Proton transport through nanoscale corrugations in two-dimensional crystals.

Defect-free graphene is impermeable to all atoms1-5 and ions6,7 under ambient conditions. Experiments that can resolve gas flows of a few atoms per hour through micrometre-sized membranes found that monocrystalline graphene is completely impermeable to helium, the smallest atom2,5. Such membranes were also shown to be impermeable to all ions, including the smallest one, lithium6,7. By contrast, graphene was reported to be highly permeable to protons, nuclei of hydrogen atoms8,9. There is no consensus, however, either on the mechanism behind the unexpectedly high proton permeability10-14 or even on whether it requires defects in graphene's crystal lattice6,8,15-17. Here, using high-resolution scanning electrochemical cell microscopy, we show that, although proton permeation through mechanically exfoliated monolayers of graphene and hexagonal boron nitride cannot be attributed to any structural defects, nanoscale non-flatness of two-dimensional membranes greatly facilitates proton transport. The spatial distribution of proton currents visualized by scanning electrochemical cell microscopy reveals marked inhomogeneities that are strongly correlated with nanoscale wrinkles and other features where strain is accumulated. Our results highlight nanoscale morphology as an important parameter enabling proton transport through two-dimensional crystals, mostly considered and modelled as flat, and indicate that strain and curvature can be used as additional degrees of freedom to control the proton permeability of two-dimensional materials.

Representations within the Intraparietal Sulcus Distinguish Numerical Tasks and Formats.

How does our brain understand the number five when it is written as an Arabic numeral, and when presented as five fingers held up? Four facets have been implicated in adult numerical processing: semantic, visual, manual, and phonological/verbal. Here, we ask how the brain represents each, using a combination of tasks and stimuli. We collected fMRI data from adult participants while they completed our novel "four number code" paradigm. In this paradigm, participants viewed one of two stimulus types to tap into the visual and manual number codes, respectively. Concurrently, they completed one of two tasks to tap into the semantic and phonological/verbal number codes, respectively. Classification analyses revealed that neural codes representing distinctions between the number comparison and phonological tasks were generalizable across format (e.g., Arabic numerals to hands) within intraparietal sulcus (IPS), angular gyrus, and precentral gyrus. Neural codes representing distinctions between formats were generalizable across tasks within visual areas such as fusiform gyrus and calcarine sulcus, as well as within IPS. Our results identify the neural facets of numerical processing within a single paradigm and suggest that IPS is sensitive to distinctions between semantic and phonological/verbal, as well as visual and manual, facets of number representations.

Concepts and recent advances in microchip electrophoresis coupled to mass spectrometry: Technologies and applications.

The online coupling of microchip electrophoresis (ME) as a fast, highly efficient, and low-cost miniaturized separation technique to mass spectrometry (MS) as an information-rich and sensitive characterization technique results in ME-MS an attractive tool for various applications. In this paper, we review the basic concepts and latest advances in technology for ME coupled to MS during the period of 2016-2021, covering microchip materials, structures, fabrication techniques, and interfacing to electrospray ionization (ESI)-MS and matrix-assisted laser desorption/ionization-MS. Two critical issues in coupling ME and ESI-MS include the electrical connection used to define the electrophoretic field strength along the separation channel and the generation of the electrospray for MS detection, as well as, a miniaturized ESI-tip. The recent commercialization of ME-MS in zone electrophoresis and isoelectric focusing modes has led to the widespread application of these techniques in academia and industry. Here we summarize recent applications of ME-MS for the separation and detection of antibodies, proteins, peptides, carbohydrates, metabolites, and so on. Throughout the paper these applications are discussed in the context of benefits and limitations of ME-MS in comparison to alternative techniques.

Evaluation of a national clinical programme for the management of self-harm in hospital emergency departments: impact on patient outcomes and the provision of care.

BACKGROUND: Emergency departments are important points of intervention, to reduce the risk of further self-harm and suicide. A national programme to standardise the management of people presenting to the emergency department with self-harm and suicidal ideation (NCPSHI) was introduced in Ireland in 2014. The aim of this study was to evaluate the impact of the NCPSHI on patient outcomes and provision of care. METHODS: Data on self-harm presentations were obtained from the National Self-Harm Registry Ireland from 2012 to 2017. The impacts of the NCPSHI on study outcomes (3-month self-harm repetition, biopsychosocial assessment provision, admission, post-discharge referral, and self-discharge) were examined at an individual and aggregate (hospital) level, using a before and after study design and interrupted time series analyses, respectively. The 15 hospitals that implemented the programme by January 2015 (of a total of 24 between 2015 and 2017) were included in the analyses. RESULTS: There were 31,970 self-harm presentations during the study period. In hospitals with no service for self-harm (n = 4), risk of patients not being assessed reduced from 31.8 to 24.7% following the introduction of the NCPSHI. Mental health referral in this hospital group increased from 42.2 to 59.0% and medical admission decreased from 27.5 to 24.3%. Signs of a reduction in self-harm repetition were observed for this hospital group, from 35.1 to 30.4% among individuals with a history of self-harm, but statistical evidence was weak. In hospitals with a pre-existing liaison psychiatry service (n = 7), risk of self-discharge was lower post-NCPSHI (17.8% vs. 14.8%). In hospitals with liaison nurse(s) pre-NCPSHI (n = 4), medical admission reduced (27.5% vs. 24.3%) and there was an increase in self-harm repetition (from 5.2 to 7.8%. for those without a self-harm history). CONCLUSION: The NCPSHI was associated with improvements in the provision of care across hospital groups, particularly those with no prior service for self-harm, highlighting the need to consider pre-existing context in implementation planning. Our evaluation emphasises the need for proper resourcing to support the implementation of clinical guidelines on the provision of care for people presenting to hospital with self-harm.

Improved Locomotor Recovery in a Rat Model of Spinal Cord Injury by BioLuminescent-OptoGenetic (BL-OG) Stimulation with an Enhanced Luminopsin.

Irrespective of the many strategies focused on dealing with spinal cord injury (SCI), there is still no way to restore motor function efficiently or an adequate regenerative therapy. One promising method that could potentially prove highly beneficial for rehabilitation in patients is to re-engage specific neuronal populations of the spinal cord following SCI. Targeted activation may maintain and strengthen existing neuronal connections and/or facilitate the reorganization and development of new connections. BioLuminescent-OptoGenetics (BL-OG) presents an avenue to non-invasively and specifically stimulate neurons; genetically targeted neurons express luminopsins (LMOs), light-emitting luciferases tethered to light-sensitive channelrhodopsins that are activated by adding the luciferase substrate coelenterazine (CTZ). This approach employs ion channels for current conduction while activating the channels through treatment with the small molecule CTZ, thus allowing non-invasive stimulation of all targeted neurons. We previously showed the efficacy of this approach for improving locomotor recovery following severe spinal cord contusion injury in rats expressing the excitatory luminopsin 3 (LMO3) under control of a pan-neuronal and motor-neuron-specific promoter with CTZ applied through a lateral ventricle cannula. The goal of the present study was to test a new generation of LMOs based on opsins with higher light sensitivity which will allow for peripheral delivery of the CTZ. In this construct, the slow-burn Gaussia luciferase variant (sbGLuc) is fused to the opsin CheRiff, creating LMO3.2. Taking advantage of the high light sensitivity of this opsin, we stimulated transduced lumbar neurons after thoracic SCI by intraperitoneal application of CTZ, allowing for a less invasive treatment. The efficacy of this non-invasive BioLuminescent-OptoGenetic approach was confirmed by improved locomotor function. This study demonstrates that peripheral delivery of the luciferin CTZ can be used to activate LMOs expressed in spinal cord neurons that employ an opsin with increased light sensitivity.

Neural Patterns are More Similar across Individuals during Successful Memory Encoding than during Failed Memory Encoding.

After experiencing the same episode, some people can recall certain details about it, whereas others cannot. We investigate how common (intersubject) neural patterns during memory encoding influence whether an episode will be subsequently remembered, and how divergence from a common organization is associated with encoding failure. Using functional magnetic resonance imaging with intersubject multivariate analyses, we measured brain activity as people viewed episodes within wildlife videos and then assessed their memory for these episodes. During encoding, greater neural similarity was observed between the people who later remembered an episode (compared with those who did not) within the regions of the declarative memory network (hippocampus, posterior medial cortex [PMC], and dorsal Default Mode Network [dDMN]). The intersubject similarity of the PMC and dDMN was episode-specific. Hippocampal encoding patterns were also more similar between subjects for memory success that was defined after one day, compared with immediately after retrieval. The neural encoding patterns were sufficiently robust and generalizable to train machine learning classifiers to predict future recall success in held-out subjects, and a subset of decodable regions formed a network of shared classifier predictions of subsequent memory success. This work suggests that common neural patterns reflect successful, rather than unsuccessful, encoding across individuals.

Image memorability is predicted by discriminability and similarity in different stages of a convolutional neural network.

The features of an image can be represented at multiple levels-from its low-level visual properties to high-level meaning. What drives some images to be memorable while others are forgettable? We address this question across two behavioral experiments. In the first, different layers of a convolutional neural network (CNN), which represent progressively higher levels of features, were used to select the images that would be shown to 100 participants through a form of prospective assignment. Here, the discriminability/similarity of an image with others, according to different CNN layers dictated the images presented to different groups, who made a simple indoor versus outdoor judgment for each scene. We found that participants remember more scene images that were selected based on their low-level discriminability or high-level similarity. A second experiment replicated these results in an independent sample of 50 participants, with a different order of postencoding tasks. Together, these experiments provide evidence that both discriminability and similarity, at different visual levels, predict image memorability.

Influences on memory for naturalistic visual episodes: sleep, familiarity, and traits differentially affect forms of recall.

The memories we form are composed of information that we extract from multifaceted episodes. Static stimuli and paired associations have proven invaluable stimuli for understanding memory, but real-life events feature spatial and temporal dimensions that help form new retrieval paths. We ask how the ability to recall semantic, temporal, and spatial aspects (the "what, when, and where") of naturalistic episodes is affected by three influences-prior familiarity, postencoding sleep, and individual differences-by testing their influence on three forms of recall: cued recall, free recall, and the extent that recalled details are recombined for a novel prompt. Naturalistic videos of events with rare animals were presented to 115 participants, randomly assigned to receive a 12- or 24-h delay with sleep and/or wakefulness. Participants' immediate and delayed recall was tested and coded by its spatial, temporal, and semantic content. We find that prior familiarity with items featured in events improved cued recall, but not free recall, particularly for temporal and spatial details. In contrast, postencoding sleep, relative to wakefulness, improved free recall, but not cued recall, of all forms of content. Finally, individuals with higher trait scores in the Survey of Autobiographical Memory spontaneously incorporated more spatial details during free recall, and more event details (at a trend level) in a novel recombination recall task. These findings show that prior familiarity, postencoding sleep, and memory traits can each enhance a different form of recall. More broadly, this work highlights that recall is heterogeneous in response to different influences on memory.

A quantitative analysis of CT angiography, large vessel occlusion, and thrombectomy rates in acute ischaemic stroke.

AIMS: To determine the workload of acute computed tomography angiography (CTA) in patients presenting with suspected acute ischaemic stroke (AIS) and rate of large vessel occlusion (LVO) and thrombectomy relative to suspected and confirmed stroke diagnoses across three stroke centres within the Republic of Ireland. MATERIALS AND METHODS: A retrospective review of data from three stroke centres, one of which provides a 24-hour thrombectomy service was undertaken. The number of CTA studies performed from January 2015 to December 2017 for suspected AIS was quantified using the national PACS in addition to occlusion location, collateral status, and rates of LVO and thrombectomy. The hospital inpatient enquiry (HIPE) system was searched for all patients with a primary discharge diagnosis of stroke and then correlated with patients who underwent CTA on admission. RESULTS: A total of 2,358 CTA studies were performed for suspected AIS during the study period across three stroke centres. LVO was demonstrated in 18.4% of suspected AIS, 18.4% of primary discharge stroke diagnoses, and 40.2% of confirmed AIS who underwent CTA. A total of 283 thrombectomies were performed of which 64.6% were LVO. Thrombectomy was performed in 12% of suspected AIS, 12% of overall primary discharge diagnoses of stroke cases, and 26% of confirmed stroke who underwent CTA. CONCLUSION: Establishing the volume of acute CTAs and rates of LVO and thrombectomy when compared to suspected AIS on admission, confirmed stroke diagnoses who underwent CTA and primary discharge diagnosis of stroke is essential for the planning and provision of stroke services worldwide.

Review of external referrals to a regional stroke centre: it is not just about thrombectomy.

AIMS: To determine the experience of a regional stroke referral centre of external referrals for endovascular thrombectomy (EVT) in patients with symptoms of acute ischaemic stroke (AIS) and large vessel occlusion (LVO). MATERIALS AND METHODS: Data were collected prospectively over two 4-month periods (2017-2018) on consecutive external referrals for EVT. Baseline demographics, imaging findings, and key time parameters were recorded. Reasons for not transferring patients and for not performing EVT were recorded. Key time intervals were calculated and compared between the transferred and non-transferred group with and without intracranial occlusion and between the transferred patients who underwent thrombectomy and those who did not. RESULTS: Two hundred and sixty-two patients were referred. Sixty-one percent (n=159) were accepted and transferred for treatment. Of those transferred, 86% (n=136) had EVT. Fourteen percent (n=23) were unsuitable for EVT on arrival due to no vessel occlusion (48% n=11), poor Alberta Stroke Program Early CT Score (ASPECTS)/established infarct (30%, n=7) haemorrhage (9%, n=2), and clinical recovery (13% n=3). One hundred and three patients (39%) were ineligible for EVT following phone discussion due to absence of intracranial occlusion (59%, n=61), low ASPECTS (22%, n=23), distal occlusion (4%, n=4), low/improving National Institutes of Health Stroke Scale (NIHSS; 10.7%, n=11), and poor modified Rankin Scale (mRS) at baseline (3%, n=3). Patients with LVO but not transferred had longer onset to hospital arrival time compared with those transferred 151.5 versus 91 minutes (p<0.005), with a trend also toward a longer door to CT/CTA 40 minutes versus 30 minutes (p=0.142). CONCLUSION: These data provide valuable insights into the service provision of a comprehensive stroke network. The present rates of EVT and futile transfers are modest compared to published data. Access to neuroradiology and specialised stroke assessment is crucial to optimise time to treatment.

Psychosocial, psychiatric and work-related risk factors associated with suicide in Ireland: optimised methodological approach of a case-control psychological autopsy study.

BACKGROUND: Suicide has profound effects on families and communities, but is a statistically rare event. Psychological autopsies using a case-control design allow researchers to examine risk factors for suicide, using a variety of sources to detail the psychological and social characteristics of decedents and to compare them to controls. The Suicide Support and Information System Case Control study (SSIS-ACE) aimed to compare psychosocial, psychiatric and work-related risk factors across three groups of subjects: suicide decedents, patients presenting to hospital with a high-risk self-harm episode, and general practice controls. METHODS: The study design includes two inter-related studies; one main case-control study: comparing suicide cases to general practice (GP) controls, and one comparative study: comparing suicide cases to patients presenting with high-risk self-harm. Consecutive cases of suicide and probable suicide are identified through coroners' registration of deaths in the defined region (Cork City and County, Ireland) and are frequency-matched for age group and gender with GP patient controls recruited from the same GP practice as the deceased. Data sources for suicide cases include coroners' records, interviews with health care professionals and proxy informants; data sources for GP controls and for high-risk self-harm controls include interviews with control, with proxy informants and with health care professionals. Interviews are semi-structured and consist of quantitative and qualitative parts. The quantitative parts include a range of validated questionnaires addressing psychiatric, psychosocial and occupational factors. The study adopts several methodological innovations, including accessing multiple data sources for suicide cases and controls simultaneously, recruiting proxy informants to examine consistency across sources. CONCLUSIONS: The study allows for the investigation of consistency across different data sources and contributes to the methodological advancement of psychological autopsy research. The study will also inform clinical and public health practice. The comparison between suicide cases and controls will allow investigation of risk and protective factors for suicide more generally, while the comparison with high-risk self-harm patients will help to identify the factors associated specifically with a fatal outcome to a self-harm episode. A further enhancement is the particular focus on specific work-related risk factors for suicide.

Semantic knowledge influences whether novel episodic associations are represented symmetrically or asymmetrically.

We provide new evidence concerning two opposing views of episodic associations: The independent-association hypothesis posits that associations are unidirectional and separately modifiable links (A→B and A←B); in contrast, the associative-symmetry hypothesis proposes that a single, bidirectional association exists between A and B (A↔B). We used a novel method to demonstrate that whether or not episodic associations are symmetric depends on whether there is a preexisting semantic relationship between A and B. In two experiments, participants studied 30 semantically unrelated and 30 semantically related pairs intermixed in a single list and then performed a series of up to eight cued-recall test cycles. All pairs were tested in each cycle, and the testing direction (A-? or B-?) alternated between cycles. Unrelated pairs exhibited associative symmetry-that is, accuracy and response times improved gradually on each test-suggesting that testing in both directions strengthened the same association. In contrast, semantically related pairs exhibited a stair-like pattern, in which performance did not change from odd to even tests when the test direction changed; it only improved between tests in the same direction. We concluded that episodic associations can have either a single bidirectional representation or separate directional representations, depending on the semantic relatedness of their constituent items.

Creatures great and small: Real-world size of animals predicts visual cortex representations beyond taxonomic category.

Human occipitotemporal cortex contains neural representations for a variety of perceptual and conceptual features. We report a study examining neural representations of real-world size along the visual ventral stream, while carefully accounting for taxonomic categories that typically co-vary with size. We recorded brain activity during a functional Magnetic Resonance Imaging (fMRI) scan from eighteen participants as they were presented with images of twelve animal species. The animals were selected to vary on a number of dimensions, including taxonomic group, real-world size and prior familiarity. We apply multivariate analysis methods, including representational similarity analysis (RSA) and machine learning classifiers, to probe the distributed patterns of neural activity evoked by these presentations. We find that the real-world size of visually presented animate items is represented in posterior, but not anterior, regions of the ventral stream. A significant linear relationship is present for real-world size representation along the ventral stream. These representations remain after controlling for factors such as taxonomic category, familiarity and models of visual similarity, and even after restricting examinations to within-taxonomic category comparisons, suggesting that size information is found for within, as well as between, taxonomic categories. These findings are consistent with real-world size having an influence on activity patterns in early regions of the visual system.

Self-Harm, Methadone Use and Drug-Related Deaths amongst Those Registered As Being of No Fixed Abode or Homeless in Ireland.

This work aims to contribute to the evidence base regarding the health of those who experience homelessness in Ireland by collating data on methadone use, drug-related deaths and emergency department presentations due to self-harm. Data from the Central Methadone Treatment List (CTL), National Self-Harm Registry Ireland and the National Drug-Related Deaths Index were analysed. The percentage on the CTL registered as being of no fixed abode (NFA) or homeless increased from 2% to 7% from 2011-2014. The absolute number of presentations with deliberate self-harm from those of NFA increased by 49% from 2007-2014. The number of drug-related deaths amongst those of NFA or homeless and who died in Dublin fluctuated from 2004-13 with an overall upward trend. There is an urgent need to adequately resource and coordinate those services which aim to address factors (social and health inequalities, mental ill-health and addiction) which lead people into - and prevent them exiting from - homelessness.

Importance of a Conserved Lys/Arg Residue for Ligand/PDZ Domain Interactions as Examined by Protein Semisynthesis.

PDZ domains are ubiquitous small protein domains that are mediators of numerous protein-protein interactions, and play a pivotal role in protein trafficking, synaptic transmission, and the assembly of signaling-transduction complexes. In recent years, PDZ domains have emerged as novel and exciting drug targets for diseases (in the brain in particular), so understanding the molecular details of PDZ domain interactions is of fundamental importance. PDZ domains bind to a protein partner at either a C-terminal peptide or internal peptide motifs. Here, we examined the importance of a conserved Lys/Arg residue in the ligand-binding site of the second PDZ domain of PSD-95, by employing a semisynthetic approach. We generated six semisynthetic PDZ domains comprising different proteogenic and nonproteogenic amino acids representing subtle changes of the conserved Lys/Arg residue. These were tested with four peptide interaction partners, representing the two different binding modes. The results highlight the role of a positively charged amino acid in the ß1-ß2 loop of PDZ domains, and show subtle differences for canonical and noncanonical interaction partners, thus providing additional insight into the mechanism of PDZ/ligand interaction.

Variation between hospitals in inpatient admission practices for self-harm patients and its impact on repeat presentation.

PURPOSE: Self-harm patient management varies markedly between hospitals, with fourfold differences in the proportion of patients who are admitted to a medical or psychiatric inpatient bed. The current study aimed to investigate whether differences in admission practices are associated with patient outcomes (repeat self-harm) while accounting for differences in patient case mix. METHODS: Data came from the National Self-Harm Registry Ireland. A prospective cohort of 43,595 self-harm patients presenting to hospital between 2007 and 2012 were included. As well as conventional regression analysis, instrumental variable (IV) methods utilising between hospital differences in rates of hospital admission were used in an attempt to gain unbiased estimates of the association of admission with risk of repeat self-harm. RESULTS: The proportion of self-harm patients admitted to a medical bed varied from 10 to 74 % between hospitals. Conventional regression and IV analysis suggested medical admission was not associated with risk of repeat self-harm. Psychiatric inpatient admission was associated with an increased risk of repeat self-harm in both conventional and IV analyses. This increased risk persisted in analyses stratified by gender and when restricted to self-poisoning patients only. CONCLUSIONS: No strong evidence was found to suggest medical admission reduces the risk of repeat self-harm. Models of health service provision that encourage prompt mental health assessment in the emergency department and avoid unnecessary medical admission of self-harm patients appear warranted. Psychiatric inpatient admission may be associated with a heightened risk of repeat self-harm in some patients, but these findings could be biased by residual confounding and require replication.

Higher levels of antibodies to the tumour-associated antigen cyclin B1 in cancer-free individuals than in patients with breast cancer.

Cyclin B1 is a checkpoint protein that regulates cell division from G2 to the M phase. Studies in mice have shown that cyclin B1 vaccine-induced immunity significantly delayed or prevented the spontaneous cancer development later in life. We hypothesized that if these results showing a protective effect of anti-cyclin B1 antibodies could be extrapolated to the human condition, cancer-free individuals should have higher levels of endogenous antibodies than patients with cancers characterized by the over-expression of this tumour-associated antigen. To test this hypothesis, we characterized a large (1739 subjects) number of multi-ethnic patients with breast cancer (which over-expresses cyclin B1) and matched controls for anti-cyclin B1 immunoglobulin (Ig)G antibodies. Multivariate analyses, after adjusting for the covariates, showed that cancer-free individuals had significantly higher levels of naturally occurring IgG antibodies to cyclin B1 than patients with breast cancer (mean ± standard deviation: 148·0 ± 73·6 versus 126·1 ± 67·8 arbitrary units per ml; P < 0·0001). These findings may have important implications for cyclin B1-based immunotherapy against breast cancer and many other cyclin B1-over-expressing malignancies.

Bilateral subcortical heterotopia with partial callosal agenesis in a mouse mutant.

Cognition and behavior depend on the precise placement and interconnection of complex ensembles of neurons in cerebral cortex. Mutations that disrupt migration of immature neurons from the ventricular zone to the cortical plate have provided major insight into mechanisms of brain development and disease. We have discovered a new and highly penetrant spontaneous mutation that leads to large nodular bilateral subcortical heterotopias with partial callosal agenesis. The mutant phenotype was first detected in a colony of fully inbred BXD29 mice already known to harbor a mutation in Tlr4. Neurons confined to the heterotopias are mainly born in midgestation to late gestation and would normally have migrated into layers 2-4 of overlying neocortex. Callosal cross-sectional area and fiber number are reduced up to 50% compared with coisogenic wildtype BXD29 substrain controls. Mutants have a pronounced and highly selective defect in rapid auditory processing. The segregation pattern of the mutant phenotype is most consistent with a two-locus autosomal recessive model, and selective genotyping definitively rules out the Tlr4 mutation as a cause. The discovery of a novel mutation with strong pleiotropic anatomical and behavioral effects provides an important new resource for dissecting molecular mechanisms and functional consequences of errors of neuronal migration.

Context reinstatement requires a schema relevant virtual environment to benefit object recall.

How does our environment impact what we will later remember? Early work in real-world environments suggested that having matching encoding/retrieval contexts improves memory. However, some laboratory-based studies have not replicated this advantageous context-dependent memory effect. Using virtual reality methods, we find support for context-dependent memory effects and examine an influence of memory schema and dynamic environments. Participants (N = 240) remembered more objects when in the same virtual environment (context) as during encoding. This traded-off with falsely "recognizing" more similar lures. Experimentally manipulating the virtual objects and environments revealed that a congruent object/environment schema aids recall (but not recognition), though a dynamic background does not. These findings further our understanding of when and how context affects our memory through a naturalistic approach to studying such effects.

Advancing early detection of suicide? A national study examining socio-demographic factors, antecedent stressors and long-term history of self-harm.

BACKGROUND: A range of factors including mental disorders, adverse events and history of self-harm are associated with suicide risk. Further examination is needed of the characteristics of suicides which occur without established risk factors, using national surveillance systems. METHODS: Data on all suicides in Ireland from 2015 to 2017 were drawn from the Irish Probable Suicide Deaths Study (IPSDS). Variables examined included socio-demographics, psychiatric history and precipitant stressors. Suicide data were linked with data on prior self-harm from the National Self-Harm Registry Ireland (NSHRI). Latent Class Analysis (LCA) was used to identify sub-groups of suicide cases. RESULTS: Of the 1809 individuals who died by suicide, 401 (22.2 %) had a history of hospital-treated self-harm. Four distinct profiles of suicides were identified. One group was marked by high levels of prior self-harm and mental health conditions. Two of the groups included few individuals with a history of self-harm but had notably high levels of mental health conditions. These two groups had relatively high levels of reported chronic pain or illness but differed in terms of socio-demographics. The final group, predominantly male, had markedly low levels of mental health conditions or self-harm but high levels of personal stressors and substance use. LIMITATIONS: The use of coronial data may be limited by bias in the collecting of information from the deceased's family members. CONCLUSIONS: A sub-group of suicide cases exists without any psychiatric or self-harm history but with salient occupational or health-related proximal stressors. Suicide prevention interventions should include occupational settings and should promote mental health literacy.