The DArk Matter Particle Explorer (DAMPE) is a high-performance space particle detector launched in orbit on 17 December 2015 by a collaboration of Chinese, Italian and Swiss scientific institutions, ...coordinated by the Chinese Academy of Sciences. It consists of a high-resolution segmented BGO electromagnetic calorimeter with a depth of 32 radiation lengths, a silicon-tungsten tracker-converter that reaches an angular resolution below 0.2°, an anti-coincidence shield and ion detector made of segmented plastic scintillators and a neutron detector made of boron-doped plastic scintillators. An overview of the experiment and a summary of the latest results coming from the observation of cosmic rays up to 100 TeV, of gamma-rays up to 10 TeV and of cosmic electrons up to 5 TeV is presented.
The DArk Matter Particle Explorer (DAMPE) is a satellite-borne detector for high-energy cosmic rays and \(\gamma\)-rays. To fully understand the detector performance and obtain reliable physical ...results, extensive simulations of the detector are necessary. The simulations are particularly important for the data analysis of cosmic ray nuclei, which relies closely on the hadronic and nuclear interactions of particles in the detector material. Widely adopted simulation softwares include the GEANT4 and FLUKA, both of which have been implemented for the DAMPE simulation tool. Here we describe the simulation tool of DAMPE and compare the results of proton shower properties in the calorimeter from the two simulation softwares. Such a comparison gives an estimate of the most significant uncertainties of our proton spectral analysis.
Objectives
To test whether quantitative susceptibility mapping (QSM) of cerebral cavernous malformations (CCMs) assessed at baseline may predict the presence or absence of haemorrhagic signs at ...1-year follow-up.
Methods
Familial CCM patients were enrolled in the longitudinal multicentre study Treat-CCM. The 3-T MRI scan allowed performing a semi-automatic segmentation of CCMs and computing the maximum susceptibility in each segmented CCM (QSMmax) at baseline. CCMs were classified as haemorrhagic and non-haemorrhagic at baseline and then subclassified according to the 1-year (t1) evolution. Between-group differences were tested, and the diagnostic accuracy of QSMmax in predicting the presence or absence of haemorrhagic signs in CCMs was calculated with ROC analyses.
Results
Thirty-three patients were included in the analysis, and a total of 1126 CCMs were segmented. QSMmax was higher in haemorrhagic CCMs than in non-haemorrhagic CCMs (
p
< 0.001). In haemorrhagic CCMs at baseline, the accuracy of QSMmax in differentiating CCMs that were still haemorrhagic from CCMs that recovered from haemorrhage at t1 calculated as area under the curve (AUC) was 0.78 with sensitivity 62.69%, specificity 82.35%, positive predictive value (PPV) 93.3% and negative predictive value (NPV) 35.9% (QSMmax cut-off ≥ 1462.95 ppb). In non-haemorrhagic CCMs at baseline, AUC was 0.91 in differentiating CCMs that bled at t1 from stable CCMs with sensitivity 100%, specificity 81.9%, PPV 5.1%, and NPV 100% (QSMmax cut-off ≥ 776.29 ppb).
Conclusions
The QSMmax in CCMs at baseline showed high accuracy in predicting the presence or absence of haemorrhagic signs at 1-year follow-up. Further effort is required to test the role of QSM in follow-up assessment and therapeutic trials in multicentre CCM studies.
Key Points
• QSM in semi-automatically segmented CCM was feasible.
• The maximum magnetic susceptibility in a single CCM at baseline may predict the presence or absence of haemorrhagic signs at 1-year follow-up.
• Multicentric studies are needed to enforce the role of QSM in predicting the CCMs’ haemorrhagic evolution in patients affected by familial and sporadic forms.
Observations in people with cerebral cavernous malformations, and in preclinical models of this disorder, suggest that the β-blocker propranolol might reduce the risk of intracerebral haemorrhage. We ...aimed to evaluate the safety and efficacy of prolonged treatment with propranolol to reduce the incidence of symptomatic intracerebral haemorrhage or focal neurological deficit in people with familial cerebral cavernous malformations.
We conducted a randomised, open-label, blinded-endpoint, phase 2 pilot trial (Treat_CCM) at six national reference centres for rare diseases in Italy. People aged 18 years or older with symptomatic familial cerebral cavernous malformation were eligible for enrolment. Participants were randomly assigned (2:1) to receive either oral propranolol (20-320 mg daily) plus standard care (intervention group), or standard care alone (control group), for 24 months. Participants, caregivers, and investigators were aware of treatment group assignment. Participants had clinical assessments and 3 T brain MRI at baseline and at 12 and 24 months. The primary outcome was new occurrence of symptomatic intracerebral haemorrhage or focal neurological deficit attributable to cerebral cavernous malformation over 24 months. Outcome assessors were masked to treatment group assignment. The primary analysis was done in the intention-to-treat population. Because of the pilot study design, we chose a one-sided 80% CI, which could either exclude a clinically meaningful effect or show a signal of efficacy. This trial is registered with EudraCT, 2017-003595-30, and ClinicalTrials.gov, NCT03589014, and is closed to recruitment.
Between April 11, 2018, and Dec 5, 2019, 95 people were assessed for eligibility and 83 were enrolled, of whom 57 were assigned to the propranolol plus standard care group and 26 to the standard care alone group. The mean age of participants was 46 years (SD 15); 48 (58%) were female and 35 (42%) were male. The incidence of symptomatic intracerebral haemorrhage or focal neurological deficit was 1·7 (95% CI 1·4-2·0) cases per 100 person-years (two 4% of 57 participants) in the propranolol plus standard care group and 3·9 (3·1-4·7) per 100 person-years (two 8% of 26) in the standard care alone group (univariable hazard ratio HR 0·43, 80% CI 0·18-0·98). The univariable HR showed a signal of efficacy, according to predefined criteria. The incidence of hospitalisation did not differ between groups (8·2 cases 95% CI 7·5-8·9 per 100 person-years in the propranolol plus standard care group vs 8·2 95% CI 7·1-9·3 per 100 person-years in the standard care alone group). One participant in the standard care alone group died of sepsis. Three participants in the propranolol plus standard care group discontinued propranolol due to side-effects (two reported hypotension and one reported weakness).
Propranolol was safe and well tolerated in this population. Propranolol might be beneficial for reducing the incidence of clinical events in people with symptomatic familial cerebral cavernous malformations, although this trial was not designed to be adequately powered to investigate efficacy. A definitive phase 3 trial of propranolol in people with symptomatic familial cerebral cavernous malformations is justified.
Italian Medicines Agency, Associazione Italiana per la Ricerca sul Cancro, Swedish Science Council, Knut and Alice Wallenberg Foundation, CARIPLO Foundation, Italian Ministry of Health.
PDF
