3,051 research outputs found
Trabectedin for Metastatic Soft Tissue Sarcoma: A Retrospective Single Center Analysis
Soft tissue sarcoma (STS) comprises a large variety of rare malignant tumors. Development of distant metastasis is frequent, even in patients undergoing initial curative surgery. Trabectedin, a tetrahydroisoquinoline alkaloid isolated from the Caribbean marine tunicate Ecteinascidia turbinata, was approved in 2007 for patients with advanced STS after failure of anthracyclines and ifosfamide, or for patients unsuited to receive these agents. In this study, we retrospectively analyzed 25 patients who had been treated with trabectedin at our institution between 2007 and 2010. The majority (72%) had been heavily pre-treated with ≥2 previous lines of chemotherapy. Response assessed by conventional RECIST criteria was low, with only one patient achieving a partial remission (PR) and 10 stable disease (SD) after three cycles of treatment. However, median progression-free survival (PFS) and overall survival (OS) were significantly prolonged in this population compared to non-responders, with 7.7 months versus 2.1 months (p < 0.0001; HR 15.37, 95% CI 4.3 to 54.5) and 12.13 months versus 5.54 months (p = 0.0137; HR 3.7, 95% CI 1.3 to 10.5), respectively. PFS for all patients was 58% at three months and 37% at six months. Side effects, including neutropenia, elevation of liver transaminases/liver function tests, and nausea/vomiting, were usually mild and manageable. However, dose reductions due to side effects were necessary in five patients. We conclude that trabectedin is an effective and generally well tolerated treatment for STS even in a heavily pre-treated patient population
Sunyaev-Zel'dovich observations of galaxy clusters out to the virial radius with the Arcminute Microkelvin Imager
We present observations using the Small Array of the Arcminute Microkelvin
Imager (AMI; 14-18 GHz) of four Abell and three MACS clusters spanning
0.171-0.686 in redshift. We detect Sunyaev-Zel'dovich (SZ) signals in five of
these without any attempt at source subtraction, although strong source
contamination is present. With radio-source measurements from high-resolution
observations, and under the assumptions of spherical -model,
isothermality and hydrostatic equilibrium, a Bayesian analysis of the data in
the visibility plane detects extended SZ decrements in all seven clusters over
and above receiver noise, radio sources and primary CMB imprints. Bayesian
evidence ratios range from 10^{11}:1 to 10^{43}:1 for six of the clusters and
3000:1 for one with substantially less data than the others. We present
posterior probability distributions for, e.g., total mass and gas fraction
averaged over radii internal to which the mean overdensity is 1000, 500 and
200, r_200 being the virial radius. Reaching r_200 involves some extrapolation
for the nearer clusters but not for the more-distant ones. We find that our
estimates of gas fraction are low (compared with most in the literature) and
decrease with increasing radius. These results appear to be consistent with the
notion that gas temperature in fact falls with distance (away from near the
cluster centre) out to the virial radius.Comment: 18 pages, 10 figures, submitted to MNRAS (updated authors and fixed
Figure 1
A randomised phase 2a study to investigate the effects of blocking interleukin-33 with tozorakimab in patients hospitalised with COVID-19:Accord-2
BACKGROUND: Increased serum interleukin (IL)-33 predicts poor outcomes in patients hospitalised with coronavirus disease 2019 (COVID-19). We examined the efficacy and safety of tozorakimab, a monoclonal antibody that neutralises IL-33, in improving outcomes in ACCORD-2 (EudraCT: 2020-001736-95).METHODS: ACCORD-2 was an open-label, phase 2a study in adults hospitalised with COVID-19. Patients were randomised 1:1 to tozorakimab 300 mg plus standard of care (SoC) or SoC alone. The primary end-point was time to clinical response (sustained clinical improvement of ≥2 points on the World Health Organization ordinal scale, discharge from hospital or fit for discharge) by day 29. Other end-points included death or respiratory failure, mortality and intensive care unit admission by day 29, and safety. Serum IL-33/soluble stimulated-2 (sST2) complex levels were measured by high-sensitivity immunoassay.RESULTS: Efficacy analyses included 97 patients (tozorakimab+SoC, n=53; SoC, n=44). Median time to clinical response did not differ between the tozorakimab and SoC arms (8.0 and 9.5 days, respectively; HR 0.96, 80% CI 0.70-1.31; one-sided p=0.33). Tozorakimab was well tolerated and the OR for risk of death or respiratory failure with treatment versus SoC was 0.55 (80% CI 0.27-1.12; p=0.26), while the OR was 0.31 (80% CI 0.09-1.06) in patents with high baseline serum IL-33/sST2 complex levels.CONCLUSIONS: Overall, ACCORD-2 results suggest that tozorakimab could be a novel therapy for patients hospitalised with COVID-19, warranting further investigation in confirmatory phase 3 studies.</p
The Maunakea Spectroscopic Explorer Book 2018
(Abridged) This is the Maunakea Spectroscopic Explorer 2018 book. It is
intended as a concise reference guide to all aspects of the scientific and
technical design of MSE, for the international astronomy and engineering
communities, and related agencies. The current version is a status report of
MSE's science goals and their practical implementation, following the System
Conceptual Design Review, held in January 2018. MSE is a planned 10-m class,
wide-field, optical and near-infrared facility, designed to enable
transformative science, while filling a critical missing gap in the emerging
international network of large-scale astronomical facilities. MSE is completely
dedicated to multi-object spectroscopy of samples of between thousands and
millions of astrophysical objects. It will lead the world in this arena, due to
its unique design capabilities: it will boast a large (11.25 m) aperture and
wide (1.52 sq. degree) field of view; it will have the capabilities to observe
at a wide range of spectral resolutions, from R2500 to R40,000, with massive
multiplexing (4332 spectra per exposure, with all spectral resolutions
available at all times), and an on-target observing efficiency of more than
80%. MSE will unveil the composition and dynamics of the faint Universe and is
designed to excel at precision studies of faint astrophysical phenomena. It
will also provide critical follow-up for multi-wavelength imaging surveys, such
as those of the Large Synoptic Survey Telescope, Gaia, Euclid, the Wide Field
Infrared Survey Telescope, the Square Kilometre Array, and the Next Generation
Very Large Array.Comment: 5 chapters, 160 pages, 107 figure
The Molecular Condensations Ahead of Herbig-Haro Objects. I. Multi-transition Observations of HH 2
We present a CSO and BIMA molecular line survey of the dense, quiescent
molecular environment ahead of HH2. The molecular gas is cold, 13 K, and
moderately dense, 3x10^5 cm^-3. A total of 14 species has been detected
(including different isotopes and deuterated species). The relative abundances
of the clump are compared with other dense molecular environments, including
quiescent dark clouds, and active low and high mass star forming regions. This
comparison confirms the peculiar chemical composition of the quiescent gas
irradiated by the HH objects. Thus, from this comparison, we found that the
HCO+, CH3OH and H2CO are strongly enhanced. SO and SO2 are weakly enhanced,
whereas HCN and CS are underabundant. The CN abundance is within the range of
value found in starless dark clouds, but it is low with respect to high mass
star forming regions. Finally, the chemical composition of HH2 confirms the
qualitative results of the Viti & Williams (1999) complex chemical model that
follows the chemical behavior of a molecular clump irradiated by a HH object.Comment: 12 pages, 7 figures, to be published in Astronomy & Astrophysic
Estimating rates of carriage acquisition and clearance and competitive ability for pneumococcal serotypes in Kenya with a Markov transition model.
BACKGROUND: There are more than 90 serotypes of Streptococcus pneumoniae, with varying biologic and epidemiologic properties. Animal studies suggest that carriage induces an acquired immune response that reduces duration of colonization in a nonserotype-specific fashion. METHODS: We studied pneumococcal nasopharyngeal carriage longitudinally in Kenyan children 3-59 months of age, following up positive swabs at days 2, 4, 8, 16, and 32 and then monthly thereafter until 2 swabs were negative for the original serotype. As previously reported, 1868/2840 (66%) of children swabbed at baseline were positive. We estimated acquisition, clearance, and competition parameters for 27 serotypes using a Markov transition model. RESULTS: Point estimates of type-specific acquisition rates ranged from 0.00025/d (type 1) to 0.0031/d (type 19F). Point estimates of time to clearance (inverse of type-specific immune clearance rate) ranged from 28 days (type 20) to 124 days (type 6A). For the serotype most resistant to competition (type 19F), acquisition of other serotypes was 52% less likely (95% confidence interval = 37%-63%) than in an uncolonized host. Fitness components (carriage duration, acquisition rate, lack of susceptibility to competition) were positively correlated with each other and with baseline prevalence, and were associated with biologic properties previously shown to associate with serotype. Duration of carriage declined with age for most serotypes. CONCLUSIONS: Common S. pneumoniae serotypes appear superior in many dimensions of fitness. Differences in rate of immune clearance are attenuated as children age and become capable of more rapid clearance of the longest-lived serotypes. These findings provide information for comparison after introduction of pneumococcal conjugate vaccine
The Pandora multi-algorithm approach to automated pattern recognition of cosmic-ray muon and neutrino events in the MicroBooNE detector
The development and operation of Liquid-Argon Time-Projection Chambers for
neutrino physics has created a need for new approaches to pattern recognition
in order to fully exploit the imaging capabilities offered by this technology.
Whereas the human brain can excel at identifying features in the recorded
events, it is a significant challenge to develop an automated, algorithmic
solution. The Pandora Software Development Kit provides functionality to aid
the design and implementation of pattern-recognition algorithms. It promotes
the use of a multi-algorithm approach to pattern recognition, in which
individual algorithms each address a specific task in a particular topology.
Many tens of algorithms then carefully build up a picture of the event and,
together, provide a robust automated pattern-recognition solution. This paper
describes details of the chain of over one hundred Pandora algorithms and tools
used to reconstruct cosmic-ray muon and neutrino events in the MicroBooNE
detector. Metrics that assess the current pattern-recognition performance are
presented for simulated MicroBooNE events, using a selection of final-state
event topologies.Comment: Preprint to be submitted to The European Physical Journal
Noise Characterization and Filtering in the MicroBooNE Liquid Argon TPC
The low-noise operation of readout electronics in a liquid argon time
projection chamber (LArTPC) is critical to properly extract the distribution of
ionization charge deposited on the wire planes of the TPC, especially for the
induction planes. This paper describes the characteristics and mitigation of
the observed noise in the MicroBooNE detector. The MicroBooNE's single-phase
LArTPC comprises two induction planes and one collection sense wire plane with
a total of 8256 wires. Current induced on each TPC wire is amplified and shaped
by custom low-power, low-noise ASICs immersed in the liquid argon. The
digitization of the signal waveform occurs outside the cryostat. Using data
from the first year of MicroBooNE operations, several excess noise sources in
the TPC were identified and mitigated. The residual equivalent noise charge
(ENC) after noise filtering varies with wire length and is found to be below
400 electrons for the longest wires (4.7 m). The response is consistent with
the cold electronics design expectations and is found to be stable with time
and uniform over the functioning channels. This noise level is significantly
lower than previous experiments utilizing warm front-end electronics.Comment: 36 pages, 20 figure
Ionization Electron Signal Processing in Single Phase LArTPCs II. Data/Simulation Comparison and Performance in MicroBooNE
The single-phase liquid argon time projection chamber (LArTPC) provides a
large amount of detailed information in the form of fine-grained drifted
ionization charge from particle traces. To fully utilize this information, the
deposited charge must be accurately extracted from the raw digitized waveforms
via a robust signal processing chain. Enabled by the ultra-low noise levels
associated with cryogenic electronics in the MicroBooNE detector, the precise
extraction of ionization charge from the induction wire planes in a
single-phase LArTPC is qualitatively demonstrated on MicroBooNE data with event
display images, and quantitatively demonstrated via waveform-level and
track-level metrics. Improved performance of induction plane calorimetry is
demonstrated through the agreement of extracted ionization charge measurements
across different wire planes for various event topologies. In addition to the
comprehensive waveform-level comparison of data and simulation, a calibration
of the cryogenic electronics response is presented and solutions to various
MicroBooNE-specific TPC issues are discussed. This work presents an important
improvement in LArTPC signal processing, the foundation of reconstruction and
therefore physics analyses in MicroBooNE.Comment: 54 pages, 36 figures; the first part of this work can be found at
arXiv:1802.0870
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