the effects of control measures on the economic burden associated with epidemics of avian influenza in italy

In 1999, Italy experienced a devastating epidemic of high-pathogenicity avian influenza (HPAI) caused by an H7N1 virus subtype. After this epidemic, a ministerial decree was passed to implement control measures for low-pathogenicity avian influenza (LPAI) due to H5 and H7 subtypes. We investigated whether these control measures have decreased the public expenditure associated with epidemics of LPAI and HPAI by comparing the direct and consequential losses of the 1999 epidemic to the losses associated with successive epidemics. The estimated total economic burden of the epidemics was about euro650 million (euro217 million in direct losses and euro433 million in consequential losses). The 1999 epidemic accounted for most of these losses (euro507 million: euro112 million in direct losses and euro395 million in consequential losses), whereas the total economic burden for the 5 successive LPAI was euro143 million (euro105 million in direct losses and euro38 million in consequential losses). These results demonstrate that the implementation of a coordinated set of disease-control measures, which included both emergency and prophylactic vaccination, was able to reduce the overall costs associated with avian influenza epidemics. The results also show that the application of adequate LPAI control measures may limit the risk of emergence of an HPAI virus in an area with a high poultry density, allowing the complete disruption of the poultry market and its huge associated costs to be avoided

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

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

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

New Young Star Candidates in BRC 27 and BRC 34

We used archival Spitzer Space Telescope mid-infrared data to search for young stellar objects (YSOs) in the immediate vicinity of two bright-rimmed clouds, BRC 27 (part of CMa R1) and BRC 34 (part of the IC 1396 complex). These regions both appear to be actively forming young stars, perhaps triggered by the proximate OB stars. In BRC 27, we find clear infrared excesses around 22 of the 26 YSOs or YSO candidates identified in the literature, and identify 16 new YSO candidates that appear to have IR excesses. In BRC 34, the one literature-identified YSO has an IR excess, and we suggest 13 new YSO candidates in this region, including a new Class I object. Considering the entire ensemble, both BRCs are likely of comparable ages, within the uncertainties of small number statistics and without spectroscopy to confirm or refute the YSO candidates. Similarly, no clear conclusions can yet be drawn about any possible age gradients that may be present across the BRCs.Comment: 54 pages, 19 figures, accepted by A

Pasta consumption and connected dietary habits: Associations with glucose control, adiposity measures, and cardiovascular risk factors in people with type 2 diabetes—TOSCA.IT study

Background: Pasta is a refined carbohydrate with a low glycemic index. Whether pasta shares the metabolic advantages of other low glycemic index foods has not really been investigated. The aim of this study is to document, in people with type-2 diabetes, the consumption of pasta, the connected dietary habits, and the association with glucose control, measures of adiposity, and major cardiovascular risk factors. Methods: We studied 2562 participants. The dietary habits were assessed with the European Prospective Investigation into Cancer and Nutrition (EPIC) questionnaire. Sex-specific quartiles of pasta consumption were created in order to explore the study aims. Results: A higher pasta consumption was associated with a lower intake of proteins, total and saturated fat, cholesterol, added sugar, and fiber. Glucose control, body mass index, prevalence of obesity, and visceral obesity were not significantly different across the quartiles of pasta intake. No relation was found with LDL cholesterol and triglycerides, but there was an inverse relation with HDL-cholesterol. Systolic blood pressure increased with pasta consumption; but this relation was not confirmed after correction for confounders. Conclusions: In people with type-2 diabetes, the consumption of pasta, within the limits recommended for total carbohydrates intake, is not associated with worsening of glucose control, measures of adiposity, and major cardiovascular risk factors