Ultra Long Period Cepheids: a primary standard candle out to the Hubble flow

The cosmological distance ladder crucially depends on classical Cepheids (with P=3-80 days), which are primary distance indicators up to 33 Mpc. Within this volume, very few SNe Ia have been calibrated through classical Cepheids, with uncertainty related to the non-linearity and the metallicity dependence of their period-luminosity (PL) relation. Although a general consensus on these effects is still not achieved, classical Cepheids remain the most used primary distance indicators. A possible extension of these standard candles to further distances would be important. In this context, a very promising new tool is represented by the ultra-long period (ULP) Cepheids (P \geq 80 days), recently identified in star-forming galaxies. Only a small number of ULP Cepheids have been discovered so far. Here we present and analyse the properties of an updated sample of 37 ULP Cepheids observed in galaxies within a very large metallicity range of 12+log(O/H) from ~7.2 to 9.2 dex. We find that their location in the colour(V-I)-magnitude diagram as well as their Wesenheit (V-I) index-period (WP) relation suggests that they are the counterparts at high luminosity of the shorter-period (P \leq 80 days) classical Cepheids. However, a complete pulsation and evolutionary theoretical scenario is needed to properly interpret the true nature of these objects. We do not confirm the flattening in the studied WP relation suggested by Bird et al. (2009). Using the whole sample, we find that ULP Cepheids lie around a relation similar to that of the LMC, although with a large spread (~0.4 mag).Comment: 8 pages, 4 figures, accepted for publication in Astrophysics & Space Scienc

Updated protocol and guest participant results from the ACCeRT clinical study

Introduction Cancer cachexia is a condition often seen at diagnosis, throughout chemotherapeutic treatments and in end stage Non-Small Cell Lung Cancer patients. These patients often experience a shorter life-expectancy and deterioration in performance status and reduced quality of life. New multi˗targeted regimens are required to be tested in this population to address these issues. Materials and methods The ACCeRT study is an open label, prospective, randomised controlled feasibility study investigating the use of eicosapentaenoic acid and COX-2 inhibitor (celecoxib) versus eicosapentaenoic acid, COX-2 inhibitor (celecoxib), progressive resistance training followed by ingestion of essential amino acids high in leucine in Non-Small Cell Lung Cancer cachectic patients. The study protocol was published in November 2011. Due to study participants and study team preferences a number of changes were made. Firstly, a change from a bolus drink containing 20 g of essential amino acids to an encapsulated form in divided doses over three days. Secondly, a change in leg strength analysis from utilising a leg/back dynamometry to a customised chair with a load cell testing extension isometric force. Thirdly, study drug dose reductions were now permitted. Fourthly, addition of two study sites which allowed participants to attend progressive resistance training sessions in their local area. Finally, a change in inclusion criteria to include participants that had received any first-line anti-cancer treatment. A guest participant was invited onto the study in April 2012, followed by the first study participant in June 2012. Results The guest participant showed trends in efficacy in a number of outcomes; stable fat free mass in the context of decreasing total body weight, with stable FAACT˗PWB, MFSI-SF physical, and WHOQOL-BREF QOL scores at week 20, all during documented disease progression now termed refractory cachexia. There were no treatment or exercise-related adverse events. Conclusion Publishing feasibility study protocols allows transparency in study interventions and assessments. The above ACCeRT regimen stabilised fat free mass and a number of physical/performance indicators and QOL in the guest participant

A multi-targeted treatment approch to cancer cachexia: Auckland's Cancer Cachexia evaluating Resistance Training (ACCeRT) trial

Abstract Background Cancer cachexia is a condition often seen at diagnosis, throughout anti-cancer treatments and in end-stage nonsmall- cell lung cancer patients. Methods and results Participants with late-stage non-small-cell lung cancer and cachexia (defined as ≥5% weight loss within 12 months) were randomly assigned 1:2 to 2.09 g of eicosapentaenoic acid (EPA) and 300 mg of cyclo-oxygenase-2 inhibitor celecoxib orally once daily vs. same dosing of EPA, celecoxib, plus two sessions per week of progressive resistance training and 20 g of oral essential amino acids high in leucine in a split dose over 3 days, after each session. Primary endpoint was the acceptability of the earlier multi-targeted approach. Main secondary endpoints included change in body weight and fat-free mass, by bioelectric impedance analysis and total quadriceps muscle volume by magnetic resonance imaging over 20 weeks. Sixty-nine patients were screened resulting in 20 patients being enrolled. Acceptability scored high, with 4.5/5 (Arm A) and 5/5 (Arm B) for EPA and 5/5 for celecoxib within both arms and 4.8/5 for progressive resistance training sessions and 4.5/5 for essential amino acids within Arm B, all at Week 20. Results showed a net gain in bioelectric impedance analysis fat-free mass of +1.3 kg, n = 2 (Arm A), compared with +0.7 kg, n = 7 (Arm B) at Week 12, and —1.5 kg, n = 2 (Arm A), compared with —1.7 kg, n = 4 (Arm B) at Week 20. Trends in efficacy in terms of improvement and/or stability in cachexia markers were seen within magnetic resonance imaging muscle volume, albumin, and C-reactive protein levels within both arms. There were no exercise-related adverse events, with one possible related adverse event of asymptomatic atrial fibrillation in one participant within Arm A. Conclusions Non-small-cell lung cancer cachectic patients are willing to be enrolled onto a multi-targeted treatment regimen and may benefit from cachexia symptom management even during the late/refractory stage

Radio Science Investigation on a Mercury Orbiter Mission

We review the results from {\it Mariner 10} regarding Mercury's gravity field and the results from radar ranging regarding topography. We discuss the implications of improving these results, including a determination of the polar component, as well as the opportunity to perform relativistic gravity tests with a future {\it Mercury Orbiter}. With a spacecraft placed in orbit with periherm at 400 km altitude, apherm at 16,800 km, period 13.45 hr and latitude of periherm at +30 deg, one can expect a significant improvement in our knowledge of Mercury's gravity field and geophysical properties. The 2000 Plus mission that evolved during the European Space Agency (ESA) {\it Mercury Orbiter} assessment study can provide a global gravity field complete through the 25th degree and order in spherical harmonics. If after completion of the main mission, the periherm could be lowered to 200 km altitude, the gravity field could be extended to 50th degree and order. We discuss the possibility that a search for a Hermean ionosphere could be performed during the mission phases featuring Earth occultations. Because of its relatively large eccentricity and close proximity to the Sun, Mercury's orbital motion provides one of the best solar-system tests of general relativity. Consequently, we emphasize the number of feasible relativistic gravity tests that can be performed within the context of the parameterized post-Newtonian formalism - a useful framework for testing modern gravitational theories. We pointed out that current results on relativistic precession of Mercury's perihelion are uncertain by 0.5 %, and we discuss the expected improvement using {\it Mercury Orbiter}. We discuss the importance of {\it Mercury Orbiter} for setting limits on a possible time variation in theComment: 23 pages, LaTeX, no figure

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

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

Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo

Despite the growing number of binary black hole coalescences confidently observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include the effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that have already been identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total source-frame mass M > 70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz emitted gravitational-wave frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place a conservative upper limit for the merger rate density of high-mass binaries with eccentricities 0 < e ≤ 0.3 at 16.9 Gpc−3 yr−1 at the 90% confidence level

Search for gravitational-wave transients associated with magnetar bursts in advanced LIGO and advanced Virgo data from the third observing run

Gravitational waves are expected to be produced from neutron star oscillations associated with magnetar giant f lares and short bursts. We present the results of a search for short-duration (milliseconds to seconds) and longduration (∼100 s) transient gravitational waves from 13 magnetar short bursts observed during Advanced LIGO, Advanced Virgo, and KAGRA’s third observation run. These 13 bursts come from two magnetars, SGR1935 +2154 and SwiftJ1818.0−1607. We also include three other electromagnetic burst events detected by FermiGBM which were identified as likely coming from one or more magnetars, but they have no association with a known magnetar. No magnetar giant flares were detected during the analysis period. We find no evidence of gravitational waves associated with any of these 16 bursts. We place upper limits on the rms of the integrated incident gravitational-wave strain that reach 3.6 × 10−²³ Hz at 100 Hz for the short-duration search and 1.1 ×10−²² Hz at 450 Hz for the long-duration search. For a ringdown signal at 1590 Hz targeted by the short-duration search the limit is set to 2.3 × 10−²² Hz. Using the estimated distance to each magnetar, we derive upper limits upper limits on the emitted gravitational-wave energy of 1.5 × 1044 erg (1.0 × 1044 erg) for SGR 1935+2154 and 9.4 × 10^43 erg (1.3 × 1044 erg) for Swift J1818.0−1607, for the short-duration (long-duration) search. Assuming isotropic emission of electromagnetic radiation of the burst fluences, we constrain the ratio of gravitational-wave energy to electromagnetic energy for bursts from SGR 1935+2154 with the available fluence information. The lowest of these ratios is 4.5 × 103

A joint Fermi-GBM and Swift-BAT analysis of gravitational-wave candidates from the third gravitational-wave observing run

We present Fermi Gamma-ray Burst Monitor (Fermi-GBM) and Swift Burst Alert Telescope (Swift-BAT) searches for gamma-ray/X-ray counterparts to gravitational-wave (GW) candidate events identified during the third observing run of the Advanced LIGO and Advanced Virgo detectors. Using Fermi-GBM onboard triggers and subthreshold gamma-ray burst (GRB) candidates found in the Fermi-GBM ground analyses, the Targeted Search and the Untargeted Search, we investigate whether there are any coincident GRBs associated with the GWs. We also search the Swift-BAT rate data around the GW times to determine whether a GRB counterpart is present. No counterparts are found. Using both the Fermi-GBM Targeted Search and the Swift-BAT search, we calculate flux upper limits and present joint upper limits on the gamma-ray luminosity of each GW. Given these limits, we constrain theoretical models for the emission of gamma rays from binary black hole mergers