Protocols for an Aboriginal-led, Multi-methods Study of the Role of Aboriginal and Torres Strait Islander Health Workers, Practitioners and Liaison Officers in Quality Acute Health Care

ObjectivesAboriginal and Torres Strait Islander Health Workers/Practitioners and Liaison Officers play an important, often critical role providing advocacy and cultural and emotional support for Aboriginal and Torres Strait Islander patients. The main goals of this research are to explore i) how Aboriginal and Torres Strait Islander Health Workers/Practitioners and Liaison Officers are integrated in the routine delivery of care for Aboriginal and Torres Strait Islander peoples in hospital, and ii) how the role of Aboriginal and Torres Strait Islander Health Workers/Practitioners and Liaison Officers facilitates quality health outcomes. MethodsThis study is being conducted in three different hospitals using a multi-method approach including: yarning and Dadirri, patient journey mapping, survey and semi-structured interviews. Ethics approval has been provided from four ethics committees covering the three project sites in Australia (Adelaide, South Australia; Sydney, New South Wales and Alice Springs, Northern Territory). SignificanceThis study uses innovative methodology founded on the privileging of Aboriginal and Torres Strait Islander knowledges to collect Aboriginal and Torres Strait Islander perspectives and understand patient journeys within acute health care systems. This project is led by Aboriginal and Torres Strait Islander researchers and guided by the Project Steering Committee comprised of stakeholders. ImplicationsThere is limited research that explores quality acute care processes and the integration of Aboriginal and Torres Strait Islander Health Workers/Practitioners work within health care teams. This research will make a valuable contribution to understanding how hospital services can achieve quality acute health care experiences for Aboriginal and Torres Strait Islander People

The MURALES survey. IV. Searching for nuclear outflows in 3C radio galaxies at z < 0.3 with MUSE observations

We analyze VLT/MUSE observations of 37 radio galaxies from the Third Cambridge catalogue (3C) with redshift $<$0.3 searching for nuclear outflows of ionized gas. These observations are part of the MURALES project (a MUse RAdio Loud Emission line Snapshot survey), whose main goal is to explore the feedback process in the most powerful radio-loud AGN. We applied a nonparametric analysis to the [O~III] $\lambda$5007 emission line, whose asymmetries and high-velocity wings reveal signatures of outflows. We find evidence of nuclear outflows in 21 sources, with velocities between $\sim$400 - 1000 km s$^{-1}$, outflowing masses of $\sim 10^5-10^7$ M$_\odot$, and a kinetic energy in the range $\sim 10^{53} - 10^{56}$ erg. In addition, evidence for extended outflows is found in the 2D gas velocity maps of 13 sources of the subclasses of high-excitation (HEG) and broad-line (BLO) radio galaxies, with sizes between 0.4 and 20 kpc. We estimate a mass outflow rate in the range 0.4 - 30 M$_\odot$ yr$^{-1}$ and an energy deposition rate of ${\dot E}_{kin} \sim 10^{42}-10^{45}$ erg s$^{-1}$. Comparing the jet power, the nuclear luminosity of the active galactic nucleus, and the outflow kinetic energy rate, we find that outflows of HEGs and BLOs are likely radiatively powered, while jets likely only play a dominant role in galaxies with low excitation. The low loading factors we measured suggest that these outflows are driven by momentum and not by energy. Based on the gas masses, velocities, and energetics involved, we conclude that the observed ionized outflows have a limited effect on the gas content or the star formation in the host. In order to obtain a complete view of the feedback process, observations exploring the complex multiphase structure of outflows are required.Comment: 40 pages; accepted for publication on A&A

Powerful Radio-Loud Quasars are Triggered by Galaxy Mergers in the Cosmic Bright Ages

While supermassive black holes are ubiquitous features of galactic nuclei, only a small minority are observed during episodes of luminous accretion. The physical mechanism(s) driving the onset of fueling and ignition in these active galactic nuclei (AGN) are still largely unknown for many galaxies and AGN-selection criteria. Attention has focused on AGN triggering by means of major galaxy mergers gravitationally funneling gas towards the galactic center, with evidence both for and against this scenario. However, several recent studies have found that radio-loud AGN overwhelmingly reside in ongoing or recent major galaxy mergers. In this study, we test the hypothesis that major galaxy mergers are important triggers for radio-loud AGN activity in powerful quasars during cosmic noon (1 < z < 2). To this end, we compare Hubble Space Telescope WFC3/IR observations of the z > 1 3CR radio-loud broad-lined quasars to three matched radio-quiet quasar control samples. We find strong evidence for major-merger activity in nearly all radio-loud AGN, in contrast to the much lower merger fraction in the radio-quiet AGN. These results suggest major galaxy mergers are key ingredients to launching powerful radio jets. Given many of our radio-loud quasars are blue, our results present a possible challenge to the "blow-out" paradigm of galaxy evolution models in which blue quasars are the quiescent end result following a period of red quasar feedback initiated by a galaxy merger. Finally, we find a tight correlation between black hole mass and host galaxy luminosity for these different high-redshift AGN samples inconsistent with those observed for local elliptical galaxies.Comment: Published by Ap

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

GWAS meta-analysis of over 29,000 people with epilepsy identifies 26 risk loci and subtype-specific genetic architecture

Epilepsy is a highly heritable disorder affecting over 50 million people worldwide, of which about one-third are resistant to current treatments. Here we report a multi-ancestry genome-wide association study including 29,944 cases, stratified into three broad categories and seven subtypes of epilepsy, and 52,538 controls. We identify 26 genome-wide significant loci, 19 of which are specific to genetic generalized epilepsy (GGE). We implicate 29 likely causal genes underlying these 26 loci. SNP-based heritability analyses show that common variants explain between 39.6% and 90% of genetic risk for GGE and its subtypes. Subtype analysis revealed markedly different genetic architectures between focal and generalized epilepsies. Gene-set analyses of GGE signals implicate synaptic processes in both excitatory and inhibitory neurons in the brain. Prioritized candidate genes overlap with monogenic epilepsy genes and with targets of current antiseizure medications. Finally, we leverage our results to identify alternate drugs with predicted efficacy if repurposed for epilepsy treatment

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

Time-resolved infrared difference spectroscopy in cells: Response of the basic region leucine zipper of aureochrome

Gött-Zink L, Baum E, Kottke T. Time-resolved infrared difference spectroscopy in cells: Response of the basic region leucine zipper of aureochrome. Frontiers in Physics. 2023;11: 1150671.Aureochromes are light, oxygen, voltage (LOV) proteins and central blue-light receptors in algae acting as light-gated transcription factors. The C-terminal LOV domain mediates blue-light recognition and the basic region leucine zipper (bZIP) domain binds a specific DNA motif as effector. LOV domains from aureochromes have been successfully applied in optogenetic tools. The light-induced response of aureochromes has been studied by a variety of biophysical techniques, but the mechanism of signal progression from LOV to bZIP remains unclear. We studied the bZIP-LOV module of aureochrome1a from the diatomPhaeodactylum tricornutumusing time-resolved rapid-scan FTIR difference spectroscopy. Time-resolved difference spectra of bZIP-LOVin vitrorevealed a time constant of 5 s for the formation of a light state dimer of the LOV domains and the concomitant loss of α-helical elements in the bZIP domain. To verify these observations in a near-native environment, in-cell infrared difference spectroscopy (ICIRD) was extended from a steady state to a time-resolved technique using LOV domains in bacterial cells. We established a time-resolved in-cell method with a resolution of 7.6 ms after the laser pulse. Using this technique, the response of bZIP-LOV was followed in living bacterial cells and the light-induced partial unfolding of bZIP was confirmed to take place in cells in a similar time range asin vitro. These results provide structural and kinetic insights into the signaling mechanism of aureochromes. The slow response points to an association of LOV to bZIP in the dark state prior to activation

Crystals of SctV from different species reveal variable symmetry for the cytosolic domain of the type III secretion system export gate

Type III secretion systems (T3SSs) are proteinaceous devices employed by Gram-negative bacteria to directly transport proteins into a host cell. Substrate recognition and secretion are strictly regulated by the export apparatus of the so-called injectisome. The export gate SctV engages chaperone-bound substrates of the T3SS in its nonameric cytoplasmic domain. Here, the purification and crystallization of the cytoplasmic domains of SctV from Photorhabdus luminescens (LscV$_C$) and Aeromonas hydrophila (AscV$_C$) are reported. Self-rotation functions revealed that LscV$_C$ forms oligomers with either eightfold or ninefold symmetry in two different crystal forms. Similarly, AscV$_C$ was found to exhibit tenfold rotational symmetry. These are the first instances of SctV proteins forming non-nonameric oligomers

Crystals of SctV from different species reveal variable symmetry for the cytosolic domain of the type III secretion system export gate

Gilzer D, Baum E, Lieske N, Kowal J, Niemann H. Crystals of SctV from different species reveal variable symmetry for the cytosolic domain of the type III secretion system export gate. Acta Crystallographica Section F : Structural Biology Communications . 2022;78(11):386-394.Type III secretion systems (T3SSs) are proteinaceous devices employed by Gram-negative bacteria to directly transport proteins into a host cell. Substrate recognition and secretion are strictly regulated by the export apparatus of the so-called injectisome. The export gate SctV engages chaperone-bound substrates of the T3SS in its nonameric cytoplasmic domain. Here, the purification and crystallization of the cytoplasmic domains of SctV from Photorhabdus luminescens (LscVC) and Aeromonas hydrophila (AscVC) are reported. Self-rotation functions revealed that LscVC forms oligomers with either eightfold or ninefold symmetry in two different crystal forms. Similarly, AscVC was found to exhibit tenfold rotational symmetry. These are the first instances of SctV proteins forming non-nonameric oligomers