The self-confinement of electrons and positrons from dark matter

Radiative emissions from electrons and positrons generated by dark matter (DM) annihilation or decay are one of the most investigated signals in indirect searches of WIMPs. Ideal targets must have large ratio of DM to baryonic matter. However, such ``dark'' systems have a poorly known level of magnetic turbulence, which determines the residence time of the electrons and positrons and therefore also the strength of the expected signal. This typically leads to significant uncertainties in the derived DM bounds. In a novel approach, we compute the self-confinement of the DM-induced electrons and positrons. Indeed, they themselves generate irregularities in the magnetic field, thus setting a lower limit on the presence of the magnetic turbulence. We specifically apply this approach to dwarf spheroidal galaxies. Finally, by comparing the expected synchrotron emission with radio data from the direction of the Draco galaxy collected at the Giant Metre Radio Telescope, we show that the proposed approach can be used to set robust and competitive bounds on WIMP DM.Comment: 18 pages, 10 figures. v2: minor revision, matches published versio

The evolving role of monoclonal antibodies in the treatment of patients with advanced renal cell carcinoma: a systematic review

Introduction: While the majority of the vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) inhibitors currently used for the therapy of metastatic renal cell carcinoma (mRCC) are small molecule agents inhibiting multiple targets, monoclonal antibodies are inhibitors of specific targets, which may decrease off-target effects while preserving on-target activity. A few monoclonal antibodies have already been approved for mRCC (bevacizumab, nivolumab), while many others may play an important role in the therapeutic scenario of mRCC. Areas covered: This review describes emerging monoclonal antibodies for treating RCC. Currently, bevacizumab, a VEGF monoclonal antibody, is approved in combination with interferon for the therapy of metastatic RCC, while nivolumab, a Programmed Death (PD)-1 inhibitor, is approved following prior VEGF inhibitor treatment. Other PD-1 and PD-ligand (L)-1 inhibitors are undergoing clinical development. Expert opinion: Combinations of inhibitors of the PD1/PD-L1 axis with VEGF inhibitors or cytotoxic T-lymphocyte antigen (CTLA)-4 inhibitors have shown promising efficacy in mRCC. The development of biomarkers predictive for benefit and rational tolerable combinations are both important pillars of research to improve outcomes in RCC

The probability of galaxy-galaxy strong lensing events in hydrodynamical simulations of galaxy clusters

Meneghetti et al. (2020) recently reported an excess of galaxy-galaxy strong lensing (GGSL) in galaxy clusters compared to expectations from the LCDM cosmological model. Theoretical estimates of the GGSL probability are based on the analysis of numerical hydrodynamical simulations in the LCDM cosmology. We quantify the impact of the numerical resolution and AGN feedback scheme adopted in cosmological simulations on the predicted GGSL probability and determine if varying these simulation properties can alleviate the gap with observations. We repeat the analysis of Meneghetti et al. (2020) on cluster-size halos simulated with different mass and force resolutions and implementing several independent AGN feedback schemes. We find that improving the mass resolution by a factor of ten and twenty-five, while using the same galaxy formation model that includes AGN feedback, does not affect the GGSL probability. We find similar results regarding the choice of gravitational softening. On the contrary, adopting an AGN feedback scheme that is less efficient at suppressing gas cooling and star formation leads to an increase in the GGSL probability by a factor between three and six. However, we notice that such simulations form overly massive subhalos whose contribution to the lensing cross-section would be significant while their Einstein radii are too large to be consistent with the observations. The primary contributors to the observed GGSL cross-sections are subhalos with smaller masses, that are compact enough to become critical for lensing. The population with these required characteristics appears to be absent in simulations.Comment: 13 pages, 11 figures. Submitted for publication on Astronomy and Astrophysic

Defining Kawasaki disease and pediatric inflammatory multisystem syndrome-temporally associated to SARS-CoV-2 infection during SARS-CoV-2 epidemic in Italy: results from a national, multicenter survey

Background: There is mounting evidence on the existence of a Pediatric Inflammatory Multisystem Syndrome-temporally associated to SARS-CoV-2 infection (PIMS-TS), sharing similarities with Kawasaki Disease (KD). The main outcome of the study were to better characterize the clinical features and the treatment response of PIMS-TS and to explore its relationship with KD determining whether KD and PIMS are two distinct entities. Methods: The Rheumatology Study Group of the Italian Pediatric Society launched a survey to enroll patients diagnosed with KD (Kawasaki Disease Group - KDG) or KD-like (Kawacovid Group - KCG) disease between February 1st 2020, and May 31st 2020. Demographic, clinical, laboratory data, treatment information, and patients' outcome were collected in an online anonymized database (RedCAP®). Relationship between clinical presentation and SARS-CoV-2 infection was also taken into account. Moreover, clinical characteristics of KDG during SARS-CoV-2 epidemic (KDG-CoV2) were compared to Kawasaki Disease patients (KDG-Historical) seen in three different Italian tertiary pediatric hospitals (Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", Trieste; AOU Meyer, Florence; IRCCS Istituto Giannina Gaslini, Genoa) from January 1st 2000 to December 31st 2019. Chi square test or exact Fisher test and non-parametric Wilcoxon Mann-Whitney test were used to study differences between two groups. Results: One-hundred-forty-nine cases were enrolled, (96 KDG and 53 KCG). KCG children were significantly older and presented more frequently from gastrointestinal and respiratory involvement. Cardiac involvement was more common in KCG, with 60,4% of patients with myocarditis. 37,8% of patients among KCG presented hypotension/non-cardiogenic shock. Coronary artery abnormalities (CAA) were more common in the KDG. The risk of ICU admission were higher in KCG. Lymphopenia, higher CRP levels, elevated ferritin and troponin-T characterized KCG. KDG received more frequently immunoglobulins (IVIG) and acetylsalicylic acid (ASA) (81,3% vs 66%; p = 0.04 and 71,9% vs 43,4%; p = 0.001 respectively) as KCG more often received glucocorticoids (56,6% vs 14,6%; p < 0.0001). SARS-CoV-2 assay more often resulted positive in KCG than in KDG (75,5% vs 20%; p < 0.0001). Short-term follow data showed minor complications. Comparing KDG with a KD-Historical Italian cohort (598 patients), no statistical difference was found in terms of clinical manifestations and laboratory data. Conclusion: Our study suggests that SARS-CoV-2 infection might determine two distinct inflammatory diseases in children: KD and PIMS-TS. Older age at onset and clinical peculiarities like the occurrence of myocarditis characterize this multi-inflammatory syndrome. Our patients had an optimal response to treatments and a good outcome, with few complications and no deaths

Association Study Between Coronary Artery Disease and rs1333049 Polymorphism at 9p21.3 Locus in Italian Population

In this study, we verify the association between the rs1333049 single nucleotide polymorphism (9p21.3) within CDKN2A-CDKN2B and coronary artery disease (CAD) in an Italian population. We replicated rs1333049_G allele association with a significantly reduced risk of CAD (OR = 0.816; 95% confidence interval [0.705â\u80\u930.945]; p = 0.0065) in 711 CAD patients and 755 normal healthy individuals. This effect is maintained even stratifying patients by gender and by risk factors. A significant association was found with age of CAD onset. Interestingly, we found a protective trend of association between the rs1333049_G allele and peripheral artery disease, a progressive atherosclerotic condition in which plaque builds up in the arteries that carry blood to the head, organs, and limbs (OR = 0.724; 95% CI [0.520â\u80\u931.007]; p = 0.054). No genotype-phenotype association was found with more severe CAD clinical parameters. If certain genetic factors predispose individuals to adverse outcomes, the knowledge of a patientâ\u80\u99s genotype may influence clinical management

Chromosomal Microarray Analysis versus Karyotyping in Fetuses with Increased Nuchal Translucency

We have carried out a retrospective study of chromosome anomalies associated with increased nuchal translucency (NT) in order to compare yield rates of karyotype, chromosome microarray analysis (CMA), and non-invasive prenatal testing (NIPT) in this condition. Presenting with increased NT or cystic hygroma ≥3.5 mm as an isolated sign, 249 fetuses underwent karyotype and/or CMA from 11 to 18 gestational weeks. Karyotype and fluorescence in situ hybridization (FISH) analyses detected 103 chromosomal anomalies including 95 aneuploidies and eight chromosomal rearrangements or derivatives. Further, seven pathogenic copy number variants (CNV), five likely pathogenic CNVs, and 15 variants of unknown significance (VOUS) were detected by CMA in fetuses with normal karyotype. Genetic testing is now facing new challenges due to results with uncertain clinical impacts. Additional investigations will be necessary to interpret these findings. More than 15% of the anomalies that we have diagnosed with invasive techniques could not be detected by NIPT. It is therefore definitely not recommended in the case of ultrasound anomalies. These results, while corroborating the use of CMA in fetuses with increased NT as a second tier after rapid aneuploidy testing, do not suggest a dismissal of karyotype analysis

An 18 gene expression-based score classifier predicts the clinical outcome in stage 4 neuroblastoma

The prognosis of children with metastatic stage 4 neuroblastoma (NB) has remained poor in the past decade