Needle in a Haystack: Finding Supermassive Black Hole-Related Flares in the Zwicky Transient Facility Public Survey

Transient accretion events onto supermassive black holes (SMBHs), such as tidal disruption events (TDEs), Bowen Fluorescence Flares (BFFs), and active galactic nuclei (AGNs), which are accompanied by sudden increases of activity, offer a new window onto the SMBH population, accretion physics, and stellar dynamics in galaxy centers. However, such transients are rare and finding them in wide-field transient surveys is challenging. Here we present the results of a systematic real-time search for SMBH-related transients in Zwicky Transient Facility (ZTF) public alerts, using various search queries. We examined 345 rising events coincident with a galaxy nucleus, with no history of previous activity, of which 223 were spectroscopically classified. Of those, five (2.2%) were TDEs, one (0.5%) was a BFF, and two (0.9%) were AGN flares. Limiting the search to blue events, the fraction of TDEs nearly doubles to 4.1%, and no TDEs are missed. Limiting the search further to candidate post-starburst galaxies increases the relative number of TDEs to 16.7%, but the absolute numbers in such a search are small. The main contamination source is supernovae (95.1% of classified events), of which the majority (82.2% of supernovae) are of Type Ia. In a comparison set of 39 events with limited photometric history, the AGN contamination increases to ~30%. Host galaxy offset is not a significant discriminant of TDEs in current ZTF data, but might be useful in higher-resolution data. Our results can be used to quantify the efficiency of various SMBH-related transient search strategies in optical surveys such as ZTF and the Legacy Survey of Space and Time.Comment: Accepted to Ap

Teacher Candidates’ Emerging Perspectives on Trauma Informed Teaching

A transdisciplinary team of candidates with teacher and social work educators describe their perspectives of trauma-informed teaching and intentions to use evidence-based practices in classrooms. We studied classroom management from a trauma-informed perspective in the first course in the program, then reflected back on these through a professional learning community created to intentionally focus on trauma informed teaching. We highlight findings around candidates’ perspectives and specific actions they attended to in order to incorporate those practices

Scientific issues related to the cytology proficiency testing regulations

The member organizations of the Cytology Education and Technology Consortium believe there are significant flaws in current cytology proficiency testing regulations. The most immediate needed modifications include lengthening the required testing interval, utilizing stringently validated and continuously monitored slides, changing the grading scheme, and changing the focus of the test from the individual to laboratory level testing. Integration of new computer-assisted and located-guided screening technologies into the testing protocols is necessary for the testing protocol to be compliant with the law

AT 2021loi: A Bowen Fluorescence Flare with a Rebrightening Episode, Occurring in a Previously-Known AGN

AT 2021loi is an optical-ultraviolet transient located at the center of its host galaxy. Its spectral features identify it as a member of the ``Bowen Fluorescence Flare'' (BFF) class. The first member of this class was considered to be related to a tidal disruption event, but enhanced accretion onto an already active supermassive black hole was suggested as an alternative explanation. AT 2021loi, having occurred in a previously-known unobscured AGN, strengthens the latter interpretation. Its light curve is similar to those of previous BFFs, showing a rebrightening approximately one year after the main peak (which was not explicitly identified, but might be the case, in all previous BFFs). An emission feature around 4680 A, seen in the pre-flare spectrum, strengthens by a factor of $\sim$2 around the optical peak of the flare, and is clearly seen as a double peaked feature then, suggesting a blend of NIII $\lambda 4640$ with HeII $\lambda4686$ as its origin. The appearance of OIII $\lambda$3133 and possible NIII $\lambda\lambda4097,4103$ (blended with H$\delta$) during the flare further support a Bowen Fluorescence classification. Here, we present ZTF, ATLAS, Keck, Las Cumbres Observatory, NEOWISE-R, $Swift$, AMI and VLA observations of AT 2021loi, making it one of the best observed BFFs to date. AT 2021loi thus provides some clarity on the nature of BFFs but also further demonstrates the diversity of nuclear transients.Comment: Submitted to ApJ. This version addresses comments from the refere

Psychological Outcomes following a nurse-led Preventative Psychological Intervention for critically ill patients (POPPI): protocol for a cluster-randomised clinical trial of a complex intervention

Introduction Acute psychological stress, as well as unusual experiences including hallucinations and delusions, are common in critical care unit patients and have been linked to post-critical care psychological morbidity such as post-traumatic stress disorder (PTSD), depression and anxiety. Little high-quality research has been conducted to evaluate psychological interventions that could alleviate longer-term psychological morbidity in the critical care unit setting. Our research team developed and piloted a nurse-led psychological intervention, aimed at reducing patient-reported PTSD symptom severity and other adverse psychological outcomes at 6 months, for evaluation in the POPPI trial.Methods and analysis This is a multicentre, parallel group, cluster-randomised clinical trial with a staggered roll-out of the intervention. The trial is being carried out at 24 (12 intervention, 12 control) NHS adult, general, critical care units in the UK and is evaluating the clinical effectiveness and cost-effectiveness of a nurse-led preventative psychological intervention in reducing patient-reported PTSD symptom severity and other psychological morbidity at 6 months. All sites deliver usual care for 5 months (baseline period). Intervention group sites are then trained to carry out the POPPI intervention, and transition to delivering the intervention for the rest of the recruitment period. Control group sites deliver usual care for the duration of the recruitment period. The trial also includes a process evaluation conducted independently of the trial team.Ethics and dissemination This protocol was reviewed and approved by the National Research Ethics Service South Central - Oxford B Research Ethics Committee (reference: 15/SC/0287). The first patient was recruited in September 2015 and results will be disseminated in 2018. The results will be presented at national and international conferences and published in peer reviewed medical journals.Trial registration number ISRCTN53448131; Pre-results

‘Multi-Epitope-Targeted’ Immune-Specific Therapy for a Multiple Sclerosis-Like Disease via Engineered Multi-Epitope Protein Is Superior to Peptides

Antigen-induced peripheral tolerance is potentially one of the most efficient and specific therapeutic approaches for autoimmune diseases. Although highly effective in animal models, antigen-based strategies have not yet been translated into practicable human therapy, and several clinical trials using a single antigen or peptidic-epitope in multiple sclerosis (MS) yielded disappointing results. In these clinical trials, however, the apparent complexity and dynamics of the pathogenic autoimmunity associated with MS, which result from the multiplicity of potential target antigens and “epitope spread”, have not been sufficiently considered. Thus, targeting pathogenic T-cells reactive against a single antigen/epitope is unlikely to be sufficient; to be effective, immunospecific therapy to MS should logically neutralize concomitantly T-cells reactive against as many major target antigens/epitopes as possible. We investigated such “multi-epitope-targeting” approach in murine experimental autoimmune encephalomyelitis (EAE) associated with a single (“classical”) or multiple (“complex”) anti-myelin autoreactivities, using cocktail of different encephalitogenic peptides vis-a-vis artificial multi-epitope-protein (designated Y-MSPc) encompassing rationally selected MS-relevant epitopes of five major myelin antigens, as “multi-epitope-targeting” agents. Y-MSPc was superior to peptide(s) in concomitantly downregulating pathogenic T-cells reactive against multiple myelin antigens/epitopes, via inducing more effective, longer lasting peripheral regulatory mechanisms (cytokine shift, anergy, and Foxp3+ CTLA4+ regulatory T-cells). Y-MSPc was also consistently more effective than the disease-inducing single peptide or peptide cocktail, not only in suppressing the development of “classical” or “complex EAE” or ameliorating ongoing disease, but most importantly, in reversing chronic EAE. Overall, our data emphasize that a “multi-epitope-targeting” strategy is required for effective immune-specific therapy of organ-specific autoimmune diseases associated with complex and dynamic pathogenic autoimmunity, such as MS; our data further demonstrate that the “multi-epitope-targeting” approach to therapy is optimized through specifically designed multi-epitope-proteins, rather than myelin peptide cocktails, as “multi-epitope-targeting” agents. Such artificial multi-epitope proteins can be tailored to other organ-specific autoimmune diseases

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

REVIEW OF THE CENTRAL AND SOUTH ATLANTIC SHELF AND DEEP-SEA BENTHOS: SCIENCE, POLICY, AND MANAGEMENT

The Central and South Atlantic represents a vast ocean area and is home to a diverse range of ecosystems and species. Nevertheless, and similar to the rest of the global south, the area is comparatively understudied yet exposed to increasing levels of multisectoral pressures. To counteract this, the level of scientific exploration in the Central and South Atlantic has increased in recent years and will likely continue to do so within the context of the United Nations (UN) Decade of Ocean Science for Sustainable Development. Here, we compile the literature to investigate the distribution of previous scientific exploration of offshore (30 m+) ecosystems in the Central and South Atlantic, both within and beyond national jurisdiction, allowing us to synthesise overall patterns of biodiversity. Furthermore, through the lens of sustainable management, we have reviewed the existing anthropogenic activities and associated management measures relevant to the region. Through this exercise, we have identified key knowledge gaps and undersampled regions that represent priority areas for future research and commented on how these may be best incorporated into, or enhanced through, future management measures such as those in discussion at the UN Biodiversity Beyond National Jurisdiction negotiations. This review represents a comprehensive summary for scientists and managers alike looking to understand the key topographical, biological, and legislative features of the Central and South Atlantic.This paper is an output of the UN Ocean Decade endorsed Challenger 150 Programme (#57). Challenger 150 is supported by the Deep Ocean Stewardship Initiative (DOSI) and the Scientific Committee on Oceanic Research’s (SCOR) working group 159 (NSF Grant OCE-1840868) for which KLH is co-chair. AEHB, KLH, KAM, SBu, and KS are supported by the UKRI funded One Ocean Hub NE/S008950/1. TA is supported by the BiodivRestore ERA-NET Cofund (GA N°101003777) with the EU and the following funding organisations: FCT, RFCT, AEI, DFG, and ANR. TA also acknowledges financial support to CESAM by FCT/MCTES (UIDP/50017/2 020+UIDB/50017/2020+ LA/P/0094/2020) through national funds. NB is supported by the John Ellerman Foundation. AB is supported by the German Research Foundation. DH, CO, AFB, LA, SBr, and KS received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 818123 (iAtlantic); this output reflects only the author’s view and the European Union cannot be held responsible for any use that may be made of the information contained therein. DH, AF, JT, and CW were additionally supported through the Cluster of Excellence “The Ocean Floor – Earth’s Uncharted Interface” (EXC-2077 – 390741603 by Deutsche Forschungsgemeinschaft). CO also extends thanks to the HWK – Institute for Advanced Study, and PM to Dr. Alberto Martín, retired professor of Universidad Simón Bolívar in Caracas, Venezuela for facilitating references used in the Venezuela section.Peer reviewe