A phase I/II study of gemcitabine and fractionated cisplatin in an outpatient setting using a 21-day schedule in patients with advanced and metastatic bladder cancer

A randomised phase III trial of MVAC (methotrexate, vincristine, doxorubicin, cisplatin) vs gemcitabine and cisplatin (GC) (G 1000 mg m(-2) days 1, 8, and 15 plus C 70 mg m(-2) day 2, q 4 wks) indicated GC had similar efficacy and lower toxicity (JCO 2000). Significant haematologic toxicities in the GC arm occurred on day 15, necessitating dose adjustments in 37% of cycles. We conducted a phase I/II dose escalation trial using GC on a 21-day cycle, with G and C split between days 1 and 8. The objective of the study to define maximum-tolerated dose and dose-limiting toxicity (DLT), objective response rate, and overall survival. In all, 32 patients with locally advanced, relapsed, or metastatic disease received: dose level 1, G/C 1000/35; level 2, 1100/35; level 3, 1200/35; level 4, 1200/45 mg m(-2) (G and C given on days 1 and 8 every 3 wks). A total of 19 patients had glomerular filtration rate <60 ml min(-1) and 19 patients had metastatic disease. Dose-limiting toxicity was haematologic (grade 4 thrombocytopenia) at dose level 2. Of 151 cycles, at day 15, platelets were <100 in 61 cycles; neutrophils <0.5, platelets <50 in 26 cycles. Only seven cycles were deferred due to haematological toxicity; four for renal toxicity (chemotherapy instituted posthydration). Overall response rate was 65.5% on an intention-to-treat analysis (75% [21/28] for assessable patients), with four complete responses (12.5%) and 17 partial responses (53%). After the median follow-up of 17.2 months (range 13.1-32.4 months), 12 patients remain alive. The overall median survival was 16 months (range 10.1-26.6 months). G plus C every 3 weeks is active and well tolerated in an outpatient setting, even in patients receiving prior platinum-based regimens and with poor renal reserve

Extended search for the invisible axion with the axion dark matter experiment

This Letter reports on a cavity haloscope search for dark matter axions in the Galactic halo in the mass range 2.81–3.31μeV. This search utilizes the combination of a low-noise Josephson parametric amplifier and a large-cavity haloscope to achieve unprecedented sensitivity across this mass range. This search excludes the full range of axion-photon coupling values predicted in benchmark models of the invisible axion that solve the strong CP problem of quantum chromodynamics

Low Frequency (100-600 MHz) Searches with Axion Cavity Haloscopes

We investigate reentrant and dielectric loaded cavities for the purpose of extending the range of axion cavity haloscopes to lower masses, below the range where the Axion Dark Matter eXperiment (ADMX) has already searched. Reentrant and dielectric loaded cavities were simulated numerically to calculate and optimize their form factors and quality factors. A prototype reentrant cavity was built and its measured properties were compared with the simulations. We estimate the sensitivity of axion dark matter searches using reentrant and dielectric loaded cavities inserted in the existing ADMX magnet at the University of Washington and a large magnet being installed at Fermilab.Comment: 33 pages, 24 figure

Search for the Cosmic Axion Background with ADMX

We report the first result of a direct search for a Cosmic ${\it axion}$ Background C$a$B - a relativistic background of axions that is not dark matter - performed with the axion haloscope, the Axion Dark Matter eXperiment (ADMX). Conventional haloscope analyses search for a signal with a narrow bandwidth, as predicted for dark matter, whereas the C$a$B will be broad. We introduce a novel analysis strategy, which searches for a C$a$B induced daily modulation in the power measured by the haloscope. Using this, we repurpose data collected to search for dark matter to set a limit on the axion photon coupling of the C$a$B originating from dark matter decay in the 800-995 MHz frequency range. We find that the present sensitivity is limited by fluctuations in the cavity readout as the instrument scans across dark matter masses. Nevertheless, we demonstrate that these challenges can be surmounted with the use of superconducting qubits as single photon counters, and allow ADMX to operate as a telescope searching for axions emerging from the decay of dark matter. The daily modulation analysis technique we introduce can be deployed for various broadband RF signals, such as other forms of a C$a$B or even high-frequency gravitational waves.Comment: 9 pages, 4 figure

Non-Virialized Axion Search Sensitive to Doppler Effects in the Milky Way Halo

The Axion Dark Matter eXperiment (ADMX) has previously excluded Dine-Fischler-Srednicki-Zhitnisky (DFSZ) axions between 680-790 MHz under the assumption that the dark matter is described by the isothermal halo model. However, the precise nature of the velocity distribution of dark matter is still unknown, and alternative models have been proposed. We report the results of a non-virialized axion search over the mass range 2.81-3.31 {\mu}eV, corresponding to the frequency range 680-800 MHz. This analysis marks the most sensitive search for non-virialized axions sensitive to Doppler effects in the Milky Way Halo to date. Accounting for frequency shifts due to the detector's motion through the Galaxy, we exclude cold flow relic axions with a velocity dispersion of order 10^-7 c with 95% confidence

A framework for the development of a global standardised marine taxon reference image database (SMarTaR-ID) to support image-based analyses

Video and image data are regularly used in the field of benthic ecology to document biodiversity. However, their use is subject to a number of challenges, principally the identification of taxa within the images without associated physical specimens. The challenge of applying traditional taxonomic keys to the identification of fauna from images has led to the development of personal, group, or institution level reference image catalogues of operational taxonomic units (OTUs) or morphospecies. Lack of standardisation among these reference catalogues has led to problems with observer bias and the inability to combine datasets across studies. In addition, lack of a common reference standard is stifling efforts in the application of artificial intelligence to taxon identification. Using the North Atlantic deep sea as a case study, we propose a database structure to facilitate standardisation of morphospecies image catalogues between research groups and support future use in multiple front-end applications. We also propose a framework for coordination of international efforts to develop reference guides for the identification of marine species from images. The proposed structure maps to the Darwin Core standard to allow integration with existing databases. We suggest a management framework where high-level taxonomic groups are curated by a regional team, consisting of both end users and taxonomic experts. We identify a mechanism by which overall quality of data within a common reference guide could be raised over the next decade. Finally, we discuss the role of a common reference standard in advancing marine ecology and supporting sustainable use of this ecosystem

Search for invisible axion dark matter with the Axion Dark Matter Experiment

This Letter reports the results from a haloscope search for dark matter axions with masses between 2.66 and 2.81μeV. The search excludes the range of axion-photon couplings predicted by plausible models of the invisible axion. This unprecedented sensitivity is achieved by operating a large-volume haloscope at subkelvin temperatures, thereby reducing thermal noise as well as the excess noise from the ultralow-noise superconducting quantum interference device amplifier used for the signal power readout. Ongoing searches will provide nearly definitive tests of the invisible axion model over a wide range of axion masses

Search for invisible axion dark matter in the 3.3-4.2 μeV mass range

We report the results from a haloscope search for axion dark matter in the 3.3-4.2 μeV mass range. This search excludes the axion-photon coupling predicted by one of the benchmark models of "invisible"axion dark matter, the Kim-Shifman-Vainshtein-Zakharov model. This sensitivity is achieved using a large-volume cavity, a superconducting magnet, an ultra low noise Josephson parametric amplifier, and sub-Kelvin temperatures. The validity of our detection procedure is ensured by injecting and detecting blind synthetic axion signals