The CeRN (RHCE*02.10) allele was described as resulting from hybrid RHCE-D-CE genes, involving either exon 4 alone or exon 4 and part of exon 3. No solution allows to distinguish between the two reported CeRN alleles. The objectives of this study were to determine the existence of both alleles, their genetic sequence and their frequencies. We investigated 17 heterozygous CeRN samples and 10 homozygous CeRN samples, and described the junction between the RHCE and RHD genes. Analysis combined classical PCR associated with Sanger sequencing, and Oxford Nanopore NGS applied to long-range PCR. We also explored CeRN allelic frequency in sub-Saharan populations from the 1000 Genomes Project and the International Genome Sample Resource. One CeRN allele sequence was observed, involving exon 4 alone with an RHCE-RHD junction approximately 400 base-pairs upstream of exon 4. We observed the CeRN allele in Gambian ethnic groups, with a maximum allelic frequency of 6.0% in the Fula group. The CeRN allele involving exon 4 and part of exon 3 was not observed here, supporting at least a low frequency, as our sample size limited the power to investigate this putative second CeRN variant. The homogeneity of the CeRN sequence observed in DNA samples and the high allelic frequency are consistent with a single genetic founder event in the Fula ancestral group.Nearly 20% of individuals in The Gambia have abnormal hemoglobin. Knowledge of CeRN genetic architecture and frequency may have significant implications for more precise molecular diagnostics and transfusion therapy. The probabilistic pipeline developed here, based on subset of samples for which both DNA and WGS data were available, showed that WGS low-coverage data can be used to investigate complex genetic variants in population studies.
How do organized scientific interests shape the agenda of science, technology, and innovation (STI) policy in the European Union (EU)? I address this question by investigating how the so-called "CERN for Artificial Intelligence (AI)" initiative, a proposal to organize Europe's AI research in a CERN-like ecosystem, made it onto the agenda of EU policymakers. Drawing on the interest group as well as agenda-setting scholarship and triangulating data from multiple sources, I argue that the Confederation of Laboratories for AI Research in Europe, a scientific interest group, pushed the initiative onto the EU's informal (pre-decisional) policy agenda through direct and indirect lobbying. I also demonstrate that CERN for AI has so far failed to enter Brussel's formal (decision) agenda because of turf battles between organized scientific interests; a lack of experience, resources, and time among its advocates; the fragmentation of EU AI research policy and funding; as well as the initiative's framing. My findings add to the study of STI policymaking in the EU, which has so far focused on individual policymakers, bureaucrats, or political institutions as policy entrepreneurs while neglecting to study the role of organized scientific interests in STI policy agenda-setting. The online version contains supplementary material available at 10.1007/s11024-024-09568-6.
Salvage therapies for adults with recurrent ependymoma are limited. A prior retrospective review of patients with recurrent ependymomas treated with bevacizumab and carboplatin reported a 75% radiographic response rate. This prospective single-arm, open-label Phase 2 study was designed to assess clinical efficacy of this regimen. Twenty-two patients were evaluated in this CERN Adult Clinical Trials network study. Adult patients (age ≥18) with recurrent ependymomas received carboplatin (AUC = 5-6) every 4 weeks and bevacizumab 10mg/kg every 2 weeks for 6 cycles, after which carboplatin was discontinued, while bevacizumab could be continued at physician's discretion. Imaging of areas involved and patient-reported outcomes (PRO) with the MD Anderson Symptom Inventory (brain and/or spine modules) were assessed at baseline and every 2 cycles. With a median follow-up time of 25.9 months (mo), the primary endpoint of 12-mo progression-free survival rate (PFS-12) greater than 50% was reached, with a rate of 76.4% (95% CI, 52.2, 89.4). The median PFS of this cohort was 18.0 mo. Two patients achieved objective partial responses (9.1%). There were no treatment-related grade ≥4 toxicities. Brain tumor responders (radiographic objective response or stable disease) experienced improved cognitive and neurological symptoms, while spine tumor patients reported worsening symptom outcomes regardless of response. Treatment with carboplatin and bevacizumab in adult recurrent ependymomas met the PFS-12 clinical efficacy endpoint. However, symptomatic worsening in spinal tumors suggests imaging stability and symptom improvement in brain disease may be related to bevacizumab pseudo-response.
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Particle nucleation from trace atmospheric vapours is important for climate since it gives rise to more than half of global cloud condensation nuclei. Sulfuric acid (H2SO4) has long been recognised to drive particle nucleation in the atmosphere and, more recently, highly oxygenated products of biogenic vapours-in particular monoterpenes such as α-pinene (C10H16)-have also been shown to nucleate under atmospheric conditions, without requiring additional vapours. This raises the question of whether a nucleation synergy exists between α-pinene oxygenated organic molecules (AP-OOM) and H2SO4, as has been suggested by early studies. Here we report new particle formation from AP-OOM and H2SO4 in the absence of base vapours such as ammonia (NH3), measured in experiments performed with the CERN CLOUD (Cosmics Leaving Outdoor Droplets) chamber at cool boundary layer temperatures of -10 °C and +5 °C. We find that AP-OOM nucleation rates increase strongly when H2SO4 concentrations exceed around 106 cm-3. The enhancement is synergistic and cannot be explained as a simple linear addition of independent chemical systems. Above this threshold, the nucleation rate depends approximately linearly on H2SO4 concentration, in contrast with the strong sensitivity to H2SO4 for H2SO4-NH3 nucleation. Nucleation rates are 10-100-fold higher in the presence of ions from galactic cosmic rays or from the CERN pion beam. Based on these measurements, we have parameterised a temperature-dependent H2SO4-AP-OOM nucleation rate in the absence of base vapours and implemented it in the EMAC (ECHAM/MESSy Atmospheric Chemistry) Earth system model. In comparison with a parameterisation developed in an earlier study [Riccobono et al., Science, 2014, 344, 717-721.], the new parameterisation indicates sharply reduced nucleation rates in the boundary layer over warm regions, and increased rates over northern boreal forests.
A hot and dense state of nuclear matter, known as the quark-gluon plasma, is created in collisions of ultrarelativistic heavy nuclei. Highly energetic quarks and gluons, collectively referred to as partons, lose energy as they travel through this matter, leading to suppressed production of particles with large transverse momenta (p_{T}). Conversely, high-p_{T} particle suppression has not been seen in proton-lead collisions, raising questions regarding the minimum system size required to observe parton energy loss. Oxygen-oxygen (OO) collisions examine a region of effective system size that lies between these two extreme cases. The CMS detector at the CERN LHC has been used to quantify charged-particle production in inclusive OO collisions for the first time via measurements of the nuclear modification factor (R_{AA}). The R_{AA} is derived by comparing particle production to expectations based on proton-proton (pp) data and has a value of unity in the absence of nuclear effects. The data for OO and pp collisions at a nucleon-nucleon center-of-mass energy sqrt[s_{NN}]=5.36  TeV correspond to integrated luminosities of 6.1  nb^{-1} and 1.02  pb^{-1}, respectively. The R_{AA} is below unity with a minimum of 0.69±0.04 around p_{T}=6  GeV. The data exhibit better agreement with theoretical models incorporating parton energy loss as compared to baseline models without energy loss.
Healthcare professionals using fluoroscopic imaging systems rank among the most highly exposed workers to ionising radiations, yet current radiation protection detectors fail to provide accurate measurements in these scenarios. The pulsed structure of the X-ray beam produced by these medical devices poses significant challenges to conventional instruments in measuring and characterising time-structured radiation fields. Furthermore, radiation protection detectors consistently overestimate staff exposure at these low energies (< 100 keV) due to the inherent limitations of the dosimetric system currently in-use. In this study, we present a new hybrid pixel detector, originally developed for particle tracking and timing measurements in high-energy physics experiments at CERN, to overcome the above-mentioned challenges. By integrating single-photon energy measurement and precise timing capabilities, the detector enables highly accurate dose quantification across a broad range of diagnostic X-ray conditions while simultaneously resolving the spectral structure of radiation fields. Our findings demonstrate the detector's suitability for advanced dosimetry assessment in clinical environments. It uniquely measures photon fluence and energy spectra in clinical X-ray fields, enabling accurate, pulse-independent determination of any exposure-related quantity. By giving access to fundamental radiation field parameters, this work lays the foundation for next-generation detectors that enhance staff safety and advance radiation epidemiology.
Objective.Very high-energy electrons (VHEEs) offer deep penetration, low scattering, and the potential for ultra-high dose rate delivery, making them promising candidates for future radiotherapy. However, the collimation of VHEE beams to achieve sharp beam penumbra remains poorly characterized. This study experimentally and computationally investigates how collimator material, thickness, and beam characteristics affect penumbra and out-of-field dose for VHEEs and establishes an initial foundation for the design of clinically feasible VHEE collimators.Approach.Tungsten, lead, and brass 5 mm diameter collimators were evaluated using film dosimetry with a 200 MeV electron beam delivered at the CERN Linear Electron Accelerator for Research and validated through Monte Carlo (MC) simulations. Experimental measurements of penumbra and out-of-field dose were compared with simulations that systematically varied material (tungsten, lead, brass), thickness (20-80 mm), and beam energy (150-250 MeV). Additional sensitivity tests quantified the impact of beam instability on field shaping.Main results.For measurements in air, penumbrae increased linearly with distance from the collimator and was smallest for tungsten. Out-of-field dose decreased with increasing thickness, falling below 0.5% for a 40 mm thick tungsten collimator. Brass exhibited the highest out-of-field dose (up to 4.8%) and broadest penumbra. MC models reproduced experimental trends within 5% for penumbrae but underestimated out-of-field dose, particularly for brass. The simulations indicated that VHEE beam divergence, beam size and collimator misalignment strongly influence beam penumbra and out-of-field dose.Significance.The presented work demonstrates that collimator material and geometry play a critical role in defining VHEE beam quality. Tungsten provided optimal attenuation and sharpness compared to brass and lead. These results establish quantitative benchmarks for VHEE collimator design and emphasize the importance of beam stability.
In the standard model of particle physics, the masses of the W and Z bosons, the carriers of the weak interaction, are uniquely related. A precise determination of their masses is important because quantum loops of heavy, undiscovered particles could modify this relationship. Although the Z mass is known to the remarkable precision of 22 parts per million (2.0 MeV), the W mass is known much less precisely. A global fit to measured electroweak observables predicts the W mass with 6 MeV uncertainty1-3. Reaching a comparable experimental precision would be a sensitive and fundamental test of the standard model, made even more urgent by a recent challenge to the global fit prediction by a measurement from the CDF Collaboration at the Fermilab Tevatron collider4. Here we report the measurement of the W mass by the CMS Collaboration at the CERN Large Hadron Collider, based on a large data sample of W → μν events collected in 2016 at the proton-proton collision energy of 13 TeV. The measurement exploits a high-granularity maximum likelihood fit to the kinematic properties of muons produced in W decays. By combining an accurate determination of experimental effects with marked in situ constraints of theoretical inputs, we reach a precise measurement of the W mass, of 80,360.2 ± 9.9 MeV, in agreement with the standard model prediction.
The outcomes of modern particle physics experiments, such as proton-proton collisions at the Large Hadron Collider at CERN (European Organization for Nuclear Research), depend crucially on the precise description of the scattering processes in terms of the fundamental forces. Among all the known forces that contribute, the limited understanding of the strong nuclear force is a key source of inaccuracy. At the fundamental level, the strong force is described by quantum chromodynamics, the theory of quarks and gluons. Their coupling, αs, becomes weaker at high energies (asymptotic freedom), enabling power series expansions in αs, but the confinement of quarks in hadronic bound states usually requires additional model assumptions. Consequently, determinations of αs from experiment mostly remain with large systematic theory errors1,2. Here we report the model-free determination of αs with unprecedented precision from low-energy experimental input combined with large-scale numerical simulations of the first-principles formulation of quantum chromodynamics on a space-time lattice. The uncertainty, about half that of all other results combined3, originates predominantly from the statistical Monte Carlo evaluation and has a clear probabilistic interpretation. The result for αs describes both low-energy hadronic physics with the help of lattice quantum chromodynamics and high-energy scattering using the perturbative expansion. By removing a source of theoretical uncertainty, our estimate of αs could enable markedly improved analyses of many high-energy experiments4. This will contribute to the likelihood that small effects of yet unknown physics are uncovered, as well as enable stringent precision tests of the Standard Model.
Neutrino detectors, particle calorimeters and some dark matter detectors require dense and massive active materials. An extremely fine segmentation is desirable to achieve precise three-dimensional particle tracking. However, such systems introduce significant challenges in construction and demand a large number of readout electronics channels, leading to extremely high costs. In this article, we propose an alternative approach to elementary particle detection that enables ultrafast three-dimensional high-resolution imaging in large volumes of unsegmented scintillator. Enabling technologies are plenoptic systems and time-resolving single-photon avalanche diode array imaging sensors. Together, they enabled us, using a plenoptic camera, to reconstruct the origin of single photons in the scintillator. A case study focused on neutrino detection demonstrates full event reconstruction with a spatial resolution of two hundred micrometres. This work paves the way for a class of particle detectors whose capabilities should be further enhanced through future developments and expanded to Cherenkov light detection, medical imaging and neutron detection.
We present MicroBooNE's first search for dark sector e^{+}e^{-} explanations of the long-standing MiniBooNE anomaly. The MiniBooNE anomaly has garnered significant attention over the past 20 years including previous MicroBooNE investigations into both anomalous electron and photon excesses, but its origin still remains unclear. In this Letter, we provide the first direct test of dark sector models in which dark neutrinos, produced through neutrino-induced scattering, decay into missing energy and visible e^{+}e^{-} pairs comprising the MiniBooNE anomaly. Many such models have recently gained traction as a viable solution to the anomaly while evading past bounds. Using an exposure of 6.87×10^{20} protons-on-target in the Booster Neutrino Beam, we implement a selection targeting forward-going, coherently produced e^{+}e^{-} events. After unblinding, we observe 95 events, which we compare with the constrained background-only prediction of 69.7±17.3. This analysis sets the world's first direct limits on these dark sector models and, at the 95% confidence level, excludes the entirety of the single dark neutrino and majority of the dual dark neutrino, parameter space that is viable as a solution to the MiniBooNE anomaly.
We construct a novel effective field theory for a compact body coupled to gravity, whose key feature is that the dynamics of gravitational perturbations is explicitly determined by known solutions in black hole perturbation theory in four dimensions. In this way, the physics of gravitational perturbations in curved space are already encoded in the effective field theory, thus bypassing the need for the higher-order calculations that constitute a major hurdle in standard approaches. Concretely, we model the compact body as a spherical shell, whose finite size regulates short-distance divergences in four dimensions and whose tidal responses are described by higher-dimensional operators. As an application, we consider scalar perturbations and derive new results for scalar Love numbers through O(G^{9}) for Schwarzschild black holes and for generic compact bodies. Finally, our analysis reveals an intriguing structure of the scalar black-hole Love numbers in terms of the Riemann zeta function, which we conjecture to hold to all orders.
To qualify epoxy resin systems for use in superconducting magnets of future particle accelerators up to peak doses beyond 100 MGy, the effects of the irradiation source, the irradiation environment and the irradiation temperature have been assessed. Identical epoxy resin samples have been irradiated with 60Co gamma rays, 24 GeV/c protons and by mixed neutron/gamma radiation in a reactor and at a spallation source up to a dose of 170 MGy. Irradiation-induced cross-linking and chain scission have been monitored by Dynamical Mechanical Analysis (DMA). When irradiations are performed with the same dose rate and in the same environment, the different radiation sources have a similar efficiency to produce radiation damage, and the total absorbed dose is a good scaling factor to compare irradiation effects in polymers. To distinguish between the influence of the irradiation temperature and of environmental oxygen, proton irradiations have been carried out in ambient air, inert gas at ambient temperature and in liquid helium. Compared to ambient air irradiation, in inert atmosphere more cross-linking is observed. Cross-linking rates are strongly reduced at 4.2 K. For some polymers the irradiation temperature has a strong influence on the chain scission rate. The most-radiation-hard epoxy resin systems maintain substantial mechanical strength up to doses beyond 100 MGy.
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Using the time-of-flight technique, we measured the beta-delayed neutron emission of ^{132}Cd. From our large-scale shell model (LSSM) calculation using the N^{3}LO interaction [Z. Y. Xu et al., Phys. Rev. Lett. 131, 022501 (2023)PRLTAO0031-900710.1103/PhysRevLett.131.022501], we suggest the decay is dominated by the transformation of a neutron in the g_{7/2} orbital, deep below the Fermi surface, into a proton in the g_{9/2} orbital. We compare the beta-decay half-lives and neutron branching ratios of nuclei with Z<50 and N≥82 obtained with our LSSM with those of leading "global" models such as finite-range droplet model (FRDM). Our calculations match known half-lives and neutron branching ratios well and suggest that current leading models overestimate the yet-to-be-measured half-lives. Our model, backed by the ^{132}Cd decay data presented here, offers robust predictive power for nuclei of astrophysical interest such as r-process waiting points.
Hereditary spastic paraplegia type 4 (SPG4), caused by variants in SPAST, is the most common form of HSP and exhibits a remarkable phenotypic heterogeneity ranging from late-onset pure presentations to severe, early-onset complex disease. Robust genotype-phenotype correlations and detailed natural history data are lacking, limiting clinical trial readiness. We analyzed 206 patients with genetically confirmed SPG4 enrolled across seven international centers, complemented by high-quality literature-derived cases. Deep phenotyping included standardized motor scales, spasticity ratings, developmental milestones, and patient-reported outcomes. We developed an extended essentiality-mapping framework to classify SPAST missense variants by integrating in silico pathogenicity predictions, evolutionary constraint, physicochemical residue connectivity, and variant enrichment within the human spastin hexamer structure. Plasma neurofilament light chain (pNfL) using was quantified using Simoa in 26 patients and 101 controls. We identified 136 distinct SPAST variants, including 10 novel variants. Variant class segregated strongly by inheritance, with de novo cases enriched for missense variants and inherited cases showing a variety of variant classes with enrichment for truncating variants. Longitudinal analysis revealed two latent trajectories: a rapidly progressive severe subgroup enriched for de novo missense variants, and a biphasic moderate subgroup enriched for inherited truncating variants. Patient stratification integrating spastin essentiality mapping (missense variants affecting essential, neutral, or context-dependent residues) with established genetic modifiers (biallelic pathogenic variants or modifier variants in trans) classified patients into predicted severe and moderate subgroups with divergent age at onset and clinical disease progression. The severe subgroup showed early developmental delays, rapid loss of ambulation, and declining quality of life, while the moderate subgroup displayed delayed but accelerating disease progression. pNfL levels were elevated in both subgroups, most pronounced in severe early disease. This study provides the most detailed natural history of SPG4 to date and introduces a biologically informed stratification framework that links variant class and location to divergent clinical trajectories. These data establish clinically meaningful benchmarks and offer a genotype-based framework to improve anticipatory care and optimize trial design for SPG4.
The James Webb Space Telescope has uncovered a population of compact, high-redshift sources, the Little Red Dots (LRDs), which may host supermassive black holes (BHs) significantly heavier than their stellar content compared with local scaling relations. These objects challenge standard models of early galaxy formation and may represent an extreme class of early BH hosts. In this Letter, we investigate whether these BHs could have a primordial origin. We first show that the direct formation of these BH masses in the early Universe is excluded by stringent cosmic microwave background μ-distortion limits. We then investigate the assembly of massive BHs from lighter, observationally allowed primordial black holes (PBHs) via hierarchical mergers, finding that, although this channel can operate depending on the merger history, it faces challenges in explaining the observations due to the rarity of the required high-redshift dark matter halos. Finally, we estimate gas accretion onto intermediate-mass PBHs, while jointly tracking metallicity evolution, and identify regions of parameter space in which such growth could reproduce the observed properties of LRDs. As a special case, we focus on the strongly lensed source QSO1, whose extremely low metallicity and large mass provide a stringent test of these formation channels.
Understanding whether primordial black holes form during strong first-order phase transition (FOPT) is a crucial open question in cosmology. We address this using a fully covariant formalism to study cosmological perturbations, highlighting previously overlooked gauge dependencies. We show that non-covariant treatments can overestimate primordial black holes and scalar-induced gravitational waves. Once gauge dependencies are accounted for, both signals are strongly suppressed, with direct implications for the FOPT interpretation of the Pulsar Timing Array signal.
We present a new class of evolution equations that govern the high-energy behavior of power-suppressed scattering amplitudes. The equations can be viewed as a renormalization group flow with respect to the relevant effective field theory cutoff. A distinct feature of the method is in the use of a multidimensional cutoff to separate the relevant scales in problems characterized by a complex factorization structure. By adjusting the renormalization group variables to the geometry of the effective theory modes, our method naturally extends to a broad spectrum of physical problems that include massive, massless, small, and wide-angle scattering. We present applications to the benchmark processes of electron-positron forward annihilation and light-quark-mediated Higgs boson production and decays.