Continuous spin excitations in the three-dimensional frustrated magnet K2Ni2(SO4)3

Continuous spin excitations are widely recognized as one of the hallmarks of novel spin states in quantum magnets, such as quantum spin liquids (QSLs). Here, we report the observation of such kind of excitations in K2Ni2(SO4)3, which consists of two sets of intersected spin-1 Ni2+ trillium lattices. Our inelastic neutron scattering measurement on single crystals clearly shows a dominant excitation continuum, which exhibits a distinct temperature-dependent behavior from that of spin waves, and is rooted in strong quantum spin fluctuations. Further using the self-consistent-gaussian-approximation method, we determined the fourth- and fifth-nearest neighbor exchange interactions are dominant. These two bonds together form a unique three-dimensional network of corner-sharing tetrahedra, which we name as ''hyper-trillium'' lattice. Our results provide direct evidence for the existence of QSL features in K2Ni2(SO4)3 and highlight the potential for the hyper-trillium lattice to host frustrated quantum magnetism.Comment: 6 pages and 5 figures, plus several pages of supplemental material, comments are welcom

Insomnia and Hypnotic Use, Recorded in the Minimum Data Set, as Predictors of Falls and Hip Fractures in Michigan Nursing Homes

To examine the relationship between insomnia, hypnotic use, falls, and hip fractures in older people. Design : Secondary analysis of a large, longitudinal, assessment database. Setting : Four hundred thirty-seven nursing homes in Michigan. Participants : Residents aged 65 and older in 2001 with a baseline Minimum Data Set assessment and a follow-up 150 to 210 days later. Measurements : Logistic regression modeled any follow-up report of fall or hip fracture. Predictors were baseline reports of insomnia (previous month) and use of hypnotics (previous week). Potential confounds taken into account included standard measures of functional status, cognitive status, intensity of resource utilization, proximity to death, illness burden, number of medications, emergency room visits, nursing home new admission, age, and sex. Results : In 34,163 nursing home residents (76% women, mean age±standard deviation 84±8), hypnotic use did not predict falls (adjusted odds ratio (AOR)=1.13, 95% confidence interval (CI)=0.98, 1.30). In contrast, insomnia did predict future falls (AOR=1.52, 95% CI=1.38, 1.66). Untreated insomnia (AOR=1.55, 95% CI=1.41, 1.71) and hypnotic-treated (unresponsive) insomnia (AOR=1.32, 95% CI=1.02, 1.70) predicted more falls than did the absence of insomnia. After adjustment for confounding variables, insomnia and hypnotic use were not associated with subsequent hip fracture. Conclusion : In elderly nursing home residents, insomnia, but not hypnotic use, is associated with a greater risk of subsequent falls. Future studies will need to confirm these findings and determine whether appropriate hypnotic use can protect against future falls.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66254/1/j.1532-5415.2005.53304.x.pd

X-ray observations of highly obscured 9.7 micron sources: an efficient method for selecting Compton-thick AGN ?

Spitzer/IRS has revealed many sources with very deep Si features at 9.7micron (tau>1). We set out to investigate whether a strong Si absorption feature is a good indicator for the presence of a heavily obscured AGN. We compile X-ray spectroscopic observations available in the literature on the optically-thick,tau(9.7)>1 sources from the IRAS Seyfert sample. We find that the majority of the high-tau optically confirmed Seyferts (6/9) in this sample are probably CT. Thus we provide direct evidence for a connection between mid-IR optically-thick galaxies and CT AGN, with the success rate being close to 70% in the local Universe. This is at least comparable, if not better, than other rates obtained with photometric information in the mid to far-IR, or even mid-IR to Xray. However, this technique cannot provide complete CT AGN samples,ie there are many CT AGN which do not show significant Si absorption, with the most notable example being N1068. Having assessed the validity of the high 9.7micron technique locally, we attempt to construct a sample of candidate CT AGN at higher redshifts. We compile a sample of 7 high-tau sources in the GOODS and 5 in the Spitzer FLS. All these have been selected to have no PAH features EW(6.2)<0.3 in order to maximize the probability that they are AGN. 6 out of 7 sources in the GOODS have been detected in X-rays, while for the five FLS sources only X-ray flux upper limits are available. The high X-ray luminosities of the detected GOODS sources corroborates that these are AGN. For FLS, ancillary optical spectroscopy reveals hidden nuclei in two more sources. SED fitting can support the presence of an AGN in the vast majority of sources. We cannot derive useful X-ray spectroscopy constraints on whether these are CT. However, the low LX/L6 ratios, suggest that at least 4 out of the 6 detected sources in GOODS may be associated with CT AGN.Comment: 12 pages, to appear in A&A; version after language editin

Magnetic field amplification and X-ray emission in galaxy minor mergers

We investigate the magnetic field evolution in a series of galaxy minor mergers using the N-body/smoothed particle hydrodynamics (SPH) code \textsc{Gadget}. The simulations include the effects of radiative cooling, star formation and supernova feedback. Magnetohydrodynamics (MHD) is implemented using the SPH method. We present 32 simulations of binary mergers of disc galaxies with mass ratios of 2:1 up to 100:1, whereby we have additionally varied the initial magnetic field strengths, disc orientations and resolutions. We investigate the amplification of a given initial magnetic field within the galaxies and an ambient intergalactic medium (IGM) during the interaction. We find that the magnetic field strengths of merger remnants with mass ratios up to 10:1 saturate at a common value of several $\mu$G. For higher mass ratios, the field strength saturates at lower values. The saturation values correspond to the equipartition value of magnetic and turbulent energy density. The initial magnetization, disc orientation and numerical resolution show only minor effects on the saturation value of the magnetic field. We demonstrate that a higher impact energy of the progenitor galaxies leads to a more efficient magnetic field amplification. The magnetic and turbulent energy densities are higher for larger companion galaxies, consistent with the higher impact energy supplied to the system. We present a detailed study of the evolution of the temperature and the bolometric X-ray luminosity within the merging systems. Thereby we find that magnetic fields cause a more efficient increase of the IGM temperature and the corresponding IGM X-ray luminosity after the first encounter. However, the presence of magnetic fields does not enhance the total X-ray luminosity. Generally, the final value of the X-ray luminosity is even clearly lower for higher initial magnetic fields.Comment: 20 pages, 12 figures. Submitted to MNRA

Small molecule binding sites on the Ras:SOS complex can be exploited for inhibition of Ras activation.

Constitutively active mutant KRas displays a reduced rate of GTP hydrolysis via both intrinsic and GTPase-activating protein-catalyzed mechanisms, resulting in the perpetual activation of Ras pathways. We describe a fragment screening campaign using X-ray crystallography that led to the discovery of three fragment binding sites on the Ras:SOS complex. The identification of tool compounds binding at each of these sites allowed exploration of two new approaches to Ras pathway inhibition by stabilizing or covalently modifying the Ras:SOS complex to prevent the reloading of Ras with GTP. Initially, we identified ligands that bound reversibly to the Ras:SOS complex in two distinct sites, but these compounds were not sufficiently potent inhibitors to validate our stabilization hypothesis. We conclude by demonstrating that covalent modification of Cys118 on Ras leads to a novel mechanism of inhibition of the SOS-mediated interaction between Ras and Raf and is effective at inhibiting the exchange of labeled GDP in both mutant (G12C and G12V) and wild type Ras

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Background: In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation &lt;92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). Findings: Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p&lt;0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p&lt;0·0001). Interpretation: In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research