192 research outputs found
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Intraperitoneal photodynamic therapy causes a capillary-leak syndrome.
BackgroundIn patients undergoing intraperitoneal (IP) photodynamic therapy (PDT), the combination of aggressive surgical debulking and light therapy causes an apparent systemic capillary-leak syndrome that necessitates significant intensive care unit (ICU) management after surgery.MethodsFrom May 1997 to May 2001, 65 patients underwent surgical debulking and PDT as part of an ongoing phase II trial for disseminated IP cancer. Perioperative data were reviewed retrospectively, and statistical analyses were performed to determine whether any identifiable factors were associated with the need for mechanical ventilation for longer than 1 day and with the occurrence of postoperative complications.ResultsForty-three women and 22 men (mean age, 49 years) were treated. Operative time averaged 9.8 hours, and mean estimated blood loss was 1450 mL. The mean crystalloid requirement for the first 48 hours after surgery was 29.3 L, and 49 patients required blood products. Twenty-four patients were intubated for longer than 24 hours, with a mean of 8.3 days for those intubated longer than 1 day. The median ICU stay was 4 days. Overall, 110 complications developed in 45 (69%) of the 65 patients. Significant complications included 6 patients with acute respiratory distress syndrome, 28 patients with infectious complications, and 4 patients with anastomotic complications. Statistical analyses revealed that surgery-related factors were significantly associated with these complication outcomes.ConclusionsPatients who undergo surgical debulking and IP PDT develop a significant capillary-leak syndrome after surgery that necessitates massive volume resuscitation, careful ICU monitoring, and, frequently, prolonged ventilatory support
Stereotactic Body Radiation Therapy (SBRT) for Liver Metastasis: Early Experience with the Cyberknife Robotic Radio-Surgery System
Background: The liver is a common site for malignant metastases. Surgical metastatic resection, ablative therapies, and external beam radiation therapy (EBRT) all have advantages and limitations. Preliminary reports reveal SBRT treats hepatic metastases with limited toxicities. We reviewed our institutionâs SBRT experience for the treatment of liver metastases to assess toxicity and outcomes.Methods: Hepatic metastases treated with SBRT were retrospectively reviewed from 2008-2010. Computed tomography (CT) identified tumor volume prior to SBRT, local recurrence and out-of-field progression after SBRT. Study endpoints were local recurrence, toxicity, and overall survival.Results: Thirty-three patients had 37 liver metastases treated with a median SBRT dose of 30Gy. Median follow-up was 8.1 months. Five lesions (13.5%) locally recurred after a median of 10.6 months. Seventeen patients had out-of-field progression (15 liver, 6 systemic) after a median of 5.1 months. Overall 23.5-month survival was 45.5%. Five patients reported nausea and seven reported pain after SBRT. There were no grade 4-5 toxicities or cases of liver failure.Conclusion: SBRT is safe and well tolerated in patients with hepatic metastases. SBRT offers a local therapy with limited toxicities to patients with lesions not amenable to traditional ablative, surgical, or regional therapies
Phase II trial of debulking surgery and photodynamic therapy for disseminated intraperitoneal tumors
Background: Photodynamic therapy (PDT) combines photosensitizer drug, oxygen, and laser light to kill tumor cells on surfaces. This is the initial report of our phase II trial, designed to evaluate the effectiveness of surgical debulking and PDT in carcinomatosis and sarcomatosis. Methods: Fifty-six patients were enrolled between April 1997 and January 2000. Patients were given Photofrin (2.5 mg/kg) intravenously 2 days before tumor-debulking surgery. Laser light was delivered to all peritoneal surfaces. Patients were followed with CT scans and laparoscopy to evaluate responses to treatment. Results: Forty-two patients were adequately debulked at surgery; these comprise the treatment group. There were 14 GI malignancies, 12 ovarian cancers and 15 sarcomas. Actuarial median survival was 21 months. Median time to recurrence was 3 months (range, 1-21 months). The most common serious toxicities were anemia (38%), liver function test (LFT) abnormalities (26%), and gastrointestinal toxicities(19%), and one patient died. Conclusions: Photofrin PDT for carcinomatosis has been successfully administered to 42 patients, with acceptable toxicity. The median survival of 21 months exceeds our expectations; however, the relative contribution of surgical resection versus PDT is unknown. Deficiencies in photosensitizer delivery, tissue oxygenation, or laser light distribution leading to recurrences may be addressed through the future use of new photosensitizers
Ring1B compacts chromatin structure and represses gene expression independent of histone ubiquitination
How polycomb group proteins repress gene expression in vivo is not known. While histone-modifying activities of the polycomb repressive complexes (PRCs) have been studied extensively, in vitro data have suggested a direct activity of the PRC1 complex in compacting chromatin. Here, we investigate higher-order chromatin compaction of polycomb targets in vivo. We show that PRCs are required to maintain a compact chromatin state at Hox loci in embryonic stem cells (ESCs). There is specific decompaction in the absence of PRC2 or PRC1. This is due to a PRC1-like complex, since decompaction occurs in Ring1B null cells that still have PRC2-mediated H3K27 methylation. Moreover, we show that the ability of Ring1B to restore a compact chromatin state and to repress Hox gene expression is not dependent on its histone ubiquitination activity. We suggest that Ring1B-mediated chromatin compaction acts to directly limit transcription in vivo
Low exposure long-baseline neutrino oscillation sensitivity of the DUNE experiment
The Deep Underground Neutrino Experiment (DUNE) will produce world-leading
neutrino oscillation measurements over the lifetime of the experiment. In this
work, we explore DUNE's sensitivity to observe charge-parity violation (CPV) in
the neutrino sector, and to resolve the mass ordering, for exposures of up to
100 kiloton-megawatt-years (kt-MW-yr). The analysis includes detailed
uncertainties on the flux prediction, the neutrino interaction model, and
detector effects. We demonstrate that DUNE will be able to unambiguously
resolve the neutrino mass ordering at a 3 (5) level, with a 66
(100) kt-MW-yr far detector exposure, and has the ability to make strong
statements at significantly shorter exposures depending on the true value of
other oscillation parameters. We also show that DUNE has the potential to make
a robust measurement of CPV at a 3 level with a 100 kt-MW-yr exposure
for the maximally CP-violating values \delta_{\rm CP}} = \pm\pi/2.
Additionally, the dependence of DUNE's sensitivity on the exposure taken in
neutrino-enhanced and antineutrino-enhanced running is discussed. An equal
fraction of exposure taken in each beam mode is found to be close to optimal
when considered over the entire space of interest
First results on ProtoDUNE-SP liquid argon time projection chamber performance from a beam test at the CERN Neutrino Platform
The ProtoDUNE-SP detector is a single-phase liquid argon time projection chamber with an active volume of 7.2Ă 6.1Ă 7.0 m3. It is installed at the CERN Neutrino Platform in a specially-constructed beam that delivers charged pions, kaons, protons, muons and electrons with momenta in the range 0.3 GeV/c to 7 GeV/c. Beam line instrumentation provides accurate momentum measurements and particle identification. The ProtoDUNE-SP detector is a prototype for the first far detector module of the Deep Underground Neutrino Experiment, and it incorporates full-size components as designed for that module. This paper describes the beam line, the time projection chamber, the photon detectors, the cosmic-ray tagger, the signal processing and particle reconstruction. It presents the first results on ProtoDUNE-SP\u27s performance, including noise and gain measurements, dE/dx calibration for muons, protons, pions and electrons, drift electron lifetime measurements, and photon detector noise, signal sensitivity and time resolution measurements. The measured values meet or exceed the specifications for the DUNE far detector, in several cases by large margins. ProtoDUNE-SP\u27s successful operation starting in 2018 and its production of large samples of high-quality data demonstrate the effectiveness of the single-phase far detector design
Long-baseline neutrino oscillation physics potential of the DUNE experiment
The sensitivity of the Deep Underground Neutrino Experiment (DUNE) to neutrino oscillation is determined, based on a full simulation, reconstruction, and event selection of the far detector and a full simulation and parameterized analysis of the near detector. Detailed uncertainties due to the flux prediction, neutrino interaction model, and detector effects are included. DUNE will resolve the neutrino mass ordering to a precision of 5Ï, for all ÎCP values, after 2 years of running with the nominal detector design and beam configuration. It has the potential to observe charge-parity violation in the neutrino sector to a precision of 3Ï (5Ï) after an exposure of 5 (10) years, for 50% of all ÎCP values. It will also make precise measurements of other parameters governing long-baseline neutrino oscillation, and after an exposure of 15 years will achieve a similar sensitivity to sin22Ξ13 to current reactor experiments
Long-baseline neutrino oscillation physics potential of the DUNE experiment
The sensitivity of the Deep Underground Neutrino Experiment (DUNE) to neutrino oscillation is determined, based on a full simulation, reconstruction, and event selection of the far detector and a full simulation and parameterized analysis of the near detector. Detailed uncertainties due to the flux prediction, neutrino interaction model, and detector effects are included. DUNE will resolve the neutrino mass ordering to a precision of 5Ï, for all ÎŽ_(CP) values, after 2 years of running with the nominal detector design and beam configuration. It has the potential to observe charge-parity violation in the neutrino sector to a precision of 3Ï (5Ï) after an exposure of 5 (10) years, for 50% of all ÎŽ_(CP) values. It will also make precise measurements of other parameters governing long-baseline neutrino oscillation, and after an exposure of 15 years will achieve a similar sensitivity to sinÂČΞââ to current reactor experiments
Prospects for beyond the Standard Model physics searches at the Deep Underground Neutrino Experiment
The Deep Underground Neutrino Experiment (DUNE) will be a powerful tool for a variety of physics topics. The high-intensity proton beams provide a large neutrino flux, sampled by a near detector system consisting of a combination of capable precision detectors, and by the massive far detector system located deep underground. This configuration sets up DUNE as a machine for discovery, as it enables opportunities not only to perform precision neutrino measurements that may uncover deviations from the present three-flavor mixing paradigm, but also to discover new particles and unveil new interactions and symmetries beyond those predicted in the Standard Model (SM). Of the many potential beyond the Standard Model (BSM) topics DUNE will probe, this paper presents a selection of studies quantifying DUNEâs sensitivities to sterile neutrino mixing, heavy neutral leptons, non-standard interactions, CPT symmetry violation, Lorentz invariance violation, neutrino trident production, dark matter from both beam induced and cosmogenic sources, baryon number violation, and other new physics topics that complement those at high-energy colliders and significantly extend the present reach
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.Comment: 15 pages, 6 figures, configurations in ancillary files, v2 corrects a
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