The ForwArd Search ExpeRiment (FASER) is an approved experiment dedicated to searching for light, extremely weakly interacting particles at the LHC. Such particles may be produced in the LHC's ...high-energy collisions and travel long distances through concrete and rock without interacting. They may then decay to visible particles in FASER, which is placed 480 m downstream of the ATLAS interaction point. In this work we briefly describe the FASER detector layout and the status of potential backgrounds. We then present the sensitivity reach for FASER for a large number of long-lived particle models, updating previous results to a uniform set of detector assumptions, and analyzing new models. In particular, we consider all of the renormalizable portal interactions, leading to dark photons, dark Higgs bosons, and heavy neutral leptons; light B−L and Li−Lj gauge bosons; axionlike particles that are coupled dominantly to photons, fermions, and gluons through nonrenormalizable operators; and pseudoscalars with Yukawa-like couplings. We find that FASER and its follow-up, FASER 2, have a full physics program, with discovery sensitivity in all of these models and potentially far-reaching implications for particle physics and cosmology.
Nanoparticle uptake: The phagocyte problem Gustafson, Heather Herd; Holt-Casper, Dolly; Grainger, David W. ...
Nano today,
08/2015, Volume:
10, Issue:
4
Journal Article
Peer reviewed
Open access
•Diverse populations of different macrophages very effectively clear nanomaterials using specific and non-specific uptake mechanisms.•Nanomaterials are very efficiently scavenged from circulating ...blood and tissues by macrophages resident in tissue and filtration organs (MPS system), severely limiting particle targeting.•To avoid rapid uptake, clearance and to improve targeting, nanomaterials that avoid both specific and non-specific macrophage recognition must be developed to improve intra- and extra-cellular targeting.•Long-term residence of non-degradable systems within macrophages in clearance organs poses a unique challenge and could initiate inflammatory mechanisms.
Phagocytes are key cellular participants determining important aspects of host exposure to nanomaterials, initiating clearance, biodistribution and the tenuous balance between host tolerance and adverse nanotoxicity. Macrophages in particular are believed to be among the first and primary cell types that process nanoparticles, mediating host inflammatory and immunological biological responses. These processes occur ubiquitously throughout tissues where nanomaterials are present, including the host mononuclear phagocytic system (MPS) residents in dedicated host filtration organs (i.e., liver, kidney spleen and lung). Thus, to understand nanomaterials exposure risks it is critical to understand how nanomaterials are recognized, internalized, trafficked and distributed within diverse types of host macrophages and how possible cell-based reactions resulting from nanomaterial exposures further inflammatory host responses in vivo. This review focuses on describing macrophage-based initiation of downstream hallmark immunological and inflammatory processes resulting from phagocyte exposure to and internalization of nanomaterials.
Neutrinos are copiously produced at particle colliders, but no collider neutrino has ever been detected. Colliders produce both neutrinos and anti-neutrinos of all flavors at very high energies, and ...they are therefore highly complementary to those from other sources. FASER, the Forward Search Experiment at the LHC, is ideally located to provide the first detection and study of collider neutrinos. We investigate the prospects for neutrino studies with FASER Formula omitted, a proposed component of FASER, consisting of emulsion films interleaved with tungsten plates with a total target mass of 1.2 t, to be placed on-axis at the front of FASER. We estimate the neutrino fluxes and interaction rates, describe the FASER Formula omitted detector, and analyze the characteristics of the signals and primary backgrounds. For an integrated luminosity of Formula omitted to be collected during Run 3 of the 14 TeV LHC in 2021-23, approximately 1300 electron neutrinos, 20,000 muon neutrinos, and 20 tau neutrinos will interact in FASER Formula omitted, with mean energies of 600 GeV to 1 TeV. With such rates and energies, FASER will measure neutrino cross sections at energies where they are currently unconstrained, will bound models of forward particle production, and could open a new window on physics beyond the standard model.
It remains unclear whether urgent endoscopic retrograde cholangiopancreatography (ERCP) with biliary sphincterotomy improves the outcome of patients with gallstone pancreatitis without concomitant ...cholangitis. We did a randomised trial to compare urgent ERCP with sphincterotomy versus conservative treatment in patients with predicted severe acute gallstone pancreatitis.
In this multicentre, parallel-group, assessor-masked, randomised controlled superiority trial, patients with predicted severe (Acute Physiology and Chronic Health Evaluation II score ≥8, Imrie score ≥3, or C-reactive protein concentration >150 mg/L) gallstone pancreatitis without cholangitis were assessed for eligibility in 26 hospitals in the Netherlands. Patients were randomly assigned (1:1) by a web-based randomisation module with randomly varying block sizes to urgent ERCP with sphincterotomy (within 24 h after hospital presentation) or conservative treatment. The primary endpoint was a composite of mortality or major complications (new-onset persistent organ failure, cholangitis, bacteraemia, pneumonia, pancreatic necrosis, or pancreatic insufficiency) within 6 months of randomisation. Analysis was by intention to treat. This trial is registered with the ISRCTN registry, ISRCTN97372133.
Between Feb 28, 2013, and March 1, 2017, 232 patients were randomly assigned to urgent ERCP with sphincterotomy (n=118) or conservative treatment (n=114). One patient from each group was excluded from the final analysis because of cholangitis (urgent ERCP group) and chronic pancreatitis (conservative treatment group) at admission. The primary endpoint occurred in 45 (38%) of 117 patients in the urgent ERCP group and in 50 (44%) of 113 patients in the conservative treatment group (risk ratio RR 0·87, 95% CI 0·64–1·18; p=0·37). No relevant differences in the individual components of the primary endpoint were recorded between groups, apart from the occurrence of cholangitis (two 2% of 117 in the urgent ERCP group vs 11 10% of 113 in the conservative treatment group; RR 0·18, 95% CI 0·04–0·78; p=0·010). Adverse events were reported in 87 (74%) of 118 patients in the urgent ERCP group versus 91 (80%) of 114 patients in the conservative treatment group.
In patients with predicted severe gallstone pancreatitis but without cholangitis, urgent ERCP with sphincterotomy did not reduce the composite endpoint of major complications or mortality, compared with conservative treatment. Our findings support a conservative strategy in patients with predicted severe acute gallstone pancreatitis with an ERCP indicated only in patients with cholangitis or persistent cholestasis.
The Netherlands Organization for Health Research and Development, Fonds NutsOhra, and the Dutch Patient Organization for Pancreatic Diseases.
Species delimitation is one of the most contested areas in modern biology, with widespread disagreement about almost every aspect of the definition and implementation of the “species” label. While ...this debate is intellectually stimulating, it also has real implications for conservation, where its impacts on taxonomic inflation or inertia can mean that specific populations receive adequate conservation measures or are ignored. Recently, the rise of next generation sequencing and phylogenomics has revolutionised phylogenetic understanding of many organismal groups but has simultaneously highlighted the porosity of genomes in terms of admixture across previously delineated species barriers. The extraordinary power of genomic data is increasingly being used to delineate species, and several publications in this domain have recently attracted significant attention and criticism. Here we revisit the question of species delimitation, but from a genomic context. We ask how and whether the large amounts of data provided by genomic methods can resolve the longstanding discussion on the validity and application of phylogenetic and allied species concepts, and how some recent examples can inform this debate. We argue that conserving adaptive potential is a priority for conservation, and no single species concept currently does that adequately on its own. Genomic data holds the potential to add unprecedented detail, but frequently falls short of this potential.
Shared decision making is a tenet of contemporary medicine and oncology practice. How involved elderly patients want to be in making treatment decisions and how physicians perceive patient ...preferences for such involvement are uncertain.
In structured interviews about multiple facets of chemotherapy treatment decision making, we asked patients age 70 years and older with a recent diagnosis of metastatic colorectal cancer (CRC) about their preferences for prognostic information and for involvement in treatment decision making. We also asked treating oncologists (n = 19) to describe their perceptions of patient preferences. Information and decision-making preferences were evaluated in relation to sociodemographic and clinical characteristics.
Seventy-three patients age 70 to 89 years completed the study interview within 16 weeks of metastatic CRC diagnosis. Most patients (n = 70; 96%) had decided to receive chemotherapy and 61 had initiated treatment. Relatively few (n = 32; 44%) wanted information about expected survival when they made a treatment decision. Preference for prognostic information was more common among men than women (56% v 29%; P < .05). About half of the patients (n = 38; 52%) preferred a passive role in the treatment decision-making process. Physician perceptions were concordant with patient preferences for information in 44% of patient-physician pairs and for decision control in 41% of patient-physician pairs.
For older patients with advanced CRC, preferences for prognostic information and for an active role in treatment decision making are not easily predictable. Physicians' perceptions are often inconsistent with patients' stated preferences. Explicit discussion of preferred decision-making styles may improve patient-physician encounters.
The tracking detector of the FASER experiment Abreu, Henso; Antel, Claire; Ariga, Akitaka ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
07/2022, Volume:
1034
Journal Article
Peer reviewed
Open access
FASER is a new experiment designed to search for new light weakly-interacting long-lived particles (LLPs) and study high-energy neutrino interactions in the very forward region of the LHC collisions ...at CERN. The experimental apparatus is situated 480 m downstream of the ATLAS interaction-point aligned with the beam collision axis. The FASER detector includes four identical tracker stations constructed from silicon microstrip detectors. Three of the tracker stations form a tracking spectrometer, and enable FASER to detect the decay products of LLPs decaying inside the apparatus, whereas the fourth station is used for the neutrino analysis. The spectrometer has been installed in the LHC complex since March 2021, while the fourth station is not yet installed. FASER will start physics data taking when the LHC resumes operation in early 2022. This paper describes the design, construction and testing of the tracking spectrometer, including the associated components such as the mechanics, readout electronics, power supplies and cooling system.
Summary Background In patients with mild gallstone pancreatitis, cholecystectomy during the same hospital admission might reduce the risk of recurrent gallstone-related complications, compared with ...the more commonly used strategy of interval cholecystectomy. However, evidence to support same-admission cholecystectomy is poor, and concerns exist about an increased risk of cholecystectomy-related complications with this approach. In this study, we aimed to compare same-admission and interval cholecystectomy, with the hypothesis that same-admission cholecystectomy would reduce the risk of recurrent gallstone-related complications without increasing the difficulty of surgery. Methods For this multicentre, parallel-group, assessor-masked, randomised controlled superiority trial, inpatients recovering from mild gallstone pancreatitis at 23 hospitals in the Netherlands (with hospital discharge foreseen within 48 h) were assessed for eligibility. Adult patients (aged ≥18 years) were eligible for randomisation if they had a serum C-reactive protein concentration less than 100 mg/L, no need for opioid analgesics, and could tolerate a normal oral diet. Patients with American Society of Anesthesiologists (ASA) class III physical status who were older than 75 years of age, all ASA class IV patients, those with chronic pancreatitis, and those with ongoing alcohol misuse were excluded. A central study coordinator randomly assigned eligible patients (1:1) by computer-based randomisation, with varying block sizes of two and four patients, to cholecystectomy within 3 days of randomisation (same-admission cholecystectomy) or to discharge and cholecystectomy 25–30 days after randomisation (interval cholecystectomy). Randomisation was stratified by centre and by whether or not endoscopic sphincterotomy had been done. Neither investigators nor participants were masked to group assignment. The primary endpoint was a composite of readmission for recurrent gallstone-related complications (pancreatitis, cholangitis, cholecystitis, choledocholithiasis needing endoscopic intervention, or gallstone colic) or mortality within 6 months after randomisation, analysed by intention to treat. The trial was designed to reduce the incidence of the primary endpoint from 8% in the interval group to 1% in the same-admission group. Safety endpoints included bile duct leakage and other complications necessitating re-intervention. This trial is registered with Current Controlled Trials, number ISRCTN72764151, and is complete. Findings Between Dec 22, 2010, and Aug 19, 2013, 266 inpatients from 23 hospitals in the Netherlands were randomly assigned to interval cholecystectomy (n=137) or same-admission cholecystectomy (n=129). One patient from each group was excluded from the final analyses, because of an incorrect diagnosis of pancreatitis in one patient (in the interval group) and discontinued follow-up in the other (in the same-admission group). The primary endpoint occurred in 23 (17%) of 136 patients in the interval group and in six (5%) of 128 patients in the same-admission group (risk ratio 0·28, 95% CI 0·12–0·66; p=0·002). Safety endpoints occurred in four patients: one case of bile duct leakage and one case of postoperative bleeding in each group. All of these were serious adverse events and were judged to be treatment related, but none led to death. Interpretation Compared with interval cholecystectomy, same-admission cholecystectomy reduced the rate of recurrent gallstone-related complications in patients with mild gallstone pancreatitis, with a very low risk of cholecystectomy-related complications. Funding Dutch Digestive Disease Foundation.
The FASER experiment at the LHC is designed to search for light, weakly-interacting particles produced in proton-proton collisions at the ATLAS interaction point that travel in the far-forward ...direction. The first results from a search for dark photons decaying to an electron-positron pair, using a dataset corresponding to an integrated luminosity of 27.0 fb−1 collected at centre-of-mass energy s=13.6 TeV in 2022 in LHC Run 3, are presented. No events are seen in an almost background-free analysis, yielding world-leading constraints on dark photons with couplings ϵ∼2×10−5−1×10−4 and masses ∼17 MeV−70 MeV. The analysis is also used to probe the parameter space of a massive gauge boson from a U(1)B−L model, with couplings gB−L∼5×10−6−2×10−5 and masses ∼15 MeV−40 MeV excluded for the first time.
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