Robust inference in composite transformation models

The aim of this paper is to base robust inference about a shape parameter indexing a composite transformation model on a quasi- prole likelihood ratio test statistic. First, a general procedure is presented in order to construct a bounded prole estimating function for shape parameters. This method is based on a standard truncation argument from the theory of robustness. Hence, a quasi-likelihood test is derived. Numerical studies and applications to real data show that its use reveals extremely powerful, leading to improved inferences with respect to classical robust Wald and score-type test statistics

Adjusted quasi-profile likelihoods from estimating functions

Higher-order adjustments for a quasi-profile likelihood for a scalar parameter of interest in the presence of nuisance parameters are discussed. Paralleling likelihood asymptotics, these adjustments aim to alleviate some of the problems inherent to the presence of nuisance parameters. Indeed, the estimating equation for the parameter of interest, when the nuisance parameter is substituted with an appropriate estimate, is not unbiased and such a bias can lead to poor inference on the parameter of interest. Following the approach of McCullagh and Tibshirani (1990), here we propose adjustments for the estimating equation for the parameter of interest. Moreover, we discuss two methods for their computation: a bootstrap simulation method, and a first-order asymptotic expression, which can be simplified under an orthogonality assumption. Some examples, in the context of generalized linear models and of robust inference, are provided

Converged multimedia services in emerging Web 2.0 session mobility scenarios

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Growth factors and experimental arterial grafts

Background: The production of growth factors from several experimental arterial conduits was determined. Methods: We implanted 105 experimental arterial grafts that were 1 cm long in the abdominal aorta of Lewis rats (average weight, 250 g). Five different types of grafts were analyzed: arterial isografts, vein grafts, arterial allografts, and polytetrafluoroethylene (PTFE) grafts with normal or decreased compliance. Animals were killed humanely 4 weeks after surgery and the production of platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), transforming growth factor-b, tumor necrosis factor-a, and interleukin-1 was analyzed. Results: Myointimal hyperplasia (MH) was evident in vein grafts, arterial allografts, and PTFE grafts, but not in arterial isografts. Growth factor production was increased for grafts prone to develop MH like vein, PTFE grafts, and arterial allografts. PDGF and bFGF were increased significantly for PTFE and vein grafts, but not for arterial allografts. The importance of bFGF and PGDF was confirmed by the capability of antibody to PDGF and to bFGF to reduce the mitogenic activity of smooth muscle cells, in vivo and in vitro, for PTFE and vein grafts, but not for arterial allografts, in which a predominant role was played by interleukin-1 and tumor necrosis factor-a. Conclusions: Agents able to neutralize this increased production of growth factors, either directly or by competition with their receptors, can prevent MH formation. (J Vasc Surg 2016;64:1444-9.) Clinical Relevance: Arterial grafts release growth factors, which can lead to myointimal hyperplasia formation and atherosclerosis progression in the arterial tree. Both phenomena can cause graft occlusion. Inhibition of growth factor release by arterial grafts can improve their clinical effectiveness

Where does galactic dust come from?

Here we investigate the origin of the dust mass (Mdust) observed in the Milky Way (MW) and of dust scaling relations found in a sample of local galaxies from the DGS and KINGFISH surveys. To this aim, we model dust production from Asymptotic Giant Branch (AGB) stars and supernovae (SNe) in simulated galaxies forming along the assembly of a Milky Way-like halo in a well resolved cosmic volume of 4cMpc using the GAMESH pipeline. We explore the impact of different sets of metallicity and mass-dependent AGB and SN dust yields on the predicted Mdust. Our results show that models accounting for grain destruction by the SN reverse shock predict a total dust mass in the MW that is a factor of ~4 lower than observed, and can not reproduce the observed galaxy-scale relations between dust and stellar masses, and dust-to-gas ratios and metallicity, with a smaller discrepancy in galaxies with low metallicity (12 + log(O/H) < 7.5) and low stellar masses (Mstar < 10^7 Msun). In agreement with previous studies, we suggest that competing processes in the interstellar medium must be at play to explain the observed trends. Our result reinforces this conclusion by showing that it holds independently of the adopted AGB and SN dust yields.Comment: 6 pages, 4 figures. Accepted version for publication in MNRA

Source and dynamics of a volcanic caldera unrest : Campi Flegrei, 1983–84

Acknowledgements We thank Tiziana Vanorio, Antonella Amoruso, Luca Crescentini, Nicholas Rawlinson, Yasuko Takei, and David Cornwell for the valuable suggestions regarding the methodology and interpretation. Reviews from Tim Greenfield and two anonymous reviewers helped improving both clarity of the manuscript and interpretation. The Royal Society of Edinburgh - Accademia dei Lincei Bilateral Agreement, the Santander Mobility Award of the College of Physical Sciences, University of Aberdeen, and the TIDES EU COST action granted L.D.S. travel grants for the realisation of this study. E.D.P. has been supported by the EPHESTO and KNOWAVES projects, funded by the Spanish Ministry of Education and Science.Peer reviewedPublisher PD

Enhancement of radiosensitivity by the novel anticancer quinolone derivative vosaroxin in preclinical glioblastoma models

Purpose: Glioblastoma multiforme (GBM) is the most aggressive brain tumor. The activity of vosaroxin, a first-in-class anticancer quinolone derivative that intercalates DNA and inhibits topoisomerase II, was investigated in GBM preclinical models as a single agent and combined with radiotherapy (RT). Results: Vosaroxin showed antitumor activity in clonogenic survival assays, with IC50 of 10-100 nM, and demonstrated radiosensitization. Combined treatments exhibited significantly higher γH2Ax levels compared with controls. In xenograft models, vosaroxin reduced tumor growth and showed enhanced activity with RT; vosaroxin/RT combined was more effective than temozolomide/RT. Vosaroxin/ RT triggered rapid and massive cell death with characteristics of necrosis. A minor proportion of treated cells underwent caspase-dependent apoptosis, in agreement with in vitro results. Vosaroxin/RT inhibited RT-induced autophagy, increasing necrosis. This was associated with increased recruitment of granulocytes, monocytes, and undifferentiated bone marrow-derived lymphoid cells. Pharmacokinetic analyses revealed adequate blood-brain penetration of vosaroxin. Vosaroxin/RT increased disease-free survival (DFS) and overall survival (OS) significantly compared with RT, vosaroxin alone, temozolomide, and temozolomide/RT in the U251-luciferase orthotopic model. Materials and Methods: Cellular, molecular, and antiproliferative effects of vosaroxin alone or combined with RT were evaluated in 13 GBM cell lines. Tumor growth delay was determined in U87MG, U251, and T98G xenograft mouse models. (DFS) and (OS) were assessed in orthotopic intrabrain models using luciferasetransfected U251 cells by bioluminescence and magnetic resonance imaging. Conclusions: Vosaroxin demonstrated significant activity in vitro and in vivo in GBM models, and showed additive/synergistic activity when combined with RT in O6- methylguanine methyltransferase-negative and -positive cell lines

The Mummies in the Church of Santa Maria delle Grazie, Calascio: A New Site in the Inner Abruzzo Region, Central Italy

The inner Abruzzo region, corresponding to the province of L’Aquila, is a land of mountains and highlands in central Italy. Its environmental conditions greatly foster spontaneous mummification, and the area is well known for the human mummies found in the last decades. We present a newly discovered collection of mummified remains in the village of Calascio, located 1,210 meters above sea level, near Gran Sasso Mountain. Here, the Franciscan convent of Santa Maria delle Grazie was built in 1594. The preliminary survey of a crypt in the conventual church allowed us to observe wooden coffins with at least seven mummified bodies still in their clothes, and several bony remains. Most likely, the mummies date back to the second half of the 19th century, and belonged to laypersons. Preservation was certainly due to the cold dry environment of the crypt. The recovery of the entire series will take place through speleological techniques according to stratigraphic relationships, in order to trace a bioanthropological profile of this small community members

Il “Corpo Santo” del Beato Timoteo da Monticchio (1444-1504) tra ricognizioni e profanazioni

Born in the outskirts of Aquila (today L’Aquila, central Italy), the Blessed Timoteo da Monticchio (1444-1504) was an important figure of the Franciscan Regular Observance. Since his death, his mortal remains were kept in the convent of Sant’Angelo d’Ocre, near L’Aquila. Timoteo’s bones underwent Canonical Recognition in 1870, and in the following year were arranged in a “Holy Body”. Further recognitions took place in 1962 and in 2004. Since the major earthquake in 2009, the convent remained locked up but unattended. In 2020, the altar hosting Timoteo’s relics in the conventual church was found desecrated, and his remains were thrown on the floor. Such events give us the opportunity to describe the peculiar arrangement of bone relics called “Holy Body” as well as to highlight the importance of periodical recognitions and related documents after relics violation.Nato nei dintorni dell’Aquila (oggi L’Aquila), il Beato Ti-moteo da Monticchio (1444-1504) fu un protagonista importante dell’Osservanza Minoritica. Sin dalla morte i suoi resti furono conservati nel convento di Sant’Angelo d’Ocre, vicino a L’Aquila. Nel 1870 i suoi resti scheletrizzati furono sottoposti a Ricognizione Canonica e, nell’anno seguente, su di essi fu allestito un “Corpo Santo”. Successive ricognizioni ebbero luogo nel 1962 e nel 2004. Dopo il sisma del 2009, il convento rimase chiuso e incustodito. Nel 2020 l’altare in cui erano conservate le reliquie di Timoteo nella chiesa conventuale fu profanato ed i suoi resti gettati sul pavimento. Tali eventi ci consentono di descrivere il peculiare allestimento delle reliquie ossee noto come “Corpo Santo”, nonché di sottolineare l’importanza delle ricognizioni periodiche e della relativa documentazione in caso di profanazione delle reliquie

The possible prognostic role of histone deacetylase and transforming growth factor β/Smad signaling in high grade gliomas treated by radio-chemotherapy: a preliminary immunohistochemical study

Glioblastoma (GBM) is the most common and aggressive tumor of the central nervous system. Unfortunately, patients affected by this disease have a very poor prognosis, due to high level of invasiveness and resistance to standard therapies. Although the molecular profile of GBM has been extensively investigated, the events responsible for its pathogenesis and progression remain largely unknown. Histone Deacetylases (HDAC) dependent epigenetic modifications and transforming growth factor (TGF)-β/Smad pathway seem to play an important role in GBM tumorigenesis, resistance to common therapies and poor clinical outcome. The aim of this study was to evaluate the involvement and the possible interaction between these two molecular cascades in the pathogenesis and prognosis of GBM. Immunohistochemistry (IHC) was performed on microdissected GBM samples, collected from 14 patients (6 men and 8 women) ranging in age from 43 to 74 years. The patients were previously divided, on the basis of their overall survival (OS), into two groups: short and long OS. Patients with poor prognosis showed hyperexpression of HDAC4 and HDAC6, an activation of the TGF-β/Smad pathway, with high levels of IL-13, Smad2, PDGF and MMP3 expression, compared to the long survivors. The short OS group exhibits a decrease in Smad 7 expression and also low levels of p21 immunostaining, which represents a common target of the two pathways. The IHC data was confirmed by quantitative analysis and Immunoblotting. Our preliminary results suggest that both HDAC4 and HDAC6 together with the TGF-β/Smad pathway may be involved in progression of GBM and this cross talking could be a useful prognostic marker in this deadly disease