Sideromimic Modification of Lactivicin Dramatically Increases Potency against Extensively Drug-Resistant <i>Stenotrophomonas maltophilia </i>Clinical Isolates

Acetamido derivatives of the naturally antibacterial non-β-lactam lactivicin (LTV) have improved activity against their penicillin binding protein targets and reduced hydrolysis by β-lactamases, but penetration into Gram-negative bacteria is still relatively poor. Here we report that modification of the LTV lactone with a catechol-type siderophore increases potency 1,000-fold against Stenotrophomonas maltophilia, a species renowned for its insusceptibility to antimicrobials. The MIC90 of modified lactone compound 17 (LTV17) against a global collection of extensively drug-resistant clinical S. maltophilia isolates was 0.063 μg · ml(-1) Sideromimic modification does not reduce the ability of LTVs to induce production of the L1 and L2 β-lactamases in S. maltophilia and does not reduce the rate at which LTVs are hydrolyzed by L1 or L2. We conclude, therefore, that lactivicin modification with a siderophore known to be preferentially used by S. maltophilia substantially increases penetration via siderophore uptake. LTV17 has the potential to be developed as a novel antimicrobial for treatment of infections by S. maltophilia More generally, our work shows that sideromimic modification in a species-targeted manner might prove useful for the development of narrow-spectrum antimicrobials that have reduced collateral effects

The first super-Earth Detection from the High Cadence and High Radial Velocity Precision Dharma Planet Survey

The Dharma Planet Survey (DPS) aims to monitor about 150 nearby very bright FGKM dwarfs (within 50 pc) during 2016$-$2020 for low-mass planet detection and characterization using the TOU very high resolution optical spectrograph (R$\approx$100,000, 380-900nm). TOU was initially mounted to the 2-m Automatic Spectroscopic Telescope at Fairborn Observatory in 2013-2015 to conduct a pilot survey, then moved to the dedicated 50-inch automatic telescope on Mt. Lemmon in 2016 to launch the survey. Here we report the first planet detection from DPS, a super-Earth candidate orbiting a bright K dwarf star, HD 26965. It is the second brightest star ($V=4.4$ mag) on the sky with a super-Earth candidate. The planet candidate has a mass of 8.47$\pm0.47M_{\rm Earth}$, period of $42.38\pm0.01$ d, and eccentricity of $0.04^{+0.05}_{-0.03}$. This RV signal was independently detected by Diaz et al. (2018), but they could not confirm if the signal is from a planet or from stellar activity. The orbital period of the planet is close to the rotation period of the star (39$-$44.5 d) measured from stellar activity indicators. Our high precision photometric campaign and line bisector analysis of this star do not find any significant variations at the orbital period. Stellar RV jitters modeled from star spots and convection inhibition are also not strong enough to explain the RV signal detected. After further comparing RV data from the star's active magnetic phase and quiet magnetic phase, we conclude that the RV signal is due to planetary-reflex motion and not stellar activity.Comment: 13 pages, 17 figures, Accepted for publication in MNRA

Patient-reported outcomes of sexual and gender minority cancer survivors in Australia

This is the peer reviewed version of the following article: Lisy K, Ward A, Schofield P, Hulbert-Williams N, Bishop J & Jefford M. (2018). Patient-reported outcomes of sexual and gender minority cancer survivors in Australia. Psycho-Oncology., which has been published in final form at https://doi.org/10.1002/pon.4956 This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.Five key points: This is the first population‐based survey of Australian cancer survivors to include lesbian, gay, bisexual, transgender, or intersex (LGBTI) identity. Few respondents (1.6%) identified as LGBTI, less than half the reported prevalence in Australia. LGBTI respondents were more likely to be younger, employed, and born in Australia. LGBTI people may experience more problems with anxiety/depression, body image and financial benefits, and greater needs for diet and lifestyle information. Commonly used patient‐reported outcome measures may not be sensitive to LGBTI issues; areas for future enquiry are proposed

The first super-Earth detection from the high cadence and high radial velocity precision Dharma Planet Survey

The Dharma Planet Survey (DPS) aims to monitor about 150 nearby very bright FGKM dwarfs (within 50 pc) during 2016–2020 for low-mass planet detection and characterization using the TOU very high resolution optical spectrograph (⁠R≈100000⁠, 380–900 nm). TOU was initially mounted to the 2-m Automatic Spectroscopic Telescope at Fairborn Observatory in 2013–2015 to conduct a pilot survey, then moved to the dedicated 50-inch automatic telescope on Mt. Lemmon in 2016 to launch the survey. Here, we report the first planet detection from DPS, a super-Earth candidate orbiting a bright K dwarf star, HD 26965. It is the second brightest star (V = 4.4 mag) on the sky with a super-Earth candidate. The planet candidate has a mass of 8.47 ± 0.47MEarth, period of 42.38 ± 0.01 d, and eccentricity of 0.04+0.05−0.03⁠. This radial velocity (RV) signal was independently detected by Díaz et al., but they could not confirm if the signal is from a planet or stellar activity. The orbital period of the planet is close to the rotation period of the star (39–44.5 d) measured from stellar activity indicators. Our high precision photometric campaign and line bisector analysis of this star do not find any significant variations at the orbital period. Stellar RV jitters modelled from star-spots and convection inhibition are also not strong enough to explain the RV signal detected. After further comparing RV data from the star’s active magnetic phase and quiet magnetic phase, we conclude that the RV signal is due to planetary-reflex motion and not stellar activity

Field Measurements of Terrestrial and Martian Dust Devils

Surface-based measurements of terrestrial and martian dust devils/convective vortices provided from mobile and stationary platforms are discussed. Imaging of terrestrial dust devils has quantified their rotational and vertical wind speeds, translation speeds, dimensions, dust load, and frequency of occurrence. Imaging of martian dust devils has provided translation speeds and constraints on dimensions, but only limited constraints on vertical motion within a vortex. The longer mission durations on Mars afforded by long operating robotic landers and rovers have provided statistical quantification of vortex occurrence (time-of-sol, and recently seasonal) that has until recently not been a primary outcome of more temporally limited terrestrial dust devil measurement campaigns. Terrestrial measurement campaigns have included a more extensive range of measured vortex parameters (pressure, wind, morphology, etc.) than have martian opportunities, with electric field and direct measure of dust abundance not yet obtained on Mars. No martian robotic mission has yet provided contemporaneous high frequency wind and pressure measurements. Comparison of measured terrestrial and martian dust devil characteristics suggests that martian dust devils are larger and possess faster maximum rotational wind speeds, that the absolute magnitude of the pressure deficit within a terrestrial dust devil is an order of magnitude greater than a martian dust devil, and that the time-of-day variation in vortex frequency is similar. Recent terrestrial investigations have demonstrated the presence of diagnostic dust devil signals within seismic and infrasound measurements; an upcoming Mars robotic mission will obtain similar measurement types

Upper limits on the strength of periodic gravitational waves from PSR J1939+2134

The first science run of the LIGO and GEO gravitational wave detectors presented the opportunity to test methods of searching for gravitational waves from known pulsars. Here we present new direct upper limits on the strength of waves from the pulsar PSR J1939+2134 using two independent analysis methods, one in the frequency domain using frequentist statistics and one in the time domain using Bayesian inference. Both methods show that the strain amplitude at Earth from this pulsar is less than a few times $10^{-22}$.Comment: 7 pages, 1 figure, to appear in the Proceedings of the 5th Edoardo Amaldi Conference on Gravitational Waves, Tirrenia, Pisa, Italy, 6-11 July 200

Improving the sensitivity to gravitational-wave sources by modifying the input-output optics of advanced interferometers

We study frequency dependent (FD) input-output schemes for signal-recycling interferometers, the baseline design of Advanced LIGO and the current configuration of GEO 600. Complementary to a recent proposal by Harms et al. to use FD input squeezing and ordinary homodyne detection, we explore a scheme which uses ordinary squeezed vacuum, but FD readout. Both schemes, which are sub-optimal among all possible input-output schemes, provide a global noise suppression by the power squeeze factor, while being realizable by using detuned Fabry-Perot cavities as input/output filters. At high frequencies, the two schemes are shown to be equivalent, while at low frequencies our scheme gives better performance than that of Harms et al., and is nearly fully optimal. We then study the sensitivity improvement achievable by these schemes in Advanced LIGO era (with 30-m filter cavities and current estimates of filter-mirror losses and thermal noise), for neutron star binary inspirals, and for narrowband GW sources such as low-mass X-ray binaries and known radio pulsars. Optical losses are shown to be a major obstacle for the actual implementation of these techniques in Advanced LIGO. On time scales of third-generation interferometers, like EURO/LIGO-III (~2012), with kilometer-scale filter cavities, a signal-recycling interferometer with the FD readout scheme explored in this paper can have performances comparable to existing proposals. [abridged]Comment: Figs. 9 and 12 corrected; Appendix added for narrowband data analysi

Search for gravitational wave bursts in LIGO's third science run

We report on a search for gravitational wave bursts in data from the three LIGO interferometric detectors during their third science run. The search targets subsecond bursts in the frequency range 100-1100 Hz for which no waveform model is assumed, and has a sensitivity in terms of the root-sum-square (rss) strain amplitude of hrss ~ 10^{-20} / sqrt(Hz). No gravitational wave signals were detected in the 8 days of analyzed data.Comment: 12 pages, 6 figures. Amaldi-6 conference proceedings to be published in Classical and Quantum Gravit

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Real-Time Imaging Reveals the Dynamics of Leukocyte Behaviour during Experimental Cerebral Malaria Pathogenesis

During experimental cerebral malaria (ECM) mice develop a lethal neuropathological syndrome associated with microcirculatory dysfunction and intravascular leukocyte sequestration. The precise spatio-temporal context in which the intravascular immune response unfolds is incompletely understood. We developed a 2-photon intravital microscopy (2P-IVM)-based brain-imaging model to monitor the real-time behaviour of leukocytes directly within the brain vasculature during ECM. Ly6Chi monocytes, but not neutrophils, started to accumulate in the blood vessels of Plasmodium berghei ANKA (PbA)-infected MacGreen mice, in which myeloid cells express GFP, one to two days prior to the onset of the neurological signs (NS). A decrease in the rolling speed of monocytes, a measure of endothelial cell activation, was associated with progressive worsening of clinical symptoms. Adoptive transfer experiments with defined immune cell subsets in recombinase activating gene (RAG)-1-deficient mice showed that these changes were mediated by Plasmodium-specific CD8+ T lymphocytes. A critical number of CD8+ T effectors was required to induce disease and monocyte adherence to the vasculature. Depletion of monocytes at the onset of disease symptoms resulted in decreased lymphocyte accumulation, suggesting reciprocal effects of monocytes and T cells on their recruitment within the brain. Together, our studies define the real-time kinetics of leukocyte behaviour in the central nervous system during ECM, and reveal a significant role for Plasmodium-specific CD8+ T lymphocytes in regulating vascular pathology in this disease. © 2014 Pai et al