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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.

This study evaluated stakeholders’ perspectives regarding participation in two hypothetical neuromodulation trials focused on individuals with Alzheimer's disease and related disorders (ADRDs). Stakeholders (i.e., individuals at risk for ADRDs [ n = 56], individuals with experience as a caregiver for someone with a cognitive disorder [ n = 60], and comparison respondents [ n = 124]) were recruited via MTurk. Primary outcomes were willingness to enroll (or enroll one's loved one), feeling lucky to have the opportunity to enroll, and feeling obligated to enroll in two protocols (transcranial magnetic stimulation, TMS; deep brain stimulation, DBS). Relative to the Comparison group, the At Risk group endorsed higher levels of “feeling lucky” regarding both research protocols, and higher willingness to participate in the TMS protocol. These findings provide tentative reassurance regarding the nature of decision making regarding neurotechnology-based research on ADRDs. Further work is needed to evaluate the full range of potential influences on research participation.

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

Digital mental health services (DMHS) have proven effectiveness and play an important role within the broader mental health system by reducing barriers to evidence-based care. However, improved understanding of the factors associated with successful treatment uptake, treatment completion and positive clinical outcomes will facilitate efforts to maximise outcomes. Previous studies have demonstrated that patient age is positively associated, and initial symptom severity negatively associated with treatment uptake and treatment completion rates in both DMHS and other mental health services. The current study sought to extend these findings by examining the effect of other patient characteristics, in particular, self-reported psychosocial difficulties, using data from a large-scale national DMHS. Using a prospective uncontrolled observational cohort study design, we collected self-reported demographic, psychosocial and clinical data from 15,882 patients who accessed the MindSpot Clinic, Australia, between 1 January and 31 December 2019. Using a series of univariate regression models and multivariate classification algorithms we found that older age, higher educational attainment, and being in a relationship were all positively associated with uptake, completion and significant symptom improvement, while higher initial symptom severity was negatively associated with those outcomes. In addition, self-reported psychosocial difficulties had a significant negative impact on uptake, completion, and symptom improvement. Consistent with previous literature, the presence of these characteristics in isolation or in combination have a significant impact on treatment uptake, completion, and symptomatic improvement. Individual and multiple psychosocial difficulties are associated with reduced capacity to participate in treatment and hence an increased treatment burden. Identifying patients with lower capacity to complete treatment, modifications to treatments and the provision of supports to reduce treatment burden may promote greater engagement and completion of treatments offered by digital mental health services.

Summary A 41-year-old male presented to the Emergency Department with a 6-month history of back and hip pain. Skeletal survey revealed bilateral pubic rami fractures and MRI of the spine demonstrated multiple thoracic and lumbar fractures. Secondary work up for osteoporosis was undertaken. There was no evidence of hyperparathyroidism and the patient was vitamin D replete. Testosterone (T) was low at 1.7 nmol/L (8.6–29.0) and gonadotrophins were undetectable. The patient failed a 1 mg dexamethasone suppression test (DST) with a morning cortisol of 570 nmol/L ( Learning points Unexplained osteoporosis requires thorough investigation and the workup for secondary causes is not complete without excluding glucocorticoid excess. MTC should be considered when searching for sources of ectopic ACTH secretion. Resistance to tyrosine kinase inhibitors is well described with MTC and clinicians should have a low threshold for screening for recurrent disease.

Background The MindSpot Clinic provides services to Australians with anxiety and depression. Routine data collection means that MindSpot has been able to monitor trends in mental health symptoms and service use prior to and during the COVID-19 pandemic, and these have been reported in two earlier studies. This third study describes user characteristics and volumes in the first 8 months of COVID-19, including a comparison between users from states and territories with significantly different COVID-19 infection rates. Methods We examined trends in demographics and symptoms for participants starting an online assessment during the COVID-19 pandemic, from March to October 2020. Participants from the state of Victoria (n = 4203), which experienced a significantly larger rate of COVID-19 infections relative to the rest of Australia, were compared to participants from the rest of Australia (n = 10,500). Results were also compared to a baseline “comparison period” prior to the COVID-19 pandemic. Results A total of 14,703 people started a mental health assessment with MindSpot between 19th March and 28th October 2020. We observed two peaks in service demand, one in the early weeks of the pandemic, and the second in August–September when COVID-19 transmission was high in Victoria. Mean symptom scores on standardised measures of distress (K-10), depression (PHQ-9) and anxiety (GAD-7) were lower during this second peak in service demand, but there were significantly higher levels of concern about COVID-19 in participants from Victoria, and a higher proportion of Victorian respondents reported that they had made significant changes in response to the pandemic. Many respondents reported changes to their mental health, such as increased feelings of worry. Most respondents reported implementing strategies to help manage the psychological impact of COVID-19, such as maintaining social connections and limiting exposure to news or social media. Conclusions We did not observe increased levels of clinical anxiety or depression on standardised symptom measures. However, there were increases in service demand, and increased levels of concern and difficulties related to COVID-19, particularly in Victoria. Encouragingly, a significant proportion of participants have implemented coping strategies. These results continue to suggest that the mental health impacts of COVID-19 represent a normal response to an abnormal situation rather than an emerging mental health crisis. This distinction is important as we develop individually appropriate and proportional mental health system responses., Highlights • We describe patient characteristics and regional variation for users of a digital mental health service in Australia. • In Australia from July to October, the state of Victoria was disproportionally affected by COVID-19. • Service demand and concern about COVID-19 were high in Victoria compared to the rest of Australia. • Encouragingly, a significant proportion of participants implemented coping strategies.

Across three experiments, we examined the efficacy of three cues from the human body-body orientation, head turning, and eye-gaze direction-to shift an observer's attention in space. Using a modified Posner cueing paradigm, we replicate the previous findings of gender differences in the gaze-cueing effect whereby female but not male participants responded significantly faster to validly cued than to invalidly cued targets. In contrast to the previous studies, we report a robust cueing effect for both male and female participants when head turning direction was used as the central cue, whereas oriented bodies proved ineffectual as cues to attention for both males and females. These results are discussed with reference to the time course of central cueing effects, gender differences in spatial attention, and current models of how cues from the human body are combined to judge another person's direction of attention.

Psychiatric researchers grapple with concerns that individuals with mental illness may be less likely to appreciate risks of research participation, particularly compared to people not suffering from mental illness. Therefore, empirical studies that directly compare the perspectives of such individuals are needed. In addition, it is important to evaluate perspectives regarding varied types of research protocols, particularly as innovative psychiatric research protocols emerge. In this pilot study, respondents with a mood disorder (n = 25) as well as respondents without a mood disorder (n = 55) were recruited using Amazon's Mechanical Turk (MTurk) platform. These respondents were surveyed regarding four psychiatric research projects (i.e., experimental medication [pill form]; non-invasive magnetic brain stimulation; experimental medication [intravenous infusion]; and implantation of a device in the brain). Regardless of health status, respondents rated the four research protocols as somewhat to highly risky. The brain-device implant protocol was seen as the most risky, while the magnetic brain stimulation project was viewed as “somewhat risky”. Respondents, on average and regardless of health status, rated their willingness at or below “somewhat willing.” Respondents were least willing to participate in the brain-device implant protocol, whereas they were “somewhat willing” to participate in the magnetic brain stimulation protocol. Trust in medical research was negatively associated with perceived risk of research protocols. Perceived risk was negatively associated with willingness to participate, even when adjusting for potential confounders, suggesting that attunement to risk crosses diagnostic, gender, and ethnic categories, and is more salient to research decision-making than trust in medical research and dispositional optimism. The findings of this study may offer reassurance about the underlying decision-making processes of individuals considering participation in innovative neuroscience studies.

In this study, participants with a self-reported history of depression, diabetes, or no illness underwent a simulated informed consent process for a hypothetical genetic study related to depression or diabetes. Participants completed a survey assessing their perceived understanding of the research process, perceptions of its risks and benefits, their satisfaction with the informed consent process, and their readiness to make a hypothetical enrollment decision. All participants indicated strong readiness to make an enrollment decision regarding the research characterized in the simulation. Participants reported understanding the consent process relatively well and being generally satisfied with it. Greater concerns were expressed regarding psychosocial risks than biological risks for genetic studies on mental disorders. Our study documented positive attitudes toward volunteering for research that involved the collection of genetic data.

Background Trends in contact with a high volume national digital mental health service (DMHS), the MindSpot Clinic, provide a unique opportunity to assess the mental health effects of the COVID-19 pandemic. Methods Three methods were used to assess changes in responses to COVID-19. First, website visits and call centre traffic were compared across two time periods: the “comparison period” (1 to 28 September 2019), and during the early weeks of the “COVID-19 pandemic” (19 March to 15 April 2020). Second, demographic and symptom data were compared across all patients who started an assessment during the comparison (n = 1650) and the COVID-19 period (n = 1668). Third, responses to questions about the impact of COVID-19 introduced to the assessment from 19 March 2020, and reports from treating therapists were examined. Results There was an 89% increase in website visits and a 90% increase in telephone calls to the clinic in the early COVID-19 period compared to the comparison period. There was a higher proportion of females in the COVID-19 sample (76.9% vs. 72.9%), and a lower proportion reported being in employment (52.8% vs. 60.8%). There was a small but significant increase in the severity of anxiety symptoms, and an increase in the number of people reporting recent onset of anxiety and depression. However, there were no differences between groups in severity of symptoms of distress or depression. Most people (94%) reported concern about the impact of COVID-19, and 88% reported making changes in lifestyle. Older adults had higher levels of concern about COVID-19. Therapists reported that patients were concerned about how to access testing, manage quarantine, financial security and the effect of social isolation. Conclusions COVID-19 has resulted in a significant increase in contact with an established DMHS, but we have not yet detected increases in baseline symptom severity. With the prospect of prolonged restriction of movement, DMHS such as MindSpot could play an important role in both providing clinical services and monitoring the mental health of the population., Highlights • Demand for service contact has increased in response to COVID-19 • Anxiety increased, and more patients reported recent onset of symptoms • High volume DMHS can provide real time data on changes in psychological symptoms in the community

Inspired by the UCC Campus engage initiative and in a quest to help final year pharmacy students develop higher-order thinking skills, students were tasked with designing and delivering outreach workshops on the “Role of the Pharmacist in Educating patients on microbes, antimicrobial usage, and infection prevention”. The assignment formed part of continuous assessment requirements for PF4015 Novel Drug Delivery module delivered to final year Pharmacy students on the B.Pharm course. These 1-hour interactive workshops were delivered to students across diverse age (primary and secondary) and socioeconomic backgrounds in schools during Science week in Nov 2016 & Nov 2017.

Pharmacists are experts in safe drug usage, and are uniquely placed to provide professional advice on a range of health related issues. It is crucial that pharmacy education embodies an emphasis on creating independent and responsible learners and prioritises life-long learning in the face of rapid change. Consequently, appropriate teaching and learning modalities are essential to prepare students. Changes in the way patient’s access information and education of pharmacists call for new ways of teaching to prepare pharmacists for a changing profession. The aim of this body of work was to support pharmacy students’ education as teachers and learners through their utilisation of technology to create short educational videos on a range of topics intended for different stakeholder groups including patients and allied healthcare professionals.

The United States Supreme Court’s often stated view that “death is different” has led to a line of decisions in which the Court carved out categorical Eighth Amendment exceptions for certain groups. These cases hold that courts should not give the death penalty to individuals within those groups. In Atkins v. Virginia, for example, the leading case within the “death is different” line, the Court held that the death penalty was not an appropriate punishment for mentally retarded offenders because it constituted cruel and unusual punishment in violation of the Eighth Amendment. The Court continued to carve out exceptions for certain groups including juveniles.Then the Court’s view regarding the Eighth Amendment’s prohibition against cruel and unusual punishment evolved. No longer was “death” the only “different;” now, juveniles could be considered “different.” Following Roper, in which the Court held that sentencing juveniles — those under the age of eighteen — to death constituted cruel and unusual punishment in violation of the Eighth Amendment, a line of cases emerged in which the Court continued to carve out more exceptions for juveniles.In each of these landmark decisions, the Court has found that to be considered a juvenile, the individual must be under the age of majority. As found in Roper, and consistently followed in the other decisions within this line of cases, the age of majority is eighteen. Although the Court acknowledged that there are some juveniles under the age of majority who have attained a level of maturity “some adults will never reach” and “the qualities that distinguish juveniles from adults do not disappear when an individual turns 18,” the Court drew a line. Thus, the age of majority is a bright-line rule.Heeding the Court’s own words, it should recognize that juveniles who are aged seventeen and those aged eighteen arguably are no different. Research also suggests this to be true. This article argues, therefore, that because of the uncertainty surrounding “juvenile” brain development and because the bright-line rule of majority prevents courts from determining if an individual under the age of eighteen, the age of majority, has the requisite culpability deserving of the categorically excluded punishments, the Court should eliminate the bright-line rule of majority. Further, although the majority of juveniles should not receive certain categorically excluded harsh punishments, a few should still receive those punishments, and it should be an option for all. Part I of this article serves as background on the bright-line rule of majority and its application in “juveniles are different” cases. Part II of this article argues that the Court should eliminate the bright-line rule of majority. Part III of this article proposes a solution to the bright-line rule problem; that is, a case-by-case analysis should decide cases involving juveniles with age being another sentencing factor considered. Age will thus act as an aggravating or mitigating factor in the sentencing phase of the criminal proceeding. Finally, Part IV of this article explains why a case-by-case analysis considering age as a sentencing factor is better than a bright-line rule of majority and addresses the potential counter-arguments to this proposal.

In a line of landmark cases beginning with Coker v. Georgia and ending, presently, with Miller v. Alabama, the United States Supreme Court has carved out categorical Eighth Amendment exceptions following its evolving standards of decency analysis. Though the analysis, as touted by the Court, is two-fold, it has, essentially, evolved itself into a one-prong standard. The Court, that is, uses the subjective judgments of the five Justice majority to compromise the objective evidence of support for a particular sanction.This article argues that the Court has ignored its original intent and what the words "evolving standards of decency" should mean. Nowhere does the Court state in Trop v. Dulles, the case that announced the standard, that the standard should be comprised of the Supreme Court Justices' opinion of what are the evolving standards of decency.Part I of this article tracks the evolution of the evolving standards of decency analysis used by the Court to carve out categorical Eighth Amendment exceptions. Part II of this article argues that there are problems with the evolving standards of decency analysis used to carve out categorical Eighth Amendment exceptions, in that, it serves as a vehicle for the five Justice majority to compromise the objective indicia. Part III of this article proposes a solution to the problem, in which, there will be a wholly objective standard. Finally, Part IV of this article argues that the proposed standard is more advantageous than the current evolving standards of decency analysis and truer to the intent of the standard.

Stress fractures occurring within the lower limbs are relatively common in athletes and military personnel. The specific bones affected are often predictable when the patient's activities are considered. We present an unusual case of bilateral distal tibial stress fractures sustained while playing as a goalkeeper in field hockey, in an otherwise healthy 46-year-old woman.