Improving patient experiences of mental health inpatient care : a randomised controlled trial

Poorer patient views of mental health inpatient treatment predict both further admissions and, for those admitted involuntarily, longer admissions. As advocated in the UK Francis report, we investigated the hypothesis that improving staff training improves patients’ views of ward care.Cluster randomised trial with stepped wedge design in 16 acute mental health wards randomised (using the ralloc procedure in Stata) by an independent statistician in three waves to staff training. A psychologist trained ward staff on evidence-based group interventions and then supported their introduction to each ward. The main outcome was blind self-report of perceptions of care (VOICE) before or up to 2 years after staff training between November 2008 and January 2013.In total, 1108 inpatients took part (616 admitted involuntarily under the English Mental Health Act). On average 51.6 staff training sessions were provided per ward. Involuntary patient's perceptions of, and satisfaction with, mental health wards improved after staff training (N582, standardised effect −0·35, 95% CI −0·57 to −0·12, p = 0·002; interaction p value 0·006) but no benefit to those admitted voluntarily (N469, −0.01, 95% CI −0.23 to 0.22, p = 0.955) and no strong evidence of an overall effect (N1058, standardised effect −0.18 s.d., 95% CI −0.38 to 0.01, p = 0.062). The training costs around £10 per patient per week. Resource allocation changed towards patient perceived meaningful contacts by an average of £12 (95% CI −£76 to £98, p = 0.774).Staff training improved the perceptions of the therapeutic environment in those least likely to want an inpatient admission, those formally detained. This change might enhance future engagement with all mental health services and prevent the more costly admissions

The Voice Characterisation Checklist:Psychometric Properties of a Brief Clinical Assessment of Voices as Social Agents

Aim: There is growing interest in tailoring psychological interventions for distressing voices and a need for reliable tools to assess phenomenological features which might influence treatment response. This study examines the reliability and internal consistency of the Voice Characterisation Checklist (VoCC), a novel 10-item tool which assesses degree of voice characterisation, identified as relevant to a new wave of relational approaches. Methods: The sample comprised participants experiencing distressing voices, recruited at baseline on the AVATAR2 trial between January 2021 and July 2022 (n = 170). Inter-rater reliability (IRR) and internal consistency analyses (Cronbach’s alpha) were conducted. Results: The majority of participants reported some degree of voice personification (94%) with high endorsement of voices as distinct auditory experiences (87%) with basic attributes of gender and age (82%). While most identified a voice intention (75%) and personality (76%), attribution of mental states (35%) to the voice (‘What are they thinking?’) and a known historical relationship (36%) were less common. The internal consistency of the VoCC was acceptable (10 items, α = 0.71). IRR analysis indicated acceptable to excellent reliability at the item-level for 9/10 items and moderate agreement between raters’ global (binary) classification of more vs. less highly characterised voices, κ = 0.549 (95% CI, 0.240–0.859), p < 0.05. Conclusion: The VoCC is a reliable and internally consistent tool for assessing voice characterisation and will be used to test whether voice characterisation moderates treatment outcome to AVATAR therapy. There is potential wider utility within clinical trials of other relational therapies as well as routine clinical practise

Human exploration of cis-lunar space via assets tele-operated from EML2 (HECATE)

This paper presents the preliminary design of the international space mission HECATE (Human Exploration of Cis-lunar space via Assets Tele-operated from EML-2), aimed at exploring the far side of the Moon via tele-robotic activities during the 2020s. The exploration is realized by astronauts from HOPE (Human Orbiting Protected Environment), a space habitat in a halo orbit around the Earth-Moon Lagrange Point 2, a critical staging location for future robotic and human deep space missions. Inside the habitat, astronauts have access to tele-robotic hardware and instruments, used to tele-operate rovers and scientific equipment on the surface of the Moon. Plans to resupply and maintain HOPE for future missions, using a solar electric tug, are given. Ultimately, HOPE represents an energetically favorable intermediate locations for missions to Mars, Near-Earth Asteroids, and beyond

Design and development of a macrocyclic series targeting phosphoinositide 3-kinase δ

A macrocyclization approach has been explored on a series of benzoxazine phosphoinositide 3-kinase δ inhibitors, resulting in compounds with improved potency, permeability, and in vivo clearance while maintaining good solubility. The thermodynamics of binding was explored via surface plasmon resonance, and the binding of lead macrocycle 19 was found to be almost exclusively entropically driven compared with progenitor 18, which demonstrated both enthalpic and entropic contributions. The pharmacokinetics of macrocycle 19 was also explored in vivo, where it showed reduced clearance when compared with the progenitor 18. This work adds to the growing body of evidence that macrocyclization could provide an alternative and complementary approach to the design of small-molecule inhibitors, with the potential to deliver differentiated properties

Towards an Integrated Framework for Assessing the Vulnerability of Species to Climate Change

Climate change is a major threat to global biodiversity. A novel integrated framework to assess vulnerability and prioritize research and management action aims to improve our ability to respond to this emerging crisis

Triple-Antiretroviral Prophylaxis to Prevent Mother-To-Child HIV Transmission through Breastfeeding—The Kisumu Breastfeeding Study, Kenya: A Clinical Trial

Timothy Thomas and colleagues report the results of the Kisumu breastfeeding study (Kenya), a single-arm trial that assessed the feasibility and safety of a triple-antiretroviral regimen to suppress maternal HIV load in late pregnancy

An atmospheric source of S in Mesoarchaean structurally-controlled gold mineralisation of the Barberton Greenstone Belt

The Barberton Greenstone Belt of southern Africa hosts several Mesoarchaean gold deposits. The ores were mostly formed in greenschist facies conditions, and occur as hydrothermal alteration zones around extensional faults that truncate and post-date the main compressional structures of the greenstone belt. Ore deposition was accompanied by the intrusion of porphyries, which has led to the hypothesis that gold may have been sourced from magmas. Because the transport of Au in the hydrothermal fluids is widely believed to have involved S complexes, tracing the origin of S may place strong constraints on the origin of Au. We measured multiple S isotopes in sulfide ore from Sheba and Fairview mines of the Barberton Greenstone Belt to distinguish “deep” S sources (e.g. magmas) from “surface” S sources (i.e. rocks of the volcano-sedimentary succession that contain S processed in the atmosphere preserved as sulfide and sulfate minerals). Ion probe (SIMS) analyses of pyrite from ore zones indicate mass-independent fractionation of S isotopes (Δ33S = −0.6‰ to +1.0‰) and the distribution of the analyses in the Δ33S–δ34S space matches the distribution peak of previously published analyses of pyrite from the entire volcano-sedimentary succession. Notwithstanding that the H2O–CO2 components of the fluids may have been introduced from a deep source external to the greenstone belt rocks, the fact that S bears an atmospheric signature suggests the hypothesis that the source of Au should also be identified in the supracrustal succession of the greenstone belt. Our findings differ from conclusions of previous studies of other Archaean shear-hosted Au deposits based on mineralogical and isotopic evidence, which suggested a magmatic or mantle source for Au, and imply that there is no single model that can be applied to this type of mineralisation in the Archaean

Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer

Background and aims: Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. The study aim was to investigate the association between DNA damage response (DDR), replication stress and novel therapeutic response in PC to develop a biomarker driven therapeutic strategy targeting DDR and replication stress in PC. Methods: We interrogated the transcriptome, genome, proteome and functional characteristics of 61 novel PC patient-derived cell lines to define novel therapeutic strategies targeting DDR and replication stress. Validation was done in patient derived xenografts and human PC organoids. Results: Patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, co-segregates with response to platinum (P < 0.001) and PARP inhibitor therapy (P < 0.001) in vitro and in vivo. We generated a novel signature of replication stress with which predicts response to ATR (P < 0.018) and WEE1 inhibitor (P < 0.029) treatment in both cell lines and human PC organoids. Replication stress was enriched in the squamous subtype of PC (P < 0.001) but not associated with DDR deficiency. Conclusions: Replication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR proficient PC, and post-platinum therapy