A study of the long term variability of RX J1856.5-3754 with XMM-Newton

We report on a detailed spectral analysis of all the available XMM-Newton data of RX J1856.5-3754, the brightest and most extensively observed nearby, thermally emitting neutron star. Very small variations (~1-2%) in the single-blackbody temperature are detected, but are probably due to an instrumental effect, since they correlate with the position of the source on the detector. Restricting the analysis to a homogeneous subset of observations, with the source at the same detector position, we place strong limits on possible spectral or flux variations from March 2005 to present-day. A slightly higher temperature (kT~61.5 eV, compared to the average value kT~61 eV) was instead measured in April 2002. If this difference is not of instrumental origin, it implies a rate of variation of about 0.15 eV/yr between April 2002 and March 2005. The high-statistics spectrum from the selected observations is well fit by the sum of two blackbody models, which extrapolate to an optical flux level in agreement with the observed value.Comment: 4 pages, to appear in the proceedings of the ERPM conference, Zielona Gora, April 201

The birthplace and age of the isolated neutron star RX J1856.5-3754

X-ray observations unveiled various types of radio-silent Isolated Neutron Stars (INSs), phenomenologically very diverse, e.g. the Myr old X-ray Dim INS (XDINSs) and the kyr old magnetars. Although their phenomenology is much diverse, the similar periods (P=2--10 s) and magnetic fields (~10^{14} G) suggest that XDINSs are evolved magnetars, possibly born from similar populations of supermassive stars. One way to test this hypothesis is to identify their parental star clusters by extrapolating backward the neutron star velocity vector in the Galactic potential. By using the information on the age and space velocity of the XDINS RX J1856.5-3754, we computed backwards its orbit in the Galactic potential and searched for its parental stellar cluster by means of a closest approach criterion. We found a very likely association with the Upper Scorpius OB association, for a neutron star age of 0.42+/-0.08 Myr, a radial velocity V_r^NS =67+/- 13$ km s^{-1}, and a present-time parallactic distance d_\pi^NS = 123^{+11}_{-15} pc. Our result confirms that the "true" neutron star age is much lower than the spin-down age (tau_{sd}=3.8 Myrs), and is in good agreement with the cooling age, as computed within standard cooling scenarios. The mismatch between the spin-down and the dynamical/cooling age would require either an anomalously large breaking index (n~20) or a decaying magnetic field with initial value B_0 ~ 10^{14} G. Unfortunately, owing to the uncertainty on the age of the Upper Scorpius OB association and the masses of its members we cannot yet draw firm conclusions on the estimated mass of the RX J1856.5-3754 progenitor.Comment: 6 pages, accepted for publication on Monthly Notices of the Royal Astronomical Societ

Toxicity of oxaliplatin rechallenge in metastatic colorectal cancer.

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Challenging chemoresistant metastatic colorectal cancer: Therapeutic strategies from the clinic and from the laboratory

As survival has improved for patients with metastatic colorectal cancer (mCRC), there is an increasing need for effective and well-tolerated third-line and subsequent-lines of treatment. Despite recent advances with the development of new-targeted therapies in this setting, there remains an unmet need to exploit oncogenic drivers of colorectal cancer and overcome acquired resistance. Potential treatment strategies include revisiting old targets such as human epidermal growth factor receptor 2, RAS, and BRAF and investigating new targets such as c-MET, the PI3 kinase, and Wnt pathways, and also the use of immune-checkpoint inhibitors. Here, we review recent phase III trials exploring approved agents, early trials investigating new drugs for chemorefractory mCRC, and the potential of capturing tumour dynamics during its evolution by liquid biopsy analysis

Observations of Isolated Neutron Stars with the ESO Multi-Conjugate Adaptive Optics Demonstrator

High-energy observations have unveiled peculiar classes of isolated neutron stars which, at variance with radio pulsars, are mostly radio silent and not powered by the star rotation. Among these objects are the magnetars, hyper-magnetized neutron stars characterized by transient X-ray/gamma-ray emission, and neutron stars with purely thermal, and in most cases stationary, X-ray emission (a.k.a., X-ray dim isolated neutron stars or XDINSs). While apparently dissimilar in their high-energy behavior and age, both magnetars and XDINSs have similar periods and unusually high magnetic fields. This suggests a tantalizing scenario where the former evolve into the latter.Discovering so far uninvestigated similarities between the multi-wavelength properties of these two classes would be a further step forward to establish an evolutionary scenario. A most promising channels is the near infrared (NIR) one, where magnetars are characterized by a distinctive spectral flattening with respect to the extrapolation of the soft X-ray spectrum.We observed the two XDINSs RX J0420.0-5022 and RX J1856.5-3754 with the Multi-Conjugate Adaptive Optics Demonstrator (MAD) at the Very Large Telescope (VLT) as part of the instrument guaranteed time observations program, to search for their NIR counterparts. Both RX J1856.5-3754 and RX J0420.0-5022 were not detected down to K_s ~20 and Ks ~21.5, respectively. In order to constrain the relation between XDINSs and magnetars it would be of importance to perform deeper NIR observations. A good candidate is 1RXS J214303.7+065419 which is the XDINS with the highest inferred magnetic field.Comment: Accepted for publication in Astronomy and Astrophysic

Characteristics of Submucous Myomas and the Risk of Anemia

Background and Objectives: Uterine fibroids still represent the most common indication for hysterectomy for benign pathologies. In the United States, more than 479,000 hysterectomies are performed annually, 46.6% for myomas and 47.7% in women aged from 18 to 44 years. By applying appropriateness criteria to this procedure, it has been estimated that overuse ranges from 16 to 70%. One of the main reasons that induce patients and gynecologists to consider hysterectomy is represented by severe anemia. Materials and Methods: This is a retrospective cohort study of 202 patients with uterine fibroids diagnosed by transvaginal ultrasound who underwent a hysteroscopic procedure. Myoma grade, size, location, and number were assessed by transvaginal scan and office hysteroscopy and correlated to the pre-treatment hemoglobin level. Results: Univariate analysis showed that anemia does not have a statistically significant association with myoma number and with age considered as a numerical predictor. In the patients with myoma type 0, there is a possibility of 81% having anemia regardless of menorrhagia. On the contrary, in patients with myoma type 1 or type 2, the possibility of having anemia varies according to the presence or absence of menorrhagia. If there is menorrhagia, the risk of moderate anemia is only present for myomas >60 mm. Conclusions: The results of this study may contribute to defining objective criteria for the management of submucous myomas and anemia. Our data suggest that submucosal myomas type 0 >10 mm should always be treated, putting patients at risk for anemia. Myomas type 2 and 3 should be treated for the risk of anemia in the presence of menorrhagia episodes or if > of 60 mm. Adequate management of anemia and myomas could reduce the rate of unnecessary hysterectomies

Probing isolated compact remnants with microlensing

We consider isolated compact remnants (ICoRs), i.e. neutrons stars and black holes that do not reside in binary systems and therefore cannot be detected as X-ray binaries. ICoRs may represent $\sim\,5$ percent of the stellar mass budget of the Galaxy, but they are very hard to detect. Here we explore the possibility of using microlensing to identify ICoRs. In a previous paper we described a simulation of neutron star evolution in phase space in the Galaxy, taking into account the distribution of the progenitors and the kick at formation. Here we first reconsider the evolution and distribution of neutron stars and black holes adding a bulge component. From the new distributions we calculate the microlensing optical depth, event rate and distribution of event time scales, comparing and contrasting the case of ICoRs and "normal stars". We find that the contribution of remnants to optical depth is slightly lower than without kinematics, owing to the evaporation from the Galaxy. On the other hand, the relative contribution to the rate of events is a factor $\sim\,5$ higher. In all, $\sim\,6-7$ percent of the events are likely related to ICoRs. In particular, $\sim\,30-40$ percent of the events with duration $>\,100$ days are possibly related to black holes. It seems therefore that microlensing observations are a suitable tool to probe the population of Galactic ICoRs.Comment: 7 pages, 14 figures. Accepted for publication in Astronomy and Astrophysic

Mechanisms of immune escape and resistance to checkpoint inhibitor therapies in mismatch repair deficient metastatic colorectal cancers

SIMPLE SUMMARY: A subset of colorectal cancers (CRCs) is characterized by a mismatch repair deficiency that is frequently associated with microsatellite instability (MSI). The compromised DNA repair machinery leads to the accumulation of tumor neoantigens affecting the sensitivity of MSI metastatic CRC to immune checkpoint inhibitors (CPIs), both upfront and in later lines of treatment. However, up to 30% of MSI CRCs exhibit primary resistance to frontline immune based therapy, and an additional subset develops acquired resistance. Here, we first discuss the clinical and molecular features of MSI CRCs and then we review how the loss of antigenicity, immunogenicity, and a hostile tumor microenvironment could influence primary and acquired resistance to CPIs. Finally, we describe strategies to improve the outcome of MSI CRC patients upon CPI treatment. ABSTRACT: Immune checkpoint inhibitors (CPIs) represent an effective therapeutic strategy for several different types of solid tumors and are remarkably effective in mismatch repair deficient (MMRd) tumors, including colorectal cancer (CRC). The prevalent view is that the elevated and dynamic neoantigen burden associated with the mutator phenotype of MMRd fosters enhanced immune surveillance of these cancers. In addition, recent findings suggest that MMRd tumors have increased cytosolic DNA, which triggers the cGAS STING pathway, leading to interferon-mediated immune response. Unfortunately, approximately 30% of MMRd CRC exhibit primary resistance to CPIs, while a substantial fraction of tumors acquires resistance after an initial benefit. Profiling of clinical samples and preclinical studies suggests that alterations in the Wnt and the JAK-STAT signaling pathways are associated with refractoriness to CPIs. Intriguingly, mutations in the antigen presentation machinery, such as loss of MHC or Beta-2 microglobulin (B2M), are implicated in initial immune evasion but do not impair response to CPIs. In this review, we outline how understanding the mechanistic basis of immune evasion and CPI resistance in MMRd CRC provides the rationale for innovative strategies to increase the subset of patients benefiting from CPIs