High power operation of an X-band gyrotwistron

We report the first experimental verification of a gyrotwistron amplifier. The device utilized a single 9.858 GHz, TE011 cavity, a heavily attenuated drift tube, and a long tapered output waveguide section. With a 440 kV, 200-245 A, 1 μs electron beam and a sharply tapered axial magnetic field, peak powers above 21 MW were achieved with a gain near 24 dB. Performance was limited by competition from a fundamental TE11 mode. A multimode code was developed to analyze this system, and simulations were in good agreement with the experiment

ALMA Observations of Asymmetric Molecular Gas Emission from a Protoplanetary Disk in the Orion Nebula

We present Atacama Large Millimeter/submillimeter Array (ALMA) observations of molecular line emission from d216-0939, one of the largest and most massive protoplanetary disks in the Orion Nebula Cluster (ONC). We model the spectrally resolved HCO$^+$ (4--3), CO (3--2), and HCN (4--3) lines observed at 0\farcs5 resolution to fit the temperature and density structure of the disk. We also weakly detect and spectrally resolve the CS (7--6) line but do not model it. The abundances we derive for CO and HCO$^+$ are generally consistent with expected values from chemical modeling of protoplanetary disks, while the HCN abundance is higher than expected. We dynamically measure the mass of the central star to be $2.17\pm0.07\,M_\odot$ which is inconsistent with the previously determined spectral type of K5. We also report the detection of a spatially unresolved high-velocity blue-shifted excess emission feature with a measurable positional offset from the central star, consistent with a Keplerian orbit at $60\pm20\,\mathrm{au}$. Using the integrated flux of the feature in HCO$^+$ (4--3), we estimate the total H$_2$ gas mass of this feature to be at least $1.8-8\,M_\mathrm{Jupiter}$, depending on the assumed temperature. The feature is due to a local temperature and/or density enhancement consistent with either a hydrodynamic vortex or the expected signature of the envelope of a forming protoplanet within the disk.Comment: 19 pages, 12 figures, accepted for publication in A

Radial Surface Density Profiles of Gas and Dust in the Debris Disk around 49 Ceti

We present ~0.4 resolution images of CO(3-2) and associated continuum emission from the gas-bearing debris disk around the nearby A star 49 Ceti, observed with the Atacama Large Millimeter/Submillimeter Array (ALMA). We analyze the ALMA visibilities in tandem with the broad-band spectral energy distribution to measure the radial surface density profiles of dust and gas emission from the system. The dust surface density decreases with radius between ~100 and 310 au, with a marginally significant enhancement of surface density at a radius of ~110 au. The SED requires an inner disk of small grains in addition to the outer disk of larger grains resolved by ALMA. The gas disk exhibits a surface density profile that increases with radius, contrary to most previous spatially resolved observations of circumstellar gas disks. While ~80% of the CO flux is well described by an axisymmetric power-law disk in Keplerian rotation about the central star, residuals at ~20% of the peak flux exhibit a departure from axisymmetry suggestive of spiral arms or a warp in the gas disk. The radial extent of the gas disk (~220 au) is smaller than that of the dust disk (~300 au), consistent with recent observations of other gas-bearing debris disks. While there are so far only three broad debris disks with well characterized radial dust profiles at millimeter wavelengths, 49 Ceti's disk shows a markedly different structure from two radially resolved gas-poor debris disks, implying that the physical processes generating and sculpting the gas and dust are fundamentally different.Comment: 20 pages, 8 figures, accepted for publication in ApJ March 31, 2017 (submitted Nov 2016

NCI-MATCH Arms N & P: Phase II study of PI3K beta inhibitor GSK2636771 in patients (pts) with cancers (ca) with PTEN mutation/deletion (mut/del) or PTEN protein loss

Background: The NCI-MATCH trial is the largest national study (1173 sites) for ptswith relapsed/ refractory solid tumors, lymphomas and myeloma, which assigns tar-geted therapies based on individual tumor molecular alterations detected using theadapted Oncomine AmpliSeq panel (143 genes) and immunohistochemistry (IHC).We hypothesized that patients with PTEN-deficient cancers enrolled to Arms N and Pmay benefit from treatment with the PI3K beta-selective inhibitor GSK2636771. Methods: Eligibility: relapsed/refractory ca, good end-organ function, and ECOG PS ≤ 1. Pts were screened for molecular alterations by centralized testing on fresh tumor biopsy and had deleterious PTEN mut/del without loss of expression (Arm N) or complete loss of cytoplasmic and nuclear PTEN staining on IHC (Arm P), and no other aberrations activating the PI3K/MTOR and MAPK pathways (mut in PIK3CA, PIK3R1, BRAF, KRAS, AKT1, TSC1/2, mTOR, RHEB, NF2, NRAS, HRAS). Pts received GSK2636771 400mg/day (28-days cycles). RECIST 1.1 overall response rate (ORR) was the primary endpoint. Results: Of 59 enrolled pts, 56 were eligible and received treatment. Of 22 pts with PTEN mut/del (Arm N: 6 uterine, 2 breast, 2 prostate, 2 head/neck ca, 10 other), all are off treatment as of analysis (14 disease progression, 4 for adverse events [AEs], 4 other). One pt (4.5%) with prostate ca (PTEN deletion, MPRSS2-ERG fusion) attained a partial response (-42%). Of 7 (32%) pts with stable disease (SD), 2 had SD \u3e 6 months (uterine leiomyosarcoma; endometrial carcinoma). Of 34 pts with loss of PTEN protein by IHC (Arm P: 7 prostate, 6 breast, 3 squamous anal ca, 2 cholangiocarcinoma, 16 other), all are off treatment as of analysis (26 disease progression, 4 for AE, 4 other). Of 9 (37.5%) pts with SD, 3 had SD \u3e 6 months (prostate cancer; squamous bladder cancer, squamous anal cancer). Median progression-free survival was 1.8 months for both arms. Gr ≥ 3 treatment-related (tr) reversible toxicities were experienced by 30% (7) and 20% (7) of pts in arms N and P, respectively. No tr Gr 5 toxicities were observed in either arm. Conclusions: Single agent GSK2636771 has very modest activity in ca with PTEN gene mutation/deletion and/or PTEN protein loss

Practice patterns for acute ischemic stroke workup: A longitudinal population‐based study

Background We examined practice patterns of inpatient testing to identify stroke etiologies and treatable risk factors for acute ischemic stroke recurrence. Methods and Results We identified stroke cases and related diagnostic testing from four 1‐year study periods (July 1993 to June 1994, 1999, 2005, and 2010) of the Greater Cincinnati/Northern Kentucky Stroke Study. Patients aged ≥18 years were included. We focused on evaluation of extracranial arteries for carotid stenosis and assessment of atrial fibrillation because randomized controlled trials supported treatment of these conditions for stroke prevention across all 4 study periods. In each study period, we also recorded stroke etiology, as determined by diagnostic testing and physician adjudication. An increasing proportion of stroke patients received assessment of both extracranial arteries and the heart over time (50%, 58%, 74%, and 78% in the 1993–1994, 1999, 2005, and 2010 periods, respectively; P &lt;0.0001 for trend), with the most dramatic individual increases in echocardiography (57%, 63%, 77%, and 83%, respectively). Concurrently, we observed a decrease in strokes of unknown etiology (47%, 48%, 41%, and 38%, respectively; P &lt;0.0001 for trend). We also found a significant increase in strokes of other known causes (32%, 25%, 45% and 59%, respectively; P &lt;0.0001 for trend). Conclusions Stroke workup for treatable causes of stroke are being used more frequently over time, and this is associated with a decrease in cryptogenic strokes. Future study of whether better determination of treatable stroke etiologies translates to a decrease in stroke recurrence at the population level will be essential. </jats:sec

Using a runway paradigm to assess the relative strength of rats' motivations for enrichment objects

Laboratory animals should be provided with enrichment objects in their cages; however, it is first necessary to test whether the proposed enrichment objects provide benefits that increase the animals’ welfare. The two main paradigms currently used to assess proposed enrichment objects are the choice test, which is limited to determining relative frequency of choice, and consumer demand studies, which can indicate the strength of a preference but are complex to design. Here, we propose a third methodology: a runway paradigm, which can be used to assess the strength of an animal’s motivation for enrichment objects, is simpler to use than consumer demand studies, and is faster to complete than typical choice tests. Time spent with objects in a standard choice test was used to rank several enrichment objects in order to compare with the ranking found in our runway paradigm. The rats ran significantly more times, ran faster, and interacted longer with objects with which they had previously spent the most time. It was concluded that this simple methodology is suitable for measuring rats’ motivation to reach enrichment objects. This can be used to assess the preference for different types of enrichment objects or to measure reward system processes

Results from the tranexamic acid for primary intracerebral haemorrhage-2 (TICH-2) trial

Background: Haematoma expansion leads to worse outcome in intracerebral haemorrhage (ICH). Tranexamic acid (TXA) is a promising haemostatic agent to prevent haematoma expansion and improve outcome after ICH. Methods: TICH-2 is a multicentre prospective double blind randomised controlled trial, which recruited patients presenting within 8 hours of primary ICH to receive intravenous TXA or placebo. Primary outcome is modified Rankin Scale at day 90 and will be analysed using ordinal logistic regression, adjusted for minimisation criteria. Secondary outcomes will be analysed using adjusted binary logistic regression and multiple linear regression; these include haematoma expansion at 24 hours, day 7 National Institute of Health Stroke Scale (NIHSS), day 90 Barthel Index, quality of life, cognition and mood. Results: A total of 2325 patients were recruited between 14th March 2013 and 30th September 2017, from 12 countries: United Kingdom (n= 1910), Italy, Georgia, Switzerland, Malaysia, Hungary, Poland, Ireland, Turkey, Sweden, Denmark and Spain. Randomisation characteristics included: age 68.9 (13.8) years; male 1301 (56.0%); time from onset to randomisation 3.6 hours [2.6, 5.0]; NIHSS 13 (7.5); Glasgow coma scale 13.4 (2.1); systolic blood pressure 172.6 (27.2) mmHg; intraventricular haemorrhage 745 (32.0%) and prior antiplatelet use 610 (26.2%). Conclusion: TICH-2 is the largest trial of TXA in spontaneous ICH and recruited over its original target of 2000 patients. The results will be available in May 2018 and will inform whether TXA should be recommended for the treatment of acute spontaneous ICH

Area-charge inequality for black holes

The inequality between area and charge $A\geq 4\pi Q^2$ for dynamical black holes is proved. No symmetry assumption is made and charged matter fields are included. Extensions of this inequality are also proved for regions in the spacetime which are not necessarily black hole boundaries.Comment: 21 pages, 2 figure