Ceftaroline Fosamil Therapy in Patients With Acute Bacterial Skin and Skin Structure Infections With Systemic Inflammatory Signs: A Retrospective Dose Comparison Across Three Pivotal Trials.

BACKGROUND: Post-hoc analysis compared pharmacokinetics and clinical outcomes of ceftaroline fosamil 600 mg every 12 (q12h) versus every 8 hours (q8h), in patients with acute bacterial skin and skin structure infections (ABSSSI) and signs of sepsis. METHODS: Clinical outcomes at test-of-cure in patients with ABSSSI and systemic inflammatory signs/systemic inflammatory response (SIRS), and ceftaroline minimum inhibitory concentrations (MICs) against baseline pathogens were compared between COVERS (ceftaroline fosamil 600 mg q8h, 2-h infusion) and the CANVAS 1 and 2 trials (ceftaroline fosamil 600 mg q12h, 1-h infusion). Ceftaroline exposures among patients in COVERS with or without markers of sepsis were compared using population pharmacokinetic (PK) modeling. RESULTS: In COVERS, 62% (312/506) and 41% (208/506) of ceftaroline fosamil-treated patients had ≥1 systemic sign or SIRS, respectively and 55% (378/693) and 22% (152/693), respectively in the CANVAS trials. Clinical cure rates for the modified intent-to-treat (MITT) population in COVERS and CANVAS were similar for ceftaroline fosamil-treated patients with ≥1 sign of sepsis (82% [255/312] and 85% [335/394]) and for those with SIRS (84% [168/199] and 85% [131/155]). Ceftaroline MIC distributions were similar across trials. Sepsis did not affect predicted individual steady-state ceftaroline exposures. CONCLUSIONS: Clinical cure rates in patients with ≥1 systemic inflammatory sign or SIRS were comparable for both ceftaroline fosamil dosage regimens. Pathogen susceptibilities to ceftaroline were similar across trials. Ceftaroline exposures were not affected by disease severity. Ceftaroline fosamil 600 mg q12h is a robust dosage regimen for most ABSSSI patients with sepsis

Early response to antibiotic treatment in European patients hospitalized with complicated skin and soft tissue infections: analysis of the REACH study

Background: The treatment of complicated skin and soft tissue infections (cSSTI) is challenging and many patients do not receive adequate first-line therapy. REACH (REtrospective Study to Assess the Clinical Management of Patients With Moderate-to-Severe cSSTI or Community-Acquired Pneumonia in the Hospital Setting) was a retrospective observational study of cSSTI patients in real-life settings in European hospitals. In this analysis, we review characteristics and outcomes of patients with an early response (<= 72 hours) compared with those without an early response to treatment. We also compare the results according to two differing definitions of early response, one of which (Definition 1) requires resolution of fever within 72 hours, in line with previous US FDA guidelines. Methods: Patients were adults hospitalized with cSSTIs 2010-2011 and requiring treatment with intravenous antibiotics. Clinical management, clinical outcomes and healthcare resource use were assessed using a descriptive analysis approach. Results: The analysis set included 600 patients, of which 363 showed early response with Definition 1 and 417 with Definition 2. Initial treatment modification was frequent, and highest in patients without early response (48.1% with Definition 1). Patients without early response were more likely to have diabetes than those with early response (31.6% vs. 22.9%,respectively) and to suffer from more severe disease (e.g. skin necrosis: 14.8% and 7.7%,respectively), to be infected with difficult-to-treat microorganisms and to have recurrent infections. Furthermore, patients without early response had a higher rate of adverse clinical outcomes (e.g. septic shock) and higher use of healthcare resources. The results obtained with the two definitions for early response were largely similar. Conclusions: This study highlights the significance of early evaluation of patients in hospitals, in potentially preventing prolonged use of inappropriate or ineffective antibacterial therapy

Neutrinos

Report of the Community Summer Study 2013 (Snowmass) Intensity Frontier Neutrino Working GroupReport of the Community Summer Study 2013 (Snowmass) Intensity Frontier Neutrino Working GroupThis document represents the response of the Intensity Frontier Neutrino Working Group to the Snowmass charge. We summarize the current status of neutrino physics and identify many exciting future opportunities for studying the properties of neutrinos and for addressing important physics and astrophysics questions with neutrinos

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figuresMajor update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figuresThe preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess

Neutrino interaction classification with a convolutional neural network in the DUNE far detector

The Deep Underground Neutrino Experiment is a next-generation neutrino oscillation experiment that aims to measure CP-violation in the neutrino sector as part of a wider physics program. A deep learning approach based on a convolutional neural network has been developed to provide highly efficient and pure selections of electron neutrino and muon neutrino charged-current interactions. The electron neutrino (antineutrino) selection efficiency peaks at 90% (94%) and exceeds 85% (90%) for reconstructed neutrino energies between 2–5 GeV. The muon neutrino (antineutrino) event selection is found to have a maximum efficiency of 96% (97%) and exceeds 90% (95%) efficiency for reconstructed neutrino energies above 2 GeV. When considering all electron neutrino and antineutrino interactions as signal, a selection purity of 90% is achieved. These event selections are critical to maximize the sensitivity of the experiment to CP-violating effects

Design, construction and operation of the ProtoDUNE-SP Liquid Argon TPC

The ProtoDUNE-SP detector is a single-phase liquid argon time projection chamber (LArTPC) that was constructed and operated in the CERN North Area at the end of the H4 beamline. This detector is a prototype for the first far detector module of the Deep Underground Neutrino Experiment (DUNE), which will be constructed at the Sandford Underground Research Facility (SURF) in Lead, South Dakota, U.S.A. The ProtoDUNE-SP detector incorporates full-size components as designed for DUNE and has an active volume of 7 × 6 × 7.2 m3. The H4 beam delivers incident particles with well-measured momenta and high-purity particle identification. ProtoDUNE-SP's successful operation between 2018 and 2020 demonstrates the effectiveness of the single-phase far detector design. This paper describes the design, construction, assembly and operation of the detector components

The Single-Phase ProtoDUNE Technical Design Report

ProtoDUNE-SP is the single-phase DUNE Far Detector prototype that is under construction and will be operated at the CERN Neutrino Platform (NP) starting in 2018. ProtoDUNE-SP, a crucial part of the DUNE effort towards the construction of the first DUNE 10-kt fiducial mass far detector module (17 kt total LAr mass), is a significant experiment in its own right. With a total liquid argon (LAr) mass of 0.77 kt, it represents the largest monolithic single-phase LArTPC detector to be built to date. It's technical design is given in this report

Experiment simulation configurations approximating DUNE TDR

The Deep Underground Neutrino Experiment (DUNE) is a next-generation long-baseline neutrino oscillation experiment consisting of a high-power, broadband neutrino beam, a highly capable near detector located on site at Fermilab, in Batavia, Illinois, and a massive liquid argon time projection chamber (LArTPC) far detector located at the 4850L of Sanford Underground Research Facility in Lead, South Dakota. The long-baseline physics sensitivity calculations presented in the DUNE Physics TDR, and in a related physics paper, rely upon simulation of the neutrino beam line, simulation of neutrino interactions in the near and far detectors, fully automated event reconstruction and neutrino classification, and detailed implementation of systematic uncertainties. The purpose of this posting is to provide a simplified summary of the simulations that went into this analysis to the community, in order to facilitate phenomenological studies of long-baseline oscillation at DUNE. Simulated neutrino flux files and a GLoBES configuration describing the far detector reconstruction and selection performance are included as ancillary files to this posting. A simple analysis using these configurations in GLoBES produces sensitivity that is similar, but not identical, to the official DUNE sensitivity. DUNE welcomes those interested in performing phenomenological work as members of the collaboration, but also recognizes the benefit of making these configurations readily available to the wider community