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Background Little is known about the safety of mental healthcare provided remotely by digital mental health services (DMHS), which do not offer face-to-face contact. Aims To examine the circumstances of suicide by patients registered with a national DMHS. Method Data from 59 033 consenting patients registered with a national DMHS, the MindSpot Clinic, between 1 January 2013 and 31 December 2016 were linked with the Australian National Death Index and documents held by the National Coronial Information System (NCIS). Data extracted included demographic information, the nature of contact, duration between last contact and death, symptom scores and information in police, autopsy, toxicology and coroners’ reports. Results Of the 59 033 patients, 90 (0.15%) died by suicide in a follow-up period of up to 5 years. The mean time between last contact and death was 560 days. Coroners’ reports were located for 81/90 patients. Most (87.0%) were receiving face-to-face care around the time of death, 60.9% had a documented previous suicide attempt, 52.2% had been in hospital in the previous 6 months and 22.2% had severe mental illness, mainly schizophrenia or bipolar disorder. Other common findings were current treatment with psychotropic medication (79.2%) and the presence of alcohol (41.6%), benzodiazepines (31.2%), and illegal drugs and non-prescribed opioids (20.8%) at time of death. Conclusions Those who died by suicide after contact with the DMHS had more severe illness, were mostly engaged with face-to-face services and often had disinhibiting substances, especially benzodiazepines, present at the time of death.

In rich false memory studies, familial informants often provide information to support researchers in planting vivid memories of events that never occurred. The goal of the current study was to assess how effectively we can retract these false memories via debriefing – i.e. to what extent can we put participants back to the way we found them? This is essential to investigate, for both ethical and theoretical reasons. Participants (n = 123) completed a false memory implantation protocol as part of a replication of the “Lost in the Mall” study (Loftus and Pickrell, 1995). By the end of the protocol, 14% of participants self-reported a memory for the fabricated event, and a further 52% believed it had happened. Participants were then fully debriefed, and memory and belief for the false event were assessed again. In a follow-up assessment three days post-debriefing, the false memory rate had dropped to 6% and false belief rates also fell precipitously to 7%. Moreover, virtually all persistent false memories were found to be non-believed memories, where participants no longer accepted that the fabricated event had occurred. Richer, more detailed memories were more resistant to correction, but were still mostly retracted. This study provides evidence that participants can be “dehoaxed” and even very convincing false memories can be retracted.

UNSTRUCTURED Innovative tools leveraging machine learning and artificial intelligence (ML/AI) are rapidly being developed for medicine, with new applications emerging in prediction, diagnosis, and treatment across a range of illnesses, patient populations, and clinical procedures. One challenge for successful innovation is the absence, to date, of a robust ethical framework informed by the perspectives of ML/AI researchers and physicians. To help articulate these perspectives, we conducted 21 semi-structured interviews with a purposive sample of ML/AI researchers (n = 10) and physicians (n = 11). We asked interviewees about their views regarding ethical considerations related to the adoption of ML/AI in medicine. Notably, both researchers and physicians described concerns regarding how ML/AI innovations are shaped in early phases even prior to their development and implementation (which from here on will be referred to as the “problem formulation” phase). Considerations encompassed assessment of research priorities and motivations, clarity and centeredness of clinical needs, professional and demographic diversity of research teams, and interdisciplinary knowledge generation and collaboration. These qualitative findings help to elucidate several ethical challenges anticipated or encountered in ML/AI for health care.

Background and Purpose: S1P receptors control endothelial cell proliferation, migration, and survival. Evidence of the ability of S1P receptor modulators to influence multiple endothelial cell functions suggests their potential use for antiangiogenic effect. The main purpose of our study was to investigate the potential of siponimod for the inhibition of ocular angiogenesis in vitro and in vivo. Experimental Approach: We investigated the effects of siponimod on the metabolic activity (MTT assay), basal proliferation and growth factor induced proliferation (BrdU assay), and migration (transwell migration assay) of human umbilical vein endothelial cells (HUVEC) and retinal microvascular endothelial cells (HRMEC). The effects of siponimod on HRMEC monolayer integrity, and barrier function under basal conditions and TNF-α induced disruption were assessed using the trans-endothelial electrical resistance (TEER) and FITC-dextran permeability assays. Siponimod’s effect on TNF-α induced claudin-5 distribution in HRMEC was investigated using immunofluorescence. Finally, the effect of siponimod on ocular neovascularization in vivo was assessed using suture-induced corneal neovascularization in albino rabbits. Key Results: Siponimod did not affect endothelial cell proliferation or metabolic activity, but significantly inhibited endothelial cell migration, increased HRMEC barrier integrity, and reduced TNF-α induced barrier disruption. Siponimod also protected against TNF-α induced disruption of claudin-5 in HRMEC. These actions are mainly mediated by S1PR1 receptor modulation. Finally, siponimod prevented the progression of suture-induced corneal neovascularization in albino rabbits. Conclusion and Implications: The effects of siponimod on various processes known to be involved in angiogenesis support its therapeutic potential in disorders associated with ocular neovascularization.

The seminal Lost in the Mall study (Loftus & Pickrell, 1995) has been enormously influential in psychology and is still cited in many legal cases. The current study directly replicated this paper, addressing key methodological weaknesses including increasing the sample size and preregistering detailed analysis plans. Participants (N = 123) completed a survey and two interviews where they discussed real and fabricated childhood events, based on information provided by an older relative. We replicated the findings of the original study, with 35% of participants reporting a false memory for getting lost in a mall as a child (compared to 25% in the original study). However, using a novel self-report measure, just 14% of participants declared that they remembered the fake event occurring, with a further 52% stating that they believed the fake event had occurred. The replication supports the claim that it is possible to plant a false memory of a childhood event.

Diagnosis and assessment of patients with prostate cancer is dependent on accurate interpretation and grading of histopathology. However, morphology does not necessarily reflect the complex biological changes occurring in prostate cancer disease progression, and current biomarkers have demonstrated limited clinical utility in patient assessment. This study aimed to develop biomarkers that accurately define prostate cancer biology by distinguishing specific pathological features that enable reliable interpretation of pathology for accurate Gleason grading of patients. Online gene expression databases were interrogated and a pathogenic pathway for prostate cancer was identified. The protein expression of key genes in the pathway, including adaptor protein containing a pleckstrin homology (PH) domain, phosphotyrosine-binding (PTB) domain, and leucine zipper motif 1 (Appl1), Sortilin and Syndecan-1, was examined by immunohistochemistry (IHC) in a pilot study of 29 patients with prostate cancer, using monoclonal antibodies designed against unique epitopes. Appl1, Sortilin, and Syndecan-1 expression was first assessed in a tissue microarray cohort of 112 patient samples, demonstrating that the monoclonal antibodies clearly illustrate gland morphologies. To determine the impact of a novel IHC-assisted interpretation (the utility of Appl1, Sortilin, and Syndecan-1 labelling as a panel) of Gleason grading, versus standard haematoxylin and eosin (H&E) Gleason grade assignment, a radical prostatectomy sample cohort comprising 114 patients was assessed. In comparison to H&E, the utility of the biomarker panel reduced subjectivity in interpretation of prostate cancer tissue morphology and improved the reliability of pathology assessment, resulting in Gleason grade redistribution for 41% of patient samples. Importantly, for equivocal IHC-assisted labelling and H&E staining results, the cancer morphology interpretation could be more accurately applied upon re-review of the H&E tissue sections. This study addresses a key issue in the field of prostate cancer pathology by presenting a novel combination of three biomarkers and has the potential to transform clinical pathology practice by standardising the interpretation of the tissue morphology. Refereed/Peer-reviewed