Biomarkers in anal cancer: from biological understanding to stratified treatment

Squamous cell carcinomas of the anus and anal canal represent a model of a cancer and perhaps the first where level 1 evidence supported primary chemoradiotherapy (CRT) in treating locoregional disease with curative intent. The majority of tumours are associated with infection with oncogenic subtypes of human papilloma virus and this plays a significant role in their sensitivity to treatment. However, not all tumours are cured with CRT and there remain opportunities to improve outcomes in terms of oncological control and also reducing late toxicities. Understanding the biology of ASCC promises to allow a more personalised approach to treatment, with the development and validation of a range of biomarkers and associated techniques that are the focus of this review

Searches for Neutrinos from Gamma-Ray Bursts using the IceCube Neutrino Observatory

Gamma-ray bursts (GRBs) are considered as promising sources of ultra-high-energy cosmic rays (UHECRs) due to their large power output. Observing a neutrino flux from GRBs would offer evidence that GRBs are hadronic accelerators of UHECRs. Previous IceCube analyses, which primarily focused on neutrinos arriving in temporal coincidence with the prompt gamma rays, found no significant neutrino excess. The four analyses presented in this paper extend the region of interest to 14 days before and after the prompt phase, including generic extended time windows and targeted precursor searches. GRBs were selected between May 2011 and October 2018 to align with the data set of candidate muon-neutrino events observed by IceCube. No evidence of correlation between neutrino events and GRBs was found in these analyses. Limits are set to constrain the contribution of the cosmic GRB population to the diffuse astrophysical neutrino flux observed by IceCube. Prompt neutrino emission from GRBs is limited to $\lesssim$1% of the observed diffuse neutrino flux, and emission on timescales up to $10^4$ s is constrained to 24% of the total diffuse flux

Searching for High-energy Neutrino Emission from Galaxy Clusters with IceCube

Galaxy clusters have the potential to accelerate cosmic rays (CRs) to ultrahigh energies via accretion shocks or embedded CR acceleration sites. The CRs with energies below the Hillas condition will be confined within the cluster and eventually interact with the intracluster medium gas to produce secondary neutrinos and gamma rays. Using 9.5 yr of muon neutrino track events from the IceCube Neutrino Observatory, we report the results of a stacking analysis of 1094 galaxy clusters with masses ≳10$^{14}$ M⊙ and redshifts between 0.01 and ∼1 detected by the Planck mission via the Sunyaev–Zel’dovich effect. We find no evidence for significant neutrino emission and report upper limits on the cumulative unresolved neutrino flux from massive galaxy clusters after accounting for the completeness of the catalog up to a redshift of 2, assuming three different weighting scenarios for the stacking and three different power-law spectra. Weighting the sources according to mass and distance, we set upper limits at a 90% confidence level that constrain the flux of neutrinos from massive galaxy clusters (≳10$^{14}$ M⊙) to be no more than 4.6% of the diffuse IceCube observations at 100 TeV, assuming an unbroken E−$^{2.5}$ power-law spectrum

Search for Astrophysical Neutrinos from 1FLE Blazars with IceCube

The majority of astrophysical neutrinos have undetermined origins. The IceCube Neutrino Observatory has observed astrophysical neutrinos but has not yet identified their sources. Blazars are promising source candidates, but previous searches for neutrino emission from populations of blazars detected in ≳GeV gamma rays have not observed any significant neutrino excess. Recent findings in multimessenger astronomy indicate that high-energy photons, coproduced with high-energy neutrinos, are likely to be absorbed and reemitted at lower energies. Thus, lower-energy photons may be better indicators of TeV–PeV neutrino production. This paper presents the first time-integrated stacking search for astrophysical neutrino emission from MeV-detected blazars in the first Fermi Large Area Telescope low energy (1FLE) catalog using ten years of IceCube muon–neutrino data. The results of this analysis are found to be consistent with a background-only hypothesis. Assuming an E$^{-2}$ neutrino spectrum and proportionality between the blazars MeV gamma-ray fluxes and TeV–PeV neutrino flux, the upper limit on the 1FLE blazar energy-scaled neutrino flux is determined to be 1.64 × 10^-12} TeV cm$^{-2}$ s$^{-1}$ at 90% confidence level. This upper limit is approximately 1% of IceCube\u27s diffuse muon–neutrino flux measurement

A Search for Coincident Neutrino Emission from Fast Radio Bursts with Seven Years of IceCube Cascade Events

This paper presents the results of a search for neutrinos that are spatially and temporally coincident with 22 unique, non-repeating Fast Radio Bursts (FRBs) and one repeating FRB (FRB121102). FRBs are a rapidly growing class of Galactic and extragalactic astrophysical objects that are considered a potential source of high-energy neutrinos. The IceCube Neutrino Observatory's previous FRB analyses have solely used track events. This search utilizes seven years of IceCube's cascade events which are statistically independent of the track events. This event selection allows probing of a longer range of extended timescales due to the low background rate. No statistically significant clustering of neutrinos was observed. Upper limits are set on the time-integrated neutrino flux emitted by FRBs for a range of extended time-windows

Constraining High-energy Neutrino Emission from Supernovae with IceCube

Core-collapse supernovae are a promising potential high-energy neutrino source class. We test for correlation between seven years of IceCube neutrino data and a catalog containing more than 1000 core-collapse supernovae of types IIn and IIP and a sample of stripped-envelope supernovae. We search both for neutrino emission from individual supernovae, and for combined emission from the whole supernova sample through a stacking analysis. No significant spatial or temporal correlation of neutrinos with the cataloged supernovae was found. The overall deviation of all tested scenarios from the background expectation yields a p-value of 93% which is fully compatible with background. The derived upper limits on the total energy emitted in neutrinos are 1.7×10$^{48}$ erg for stripped-envelope supernovae, 2.8×10$^{48}$ erg for type IIP, and 1.3×10$^{49}$ erg for type IIn SNe, the latter disfavouring models with optimistic assumptions for neutrino production in interacting supernovae. We conclude that strippe-envelope supernovae and supernovae of type IIn do not contribute more than 14.6% and 33.9% respectively to the diffuse neutrino flux in the energy range of about 10$^3$−10$^5$ GeV, assuming that the neutrino energy spectrum follows a power-law with an index of −2.5. Under the same assumption, we can only constrain the contribution of type IIP SNe to no more than 59.9%. Thus core-collapse supernovae of types IIn and stripped-envelope supernovae can both be ruled out as the dominant source of the diffuse neutrino flux under the given assumptions

Measurement of atmospheric neutrino mixing with improved IceCube DeepCore calibration and data processing

We describe a new data sample of IceCube DeepCore and report on the latest measurement of atmospheric neutrino oscillations obtained with data recorded between 2011–2019. The sample includes significant improvements in data calibration, detector simulation, and data processing, and the analysis benefits from a sophisticated treatment of systematic uncertainties, with significantly greater level of detail since our last study. By measuring the relative fluxes of neutrino flavors as a function of their reconstructed energies and arrival directions we constrain the atmospheric neutrino mixing parameters to be sin2θ23=0.51±0.05 and Δm232=2.41±0.07×10−3  eV2, assuming a normal mass ordering. The errors include both statistical and systematic uncertainties. The resulting 40% reduction in the error of both parameters with respect to our previous result makes this the most precise measurement of oscillation parameters using atmospheric neutrinos. Our results are also compatible and complementary to those obtained using neutrino beams from accelerators, which are obtained at lower neutrino energies and are subject to different sources of uncertainties

Searches for Neutrinos from LHAASO ultra-high-energy {\gamma}-ray sources using the IceCube Neutrino Observatory

Galactic PeVatrons are Galactic sources theorized to accelerate cosmic rays up to PeV in energy. The accelerated cosmic rays are expected to interact hadronically with nearby ambient gas or the interstellar medium, resulting in {\gamma}-rays and neutrinos. Recently, the Large High Altitude Air Shower Observatory (LHAASO) identified 12 {\gamma}-ray sources with emissions above 100 TeV, making them candidates for PeV cosmic-ray accelerators (PeVatrons). While at these high energies the Klein-Nishina effect suppresses exponentially leptonic emission from Galactic sources, evidence for neutrino emission would unequivocally confirm hadronic acceleration. Here, we present the results of a search for neutrinos from these {\gamma}-ray sources and stacking searches testing for excess neutrino emission from all 12 sources as well as their subcatalogs of supernova remnants and pulsar wind nebulae with 11 years of track events from the IceCube Neutrino Observatory. No significant emissions were found. Based on the resulting limits, we place constraints on the fraction of {\gamma}-ray flux originating from the hadronic processes in the Crab Nebula and LHAASOJ2226+6057