A Reemerging Bright Soft X-Ray State of the Changing-look Active Galactic Nucleus 1ES 1927+654:A Multiwavelength View

1ES1927+654 is a nearby active galactic nucleus (AGN) that has shown an enigmatic outburst in optical/UV followed by X-rays, exhibiting strange variability patterns at timescales of months to years. Here we report the unusual X-ray, UV, and radio variability of the source in its postflare state (2022 January–2023 May). First, we detect an increase in the soft X-ray (0.3–2 keV) flux from 2022 May to 2023 May by almost a factor of 5, which we call the bright soft state. The hard X-ray 2–10 keV flux increased by a factor of 2, while the UV flux density did not show any significant changes (≤30%) in the same period. The integrated energy pumped into the soft and hard X-rays during this period of 11 months is ∼3.57 × 10 ^50 erg and 5.9 × 10 ^49 erg, respectively. From the energetics, it is evident that whatever is producing the soft excess (SE) is pumping out more energy than either the UV or hard X-ray source. Since the energy source presumably is ultimately the accretion of matter onto the supermassive black hole, the SE-emitting region must be receiving the majority of this energy. In addition, the source does not follow the typical disk–corona relation found in AGNs, neither in the initial flare (from 2017 to 2019) nor in the current bright soft state (2022–2023). We found that the core (<1 pc) radio emission at 5 GHz gradually increased until 2022 March, but showed a dip in 2022 August. The Güdel–Benz relation ( L _radio / L _X-ray ∼ 10 ^−5 ), however, is still within the expected range for radio-quiet AGNs, and further follow-up radio observations are currently being undertaken

Cerebral Palsy:Early Markers of Clinical Phenotype and Functional Outcome

The Prechtl General Movement Assessment (GMA) has become a cornerstone assessment in early identification of cerebral palsy (CP), particularly during the fidgety movement period at 3-5 months of age. Additionally, assessment of motor repertoire, such as antigravity movements and postural patterns, which form the Motor Optimality Score (MOS), may provide insight into an infant's later motor function. This study aimed to identify early specific markers for ambulation, gross motor function (using the Gross Motor Function Classification System, GMFCS), topography (unilateral, bilateral), and type (spastic, dyskinetic, ataxic, and hypotonic) of CP in a large worldwide cohort of 468 infants. We found that 95% of children with CP did not have fidgety movements, with 100% having non-optimal MOS. GMFCS level was strongly correlated to MOS. An MOS > 14 was most likely associated with GMFCS outcomes I or II, whereas GMFCS outcomes IV or V were hardly ever associated with an MOS > 8. A number of different movement patterns were associated with more severe functional impairment (GMFCS III-V), including atypical arching and persistent cramped-synchronized movements. Asymmetrical segmental movements were strongly associated with unilateral CP. Circular arm movements were associated with dyskinetic CP. This study demonstrated that use of the MOS contributes to understanding later CP prognosis, including early markers for type and severity

Research approvals iceberg: how a 'low-key' study in England needed 89 professionals to approve it and how we can do better.

BACKGROUND: The red tape and delays around research ethics and governance approvals frequently frustrate researchers yet, as the lesser of two evils, are largely accepted as unavoidable. Here we quantify aspects of the research ethics and governance approvals for one interview- and questionnaire-based study conducted in England which used the National Health Service (NHS) procedures and the electronic Integrated Research Application System (IRAS). We demonstrate the enormous impact of existing approvals processes on costs of studies, including opportunity costs to focus on the substantive research, and suggest directions for radical system change. MAIN TEXT: We have recorded 491 exchanges with 89 individuals involved in research ethics and governance approvals, generating 193 pages of email text excluding attachments. These are conservative estimates (e.g. only records of the research associate were used). The exchanges were conducted outside IRAS, expected to be the platform where all necessary documents are provided and questions addressed. Importantly, the figures exclude the actual work of preparing the ethics documentation (such as the ethics application, information sheets and consent forms). We propose six areas of work to enable system change: 1. Support the development of a broad range of customised research ethics and governance templates to complement generic, typically clinical trials orientated, ones; 2. Develop more sophisticated and flexible frameworks for study classification; 3. Link with associated processes for assessment, feedback, monitoring and reporting, such as ones involving funders and patient and public involvement groups; 4. Invest in a new generation IT infrastructure; 5. Enhance system capacity through increasing online reviewer participation and training; and 6. Encourage researchers to quantify the approvals processes for their studies. CONCLUSION: Ethics and governance approvals are burdensome for historical reasons and not because of the nature of the task. There are many opportunities to improve their efficiency and analytic depth in an age of innovation, increased connectivity and distributed working. If we continue to work under current systems, we are perpetuating, paradoxically, an unethical system of research approvals by virtue of its wastefulness and impoverished ethical debate

Proceedings of Patient Reported Outcome Measure’s (PROMs) Conference Oxford 2017: Advances in Patient Reported Outcomes Research

A33-Effects of Out-of-Pocket (OOP) Payments and Financial Distress on Quality of Life (QoL) of People with Parkinson’s (PwP) and their Carer

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK)

IntroductionContinuous renal replacement therapy (CRRT) is used for the symptomatic management of acute kidney injury (AKI) and fluid overload (FO). Contemporary reports on pediatric CRRT are small and single center in design. Large international studies evaluating CRRT practice and outcomes are lacking. Herein, we describe the design of a multinational collaborative.MethodsThe Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK) is an international collaborative of pediatric specialists whose mission is to improve short- and long-term outcomes of children treated with CRRT. The aims of this multicenter retrospective study are to describe the epidemiology, liberation patterns, association of fluid balance and timing of CRRT initiation, and CRRT prescription with outcomes.ResultsWe included children (n&nbsp;= 996, 0-25 years) admitted to an intensive care unit (ICU) and treated with CRRT for AKI or FO at 32 centers (in 7 countries) from 2018 to 2021. Demographics and clinical characteristics before CRRT initiation, during the first 7 days of both CRRT, and liberation were collected. Outcomes include the following: (i) major adverse kidney events at 90 days (mortality, dialysis dependence, and persistent kidney dysfunction), and (ii) functional outcomes (functional stats scale).ConclusionThe retrospective WE-ROCK study represents the largest international registry of children receiving CRRT for AKI or FO. It will serve as a broad and invaluable resource for the field of pediatric critical care nephrology that will improve our understanding of practice heterogeneity and the association of CRRT with clinical and patient-centered outcomes. This will generate preliminary data for future interventional trials in this area