The Next Generation of Axion Helioscopes: The International Axion Observatory (IAXO)

The International Axion Observatory (IAXO) is a proposed 4th-generation axion helioscope with the primary physics research goal to search for solar axions via their Primakoff conversion into photons of 1 \u2013 10 keV energies in a strong magnetic field. IAXO will achieve a sensitivity to the axion-photon coupling ga\u3b3 down to a few 710 1212 GeV 121 for a wide range of axion masses up to 3c 0.25 eV. This is an improvement over the currently best (3rd generation) axion helioscope, the CERN Axion Solar Telescope (CAST), of about 5 orders of magnitude in signal strength, corresponding to a factor 3c 20 in the axion photon coupling. IAXO's sensitivity relies on the construction of a large superconducting 8-coil toroidal magnet of 20 m length optimized for axion research. Each of the eight 60 cm diameter magnet bores is equipped with x-ray optics focusing the signal photons into 3c 0.2 cm2 spots that are imaged by very low background x-ray detectors. The magnet will be built into a structure with elevation and azimuth drives that will allow solar tracking for 12 hours each day. This contribution is a summary of our papers [1], [2] and [3] and we refer to these for further details

Preliminary safety and efficacy of first-line pertuzumab combined with trastuzumab and taxane therapy for HER2-positive locally recurrent or metastatic breast cancer (PERUSE).

BACKGROUND: Pertuzumab combined with trastuzumab and docetaxel is the standard first-line therapy for HER2-positive metastatic breast cancer, based on results from the phase III CLEOPATRA trial. PERUSE was designed to assess the safety and efficacy of investigator-selected taxane with pertuzumab and trastuzumab in this setting. PATIENTS AND METHODS: In the ongoing multicentre single-arm phase IIIb PERUSE study, patients with inoperable HER2-positive advanced breast cancer (locally recurrent/metastatic) (LR/MBC) and no prior systemic therapy for LR/MBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab [8\u2009mg/kg loading dose, then 6\u2009mg/kg every 3\u2009weeks (q3w)] and pertuzumab (840\u2009mg loading dose, then 420\u2009mg q3w) until disease progression or unacceptable toxicity. The primary end point was safety. Secondary end points included overall response rate (ORR) and progression-free survival (PFS). RESULTS: Overall, 1436 patients received at least one treatment dose (initially docetaxel in 775 patients, paclitaxel in 589, nab-paclitaxel in 65; 7 discontinued before starting taxane). Median age was 54\u2009years; 29% had received prior trastuzumab. Median treatment duration was 16\u2009months for pertuzumab and trastuzumab and 4\u2009months for taxane. Compared with docetaxel-containing therapy, paclitaxel-containing therapy was associated with more neuropathy (all-grade peripheral neuropathy 31% versus 16%) but less febrile neutropenia (1% versus 11%) and mucositis (14% versus 25%). At this preliminary analysis (52 months' median follow-up), median PFS was 20.6 [95% confidence interval (CI) 18.9-22.7] months overall (19.6, 23.0 and 18.1\u2009months with docetaxel, paclitaxel and nab-paclitaxel, respectively). ORR was 80% (95% CI 78%-82%) overall (docetaxel 79%, paclitaxel 83%, nab-paclitaxel 77%). CONCLUSIONS: Preliminary findings from PERUSE suggest that the safety and efficacy of first-line pertuzumab, trastuzumab and taxane for HER2-positive LR/MBC are consistent with results from CLEOPATRA. Paclitaxel appears to be a valid alternative taxane backbone to docetaxel, offering similar PFS and ORR with a predictable safety profile. CLINICALTRIALS.GOV: NCT01572038

Brief Report - Extended Interval between Enzyme Therapy Infusions for Adult Patients with Gaucher's Disease Type 1

BACKGROUND: Enzyme replacement therapy (ERT) for Gaucher's disease with alglucerase or imiglucerase is efficacious, well-tolerated and safe. However, cost considerations, visits to medical facilities, potentially duration of theray for life, are issues of major concern to a proportion of treated patients and has, in some cases, led to the withdrawal of therapy. AIMS: To elucidate whether an extension of the interval between enzyme infusions to once every three weeks is as effective in maintaining the clinical responses achieved with the bi-monthly regimen. MATERIALS AND METHODS: Four patients with an optimal response to ERT (at 30 units/kg every two weeks for an average of 27 months), were subjected to enzyme dose/frequency changes that essentially constituted a reduction in cumulative dose over the treatment period. Patients were assessed every 6 months for alterations in haematological parameters, plasma chitotriosidase levels, liver and spleen size, and bone symptoms. RESULTS: All patients had to resume the previous infusion schedule of once every two weeks; one because of new bone marrow infiltrates, two because of visceral enlargement, and the fourth due to progressive anaemia. CONCLUSIONS: This limited experience suggests that a reduction in enzyme dose associated with an extended interval between infusions may lead to variable disease control, and underscores the need for individualization of enzyme therapy. (J Postgrad Med 2003;49:127-131

Placebo effect characteristics observed in a single, international, longitudinal study in Huntington's disease.

Item does not contain fulltextBACKGROUND: Classically, clinical trials are based on the placebo-control design. Our aim was to analyze the placebo effect in Huntington's disease. METHODS: Placebo data were obtained from an international, longitudinal, placebo-controlled trial for Huntington's disease (European Huntington's Disease Initiative Study Group). One-hundred and eighty patients were evaluated using the Unified Huntington Disease Rating Scale over 36 months. A placebo effect was defined as an improvement of at least 50% over baseline scores in the Unified Huntington Disease Rating Scale, and clinically relevant when at least 10% of the population met it. RESULTS: Only behavior showed a significant placebo effect, and the proportion of the patients with placebo effect ranged from 16% (first visit) to 41% (last visit). Nondepressed patients with better functional status were most likely to be placebo-responders over time. CONCLUSIONS: In Huntington's disease, behavior seems to be more vulnerable to placebo than overall motor function, cognition, and function1 maart 201

Results and perspectives of the solar axion search with the CAST experiment

The status of the solar axion search with the CERN Axion Solar Telescope (CAST) will be presented. Recent results obtained by the use of 3He as a buffer gas has allowed us to extend our sensitivity to higher axion masses than our previous measurements with 4He. With about 1 h of data taking at each of 252 different pressure settings we have scanned the axion mass range 0.39 eV 64ma 64 0.64 eV. From the absence of an excess of x rays when the magnet was pointing to the Sun we set a typical upper limit on the axion-photon coupling of ga\u3b3 642.3 710 1210 GeV 121 at 95% C.L., the exact value depending on the pressure setting. CAST published results represent the best experimental limit on the photon couplings to axions and other similar exotic particles dubbed WISPs (Weakly Interacting Slim Particles) in the considered mass range and for the first time the limit enters the region favored by QCD axion models. Preliminary sensitivities for axion masses up to 1.16 eV will also be shown reaching mean upper limits on the axion-photon coupling of ga\u3b3 643.5 710 1210 GeV 121 at 95% C.L. Expected sensibilities for the extension of the CAST program up to 2014 will be presented. Moreover long term options for a new helioscope experiment will be evoked

TOI-1442 b and TOI-2445 b: two ultra-short period super-Earths around M dwarfs

Context. Exoplanets with orbital periods of less than one day are know as Ultra-short period (USP) planets. They are relatively rare products of planetary formation and evolution processes, but especially favourable to current planet detection methods. At the time of writing, 120 USP planets have already been confirmed. Aims. We aim to confirm the planetary nature of two new transiting planet candidates announced by the NASA's Transiting Exoplanet Survey Satellite (TESS), registered as TESS Objects of Interest (TOIs) TOI-1442.01 and TOI-2445.01. Methods. We use the TESS data, ground-based photometric light-curves and Subaru/IRD spectrograph radial velocity (RV) measurements to validate both planetary candidates and to establish their physical properties. Results. TOI-1442 b is a hot super-Earth with an orbital period of $P = 0.4090682 \pm 0.0000004 \, d$, a radius of $R_{\mathrm{p}} = 1.15 \pm 0.06 \, R_{\oplus}$, equilibrium temperature of $T_{\mathrm{p,eq}} = 1357_{-42}^{+49} \, K$, and a mass $M_{\mathrm{p}} < 18 \, M_{\oplus}$ at 3$\sigma$. TOI-2445 b is also a hot super-Earth/mini-Neptune with an orbital period of $P = 0.3711286 \pm 0.0000004 \, d$, a radius of $R_{\mathrm{p}} = 1.33 \pm 0.09 \, R_{\oplus}$, equilibrium temperature of $T_{\mathrm{p,eq}} = 1330_{-56}^{+61} \, K$, and a mass $M_{\mathrm{p}} < 38 \, M_{\oplus}$ at 3$\sigma$. Their physical properties align with current empirical trends and formation theories of USP planets. More RV measurements will be useful to constrain the planetary masses and mean densities, as well as the predicted presence of outer planetary companions

Conceptual design of the International Axion Observatory (IAXO)

The International Axion Observatory (IAXO) will be a forth generation axion helioscope. As its primary physics goal, IAXO will look for axions or axion-like particles (ALPs) originating in the Sun via the Primakoff conversion of the solar plasma photons. In terms of signal-to-noise ratio, IAXO will be about 4\u20135 orders of magnitude more sensitive than CAST, currently the most powerful axion helioscope, reaching sensitivity to axion-photon couplings down to a few 7 10 1212 GeV 121 and thus probing a large fraction of the currently unexplored axion and ALP parameter space. IAXO will also be sensitive to solar axions produced by mechanisms mediated by the axion-electron coupling gae with sensitivity \u2014 for the first time \u2014 to values of gae not previously excluded by astrophysics. With several other possible physics cases, IAXO has the potential to serve as a multi-purpose facility for generic axion and ALP research in the next decade. In this paper we present the conceptual design of IAXO, which follows the layout of an enhanced axion helioscope, based on a purpose-built 20 m-long 8-coils toroidal superconducting magnet. All the eight 60cm-diameter magnet bores are equipped with focusing x-ray optics, able to focus the signal photons into ~ 0.2 cm2 spots that are imaged by ultra-low-background Micromegas x-ray detectors. The magnet is built into a structure with elevation and azimuth drives that will allow for solar tracking for ~ 12 h each day

Erratum to "Worldwide comparison of ovarian cancer survival: Histological group and stage at diagnosis (CONCORD-2)" [Gynecol. Oncol. 144 (2017) 396-404]

Objective. Ovarian cancer comprises several histological groups with widely differing levels of survival. We aimed to explore international variation in survival for each group to help interpret international differences in survival from all ovarian cancers combined. We also examined differences in stage-specific survival. Methods. The CONCORD programme is the largest population-based study of global trends in cancer survival, including data from 60 countries for 695,932 women (aged 15\u201399 years) diagnosed with ovarian cancer during 1995\u20132009. We defined six histological groups: type I epithelial, type II epithelial, germ cell, sex cord-stromal, other specific non-epithelial and non-specific morphology, and estimated age-standardised 5-year net survival for each country by histological group. We also analysed data from67 cancer registries for 233,659 women diagnosed from 2001 to 2009, for whom information on stage at diagnosis was available. We estimated agestandardised 5-year net survival by stage at diagnosis (localised or advanced). Results. Survival fromtype I epithelial ovarian tumours for women diagnosed during 2005\u201309 ranged from40 to 70%. Survival from type II epithelial tumours was much lower (20\u201345%). Survival fromgermcell tumours was higher than that of type II epithelial tumours, but also varied widely between countries. Survival for sex-cord stromal tumours was higher than for the five other groups. Survival from localised tumours was much higher than for advanced disease (80% vs. 30%). Conclusions. There is wide variation in survival between histological groups, and stage at diagnosis remains an important factor in ovarian cancer survival. International comparisons of ovarian cancer survival should incorporate histology

Erratum to "The histology of ovarian cancer: Worldwide distribution and implications for international survival comparisons (CONCORD-2)" [Gynecol. Oncol. 144 (2017) 405-413]

Objective. Ovarian cancers comprise several histologically distinct tumour groups with widely different prognosis. We aimed to describe the worldwide distribution of ovarian cancer histology and to understand what role this may play in international variation in survival. Methods. The CONCORD programme is the largest population-based study of global trends in cancer survival. Data on 681,759 women diagnosed during 1995\u20132009 with cancer of the ovary, fallopian tube, peritoneum and retroperitonum in 51 countries were included.We categorised ovarian tumours into six histological groups, and explored the worldwide distribution of histology. Results. During 2005\u20132009, type II epithelial tumours were the most common. The proportion was much higher in Oceania (73.1%), North America (73.0%) and Europe (72.6%) than in Central and South America (65.7%) and Asia (56.1%). By contrast, type I epithelial tumours were more common in Asia (32.5%), compared with only 19.4% in North America. From 1995 to 2009, the proportion of type II epithelial tumours increased from 68.6% to 71.1%, while the proportion of type I epithelial tumours fell from 23.8% to 21.2%. The proportions of germ cell tumours, sex cord-stromal tumours, other specific non-epithelial tumours and tumours of non-specific morphology all remained stable over time. Conclusions. The distribution of ovarian cancer histology varieswidely worldwide. Type I epithelial, germcell and sex cord-stromal tumours are generally associated with higher survival than type II tumours, so the proportion of these tumours may influence survival estimates for all ovarian cancers combined. The distribution of histological groups should be considered when comparing survival between countries and regions