Search

The Data Acquisition System (DAQ) for the LUX-ZEPLIN (LZ) dark matter detector is described. The signals from 745 PMTs, distributed across three subsystems, are sampled with 100-MHz 32-channel digitizers (DDC-32s). A basic waveform analysis is carried out on the on-board Field Programmable Gate Arrays (FPGAs) to extract information about the observed scintillation and electroluminescence signals. This information is used to determine if the digitized waveforms should be preserved for offline analysis. The system is designed around the Kintex-7 FPGA. In addition to digitizing the PMT signals and providing basic event selection in real time, the flexibility provided by the use of FPGAs allows us to monitor the performance of the detector and the DAQ in parallel to normal data acquisition. The hardware and software/firmware of this FPGA-based Architecture for Data acquisition and Realtime monitoring (FADR) are discussed and performance measurements are described.

The ^{244}Pu(^{50}Ti,xn)^{294-x}Lv reaction was investigated at Lawrence Berkeley National Laboratory's 88-Inch Cyclotron. The experiment was aimed at the production of a superheavy element with Z≥114 by irradiating an actinide target with a beam heavier than ^{48}Ca. Produced Lv ions were separated from the unwanted beam and nuclear reaction products using the Berkeley Gas-filled Separator and implanted into a newly commissioned focal-plane detector system. Two decay chains were observed and assigned to the decay of ^{290}Lv. The production cross section was measured to be σ_{prod}=0.44(_{-0.28}^{+0.58})  pb at a center-of-target center-of-mass energy of 220(3) MeV. This represents the first published measurement of the production of a superheavy element near the "island of stability," with a beam of ^{50}Ti and is an essential precursor in the pursuit of searching for new elements beyond Z=118.

Many terrestrial plant communities, especially forests, have been shown to lag in response to rapid climate change. Grassland communities may respond more quickly to novel climates, as they consist mostly of short-lived species, which are directly exposed to macroclimate change. Here we report the rapid response of grassland communities to climate change in the California Floristic Province. We estimated 349 vascular plant species' climatic niches from 829,337 occurrence records, compiled 15 long-term community composition datasets from 12 observational studies and 3 global change experiments, and analysed community compositional shifts in the climate niche space. We show that communities experienced significant shifts towards species associated with warmer and drier locations at rates of 0.0216 ± 0.00592 °C yr-1 (mean ± s.e.) and -3.04 ± 0.742 mm yr-1, and these changes occurred at a pace similar to that of climate warming and drying. These directional shifts were consistent across observations and experiments. Our findings contrast with the lagged responses observed in communities dominated by long-lived plants and suggest greater biodiversity changes than expected in the near future.

Research on action-based timing has shed light on the temporal dynamics of sensorimotor coordination. This study investigates the neural mechanisms underlying action-based timing, particularly during finger-tapping tasks involving synchronized and syncopated patterns. Twelve healthy participants completed a continuation task, alternating between tapping in time with an auditory metronome (pacing) and continuing without it (continuation). Electroencephalography data were collected to explore how neural activity changes across these coordination modes and phases. We applied deep learning methods to classify single-trial electroencephalography data and predict behavioral timing conditions. Results showed significant classification accuracy for distinguishing between pacing and continuation phases, particularly during the presence of auditory cues, emphasizing the role of auditory input in motor timing. However, when auditory components were removed from the electroencephalography data, the differentiation between phases became inconclusive. Mean accuracy asynchrony, a measure of timing error, emerged as a superior predictor of performance variability compared to inter-response interval. These findings highlight the importance of auditory cues in modulating motor timing behaviors and present the challenges of isolating motor activation in the absence of auditory stimuli. Our study offers new insights into the neural dynamics of motor timing and demonstrates the utility of deep learning in analyzing single-trial electroencephalography data.

The associated production of Higgs and W bosons via vector-boson fusion is highly sensitive to the relative sign of the Higgs boson couplings to W and Z bosons. In this Letter, two searches for this process are presented, using 140  fb−1 of proton-proton collision data at s=13  TeV recorded by the ATLAS detector at the LHC. The first search targets scenarios with opposite-sign couplings of the W and Z bosons to the Higgs boson, while the second targets standard model-like scenarios with same-sign couplings. Both analyses consider Higgs boson decays into a pair of b quarks and W boson decays with an electron or muon. The data exclude the opposite-sign coupling hypothesis with a significance beyond 5σ, and the observed (expected) upper limit set on the cross section for vector-boson fusion WH production is 9.0 (8.7) times the standard model value at 95% confidence level. © 2024 CERN, for the ATLAS Collaboration 2024 CERN

IntroductionCardiovascular health is important for brain aging, yet its role in the clinical manifestation of autosomal dominant or atypical forms of dementia has not been fully elucidated. We examined relationships between Life's Simple 7 (LS7) and clinical trajectories in individuals with autosomal dominant frontotemporal lobar degeneration (FTLD).MethodsTwo hundred forty-seven adults carrying FTLD pathogenic genetic variants (53% asymptomatic) and 189 non-carrier controls completed baseline LS7, and longitudinal neuroimaging and neuropsychological testing.ResultsAmong variant carriers, higher baseline LS7 is associated with slower accumulation of frontal white matter hyperintensities (WMHs), as well as slower memory and language declines. Higher baseline LS7 associated with larger baseline frontotemporal volume, but not frontotemporal volume trajectories.DiscussionBetter baseline cardiovascular health related to slower cognitive decline and accumulation of frontal WMHs in autosomal dominant FTLD. Optimizing cardiovascular health may be an important modifiable approach to bolster cognitive health and brain integrity in FTLD.HighlightsBetter cardiovascular health associates with slower cognitive decline in frontotemporal lobar degeneration (FTLD). Lifestyle relates to the accumulation of frontal white matter hyperintensities in FTLD. More optimal cardiovascular health associates with greater baseline frontotemporal lobe volume. Optimized cardiovascular health relates to more favorable outcomes in genetic dementia.

BackgroundAs differentiating between lipomas and atypical lipomatous tumors (ALTs) based on imaging is challenging and requires biopsies, radiomics has been proposed to aid the diagnosis. This study aimed to externally and prospectively validate a radiomics model differentiating between lipomas and ALTs on MRI in three large, multi-center cohorts, and extend it with automatic and minimally interactive segmentation methods to increase clinical feasibility.MethodsThree study cohorts were formed, two for external validation containing data from medical centers in the United States (US) collected from 2008 until 2018 and the United Kingdom (UK) collected from 2011 until 2017, and one for prospective validation consisting of data collected from 2020 until 2021 in the Netherlands. Patient characteristics, MDM2 amplification status, and MRI scans were collected. An automatic segmentation method was developed to segment all tumors on T1-weighted MRI scans of the validation cohorts. Segmentations were subsequently quality scored. In case of insufficient quality, an interactive segmentation method was used. Radiomics performance was evaluated for all cohorts and compared to two radiologists.FindingsThe validation cohorts included 150 (54% ALT), 208 (37% ALT), and 86 patients (28% ALT) from the US, UK and NL. Of the 444 cases, 78% were automatically segmented. For 22%, interactive segmentation was necessary due to insufficient quality, with only 3% of all patients requiring manual adjustment. External validation resulted in an AUC of 0.74 (95% CI: 0.66, 0.82) in US data and 0.86 (0.80, 0.92) in UK data. Prospective validation resulted in an AUC of 0.89 (0.83, 0.96). The radiomics model performed similar to the two radiologists (US: 0.79 and 0.76, UK: 0.86 and 0.86, NL: 0.82 and 0.85).InterpretationThe radiomics model extended with automatic and minimally interactive segmentation methods accurately differentiated between lipomas and ALTs in two large, multi-center external cohorts, and in prospective validation, performing similar to expert radiologists, possibly limiting the need for invasive diagnostics.FundingHanarth fonds.

Telehealth continues to play an important role in specialty diabetes care, but there are variations in how this care is delivered. This article reports on clinician and clinic staff perspectives on providing specialty telehealth diabetes care at four large academic medical centers in California and provides several key recommendations for optimizing telehealth-delivered diabetes care.

Quasi-periodic eruptions (QPEs) are luminous bursts of soft X-rays from the nuclei of galaxies, repeating on timescales of hours to weeks1-5. The mechanism behind these rare systems is uncertain, but most theories involve accretion disks around supermassive black holes (SMBHs) undergoing instabilities6-8 or interacting with a stellar object in a close orbit9-11. It has been suggested that this disk could be created when the SMBH disrupts a passing star8,11, implying that many QPEs should be preceded by observable tidal disruption events (TDEs). Two known QPE sources show long-term decays in quiescent luminosity consistent with TDEs4,12 and two observed TDEs have exhibited X-ray flares consistent with individual eruptions13,14. TDEs and QPEs also occur preferentially in similar galaxies15. However, no confirmed repeating QPEs have been associated with a spectroscopically confirmed TDE or an optical TDE observed at peak brightness. Here we report the detection of nine X-ray QPEs with a mean recurrence time of approximately 48 h from AT2019qiz, a nearby and extensively studied optically selected TDE16. We detect and model the X-ray, ultraviolet (UV) and optical emission from the accretion disk and show that an orbiting body colliding with this disk provides a plausible explanation for the QPEs.

In 2015, the largest recorded harmful algal bloom (HAB) occurred in the Northeast Pacific, causing nearly 100 million dollars in damages to fisheries and killing many protected marine mammals. Dominated by the toxic diatom Pseudo-nitzschia australis, this bloom produced high levels of the neurotoxin domoic acid (DA). Through molecular and transcriptional characterization of 52 near-weekly phytoplankton net-tow samples collected at a bloom hotspot in Monterey Bay, California, we identified active transcription of known DA biosynthesis (dab) genes from the three identified toxigenic species, including P. australis as the primary origin of toxicity. Elevated expression of silicon transporters (sit1) during the bloom supports the previously hypothesized role of dissolved silica (Si) exhaustion in contributing to bloom physiology and toxicity. We find that coexpression of the dabA and sit1 genes serves as a robust predictor of DA one week in advance, potentially enabling the forecasting of DA-producing HABs. We additionally present evidence that low levels of iron could have colimited the diatom population along with low Si. Iron limitation represents an overlooked driver of both toxin production and ecological success of the low-iron-adapted Pseudo-nitzschia genus during the 2015 bloom, and increasing pervasiveness of iron limitation may fuel the escalating magnitude and frequency of toxic Pseudo-nitzschia blooms globally. Our results advance understanding of bloom physiology underlying toxin production, bloom prediction, and the impact of global change on toxic blooms.

Preceding a core-collapse supernova (CCSN), various processes produce an increasing amount of neutrinos of all flavors characterized by mounting energies from the interior of massive stars. Among them, the electron antineutrinos are potentially detectable by terrestrial neutrino experiments such as KamLAND and Super-Kamiokande (SK) via inverse beta decay interactions. Once these pre-supernova (pre-SN) neutrinos are observed, an early warning of the upcoming CCSN can be provided. In light of this, KamLAND and SK, both located in the Kamioka mine in Japan, have been monitoring pre-SN neutrinos since 2015 and 2021, respectively. Recently, we performed a joint study between KamLAND and SK on pre-SN neutrino detection. A pre-SN alert system combining the KamLAND detector and the SK detector was developed and put into operation, which can provide a supernova alert to the astrophysics community. Fully leveraging the complementary properties of these two detectors, the combined alert is expected to resolve a pre-SN neutrino signal from a 15 M ⊙ star within 510 pc of the Earth at a significance level corresponding to a false alarm rate of no more than 1 per century. For a Betelgeuse-like model with optimistic parameters, it can provide early warnings up to 12 hr in advance.

Abstract: The ratio of branching ratios of the W boson to muons and electrons, $$R^{\,\mu /e}_W={{\mathcal {B}}(W\rightarrow \mu u )}$$ R W μ / e = B ( W → μ ν ) /$${{\mathcal {B}}(W\rightarrow eu )}$$ B ( W → e ν ) , has been measured using $$140\,\text{ fb}^{-1}\,$$ 140 fb - 1 of pp collision data at $$\sqrt{s}=13$$ s = 13  $$\text {T}\text {e}\hspace{-1.00006pt}\text {V}$$ Te V collected with the ATLAS detector at the LHC, probing the universality of lepton couplings. The ratio is obtained from measurements of the $$t\bar{t}$$ t t ¯ production cross-section in the ee, $$e\mu $$ e μ and $$\mu \mu $$ μ μ dilepton final states. To reduce systematic uncertainties, it is normalised by the square root of the corresponding ratio $$R^{\,\mu \mu /ee}_Z$$ R Z μ μ / e e for the Z boson measured in inclusive $$Z\rightarrow ee$$ Z → e e and $$Z\rightarrow \mu \mu $$ Z → μ μ events. By using the precise value of $$R^{\,\mu \mu /ee}_Z$$ R Z μ μ / e e determined from $$e^+e^-$$ e + e - colliders, the ratio $$R^{\,\mu /e}_W$$ R W μ / e is determined to be $$\begin{aligned} R^{\,\mu /e}_W&= 0.9995\pm 0.0022\,\mathrm {(stat)}\,\pm 0.0036\,\mathrm {(syst)}\\ &\quad \pm 0.0014\,\mathrm {(ext)} . \end{aligned}$$ R W μ / e = 0.9995 ± 0.0022 ( stat ) ± 0.0036 ( syst ) ± 0.0014 ( ext ) . The three uncertainties correspond to data statistics, experimental systematics and the external measurement of $$R^{\,\mu \mu /ee}_Z$$ R Z μ μ / e e , giving a total uncertainty of 0.0045, and confirming the Standard Model assumption of lepton flavour universality in W-boson decays at the 0.5% level.

Abstract: Pixel sensors in 3D technology equip the outer ends of the staves of the Insertable B Layer (IBL), the innermost layer of the ATLAS Pixel Detector, which was installed before the start of LHC Run 2 in 2015. 3D pixel sensors are expected to exhibit more tolerance to radiation damage and are the technology of choice for the innermost layer in the ATLAS tracker upgrade for the HL-LHC programme. While the LHC has delivered an integrated luminosity of  ≃ 235 fb-1 since the start of Run 2, the 3D sensors have received a non-ionising energy deposition corresponding to a fluence of ≃ 8.5 × 1014 1 MeV neutron-equivalent cm-2 averaged over the sensor area. This paper presents results of measurements of the 3D pixel sensors' response during Run 2 and the first two years of Run 3, with predictions of its evolution until the end of Run 3 in 2025. Data are compared with radiation damage simulations, based on detailed maps of the electric field in the Si substrate, at various fluence levels and bias voltage values. These results illustrate the potential of 3D technology for pixel applications in high-radiation environments.

Tree growth and longevity trade-offs fundamentally shape the terrestrial carbon balance. Yet, we lack a unified understanding of how such trade-offs vary across the world's forests. By mapping life history traits for a wide range of species across the Americas, we reveal considerable variation in life expectancies from 10 centimeters in diameter (ranging from 1.3 to 3195 years) and show that the pace of life for trees can be accurately classified into four demographic functional types. We found emergent patterns in the strength of trade-offs between growth and longevity across a temperature gradient. Furthermore, we show that the diversity of life history traits varies predictably across forest biomes, giving rise to a positive relationship between trait diversity and productivity. Our pan-latitudinal assessment provides new insights into the demographic mechanisms that govern the carbon turnover rate across forest biomes.

Early adolescent drinking onset is linked to myriad negative consequences. Using the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) baseline to year 8 data, this study (1) leveraged best subsets selection and Cox Proportional Hazards regressions to identify the most robust predictors of adolescent first and regular drinking onset, and (2) examined the clinical utility of drinking onset in forecasting later binge drinking and withdrawal effects. Baseline predictors included youth psychodevelopmental characteristics, cognition, brain structure, family, peer, and neighborhood domains. Participants (N=538) were alcohol-naïve at baseline. The strongest predictors of first and regular drinking onset were positive alcohol expectancies (Hazard Ratios [HRs]=1.67-1.87), easy home alcohol access (HRs=1.62-1.67), more parental solicitation (e.g., inquiring about activities; HRs=1.72-1.76), and less parental control and knowledge (HRs=.72-.73). Robust linear regressions showed earlier first and regular drinking onset predicted earlier transition into binge and regular binge drinking (βs=0.57-0.95). Zero-inflated Poisson regressions revealed that delayed first and regular drinking increased the likelihood (Incidence Rate Ratios [IRR]=1.62 and IRR=1.29, respectively) of never experiencing withdrawal. Findings identified behavioral and environmental factors predicting temporal paths to youthful drinking, dissociated first from regular drinking initiation, and revealed adverse sequelae of younger drinking initiation, supporting efforts to delay drinking onset.

Genetically heterogeneous UM-HET3 mice born in 2020 were used to test possible lifespan effects of alpha-ketoglutarate (AKG), 2,4-dinitrophenol (DNP), hydralazine (HYD), nebivolol (NEBI), 16α-hydroxyestriol (OH_Est), and sodium thiosulfate (THIO), and to evaluate the effects of canagliflozin (Cana) when started at 16 months of age. OH_Est produced a 15% increase (p = 0.0001) in median lifespan in males but led to a significant (7%) decline in female lifespan. Cana, started at 16 months, also led to a significant increase (14%, p = 0.004) in males and a significant decline (6%, p = 0.03) in females. Cana given to mice at 6 months led, as in our previous study, to an increase in male lifespan without any change in female lifespan, suggesting that this agent may lead to female-specific late-life harm. We found that blood levels of Cana were approximately 20-fold higher in aged females than in young males, suggesting a possible mechanism for the sex-specific disparities in its effects. NEBI was also found to produce a female-specific decline (4%, p = 0.03) in lifespan. None of the other tested drugs provided a lifespan benefit in either sex. These data bring to 7 the list of ITP-tested drugs that induce at least a 10% lifespan increase in one or both sexes, add a fourth drug with demonstrated mid-life benefits on lifespan, and provide a testable hypothesis that might explain the sexual dimorphism in lifespan effects of the SGLT2 inhibitor Cana.

BackgroundSex differences in immune-based disorders are well-established, with female sex associated with a markedly heightened risk of autoimmune disease. Female sex is also overrepresented in other conditions associated with elevated inflammation, including depression, chronic pain, and chronic fatigue. The mechanisms underlying these disparities are unclear. This study used an experimental model of inflammatory challenge to interrogate molecular mechanisms that may contribute to female vulnerability to disorders with an inflammatory basis.MethodIn this analysis of a secondary outcome from a randomized controlled trial, 111 participants (67 female) received either a bolus injection of endotoxin (n = 59) or placebo (n = 52). Participants provided blood samples before and 0.5 h post-injection for assessment of differential activation of key pro-inflammatory (i.e., activator protein (AP)-1; nuclear factor (NF)-κB) and immunoregulatory (i.e., glucocorticoid receptor (GR); cAMP response element binding protein (CREB)) signaling pathways via genome-wide expression profiling and promoter-based bioinformatics analyses.ResultsRelative to males, females exhibited greater endotoxin-induced increases in bioinformatic measures of CREB transcription factor activity (p's

Results from a wide range of searches targeting different experimental signatures with and without missing transverse momentum (ETmiss) are used to constrain a Two-Higgs-Doublet Model (2HDM) with an additional pseudo-scalar mediating the interaction between ordinary and dark matter (2HDM+a). The analyses use up to 139 fb-1 of proton-proton collision data at a centre-of-mass energy s=13 TeV recorded with the ATLAS detector at the Large Hadron Collider during 2015-2018. The results from three of the most sensitive searches are combined statistically. These searches target signatures with large ETmiss and a leptonically decaying Z boson; large ETmiss and a Higgs boson decaying to bottom quarks; and production of charged Higgs bosons in final states with top and bottom quarks, respectively. Constraints are derived for several common and new benchmark scenarios in the 2HDM+a.

This paper presents a search for exotic decays of the Higgs boson into a pair of new pseudoscalar particles, H→aa, where one pseudoscalar decays into a b-quark pair and the other decays into a τ-lepton pair, in the mass range 12≤ma≤60  GeV. The analysis uses pp collision data at s=13  TeV collected with the ATLAS detector at the LHC, corresponding to an integrated luminosity of 140  fb−1. No significant excess above the Standard Model (SM) prediction is observed. Assuming the SM Higgs boson production cross section, the search sets upper limits at 95% confidence level on the branching ratio of Higgs bosons decaying into bb¯τ+τ−, B(H→aa→bb¯τ+τ−), between 2.2% and 3.9% depending on the pseudoscalar mass. © 2024 CERN, for the ATLAS Collaboration 2024 CERN

In the United States, hundreds of thousands of undocumented orphan wells have been abandoned, leaving the burden of managing environmental hazards to governmental agencies or the public. These wells, a result of over a century of fossil fuel extraction without adequate regulation, lack basic information like location and depth, emit greenhouse gases, and leak toxic substances into groundwater. For most of these wells, basic information such as well location and depth is unknown or unverified. Addressing this issue necessitates innovative and interdisciplinary approaches for locating, characterizing, and mitigating their environmental impacts. Our survey of the United States revealed the need for tools to identify well locations and assess conditions, prompting the development of technologies including machine learning to automatically extract information from old records (95%+ accuracy), remote sensing technologies like aero-magnetometers to find buried wells, and cost-effective methods for estimating methane emissions. Notably, fixed-wing drones equipped with magnetometers have emerged as cost-effective and efficient for discovering unknown wells, offering advantages over helicopters and quadcopters. Efforts also involved leveraging local knowledge through outreach to state and tribal governments as well as citizen science initiatives. These initiatives aim to significantly contribute to environmental sustainability by reducing greenhouse gases and improving air and water quality.

In May and June of 2021, marine microbial samples were collected for DNA sequencing in East Sound, WA, USA every 4 hours for 22 days. This high temporal resolution sampling effort captured the last 3 days of a Rhizosolenia sp. bloom, the initiation and complete bloom cycle of Chaetoceros socialis (8 days), and the following bacterial bloom (2 days). Metagenomes were completed on the time series, and the dataset includes 128 size-fractionated microbial samples (0.22-1.2 μm), providing gene abundances for the dominant members of bacteria, archaea, and viruses. This dataset also has time-matched nutrient analyses, flow cytometry data, and physical parameters of the environment at a single point of sampling within a coastal ecosystem that experiences regular bloom events, facilitating a range of modeling efforts that can be leveraged to understand microbial community structure and their influences on the growth, maintenance, and senescence of phytoplankton blooms.

Abstract: This paper presents a measurement of the production cross-section of a Z boson in association with b- or c-jets, in proton–proton collisions at $$\sqrt{s} = 13$$ s = 13 TeV with the ATLAS experiment at the Large Hadron Collider using data corresponding to an integrated luminosity of 140 $$\hbox {fb}^{-1}$$ fb - 1 . Inclusive and differential cross-sections are measured for events containing a Z boson decaying into electrons or muons and produced in association with at least one b-jet, at least one c-jet, or at least two b-jets with transverse momentum $$p_\text {T} > 20$$ p T > 20 GeV and rapidity $$|y| < 2.5$$ | y | < 2.5 . Predictions from several Monte Carlo generators based on next-to-leading-order matrix elements interfaced with a parton-shower simulation, with different choices of flavour schemes for initial-state partons, are compared with the measured cross-sections. The results are also compared with novel predictions, based on infrared and collinear safe jet flavour dressing algorithms. Selected $$Z + \ge 1~c$$ Z + ≥ 1 c -jet observables, optimized for sensitivity to intrinsic-charm, are compared with benchmark models with different intrinsic-charm fractions.

Phenotypic data are critical for understanding biological mechanisms and consequences of genomic variation, and are pivotal for clinical use cases such as disease diagnostics and treatment development. For over a century, vast quantities of phenotype data have been collected in many different contexts covering a variety of organisms. The emerging field of phenomics focuses on integrating and interpreting these data to inform biological hypotheses. A major impediment in phenomics is the wide range of distinct and disconnected approaches to recording the observable characteristics of an organism. Phenotype data are collected and curated using free text, single terms or combinations of terms, using multiple vocabularies, terminologies, or ontologies. Integrating these heterogeneous and often siloed data enables the application of biological knowledge both within and across species. Existing integration efforts are typically limited to mappings between pairs of terminologies; a generic knowledge representation that captures the full range of cross-species phenomics data is much needed. We have developed the Unified Phenotype Ontology (uPheno) framework, a community effort to provide an integration layer over domain-specific phenotype ontologies, as a single, unified, logical representation. uPheno comprises (1) a system for consistent computational definition of phenotype terms using ontology design patterns, maintained as a community library; (2) a hierarchical vocabulary of species-neutral phenotype terms under which their species-specific counterparts are grouped; and (3) mapping tables between species-specific ontologies. This harmonized representation supports use cases such as cross-species integration of genotype-phenotype associations from different organisms and cross-species informed variant prioritization.

PurposeTo assess the safety and efficacy of the third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor osimertinib as neoadjuvant therapy in patients with surgically resectable stage I-IIIA EGFR-mutated non-small cell lung cancer (NSCLC).Patients and methodsThis was a multi-institutional phase II trial of neoadjuvant osimertinib for patients with surgically resectable stage I-IIIA (American Joint Committee on Cancer [AJCC] V7) EGFR-mutated (L858R or exon 19 deletion) NSCLC (ClinicalTrials.gov identifier: NCT03433469). Patients received osimertinib 80 mg orally once daily for up to two 28-day cycles before surgical resection. The primary end point was major pathological response (MPR) rate. Secondary safety and efficacy end points were also assessed. Exploratory end points included pretreatment and post-treatment tumor mutation profiling.ResultsA total of 27 patients were enrolled and treated with neoadjuvant osimertinib for a median 56 days before surgical resection. Twenty-four (89%) patients underwent subsequent surgery; three (11%) patients were converted to definitive chemoradiotherapy. The MPR rate was 14.8% (95% CI, 4.2 to 33.7). No pathological complete responses were observed. The ORR was 52%, and the median DFS was 40.9 months. One treatment-related serious adverse event (AE) occurred (3.7%). No patients were unable to undergo surgical resection or had surgery delayed because of an AE. The most common co-occurring tumor genomic alterations were in TP53 (42%) and RBM10 (21%).ConclusionTreatment with neoadjuvant osimertinib in surgically resectable (stage IA-IIIA, AJCC V7) EGFR-mutated NSCLC did not meet its primary end point for MPR rate. However, neoadjuvant osimertinib did not lead to unanticipated AEs, surgical delays, nor result in a significant unresectability rate.

This Letter presents results from a combination of searches for Higgs boson pair production using 126-140  fb^{-1} of proton-proton collision data at sqrt[s]=13  TeV recorded with the ATLAS detector. At 95% confidence level (CL), the upper limit on the production rate is 2.9 times the standard model (SM) prediction, with an expected limit of 2.4 assuming no Higgs boson pair production. Constraints on the Higgs boson self-coupling modifier κ_{λ}=λ_{HHH}/λ_{HHH}^{SM}, and the quartic HHVV coupling modifier κ_{2V}=g_{HHVV}/g_{HHVV}^{SM}, are derived individually, fixing the other parameter to its SM value. The observed 95% CL intervals are -1.2

This Letter presents the first study of the energy dependence of diboson polarization fractions in WZ→ℓνℓ′ℓ′(ℓ,ℓ′=e,μ) production. The dataset used corresponds to an integrated luminosity of 140  fb−1 of proton-proton collisions at a center-of-mass energy of 13 TeV recorded by the ATLAS detector. Two fiducial regions with an enhanced presence of events featuring two longitudinally polarized bosons are defined. A nonzero fraction of events with two longitudinally polarized bosons is measured with an observed significance of 5.3 standard deviations in the region with 100200  GeV, where pTZ is the transverse momentum of the Z boson. This Letter also reports the first study of the radiation-amplitude-zero effect. Events with two transversely polarized bosons are analyzed for the ΔY(ℓWZ) and ΔY(WZ) distributions defined respectively as the rapidity difference between the lepton from the W boson decay and the Z boson and the rapidity difference between the W boson and the Z boson. Significant suppression of events near zero is observed in both distributions. Unfolded ΔY(ℓWZ) and ΔY(WZ) distributions are also measured and compared to theoretical predictions. © 2024 CERN, for the ATLAS Collaboration 2024 CERN

Limited estimates exist on risk factors for epithelial ovarian cancer (EOC) in Asian, Hispanic, and Native Hawaiian/Pacific Islander women. Participants in this study included 1734 Asian (n = 785 case and 949 control participants), 266 Native Hawaiian/Pacific Islander (n = 99 case and 167 control participants), 1149 Hispanic (n = 505 case and 644 control participants), and 24 189 White (n = 9981 case and 14 208 control participants) from 11 studies in the Ovarian Cancer Association Consortium. Logistic regression models estimated odds ratios (ORs) and 95% CIs for risk associations by race and ethnicity. Heterogeneity in EOC risk associations by race and ethnicity (P ≤ .02) was observed for oral contraceptive (OC) use, parity, tubal ligation, and smoking. We observed inverse associations with EOC risk for OC use and parity across all groups; associations were strongest in Native Hawaiian/Pacific Islander and Asian women. The inverse association for tubal ligation with risk was most pronounced for Native Hawaiian/Pacific Islander participants (odds ratio (OR) = 0.25; 95% CI, 0.13-0.48) compared with Asian and White participants (OR = 0.68 [95% CI, 0.51-0.90] and OR = 0.78 [95% CI, 0.73-0.85], respectively). Differences in EOC risk factor associations were observed across racial and ethnic groups, which could be due, in part, to varying prevalence of EOC histotypes. Inclusion of greater diversity in future studies is essential to inform prevention strategies. This article is part of a Special Collection on Gynecological Cancers.

By age 40 years, over 90% of adults with Down syndrome have Alzheimer's disease pathology and most progress to dementia. Despite having few systemic vascular risk factors, individuals with Down syndrome have elevated cerebrovascular disease markers that track with the clinical progression of Alzheimer's disease, suggesting a role of cerebrovascular disease that is hypothesized to be mediated by inflammatory factors. This study examined the pathways through which small vessel cerebrovascular disease contributes to Alzheimer's disease-related pathophysiology and neurodegeneration in adults with Down syndrome. One hundred eighty-five participants from the Alzheimer's Biomarkers Consortium-Down Syndrome [mean (SD) age = 45.2 (9.3) years] with available MRI and plasma biomarker data were included in this study. White matter hyperintensity (WMH) volumes were derived from T2-weighted fluid-attenuated inversion recovery MRI scans, and plasma biomarker concentrations of amyloid beta 42/40, phosphorylated tau 217, astrocytosis (glial fibrillary acidic protein) and neurodegeneration (neurofilament light chain) were measured with ultrasensitive immunoassays. We examined the bivariate relationships of WMH, amyloid beta 42/40, phosphorylated tau 217 and glial fibrillary acidic protein with age-residualized neurofilament light chain across Alzheimer's disease diagnostic groups. A series of mediation and path analyses examined statistical pathways linking WMH and Alzheimer's disease pathophysiology to promote neurodegeneration in the total sample and groups stratified by clinical diagnosis. There was a direct and indirect bidirectional effect through the glial fibrillary acidic protein of WMH on phosphorylated tau 217 concentration, which was associated with neurofilament light chain concentration in the entire sample. Amongst cognitively stable participants, WMH was directly and indirectly, through glial fibrillary acidic protein, associated with phosphorylated tau 217 concentration, and in those with mild cognitive impairment, there was a direct effect of WMH on phosphorylated tau 217 and neurofilament light chain concentrations. There were no associations of WMH with biomarker concentrations among those diagnosed with dementia. The findings from this cross-sectional study suggest that among individuals with Down syndrome, cerebrovascular disease promotes neurodegeneration by increasing astrocytosis and tau pathophysiology in the presymptomatic phases of Alzheimer's disease, but future studies will need to confirm these associations with longitudinal data. This work joins an emerging literature that implicates cerebrovascular disease and its interface with neuroinflammation as a core pathological feature of Alzheimer's disease in adults with Down syndrome.

IntroductionTau-positron emission tomography (PET) outcome data of patients with Alzheimer's disease (AD) cannot currently be meaningfully compared or combined when different tracers are used due to differences in tracer properties, instrumentation, and methods of analysis.MethodsUsing head-to-head data from five cohorts with tau PET radiotracers designed to target tau deposition in AD, we tested a joint propagation model (JPM) to harmonize quantification (units termed "CenTauR" [CTR]). JPM is a statistical model that simultaneously models the relationships between head-to-head and anchor point data. JPM was compared to a linear regression approach analogous to the one used in the amyloid PET Centiloid scale.ResultsA strong linear relationship was observed between CTR values across brain regions. Using the JPM approach, CTR estimates were similar to, but more accurate than, those derived using the linear regression approach.DiscussionPreliminary findings using the JPM support the development and adoption of a universal scale for tau-PET quantification.HighlightsTested a novel joint propagation model (JPM) to harmonize quantification of tau PET. Units of common scale are termed "CenTauRs". Tested a Centiloid-like linear regression approach. Using five cohorts with head-to-head tau PET, JPM outperformed linearregressionbased approach. Strong linear relationship was observed between CenTauRs values across brain regions.

We report the identification of 15 galaxy candidates at z ≥ 9 using the initial COSMOS-Web JWST observations over 77 arcmin2 through four Near Infrared Camera filters (F115W, F150W, F277W, and F444W) with an overlap with the Mid-Infrared Imager (F770W) of 8.7 arcmin2. We fit the sample using several publicly available spectral energy distribution (SED) fitting and photometric redshift codes and determine their redshifts between z = 9.3 and z = 10.9 (〈z〉 = 10.0), UV magnitudes between M UV = −21.2 and −19.5 (with 〈M UV〉 = −20.2), and rest-frame UV slopes (〈β〉 = −2.4). These galaxies are, on average, more luminous than most z ≥ 9 candidates discovered by JWST so far in the literature, while exhibiting similar blue colors in their rest-frame UV. The rest-frame UV slopes derived from SED fitting are blue (β ∼ [−2.0, −2.7]) without reaching extremely blue values as reported in other recent studies at these redshifts. The blue color is consistent with models that suggest the underlying stellar population is not yet fully enriched in metals like similarly luminous galaxies in the lower-redshift Universe. The derived stellar masses with 〈 log 10 ( M ⋆/M ⊙)〉 ≈ 8-9 are not in tension with the standard Lambda cold dark matter (ΛCDM) model, and our measurement of the volume density of such UV-luminous galaxies aligns well with previously measured values presented in the literature at z ∼ 9-10. Our sample of galaxies, although compact, is significantly resolved.

We present the model we developed to reconstruct the CUORE radioactive background based on the analysis of an experimental exposure of 1038.4 kg yr. The data reconstruction relies on a simultaneous Bayesian fit applied to energy spectra over a broad energy range. The high granularity of the CUORE detector, together with the large exposure and extended stable operations, allow for an in-depth exploration of both spatial and time dependence of backgrounds. We achieve high sensitivity to both bulk and surface activities of the materials of the setup, detecting levels as low as 10 nBq kg-1 and 0.1 nBq cm-2, respectively. We compare the contamination levels we extract from the background model with prior radio-assay data, which informs future background risk mitigation strategies. The results of this background model play a crucial role in constructing the background budget for the CUPID experiment as it will exploit the same CUORE infrastructure.

A search is presented for the pair production of heavy vectorlike quarks (VLQs) that each decay into a W boson and a light quark. This study focuses on events where one W boson decays into leptons and the other into hadrons. The search analyzed 140  fb−1 of pp collision data with s=13  TeV, recorded by the ATLAS detector from 2015 to 2018 during run 2 of the Large Hadron Collider. The final state is characterized by a high-transverse-momentum isolated electron or muon, large missing transverse momentum, multiple small-radius jets, and a single large-radius jet identified as originating from the hadronic decay of a boosted W boson. With higher center-of-mass energy and integrated luminosity than in the run 1 search, and improved analysis tools, this analysis excludes VLQs (Q) with masses below 1530 GeV at 95% confidence level for the branching ratio B(Q→Wq)=1, an improvement of 840 GeV on the previous ATLAS limit. © 2024 CERN, for the ATLAS Collaboration 2024 CERN

The financial impact of liver transplantation has been underexplored. We aimed to identify associations between high financial burden (≥10% annual income spent on out-of-pocket medical costs) and work productivity, financial distress (coping behaviors in response to the financial burden), and financial toxicity (health-related quality of life, HRQOL) among adult recipients of liver transplant. Between June 2021 and May 2022, we surveyed 207 adult recipients of liver transplant across 5 US transplant centers. Financial burden and distress were measured by 25 items adapted from national surveys of cancer survivors. Participants also completed the Work Productivity and Activity Impairment and EQ-5D-5L HRQOL questionnaires. In total, 23% of recipients reported high financial burden which was significantly associated with higher daily activity impairment (32.9% vs. 23.3%, p =0.048). In adjusted analyses, the high financial burden was significantly and independently associated with delayed or foregone medical care (adjusted odds ratio, 3.95; 95% CI, 1.85-8.42) and being unable to afford basic necessities (adjusted odds ratio, 5.12; 95% CI: 1.61-16.37). Recipients experiencing high financial burden had significantly lower self-reported HRQOL as measured by the EQ-5D-5L compared to recipients with low financial burden (67.8 vs. 76.1, p =0.008) and an age-matched and sex-matched US general population (67.8 vs. 79.1, p

We present a computationally efficient galaxy archetype-based redshift estimation and spectral classification method for the Dark Energy Survey Instrument (DESI) survey. The DESI survey currently relies on a redshift fitter and spectral classifier using a linear combination of principal component analysis-derived templates, which is very efficient in processing large volumes of DESI spectra within a short time frame. However, this method occasionally yields unphysical model fits for galaxies and fails to adequately absorb calibration errors that may still be occasionally visible in the reduced spectra. Our proposed approach improves upon this existing method by refitting the spectra with carefully generated physical galaxy archetypes combined with additional terms designed to absorb data reduction defects and provide more physical models to the DESI spectra. We test our method on an extensive data set derived from the survey validation (SV) and Year 1 (Y1) data of DESI. Our findings indicate that the new method delivers marginally better redshift success for SV tiles while reducing catastrophic redshift failure by 10%-30%. At the same time, results from millions of targets from the main survey show that our model has relatively higher redshift success and purity rates (0.5%-0.8% higher) for galaxy targets while having similar success for QSOs. These improvements also demonstrate that the main DESI redshift pipeline is generally robust. Additionally, it reduces the false-positive redshift estimation by 5%−40% for sky fibers. We also discuss the generic nature of our method and how it can be extended to other large spectroscopic surveys, along with possible future improvements.

A search for heavy Majorana neutrinos in scattering of same-sign W boson pairs in proton–proton collisions at s=13 TeV at the LHC is reported. The dataset used corresponds to an integrated luminosity of 140 fb−1, collected with the ATLAS detector during 2015–2018. The search is performed in final states including a same-sign ee or eμ pair and at least two jets with large invariant mass and a large rapidity difference. No significant excess of events with respect to the Standard Model background predictions is observed. The results are interpreted in a benchmark scenario of the Phenomenological Type-I Seesaw model. New constraints are set on the values of the |VeN|2 and |VeNVμN⁎| parameters for heavy Majorana neutrino masses between 50 GeV and 20 TeV, where VℓN is the matrix element describing the mixing of the heavy Majorana neutrino mass eigenstate with the Standard Model neutrino of flavour ℓ=e,μ. The sensitivity to the Weinberg operator is investigated and constraints on the effective ee and eμ Majorana neutrino masses are reported. The statistical combination of the ee and eμ channels with the previously published μμ channel is performed.