Cancer: EORTC Lymphoma Group and the Groupe d'Etude des Lymphomes de l'Adulte.

Contains fulltext : 51705.pdf (publisher's version ) (Open Access)PURPOSE: To analyze fertility in male patients treated with various combinations of radiotherapy and chemotherapy, with or without alkylating agents, or with radiotherapy alone for Hodgkin's lymphoma. PATIENTS AND METHODS: Follicle-stimulating hormone (FSH) levels were measured in patients with early-stage upper-diaphragmatic disease enrolled in four European Organisation for Research and Treatment of Cancer (EORTC) trials (H6-H9). Median follow-up after therapy was 32 months. Patients with FSH measurement at least 12 months after end of treatment (n = 355) were selected to assess post-treatment fertility. Patients with FSH measurement 0 to 9 months after therapy (n = 349) were selected to analyze fertility recovery; of these, patients with elevated FSH (> 10 U/L; n = 101) were followed until recovery. Factors predictive for therapy-related infertility were assessed by logistic regression. RESULTS: The proportion of elevated FSH was 3% and 8% in patients treated with radiotherapy only or with nonalkylating chemotherapy (doxorubicin, bleomycin, vinblastine, dacarbazine [ABVD], epirubicin, bleomycin, vinblastine, prednisone [EBVP]); it was 60% (P < .001) after chemotherapy containing alkylating agents (mechlorethamine, vincristine, procarbazine, prednisone [MOPP], MOPP/doxorubicin, bleomycin, vinblastine [ABV], bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone [BEACOPP]). After a median time of 19 months, recovery of fertility occurred in 82% of patients treated without alkylating chemotherapy. This proportion was 30%, statistically (P < .001) lower in those treated with alkylating chemotherapy, and median time to recovery was 27 months. The post-treatment proportion of elevated FSH increased significantly (P < .001) with the dose of alkylating chemotherapy administered, and recovery was less frequent and slower after higher doses. Age more than 50 years and stage II disease also contributed to poor outcome. CONCLUSION: Fertility can be secured after nonalkylating chemotherapy for Hodgkin's lymphoma. In contrast, alkylating chemotherapy has a dismal effect, even after a limited number of cycles

HST Imaging of the Ionizing Radiation from a Star-forming Galaxy at z = 3.794

We report on the HST detection of the Lyman-continuum (LyC) radiation emitted by a galaxy at redshift z=3.794, dubbed Ion1 (Vanzella et al. 2012). The LyC from Ion1 is detected at rest-frame wavelength 820$\sim$890 \AA with HST WFC3/UVIS in the F410M band ($m_{410}=27.60\pm0.36$ magnitude (AB), peak SNR = 4.17 in a circular aperture with radius r = 0.12'') and at 700$\sim$830 \AA with the VLT/VIMOS in the U-band ($m_U = 27.84\pm0.19$ magnitude (AB), peak SNR = 6.7 with a r = 0.6'' aperture). A 20-hr VLT/VIMOS spectrum shows low- and high-ionization interstellar metal absorption lines, the P-Cygni profile of CIV and Ly$\alpha$ in absorption. The latter spectral feature differs from what observed in known LyC emitters, which show strong Ly$\alpha$ emission. An HST far-UV color map reveals that the LyC emission escapes from a region of the galaxy that is bluer than the rest, presumably because of lower dust obscuration. The F410M image shows that the centroid of the LyC emission is offset from the centroid of the non-ionizing UV emission by 0.12''$\pm$0.03'', corresponding to 0.85$\pm$0.21 kpc (physical), and that its morphology is likely moderately resolved. These morphological characteristics favor a scenario where the LyC photons produced by massive stars escape from low HI column-density "cavities" in the ISM, possibly carved by stellar winds and/or supernova. We also collect the VIMOS U-band images of a sample of 107 Lyman-break galaxies with spectroscopic redshifts at $3.40<z<3.95$, i.e. sampling the LyC, and stack them with inverse-variance weights. No LyC emission is detected in the stacked image, resulting in a 32.5 magnitude (AB) flux limit (1$\sigma$) and an upper limit of absolute LyC escape fraction $f_{esc}^{abs} < 0.63\%$. LyC emitters like Ion1 are very likely at the bright-end of the LyC luminosity function.Comment: 24 pages, 13 figures, accepted for publication in Ap

IL-21 production by CD4+ effector T cells and frequency of circulating follicular helper T cells are increased in type 1 diabetes patients.

AIMS/HYPOTHESIS: Type 1 diabetes results from the autoimmune destruction of insulin-secreting pancreatic beta cells by T cells. Despite the established role of T cells in the pathogenesis of the disease, to date, with the exception of the identification of islet-specific T effector (Teff) cells, studies have mostly failed to identify reproducible alterations in the frequency or function of T cell subsets in peripheral blood from patients with type 1 diabetes. METHODS: We assessed the production of the proinflammatory cytokines IL-21, IFN-γ and IL-17 in peripheral blood mononuclear cells from 69 patients with type 1 diabetes and 61 healthy donors. In an additional cohort of 30 patients with type 1 diabetes and 32 healthy donors, we assessed the frequency of circulating T follicular helper (Tfh) cells in whole blood. IL-21 and IL-17 production was also measured in peripheral blood mononuclear cells (PBMCs) from a subset of 46 of the 62 donors immunophenotyped for Tfh. RESULTS: We found a 21.9% (95% CI 5.8, 40.2; p = 3.9 × 10(-3)) higher frequency of IL-21(+) CD45RA(-) memory CD4(+) Teffs in patients with type 1 diabetes (geometric mean 5.92% [95% CI 5.44, 6.44]) compared with healthy donors (geometric mean 4.88% [95% CI 4.33, 5.50]). Consistent with this finding, we found a 14.9% increase in circulating Tfh cells in the patients (95% CI 2.9, 26.9; p = 0.016). CONCLUSIONS/INTERPRETATION: These results indicate that increased IL-21 production is likely to be an aetiological factor in the pathogenesis of type 1 diabetes that could be considered as a potential therapeutic target.This work was supported by the JDRF UK Centre for Diabetes - Genes, Autoimmunity and Prevention (D-GAP; 4-2007-1003) in collaboration with M. Peakman and T. Tree at King’s College London, the JDRF, the Wellcome Trust (WT; WT061858/091157 and 083650/Z/07/Z) and the National Institute for Health Research Cambridge Biomedical Research Centre (CBRC). The Cambridge Institute for Medical Research (CIMR) is in receipt of a Wellcome Trust Strategic Award (100140). RCF is funded by a JDRF post-doctoral fellowship (3-2011-374). CW is funded by the Wellcome Trust (088998). The funding organisations had no involvement with the design and conduct of the study; collection,management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.This is the final published version. It first appeared at http://link.springer.com/article/10.1007%2Fs00125-015-3509-8

New neighbours. III. 21 new companions to nearby dwarfs, discovered with adaptive optics

We present some results of a CFHT adaptive optics search for companions to nearby dwarfs. We identify 21 new components in solar neighbourhood systems, of which 13 were found while surveying a volume-limited sample of M dwarfs within 12pc. We are obtaining complete observations for this subsample, to derive unbiased multiplicity statistics for the very-low-mass disk population. Additionally, we resolve for the first time 6 known spectroscopic or astrometric binaries, for a total of 27 newly resolved companions. A fair fraction of the new binaries has favourable parameters for accurate mass determinations. The newly resolved companion of Gl120.1C had an apparent spectroscopic minimum mass in the brown-dwarf range (Duquennoy & Mayor 1991) and it contributed to the statistical evidence that a few percent of solar type stars might have close-in brown-dwarf companions. We find that Gl~120.1C actually is an unrecognised double-lined spectroscopic pair. Its radial-velocity amplitude had therefore been strongly underestimated by Duquennoy & Mayor, and it does not truly belong to their sample of single-lined systems with minimum spectroscopic mass below the substellar limit. We also present the first direct detection of Gl~494B, an astrometric brown-dwarf candidate. Its luminosity does straddle the substellar limit, and it is a brown dwarf if its age is less than 300Myr. A few more years of observations will ascertain its mass and status from first principles.Comment: Accepted by Astronomy & Astrophysic