DM-like anomalies in neutron multiplicity spectra

Publisher Copyright: © 2022 Institute of Physics Publishing. All rights reserved.A new experiment collects data, since November 2019, at a depth of 210 m.w.e. in the Callio Lab in the Pyhasalmi mine in Finland. The setup, called NEMESIS (New Emma MEasurementS Including neutronS), incorporates infrastructure from the EMMA experiment with neutron and large-area plastic scintillator detectors. The experiment's primary aim is to combine muon tracking with position-sensitive neutron detection to measure precision yields, multiplicities, and lateral distributions of high-multiplicity neutron events induced by cosmic muons in various materials. The data are relevant for background evaluation of the deep-underground searches for Dark Matter (DM), neutrino-less double beta decay, etc. Preliminary analysis revealed anomalies in muon-suppressed neutron multiplicity spectra collected during a 344-day run (live time) with a 565 kg Pb target. The spectra, otherwise well described by an exponential fit, show three peaks at high multiplicities. Although still at a low statistical significance, these small excesses match the outcome of an earlier measurement. The nature of the anomalies remains unclear, but, in principle, they may be a signature of self-annihilation of a WIMP with a mass close to 13 GeV/c2. With that assumption, the expected cross-section would be around 10-42 cm2 for Spin-Dependent or 10-46 cm2 for Spin Independent interactions. We propose verifying this hypothesis with an upgraded NEMESIS experiment, able to collect an order of magnitude more data than this measurement. Based on the statistical uncertainty, analysis of the event rate indicates that cross-section limits for DM mass range of approximately 3-40 GeV/c2 can be investigated with such a setup.Peer reviewe

NEMESIS setup for Indirect Detection of WIMPs

We summarize the evidence for DM-like anomalies in neutron multiplicity spectra collected underground with Pb targets by three independent experiments: NEMESIS (at 210 m.w.e.) NMDS (at 583 m.w.e.), and ZEPLIN-II (at 2850 m.w.e.). A new analysis shows small but persistent anomalies at high neutron multiplicities. Adjusted for differences in detection efficiencies, the positions of the anomalies are consistent between the three systems. Also, the intensities match when corrected for the acquisition time and estimated detection efficiency. While the three measurements are inconclusive when analyzed separately, together, they exclude a statistical fluke to better than one in a million. To prove the existence of the anomalies above the 5-sigma discovery threshold, we propose to upgrade the current NEMESIS setup. The upgrade concept and the critical components of the new experiment are described. The upgraded setup would already acquire the needed data sample during the first year of operation. Additional information, vital for the physics interpretation of the analysis, will be obtained with a Cu target.Peer reviewe

New NEMESIS Results

Funding Information: This work has been supported in part by the EU INTERREG for the Baltic Sea programme within the BSUIN project, and by the Polish Ministry of Science and Higher Education (Grant no. Funding Information: This work has been supported in part by the EU INTERREG for the Baltic Sea programme within the BSUIN project, and by the Polish Ministry of Science and Higher Education (Grant no. 3988/INTERREG BSR/2018/2). Publisher Copyright: © Copyright owned by the author(s) under the terms of the Creative Commons.Preliminary results from a 349-day run (live time) with a 565 kg Pb target and a 166-day background measurement are presented. Three minor anomalies were detected in muon-suppressed neutron multiplicity spectra. The multiplicities of these small excesses match the outcome of an earlier, similar but independent measurement. The nature of the anomalies remains unclear, but, in principle, they may be a signature of self-annihilation of a Weakly Interacting Massive Particle (WIMP) with a mass around 10 GeV/c2. If our interpretation is correct, the expected cross section would be of the order of 10-42 cm2 for Spin Dependent and 10-46 cm2 for Spin Independent interactions. Analysis of the event rate, based on the statistical uncertainty, indicates that cross-section limits for Dark Matter (DM) mass range of approximately 3-40 GeV/c2 can be investigated with an upgraded NEMESIS setup.Peer reviewe

Phase I study of sorafenib combined with radiation therapy and temozolomide as first-line treatment of high-grade glioma.

BACKGROUND: Sorafenib (Sb) is a multiple kinase inhibitor targeting both tumour cell proliferation and angiogenesis that may further act as a potent radiosensitizer by arresting cells in the most radiosensitive cell cycle phase. This phase I open-label, noncontrolled dose escalation study was performed to determine the safety and maximum tolerated dose (MTD) of Sb in combination with radiation therapy (RT) and temozolomide (TMZ) in 17 patients with newly diagnosed high-grade glioma. METHODS: Patients were treated with RT (60 Gy in 2 Gy fractions) combined with TMZ 75 mg m(-2) daily, and Sb administered at three dose levels (200 mg daily, 200 mg BID, and 400 mg BID) starting on day 8 of RT. Thirty days after the end of RT, patients received monthly TMZ (150-200 mg m(-2) D1-5/28) and Sb (400 mg BID). Pharmacokinetic (PK) analyses were performed on day 8 (TMZ) and on day 21 (TMZ&Sb) (Clinicaltrials ID: NCT00884416). RESULTS: The MTD of Sb was established at 200 mg BID. Dose-limiting toxicities included thrombocytopenia (two patients), diarrhoea (one patient) and hypercholesterolaemia (one patient). Sb administration did not affect the mean area under the curve(0-24) and mean Cmax of TMZ and its metabolite 5-amino-imidazole-4-carboxamide (AIC). Tmax of both TMZ and AIC was delayed from 0.75 (TMZ alone) to 1.5 h (combined TMZ/Sb). The median progression-free survival was 7.9 months (95% confidence interval (CI): 5.4-14.55), and the median overall survival was 17.8 months (95% CI: 14.7-25.6). CONCLUSIONS: Although Sb can be combined with RT and TMZ, significant side effects and moderate outcome results do not support further clinical development in malignant gliomas. The robust PK data of the TMZ/Sb combination could be useful in other cancer settings

Expression, mutation and copy number analysis of platelet-derived growth factor receptor A (PDGFRA) and its ligand PDGFA in gliomas

BACKGROUND: Malignant gliomas are the most prevalent type of primary brain tumours but the therapeutic armamentarium for these tumours is limited. Platelet-derived growth factor (PDGF) signalling has been shown to be a key regulator of glioma development. Clinical trials evaluating the efficacy of anti-PDGFRA therapies on gliomas are ongoing. In this study, we intended to analyse the expression of PDGFA and its receptor PDGFRA, as well as the underlying genetic (mutations and amplification) mechanisms driving their expression in a large series of human gliomas. METHODS: PDGFA and PDGFRA expression was evaluated by immunohistochemistry in a series of 160 gliomas of distinct World Health Organization (WHO) malignancy grade. PDGFRA-activating gene mutations (exons 12, 18 and 23) were assessed in a subset of 86 cases by PCR-single-strand conformational polymorphism (PCR-SSCP), followed by direct sequencing. PDGFRA gene amplification analysis was performed in 57 cases by quantitative real-time PCR (QPCR) and further validated in a subset of cases by chromogenic in situ hybridisation (CISH) and microarray-based comparative genomic hybridisation (aCGH). RESULTS: PDGFA and PDGFRA expression was found in 81.2% (130 out of 160) and 29.6% (48 out of 160) of gliomas, respectively. Its expression was significantly correlated with histological type of the tumours; however, no significant association between the expression of the ligand and its receptor was observed. The absence of PDGFA expression was significantly associated with the age of patients and with poor prognosis. Although PDGFRA gene-activating mutations were not found, PDGFRA gene amplification was observed in 21.1% (12 out of 57) of gliomas. No association was found between the presence of PDGFRA gene amplification and expression, excepting for grade II diffuse astrocytomas. CONCLUSION: The concurrent expression of PDGFA and PDGFRA in different subtypes of gliomas, reinforce the recognised significance of this signalling pathway in gliomas. PDGFRA gene amplification rather than gene mutation may be the underlying genetic mechanism driving PDGFRA overexpression in a portion of gliomas. Taken together, our results could provide in the future a molecular basis for PDGFRA-targeted therapies in gliomas