Editorial: Design and Implementation of Rehabilitation Interventions for People With Complex Psychosis

Introduction Between one fifth and one quarter of people who become unwell with a psychotic disorder will develop particularly complex problems (1). These include severe, treatment-resistant symptoms and cognitive impairments that affect motivation, organizational, and social skills. Co-existing mental, neurodevelopmental, and physical health conditions can often complicate recovery further, and up to three quarters have been found to be vulnerable to self-neglect and/or exploitation by others (2). Despite their high levels of need, this group has been missing from recent mental health policy internationally, resulting in inadequate treatment and, worryingly, increasing levels of institutionalization (3). The publication in 2020 of the first National Institute for Health and Care Excellence (NICE) Guideline on the mental health rehabilitation of adults with complex psychosis (4) is therefore a very welcome and important milestone, but there is an ongoing, urgent need for research to identify effective interventions for this group. In this Research Topic we aimed to collate relevant work that can help to address this evidence gap

Life in 90 words: opportunities for person-centred care amidst COVID-19

Objective: Coronavirus disease 2019 and the consequent public health and social distancing measures significantly impacted on service continuity for mental health patients. This article reports on contingency planning initiative in the Australian public sector. Methods: Ninety-word care synopses were developed for each patient. These formed the basis for guided conversations between case managers and consultant psychiatrists to ensure safe service provision and retain a person-centred focus amidst the threat of major staffing shortfalls. Results: This process identified vulnerable patient groups with specific communication needs and those most at risk through service contraction. The challenges and opportunities for promoting safety and self-management through proactive telehealth came up repeatedly. The guided conversations also raised awareness of the shared experience between patients and professionals of coronavirus disease 2019. Conclusion: There is a parallel pandemic of anxiety which creates a unique opportunity to connect at a human level

Strongly lensed SNe Ia in the era of LSST: observing cadence for lens discoveries and time-delay measurements

The upcoming Large Synoptic Survey Telescope (LSST) will detect many strongly lensed Type Ia supernovae (LSNe Ia) for time-delay cosmography. This will provide an independent and direct way for measuring the Hubble constant $H_0$, which is necessary to address the current $4.4 \sigma$ tension in $H_0$ between the local distance ladder and the early Universe measurements. We present a detailed analysis of different observing strategies for the LSST, and quantify their impact on time-delay measurement between multiple images of LSNe Ia. For this, we produced microlensed mock-LSST light curves for which we estimated the time delay between different images. We find that using only LSST data for time-delay cosmography is not ideal. Instead, we advocate using LSST as a discovery machine for LSNe Ia, enabling time delay measurements from follow-up observations from other instruments in order to increase the number of systems by a factor of 2 to 16 depending on the observing strategy. Furthermore, we find that LSST observing strategies, which provide a good sampling frequency (the mean inter-night gap is around two days) and high cumulative season length (ten seasons with a season length of around 170 days per season), are favored. Rolling cadences subdivide the survey and focus on different parts in different years; these observing strategies trade the number of seasons for better sampling frequency. In our investigation, this leads to half the number of systems in comparison to the best observing strategy. Therefore rolling cadences are disfavored because the gain from the increased sampling frequency cannot compensate for the shortened cumulative season length. We anticipate that the sample of lensed SNe Ia from our preferred LSST cadence strategies with rapid follow-up observations would yield an independent percent-level constraint on $H_0$.Comment: 25 pages, 22 figures; accepted for publication in A&

Multi-parameter phenotyping of platelets and characterisation of the effects of agonists using machine learning

Platelet function is driven by the expression of specialised surface markers. The concept of distinct circulating sub-populations of platelets has emerged in recent years, but their exact nature remains debatable. Objective To design a spectral flow cytometry-based phenotyping workflow to provide a more comprehensive characterisation, at a global and individual level, of surface markers in resting and activated healthy platelets. Secondly, to apply this workflow to investigate how responses differ according to platelet age. Methods A 14-marker flow cytometry panel was developed and applied to vehicle- or agonist-stimulated platelet-rich plasma and whole blood samples obtained from healthy volunteers, or to platelets sorted according to SYTO-13 staining intensity as an indicator of platelet age. Data were analysed using both user-led and independent approaches incorporating novel machine learning-based algorithms. Results The assay detected differences in marker expression in healthy platelets, at rest and on agonist activation, in both platelet rich plasma and whole blood samples, that are consistent with the literature. Machine learning identified stimulated populations of platelets with high accuracy (>80%). Similarly, machine learning differentiation between young and old platelet populations achieved 76% accuracy, primarily weighted by FSC-A, CD41, SSC-A, GPVI, CD61, and CD42b expression patterns. Conclusions Our approach provides a powerful phenotypic assay coupled with robust bioinformatic and machine learning workflows for deep analysis of platelet sub-populations. Cleave-able receptors, GPVI and CD42b, contribute to defining shared and unique sub-populations. This adoptable, low-volume approach will be valuable in deep characterisation of platelets in disease

Scintillation Pulse Shape Discrimination in a Two-Phase Xenon Time Projection Chamber

The energy and electric field dependence of pulse shape discrimination in liquid xenon have been measured in a 10 gm two-phase xenon time projection chamber. We have demonstrated the use of the pulse shape and charge-to-light ratio simultaneously to obtain a leakage below that achievable by either discriminant alone. A Monte Carlo is used to show that the dominant fluctuation in the pulse shape quantity is statistical in nature, and project the performance of these techniques in larger detectors. Although the performance is generally weak at low energies relevant to elastic WIMP recoil searches, the pulse shape can be used in probing for higher energy inelastic WIMP recoils.Comment: 7 pages, 11 figure

Immunomodulatory drugs in sepsis: a systematic review and meta-analysis

\ua9 2024 The Authors. Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists. Dysregulation of the host immune response has a central role in the pathophysiology of sepsis. There has been much interest in immunomodulatory drugs as potential therapeutic adjuncts in sepsis. We conducted a systematic review and meta-analysis of randomised controlled trials evaluating the safety and clinical effectiveness of immunomodulatory drugs as adjuncts to standard care in the treatment of adults with sepsis. Our primary outcomes were serious adverse events and all-cause mortality. Fifty-six unique, eligible randomised controlled trials were identified, assessing a range of interventions including cytokine inhibitors; anti-inflammatories; immune cell stimulators; platelet pathway inhibitors; and complement inhibitors. At 1-month follow-up, the use of cytokine inhibitors was associated with a decreased risk of serious adverse events, based on 11 studies involving 7138 patients (RR (95%CI) 0.95 (0.90–1.00), I2 = 0%). The only immunomodulatory drugs associated with an increased risk of serious adverse events were toll-like receptor 4 antagonists (RR (95%CI) 1.18 (1.04–1.34), I2 = 0% (two trials, 567 patients)). Based on 18 randomised controlled trials, involving 11,075 patients, cytokine inhibitors reduced 1-month mortality (RR (95%CI) 0.88 (0.78–0.98), I2 = 57%). Mortality reduction was also shown in the subgroup of 13 randomised controlled trials that evaluated anti-tumour necrosis factor α interventions (RR (95%CI) 0.93 (0.87–0.99), I2 = 0%). Anti-inflammatory drugs had the largest apparent effect on mortality at 2 months at any dose (two trials, 228 patients, RR (95%CI) 0.64 (0.51–0.80), I2 = 0%) and at 3 months at any dose (three trials involving 277 patients, RR (95%CI) 0.67 (0.55–0.81), I2 = 0%). These data indicate that, except for toll-like receptor 4 antagonists, there is no evidence of safety concerns for the use of immunomodulatory drugs in sepsis, and they may show some short-term mortality benefit for selected drugs

Measurement of telescope transmission using a Collimated Beam Projector

With the increasingly large number of type Ia supernova being detected by current-generation survey telescopes, and even more expected with the upcoming Rubin Observatory Legacy Survey of Space and Time, the precision of cosmological measurements will become limited by systematic uncertainties in flux calibration rather than statistical noise. One major source of systematic error in determining SNe Ia color evolution (needed for distance estimation) is uncertainty in telescope transmission, both within and between surveys. We introduce here the Collimated Beam Projector (CBP), which is meant to measure a telescope transmission with collimated light. The collimated beam more closely mimics a stellar wavefront as compared to flat-field based instruments, allowing for more precise handling of systematic errors such as those from ghosting and filter angle-of-incidence dependence. As a proof of concept, we present CBP measurements of the StarDICE prototype telescope, achieving a standard (1 sigma) uncertainty of 3 % on average over the full wavelength range measured with a single beam illumination

Impact of Property Covariance on Cluster Weak Lensing Scaling Relations

We present an investigation into a hitherto unexplored systematic that affects the accuracy of galaxy cluster mass estimates with weak gravitational lensing. Specifically, we study the covariance between the weak lensing signal, ΔΣ, and the ‘true’ cluster galaxy number count, Ngal, as measured within a spherical volume that is void of projection effects. By quantifying the impact of this covariance on mass calibration, this work reveals a significant source of systematic uncertainty. Using the MDPL2 simulation with galaxies traced by the SAGE semi-analytic model, we measure the intrinsic property covariance between these observables within the three-dimensional vicinity of the cluster, spanning a range of dynamical mass and redshift values relevant for optical cluster surveys. Our results reveal a negative covariance at small radial scales (R ≲ R200c) and a null covariance at large scales (R ≳ R200c) across most mass and redshift bins. We also find that this covariance results in a 2–3 per cent bias in the halo mass estimates in most bins. Furthermore, by modelling Ngal and ΔΣ as multi-(log)-linear equations of secondary halo properties, we provide a quantitative explanation for the physical origin of the negative covariance at small scales. Specifically, we demonstrate that the Ngal–ΔΣ covariance can be explained by the secondary properties of haloes that probe their formation history. We attribute the difference between our results and the positive bias seen in other works with (mock)-cluster finders to projection effects. These findings highlight the importance of accounting for the covariance between observables in cluster mass estimation, which is crucial for obtaining accurate constraints on cosmological parameters