Observation of Seven Astrophysical Tau Neutrino Candidates with IceCube.

We report on a measurement of astrophysical tau neutrinos with 9.7 yr of IceCube data. Using convolutional neural networks trained on images derived from simulated events, seven candidate ν_{τ} events were found with visible energies ranging from roughly 20 TeV to 1 PeV and a median expected parent ν_{τ} energy of about 200 TeV. Considering backgrounds from astrophysical and atmospheric neutrinos, and muons from π^{±}/K^{±} decays in atmospheric air showers, we obtain a total estimated background of about 0.5 events, dominated by non-ν_{τ} astrophysical neutrinos. Thus, we rule out the absence of astrophysical ν_{τ} at the 5σ level. The measured astrophysical ν_{τ} flux is consistent with expectations based on previously published IceCube astrophysical neutrino flux measurements and neutrino oscillations.

Multidimensional Analysis of the Adult Human Heart in Health and Disease using Hierarchical Phase-Contrast Tomography (HiP-CT).

Cardiovascular diseases (CVDs) are a leading cause of death worldwide. Current clinical imaging modalities provide resolution adequate for diagnosis but are unable to provide detail of structural changes in the heart, across length-scales, necessary for understanding underlying pathophysiology of disease. Hierarchical Phase-Contrast Tomography (HiP-CT), using new (4th) generation synchrotron sources, potentially overcomes this limitation, allowing micron resolution imaging of intact adult organs with unprecedented detail. In this proof of principle study (n=2), we show the utility of HiP-CT to image whole adult human hearts ex-vivo: one 'control' without known cardiac disease and one with multiple known cardiopulmonary pathologies. The resulting multiscale imaging was able to demonstrate exemplars of anatomy in each cardiac segment along with novel findings in the cardiac conduction system, from gross (20 um/voxel) to cellular scale (2.2 um/voxel), non-destructively, thereby bridging the gap between macroscopic and microscopic investigations. We propose that the technique represents a significant step in virtual autopsy methods for studying structural heart disease, facilitating research into abnormalities across scales and age-groups. It opens up possibilities for understanding and treating disease; and provides a cardiac 'blueprint' with potential for in-silico simulation, device design, virtual surgical training, and bioengineered heart in the future.

Imaging Cerebral Blood Vessels Using Near-Infrared Optical Tomography: A Simulation Study.

Cerebral veins have received increasing attention due to their importance in preoperational planning and the brain oxygenation measurement. There are different modalities to image those vessels, such as magnetic resonance angiography (MRA) and recently, contrast-enhanced (CE) 3D gradient-echo sequences. However, the current techniques have certain disadvantages, i.e., the long examination time, the requirement of contrast agents or inability to measure oxygenation. Near-infrared optical tomography (NIROT) is emerging as a viable new biomedical imaging modality that employs near infrared light (650-950 nm) to image biological tissue. It was proven to easily penetrate the skull and therefore enables the brain vessels to be assessed. NIROT utilizes safe non-ionizing radiation and can be applied in e.g., early detection of neonatal brain injury and ischemic strokes. The aim is to develop non-invasive label-free dynamic time domain (TD) NIROT to image the brain vessels. A simulation study was performed with the software (NIRFAST) which models light propagation in tissue with the finite element method (FEM). Both a simple shape mesh and a real head mesh including all the segmented vessels from MRI images were simulated using both FEM and a hybrid FEM-U-Net network, we were able to visualize the superficial vessels with NIROT with a Root Mean Square Error (RMSE) lower than 0.079.

Observation of high-energy neutrinos from the Galactic plane.

The origin of high-energy cosmic rays, atomic nuclei that continuously impact Earth's atmosphere, is unknown. Because of deflection by interstellar magnetic fields, cosmic rays produced within the Milky Way arrive at Earth from random directions. However, cosmic rays interact with matter near their sources and during propagation, which produces high-energy neutrinos. We searched for neutrino emission using machine learning techniques applied to 10 years of data from the IceCube Neutrino Observatory. By comparing diffuse emission models to a background-only hypothesis, we identified neutrino emission from the Galactic plane at the 4.5σ level of significance. The signal is consistent with diffuse emission of neutrinos from the Milky Way but could also arise from a population of unresolved point sources.

How social media can help to understand treatment experiences of survivors of rare cancers: Findings from the Granulosa Cell Tumor Survivor Sisters Facebook group member survey.

BACKGROUND: Engaging with online social media consumer groups for rare cancers may help to develop collaborations between consumers and researchers. This study, a collaboration with the Granulosa Cell Tumor-Survivor Sisters (GCT-SS) Facebook group, explores the results of their survey of member's treatment and follow-up experiences. METHODS: Members of the closed multinational GCT-SS Facebook group completed a 43-item survey covering symptoms, diagnosis, treatment, recurrence, follow-up, and possible risk factors for GCT. Group members could have adult (aGCT) or juvenile (jGCT) disease. Data was collected via an online survey between 2014 and 2019. RESULTS: A total of 743 members (average 4.4 years [SD = 5.9] post-diagnosis) participated including 52 with jGCT. A total of 67% had stage I disease and 8% had stage III-IV at diagnosis, although 30% of aGCT and 25% of jGCT reported recurrent disease at survey completion. A total of 48% of aGCT had laparoscopic surgery, tumor encapsulation was reported by 49%, and tumor bagging reported by 29% overall (37% laparoscopic; 8% open). Recurrence rates were higher when the tumor was cut or ruptured (ruptured: p < .001; cut: p = .01). A total of 19% of aGCT had chemotherapy with this most common for stage II-III disease. Bleomycin, etoposide, and cisplatin protocols became less common over time (diagnosed before 2015: 47% vs. diagnosed post-2015: 21%). CONCLUSIONS: This is one of the largest surveys of GCT treatment. Members of the GCT-SS group report treatment patterns generally in line with those found from clinical audits. Using naturally forming consumer groups may assist with developing the evidence base for care and supporting those living with GCT ovarian cancer. PLAIN LANGUAGE SUMMARY: This study is a collaboration between members of Granulosa Cell Tumor-Survivor Sisters (GCT-SS) Facebook group and researchers to assess members' experiences of treatment and follow-up. A total of 743 members (52 with juvenile GCT) completed an online survey. A total of 67% had stage I disease at diagnosis. Treatment patterns were generally in line with those found from clinical audits: 95% had surgery and 19% of those with adult GCT had chemotherapy. A total of 30% reported recurrent disease, with recurrence occurring within 5 years of diagnosis for 33%. Using naturally forming consumer groups may assist with developing the evidence base for care and supporting those living with GCT ovarian cancer.

Preparation of large biological samples for high-resolution, hierarchical, synchrotron phase-contrast tomography with multimodal imaging compatibility.

Imaging across different scales is essential for understanding healthy organ morphology and pathophysiological changes. The macro- and microscale three-dimensional morphology of large samples, including intact human organs, is possible with X-ray microtomography (using laboratory or synchrotron sources). Preparation of large samples for high-resolution imaging, however, is challenging due to limitations such as sample shrinkage, insufficient contrast, movement of the sample and bubble formation during mounting or scanning. Here, we describe the preparation, stabilization, dehydration and mounting of large soft-tissue samples for X-ray microtomography. We detail the protocol applied to whole human organs and hierarchical phase-contrast tomography at the European Synchrotron Radiation Facility, yet it is applicable to a range of biological samples, including complete organisms. The protocol enhances the contrast when using X-ray imaging, while preventing sample motion during the scan, even with different sample orientations. Bubbles trapped during mounting and those formed during scanning (in the case of synchrotron X-ray imaging) are mitigated by multiple degassing steps. The sample preparation is also compatible with magnetic resonance imaging, computed tomography and histological observation. The sample preparation and mounting require 24-36 d for a large organ such as a whole human brain or heart. The preparation time varies depending on the composition, size and fragility of the tissue. Use of the protocol enables scanning of intact organs with a diameter of 150 mm with a local voxel size of 1 µm. The protocol requires users with expertise in handling human or animal organs, laboratory operation and X-ray imaging.

Effects of Different Optical Properties of Head Tissues on Near-Infrared Spectroscopy Using Monte Carlo Simulations.

In near-infrared spectroscopy (NIRS), it is crucial to have an accurate and realistic model of photon transport in the adult head for obtaining accurate brain oxygenation values. There are several studies on the influence of thickness, the morphology of extracerebral layers, and source-detector distance on the sensitivity of NIRS to the brain. However, the optical properties of the different layers vary between different publications. How is the performance of NIRS affected when the real optical properties differ from the assumed ones?We aim to investigate the influence of variation in scattering and absorption in a five-layered head model (scalp, skull, CSF, grey and white matter). We performed Monte Carlo simulations focusing on a five-layered slab mesh. The range of optical properties is based on a review of the published literature. We assessed the effect on light propagation by measuring the difference in the mean partial path lengths, attenuation, and the number of the detected photons between the different optical properties performing Monte Carlo simulations. For changes in the reduced scattering, we found that the upper layers tend to have a negative impact. In contrast, changes in lower layers tend to impact the brain's influence metrics positively. Furthermore, for small source-detector distances, the relative percentage difference between lower and higher values is greater than larger distances. Conclusions: We conclude that the assumption of different optical properties has a substantial effect on the sensitivity to the brain. This means that it is important to determine the correct optical properties for NIRS measurements in vitro and in vivo.

Development and Validation of Robust and Cost-Effective Liquid Heterogeneous Phantom for Time Domain Near-Infrared Optical Tomography.

Diffused light imaging techniques, such as near-infrared optical tomography (NIROT), require a stable platform for testing and validation that imitates tissue optical properties. The aim of this work was to build a robust, but flexible liquid phantom for BORL time-domain NIROT system Pioneer. The phantom was designed to assess penetration depth and resolution of the system, and to provide a heterogeneous inner structure that can be changed in controllable manner with adjustable optical properties. We used only in-house produced 3D-printed elements and mechanics of a budget 3D-printer to build the phantom, and managed to keep the overall costs below $500. We achieved stable and repeatable movement of an arbitrary structure in 3+1 degree of freedom inside the phantom and demonstrated its performance in a series of tests. Thus, we presented a universal and cost-effective solution for testing NIROT, that can be easily customised to various systems or testing paradigms.

Evidence for neutrino emission from the nearby active galaxy NGC 1068.

A supermassive black hole, obscured by cosmic dust, powers the nearby active galaxy NGC 1068. Neutrinos, which rarely interact with matter, could provide information on the galaxy's active core. We searched for neutrino emission from astrophysical objects using data recorded with the IceCube neutrino detector between 2011 and 2020. The positions of 110 known gamma-ray sources were individually searched for neutrino detections above atmospheric and cosmic backgrounds. We found that NGC 1068 has an excess of [Formula: see text] neutrinos at tera-electron volt energies, with a global significance of 4.2σ, which we interpret as associated with the active galaxy. The flux of high-energy neutrinos that we measured from NGC 1068 is more than an order of magnitude higher than the upper limit on emissions of tera-electron volt gamma rays from this source.

Search for Unstable Sterile Neutrinos with the IceCube Neutrino Observatory.

We present a search for an unstable sterile neutrino by looking for a resonant signal in eight years of atmospheric ν_{µ} data collected from 2011 to 2019 at the IceCube Neutrino Observatory. Both the (stable) three-neutrino and the 3+1 sterile neutrino models are disfavored relative to the unstable sterile neutrino model, though with p values of 2.8% and 0.81%, respectively, we do not observe evidence for 3+1 neutrinos with neutrino decay. The best-fit parameters for the sterile neutrino with decay model from this study are Δm_{41}^{2}=6.7_{-2.5}^{+3.9} eV^{2}, sin^{2}2θ_{24}=0.33_{-0.17}^{+0.20}, and g^{2}=2.5π±1.5π, where g is the decay-mediating coupling. The preferred regions of the 3+1+decay model from short-baseline oscillation searches are excluded at 90% C.L.

Strong Constraints on Neutrino Nonstandard Interactions from TeV-Scale ν_{µ} Disappearance at IceCube.

We report a search for nonstandard neutrino interactions (NSI) using eight years of TeV-scale atmospheric muon neutrino data from the IceCube Neutrino Observatory. By reconstructing incident energies and zenith angles for atmospheric neutrino events, this analysis presents unified confidence intervals for the NSI parameter ε_{µτ}. The best-fit value is consistent with no NSI at a p value of 25.2%. With a 90% confidence interval of -0.0041≤ε_{µτ}≤0.0031 along the real axis and similar strength in the complex plane, this result is the strongest constraint on any NSI parameter from any oscillation channel to date.

Search for Relativistic Magnetic Monopoles with Eight Years of IceCube Data.

We present an all-sky 90% confidence level upper limit on the cosmic flux of relativistic magnetic monopoles using 2886 days of IceCube data. The analysis was optimized for monopole speeds between 0.750c and 0.995c, without any explicit restriction on the monopole mass. We constrain the flux of relativistic cosmic magnetic monopoles to a level below 2.0×10^{-19} cm^{-2} s^{-1} sr^{-1} over the majority of the targeted speed range. This result constitutes the most strict upper limit to date for magnetic monopoles with ß≳0.8 and up to ß∼0.995 and fills the gap between existing limits on the cosmic flux of nonrelativistic and ultrarelativistic magnetic monopoles.

Imaging intact human organs with local resolution of cellular structures using hierarchical phase-contrast tomography.

Imaging intact human organs from the organ to the cellular scale in three dimensions is a goal of biomedical imaging. To meet this challenge, we developed hierarchical phase-contrast tomography (HiP-CT), an X-ray phase propagation technique using the European Synchrotron Radiation Facility (ESRF)'s Extremely Brilliant Source (EBS). The spatial coherence of the ESRF-EBS combined with our beamline equipment, sample preparation and scanning developments enabled us to perform non-destructive, three-dimensional (3D) scans with hierarchically increasing resolution at any location in whole human organs. We applied HiP-CT to image five intact human organ types: brain, lung, heart, kidney and spleen. HiP-CT provided a structural overview of each whole organ followed by multiple higher-resolution volumes of interest, capturing organotypic functional units and certain individual specialized cells within intact human organs. We demonstrate the potential applications of HiP-CT through quantification and morphometry of glomeruli in an intact human kidney and identification of regional changes in the tissue architecture in a lung from a deceased donor with coronavirus disease 2019 (COVID-19).

Dynamic contrast-enhanced magnetic resonance imaging for monitoring neovascularization during bone regeneration-a randomized in vivo study in rabbits.

OBJECTIVES: Micro-computed tomography (µ-CT) and histology, the current gold standard methods for assessing the formation of new bone and blood vessels, are invasive and/or destructive. With that in mind, a more conservative tool, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), was tested for its accuracy and reproducibility in monitoring neovascularization during bone regeneration. Additionally, the suitability of blood perfusion as a surrogate of the efficacy of osteoplastic materials was evaluated. MATERIALS AND METHODS: Sixteen rabbits were used and equally divided into four groups, according to the time of euthanasia (2, 3, 4, and 6 weeks after surgery). The animals were submitted to two 8-mm craniotomies that were filled with blood or autogenous bone. Neovascularization was assessed in vivo through DCE-MRI, and bone regeneration, ex vivo, through µ-CT and histology. RESULTS: The defects could be consistently identified, and their blood perfusion measured through DCE-MRI, there being statistically significant differences within the blood clot group between 3 and 6 weeks (p = 0.029), and between the former and autogenous bone at six weeks (p = 0.017). Nonetheless, no significant correlations between DCE-MRI findings on neovascularization and µ-CT (r =-0.101, 95% CI [-0.445; 0.268]) or histology (r = 0.305, 95% CI [-0.133; 0.644]) findings on bone regeneration were observed. CONCLUSIONS: These results support the hypothesis that DCE-MRI can be used to monitor neovascularization but contradict the premise that it could predict bone regeneration as well.

Multiscale three-dimensional imaging of intact human organs down to the cellular scale using hierarchical phase-contrast tomography.

Human organs are complex, three-dimensional and multiscale systems. Spatially mapping the human body down through its hierarchy, from entire organs to their individual functional units and specialised cells, is a major obstacle to fully understanding health and disease. To meet this challenge, we developed hierarchical phase-contrast tomography (HiP-CT), an X-ray phase propagation technique utilising the European Synchrotron Radiation Facility's Extremely Brilliant Source: the world's first high-energy 4 th generation X-ray source. HiP-CT enabled three-dimensional and non-destructive imaging at near-micron resolution in soft tissues at one hundred thousand times the voxel size whilst maintaining the organ's structure. We applied HiP-CT to image five intact human parenchymal organs: brain, lung, heart, kidney and spleen. These were hierarchically assessed with HiP-CT, providing a structural overview of the whole organ alongside detail of the organ's individual functional units and cells. The potential applications of HiP-CT were demonstrated through quantification and morphometry of glomeruli in an intact human kidney, and identification of regional changes to the architecture of the air-tissue interface and alveolar morphology in the lung of a deceased COVID-19 patient. Overall, we show that HiP-CT is a powerful tool which can provide a comprehensive picture of structural information for whole intact human organs, encompassing precise details on functional units and their constituent cells to better understand human health and disease.

eV-Scale Sterile Neutrino Search Using Eight Years of Atmospheric Muon Neutrino Data from the IceCube Neutrino Observatory.

The results of a 3+1 sterile neutrino search using eight years of data from the IceCube Neutrino Observatory are presented. A total of 305 735 muon neutrino events are analyzed in reconstructed energy-zenith space to test for signatures of a matter-enhanced oscillation that would occur given a sterile neutrino state with a mass-squared differences between 0.01 and 100 eV^{2}. The best-fit point is found to be at sin^{2}(2θ_{24})=0.10 and Δm_{41}^{2}=4.5 eV^{2}, which is consistent with the no sterile neutrino hypothesis with a p value of 8.0%.

Characteristics of the Diffuse Astrophysical Electron and Tau Neutrino Flux with Six Years of IceCube High Energy Cascade Data.

We report on the first measurement of the astrophysical neutrino flux using particle showers (cascades) in IceCube data from 2010-2015. Assuming standard oscillations, the astrophysical neutrinos in this dedicated cascade sample are dominated (∼90%) by electron and tau flavors. The flux, observed in the sensitive energy range from 16 TeV to 2.6 PeV, is consistent with a single power-law model as expected from Fermi-type acceleration of high energy particles at astrophysical sources. We find the flux spectral index to be γ=2.53±0.07 and a flux normalization for each neutrino flavor of ϕ_{astro}=1.66_{-0.27}^{+0.25} at E_{0}=100 TeV, in agreement with IceCube's complementary muon neutrino results and with all-neutrino flavor fit results. In the measured energy range we reject spectral indices γ≤2.28 at ≥3σ significance level. Because of high neutrino energy resolution and low atmospheric neutrino backgrounds, this analysis provides the most detailed characterization of the neutrino flux at energies below ∼100 TeV compared to previous IceCube results. Results from fits assuming more complex neutrino flux models suggest a flux softening at high energies and a flux hardening at low energies (p value ≥0.06). The sizable and smooth flux measured below ∼100 TeV remains a puzzle. In order to not violate the isotropic diffuse gamma-ray background as measured by the Fermi Large Area Telescope, it suggests the existence of astrophysical neutrino sources characterized by dense environments which are opaque to gamma rays.

Time-Integrated Neutrino Source Searches with 10 Years of IceCube Data.

This Letter presents the results from pointlike neutrino source searches using ten years of IceCube data collected between April 6, 2008 and July 10, 2018. We evaluate the significance of an astrophysical signal from a pointlike source looking for an excess of clustered neutrino events with energies typically above ∼1 TeV among the background of atmospheric muons and neutrinos. We perform a full-sky scan, a search within a selected source catalog, a catalog population study, and three stacked Galactic catalog searches. The most significant point in the northern hemisphere from scanning the sky is coincident with the Seyfert II galaxy NGC 1068, which was included in the source catalog search. The excess at the coordinates of NGC 1068 is inconsistent with background expectations at the level of 2.9σ after accounting for statistical trials from the entire catalog. The combination of this result along with excesses observed at the coordinates of three other sources, including TXS 0506+056, suggests that, collectively, correlations with sources in the northern catalog are inconsistent with background at 3.3σ significance. The southern catalog is consistent with background. These results, all based on searches for a cumulative neutrino signal integrated over the 10 years of available data, motivate further study of these and similar sources, including time-dependent analyses, multimessenger correlations, and the possibility of stronger evidence with coming upgrades to the detector.

Constraints on Minute-Scale Transient Astrophysical Neutrino Sources.

High-energy neutrino emission has been predicted for several short-lived astrophysical transients including gamma-ray bursts (GRBs), core-collapse supernovae with choked jets, and neutron star mergers. IceCube's optical and x-ray follow-up program searches for such transient sources by looking for two or more muon neutrino candidates in directional coincidence and arriving within 100 s. The measured rate of neutrino alerts is consistent with the expected rate of chance coincidences of atmospheric background events and no likely electromagnetic counterparts have been identified in Swift follow-up observations. Here, we calculate generic bounds on the neutrino flux of short-lived transient sources. Assuming an E^{-2.5} neutrino spectrum, we find that the neutrino flux of rare sources, like long gamma-ray bursts, is constrained to <5% of the detected astrophysical flux and the energy released in neutrinos (100 GeV to 10 PeV) by a median bright GRB-like source is <10^{52.5} erg. For a harder E^{-2.13} neutrino spectrum up to 30% of the flux could be produced by GRBs and the allowed median source energy is <10^{52} erg. A hypothetical population of transient sources has to be more common than 10^{-5} Mpc^{-3} yr^{-1} (5×10^{-8} Mpc^{-3} yr^{-1} for the E^{-2.13} spectrum) to account for the complete astrophysical neutrino flux.

A comparative performance analysis of stand-alone, off-grid solar-powered sodium hypochlorite generators.

Sodium hypochlorite (NaClO) is a chemical commodity widely employed as a disinfection agent in water treatment applications. Its production commonly follows electrochemical routes in an undivided reactor. Powering the process with photovoltaic (PV) electricity holds the potential to install stand-alone, independent generators and reduce the NaClO production cost. This study reports the comparative assessment of autonomous, solar-powered sodium hypochlorite generators employing different photovoltaic (PV) technologies: silicon hetero-junction (SHJ) and multi-junction (MJ) solar cells. For Si hetero-junctions, the series connection of either four or five SHJ (4SHJ and 5SHJ, respectively) cells was implemented to obtain the reaction potential required. MJ cells were illuminated by a novel planar solar concentrator that guarantees solar tracking with minimal linear displacements. The three solar-hypochlorite generators were tested under real atmospheric conditions, demonstrating solar-to-chemical conversion efficiencies (SCE) of 9.8% for 4SHJ, 14.2% for 5SHJ and 25.1% for MJ solar cells, respectively. Simulations based on weather databases allowed us to assess efficiencies throughout the entire model year and resulted in specific sodium hypochlorite yearly production rates between 7.2-28 gNaClO cm-2 (referred to the PV surface), depending on the considered PV technology, location, and deployment of electronics converters. The economic viability and competitiveness of solar hypochlorite generators have been investigated and compared with an analog disinfection system deploying ultraviolet lamps. Our study demonstrates the feasibility of off-grid, solar-hypochlorite generators, and points towards the implementation of SHJ solar cells as a reliable technology for stand-alone solar-chemical devices.