The usability and reliability of a smartphone application for monitoring future dementia risk in ageing UK adults.

BACKGROUND: The rising number of dementia diagnoses and imminent adoption of disease-modifying treatments necessitate innovative approaches to identify individuals at risk, monitor disease course and intervene non-pharmacologically earlier in the disease course. Digital assessments of dementia risk and cognitive function have the potential to outperform traditional in-person assessments in terms of their affordability, accuracy and longitudinal tracking abilities. However, their accessibility and reliability in older adults is unclear. AIMS: To evaluate the usability and reliability of a smartphone assessment of lifestyle and cognitive factors relevant to dementia risk in a group of UK-based older adults. METHOD: Cognitively healthy adults (n = 756) recruited through the Dementias Platform UK Great Minds volunteer register completed three assessments of cognitive function and dementia risk over a 3-month period and provided usability feedback on the Five Lives smartphone application (app). We evaluated cognitive test scores for age, gender and higher education effects, normality distributions, test-retest reliability and their relationship with participants' lifestyle dementia risk factors. RESULTS: Participants found the app 'easy to use', 'quick to complete' and 'enjoyable'. The cognitive tests showed normal or near-to-normal distributions, variable test-retest reliabilities and age-related effects. Only tests of verbal ability showed gender and education effects. The cognitive tests did not correlate with lifestyle dementia risk scores. CONCLUSIONS: The Five Lives assessment demonstrates high usability and reliability among older adults. These findings highlight the potential of digital assessments in dementia research and clinical practice, enabling improved accessibility and better monitoring of cognitive health on a larger scale than traditional in-person assessments.

Oral and long-acting injectable antipsychotic discontinuation and relationship to side effects in people with first episode psychosis: a longitudinal analysis of electronic health record data.

Background: Discontinuation of treatment in people with first episode psychosis (FEP) is common, but the extent to which this is related to specific adverse effects of antipsychotic medications is unclear. Objectives: To investigate whether antipsychotic discontinuation is associated with the prescription of particular antipsychotics and particular adverse effects. Design: Retrospective cohort study. Methods: We assembled de-identified electronic health record (EHR) data from 2309 adults with FEP who received care from the South London and Maudsley NHS Foundation Trust between 1st April 2008 and 31st March 2019. Associations between antipsychotic medications, clinician-recorded side effects and treatment discontinuation were investigated across a mean follow-up period of 34.2 months using Cox regression. Results: The mean age of patients was 26.7 years and 1492 (64.6%) were male. Among first prescribed antipsychotic medications, discontinuation occurred earlier with haloperidol [hazard ratio (HR) = 2.78, 95% CI = 1.69-4.60] and quetiapine (HR = 1.43, 95% CI = 1.16-1.80) than with olanzapine. Discontinuation occurred sooner when there was evidence of extrapyramidal symptoms (HR = 1.33, 95% CI = 1.08-1.64) or sexual dysfunction (HR = 1.59, 95% CI = 1.03-2.46). Among antipsychotics prescribed at any point during treatment, lurasidone (HR = 1.40, 95% CI = 1.10-1.78) and aripiprazole (HR = 1.09, 95% CI = 1.01-1.19) were associated with earlier discontinuation than olanzapine. Conversely, clozapine (HR = 0.55, 95% CI = 0.41-0.73) and paliperidone 1-monthly (PP1M) long-acting injectable (HR = 0.80, 95% CI = 0.68-0.94) were associated with later discontinuation. Unexpectedly, for antipsychotics prescribed at any stage of treatment, sedation (HR = 0.89, 95% CI = 0.81-0.97), weight gain (HR = 0.73, 95% CI = 0.64-0.83), and multiple side effects (HR = 0.83, 95% CI = 0.76-0.90) were associated with later discontinuation. Conclusion: Earlier treatment discontinuation associated with sexual or extrapyramidal side effects could be related to their rapid onset and poor tolerability. Later treatment discontinuation associated with clozapine and PP1M could be related to the relative efficacy of these treatments. These findings merit consideration when selecting antipsychotic therapy for people with FEP.

Geophysical evidence for an enriched molten silicate layer above Mars's core.

The detection of deep reflected S waves on Mars inferred a core size of 1,830 ± 40 km (ref. 1), requiring light-element contents that are incompatible with experimental petrological constraints. This estimate assumes a compositionally homogeneous Martian mantle, at odds with recent measurements of anomalously slow propagating P waves diffracted along the core-mantle boundary2. An alternative hypothesis is that Mars's mantle is heterogeneous as a consequence of an early magma ocean that solidified to form a basal layer enriched in iron and heat-producing elements. Such enrichment results in the formation of a molten silicate layer above the core, overlain by a partially molten layer3. Here we show that this structure is compatible with all geophysical data, notably (1) deep reflected and diffracted mantle seismic phases, (2) weak shear attenuation at seismic frequency and (3) Mars's dissipative nature at Phobos tides. The core size in this scenario is 1,650 ± 20 km, implying a density of 6.5 g cm-3, 5-8% larger than previous seismic estimates, and can be explained by fewer, and less abundant, alloying light elements than previously required, in amounts compatible with experimental and cosmochemical constraints. Finally, the layered mantle structure requires external sources to generate the magnetic signatures recorded in Mars's crust.

Dynamic population normalisation in wastewater-based epidemiology for improved understanding of the SARS-CoV-2 prevalence: a multi-site study.

Wastewater-based epidemiology (WBE) is a valuable tool for monitoring the circulation of COVID-19. However, while variations in population size are recognised as major sources of uncertainty, wastewater SARS-CoV-2 measurements are not routinely population-normalised. This paper aims to determine whether dynamic population normalisation significantly alters SARS-CoV-2 dynamics observed through wastewater monitoring, and whether it is beneficial or necessary to provide an understanding of COVID-19 epidemiology. Data from 394 sites in England are used, and normalisation is implemented based on ammoniacal nitrogen and orthophosphate concentrations. Raw and normalised wastewater SARS-CoV-2 metrics are evaluated at the site and spatially aggregated levels are compared against indicators of prevalence based on the Coronavirus Infection Survey and Test and Trace polymerase chain reaction test results. Normalisation is shown, on average, to have a limited impact on overall temporal trends. However, significant variability in the degree to which it affects local-level trends is observed. This is not evident from previous WBE studies focused on single sites and, critically, demonstrates that while the impact of normalisation on SARS-CoV-2 trends is small on average, this may not always be the case. When averaged across many sites, normalisation strengthens the correlation between wastewater SARS-CoV-2 data and prevalence indicators; however, confidence in the improvement is low.

First observations of core-transiting seismic phases on Mars.

We present the first observations of seismic waves propagating through the core of Mars. These observations, made using seismic data collected by the InSight geophysical mission, have allowed us to construct the first seismically constrained models for the elastic properties of Mars' core. We observe core-transiting seismic phase SKS from two farside seismic events detected on Mars and measure the travel times of SKS relative to mantle traversing body waves. SKS travels through the core as a compressional wave, providing information about bulk modulus and density. We perform probabilistic inversions using the core-sensitive relative travel times together with gross geophysical data and travel times from other, more proximal, seismic events to seek the equation of state parameters that best describe the liquid iron-alloy core. Our inversions provide constraints on the velocities in Mars' core and are used to develop the first seismically based estimates of its composition. We show that models informed by our SKS data favor a somewhat smaller (median core radius = 1,780 to 1,810 km) and denser (core density = 6.2 to 6.3 g/cm3) core compared to previous estimates, with a P-wave velocity of 4.9 to 5.0 km/s at the core-mantle boundary, with the composition and structure of the mantle as a dominant source of uncertainty. We infer from our models that Mars' core contains a median of 20 to 22 wt% light alloying elements when we consider sulfur, oxygen, carbon, and hydrogen. These data can be used to inform models of planetary accretion, composition, and evolution.

Seismic evidence for a 1000 km mantle discontinuity under the Pacific.

Seismic discontinuities in the mantle are indicators of its thermo-chemical state and offer clues to its dynamics. Ray-based seismic methods, though limited by the approximations made, have mapped mantle transition zone discontinuities in detail, but have yet to offer definitive conclusions on the presence and nature of mid-mantle discontinuities. Here, we show how to use a wave-equation-based imaging method, reverse-time migration of precursors to surface-reflected seismic body waves, to uncover both mantle transition zone and mid-mantle discontinuities, and interpret their physical nature. We observe a thinned mantle transition zone southeast of Hawaii, and a reduction in impedance contrast around 410 km depth in the same area, suggesting a hotter-than-average mantle in the region. Here, we furthermore reveal a 4000-5000 km-wide reflector in new images of the mid mantle below the central Pacific, at 950-1050 km depth. This deep discontinuity exhibits strong topography and generates reflections with polarity opposite to those originating at the 660 km discontinuity, implying an impedance reversal near 1000 km. We link this mid-mantle discontinuity to the upper reaches of deflected mantle plumes upwelling in the region. Reverse-time migration full-waveform imaging is a powerful approach to imaging Earth's interior, capable of broadening our understanding of its structure and dynamics and shrinking modeling uncertainties.

Seismic detection of a deep mantle discontinuity within Mars by InSight.

Constraining the thermal and compositional state of the mantle is crucial for deciphering the formation and evolution of Mars. Mineral physics predicts that Mars' deep mantle is demarcated by a seismic discontinuity arising from the pressure-induced phase transformation of the mineral olivine to its higher-pressure polymorphs, making the depth of this boundary sensitive to both mantle temperature and composition. Here, we report on the seismic detection of a midmantle discontinuity using the data collected by NASA's InSight Mission to Mars that matches the expected depth and sharpness of the postolivine transition. In five teleseismic events, we observed triplicated P and S waves and constrained the depth of this discontinuity to be 1,006 [Formula: see text] 40 km by modeling the triplicated waveforms. From this depth range, we infer a mantle potential temperature of 1,605 [Formula: see text] 100 K, a result consistent with a crust that is 10 to 15 times more enriched in heat-producing elements than the underlying mantle. Our waveform fits to the data indicate a broad gradient across the boundary, implying that the Martian mantle is more enriched in iron compared to Earth. Through modeling of thermochemical evolution of Mars, we observe that only two out of the five proposed composition models are compatible with the observed boundary depth. Our geodynamic simulations suggest that the Martian mantle was relatively cold 4.5 Gyr ago (1,720 to 1,860 K) and are consistent with a present-day surface heat flow of 21 to 24 mW/m2.

Association between depressive symptoms and cognitive-behavioural therapy receipt within a psychosis sample: a cross-sectional study.

OBJECTIVES: To examine whether depressive symptoms predict receipt of cognitive-behavioural therapy for psychosis (CBTp) in individuals with psychosis. DESIGN: Retrospective cross-sectional analysis of electronic health records (EHRs) of a clinical cohort. SETTING: A secondary National Health Service mental healthcare service serving four boroughs of south London, UK. PARTICIPANTS: 20 078 patients diagnosed with an International Classification of Diseases, version 10 (ICD-10) code between F20 and 29 extracted from an EHR database. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary: Whether recorded depressive symptoms predicted CBTp session receipt, defined as at least one session of CBTp identified from structured EHR fields supplemented by a natural language processing algorithm. Secondary: Whether age, gender, ethnicity, symptom profiles (positive, negative, manic and disorganisation symptoms), a comorbid diagnosis of depression, anxiety or bipolar disorder, general CBT receipt prior to the primary psychosis diagnosis date or type of psychosis diagnosis predicted CBTp receipt. RESULTS: Of patients with a psychotic disorder, only 8.2% received CBTp. Individuals with at least one depressive symptom recorded, depression symptom severity and 12 out of 15 of the individual depressive symptoms independently predicted CBTp receipt. Female gender, White ethnicity and presence of a comorbid affective disorder or primary schizoaffective diagnosis were independently positively associated with CBTp receipt within the whole sample and the top 25% of mentioned depressive symptoms. CONCLUSIONS: Individuals with a psychotic disorder who had recorded depressive symptoms were significantly more likely to receive CBTp sessions, aligning with CBTp guidelines of managing depressive symptoms related to a psychotic experience. However, overall receipt of CBTp is low and more common in certain demographic groups, and needs to be increased.

Associations of presenting symptoms and subsequent adverse clinical outcomes in people with unipolar depression: a prospective natural language processing (NLP), transdiagnostic, network analysis of electronic health record (EHR) data.

OBJECTIVE: To investigate the associations of symptoms of mania and depression with clinical outcomes in people with unipolar depression. DESIGN: A natural language processing electronic health record study. We used network analysis to determine symptom network structure and multivariable Cox regression to investigate associations with clinical outcomes. SETTING: The South London and Maudsley Clinical Record Interactive Search database. PARTICIPANTS: All patients presenting with unipolar depression between 1 April 2006 and 31 March 2018. EXPOSURE: (1) Symptoms of mania: Elation; Grandiosity; Flight of ideas; Irritability; Pressured speech. (2) Symptoms of depression: Disturbed mood; Anhedonia; Guilt; Hopelessness; Helplessness; Worthlessness; Tearfulness; Low energy; Reduced appetite; Weight loss. (3) Symptoms of mania or depression (overlapping symptoms): Poor concentration; Insomnia; Disturbed sleep; Agitation; Mood instability. MAIN OUTCOMES: (1) Bipolar or psychotic disorder diagnosis. (2) Psychiatric hospital admission. RESULTS: Out of 19 707 patients, at least 1 depression, overlapping or mania symptom was present in 18 998 (96.4%), 15 954 (81.0%) and 4671 (23.7%) patients, respectively. 2772 (14.1%) patients subsequently developed bipolar or psychotic disorder during the follow-up period. The presence of at least one mania (HR 2.00, 95% CI 1.85 to 2.16), overlapping symptom (HR 1.71, 95% CI 1.52 to 1.92) or symptom of depression (HR 1.31, 95% CI 1.07 to 1.61) were associated with significantly increased risk of onset of a bipolar or psychotic disorder. Mania (HR 1.95, 95% CI 1.77 to 2.15) and overlapping symptoms (HR 1.76, 95% CI 1.52 to 2.04) were associated with greater risk for psychiatric hospital admission than symptoms of depression (HR 1.41, 95% CI 1.06 to 1.88). CONCLUSIONS: The presence of mania or overlapping symptoms in people with unipolar depression is associated with worse clinical outcomes. Symptom-based approaches to defining clinical phenotype may facilitate a more personalised treatment approach and better predict subsequent clinical outcomes than psychiatric diagnosis alone.

Analysis of mental and physical disorders associated with COVID-19 in online health forums: a natural language processing study.

OBJECTIVES: Online health forums provide rich and untapped real-time data on population health. Through novel data extraction and natural language processing (NLP) techniques, we characterise the evolution of mental and physical health concerns relating to the COVID-19 pandemic among online health forum users. SETTING AND DESIGN: We obtained data from three leading online health forums: HealthBoards, Inspire and HealthUnlocked, from the period 1 January 2020 to 31 May 2020. Using NLP, we analysed the content of posts related to COVID-19. PRIMARY OUTCOME MEASURES: (1) Proportion of forum posts containing COVID-19 keywords; (2) proportion of forum users making their very first post about COVID-19; (3) proportion of COVID-19-related posts containing content related to physical and mental health comorbidities. RESULTS: Data from 739 434 posts created by 53 134 unique users were analysed. A total of 35 581 posts (4.8%) contained a COVID-19 keyword. Posts discussing COVID-19 and related comorbid disorders spiked in early March to mid-March around the time of global implementation of lockdowns prompting a large number of users to post on online health forums for the first time. Over a quarter of COVID-19-related thread titles mentioned a physical or mental health comorbidity. CONCLUSIONS: We demonstrate that it is feasible to characterise the content of online health forum user posts regarding COVID-19 and measure changes over time. The pandemic and corresponding public response has had a significant impact on posters' queries regarding mental health. Social media data sources such as online health forums can be harnessed to strengthen population-level mental health surveillance.

Seismic detection of the martian core.

Clues to a planet's geologic history are contained in its interior structure, particularly its core. We detected reflections of seismic waves from the core-mantle boundary of Mars using InSight seismic data and inverted these together with geodetic data to constrain the radius of the liquid metal core to 1830 ± 40 kilometers. The large core implies a martian mantle mineralogically similar to the terrestrial upper mantle and transition zone but differing from Earth by not having a bridgmanite-dominated lower mantle. We inferred a mean core density of 5.7 to 6.3 grams per cubic centimeter, which requires a substantial complement of light elements dissolved in the iron-nickel core. The seismic core shadow as seen from InSight's location covers half the surface of Mars, including the majority of potentially active regions-e.g., Tharsis-possibly limiting the number of detectable marsquakes.

Gender differences in clinical presentation and illicit substance use during first episode psychosis: a natural language processing, electronic case register study.

OBJECTIVE: To determine whether gender differences in symptom presentation at first episode psychosis (FEP) remain even when controlling for substance use, age and ethnicity, using natural language processing applied to electronic health records (EHRs). DESIGN, SETTING AND PARTICIPANTS: Data were extracted from EHRs of 3350 people (62% male patients) who had presented to the South London and Maudsley NHS Trust with a FEP between 1 April 2007 and 31 March 2017. Logistic regression was used to examine gender differences in the presentation of positive, negative, depressive, mania and disorganisation symptoms. EXPOSURES FOR OBSERVATIONAL STUDIES: Gender (male vs female). MAIN OUTCOMES AND MEASURES: Presence of positive, negative, depressive, mania and disorganisation symptoms at initial clinical presentation. RESULTS: Eight symptoms were significantly more prevalent in men (poverty of thought, negative symptoms, social withdrawal, poverty of speech, aggression, grandiosity, paranoia and agitation). Conversely, tearfulness, low energy, reduced appetite, low mood, pressured speech, mood instability, flight of ideas, guilt, mutism, insomnia, poor concentration, tangentiality and elation were more prevalent in women than men. Negative symptoms were more common among men (OR 1.85, 95% CI 1.33 to 2.62) and depressive and manic symptoms more common among women (OR 0.30, 95% CI 0.26 to 0.35). After adjustment for illicit substance use, the strength of associations between gender and negative, manic and depression symptoms increased, whereas gender differences in aggression, agitation, paranoia and grandiosity became insignificant. CONCLUSIONS: There are clear gender differences in the clinical presentation of FEP. Our findings suggest that gender can have a substantial influence on the nature of clinical presentation in people with psychosis, and that this is only partly explained by exposure to illicit substance use.

Impact of the COVID-19 pandemic on remote mental healthcare and prescribing in psychiatry: an electronic health record study.

OBJECTIVES: The recent COVID-19 pandemic has disrupted mental healthcare delivery, with many services shifting from in-person to remote patient contact. We investigated the impact of the pandemic on the use of remote consultation and on the prescribing of psychiatric medications. DESIGN AND SETTING: The Clinical Record Interactive Search tool was used to examine deidentified electronic health records of people receiving mental healthcare from the South London and Maudsley (SLaM) NHS Foundation Trust. Data from the period before and after the onset of the pandemic were analysed using linear regression, and visualised using locally estimated scatterplot smoothing. PARTICIPANTS: All patients receiving care from SLaM between 7 January 2019 and 20 September 2020 (around 37 500 patients per week). OUTCOME MEASURES: (i) The number of clinical contacts (in-person, remote or non-attended) with mental healthcare professionals per week.(ii) Prescribing of antipsychotic and mood stabiliser medications per week. RESULTS: Following the onset of the pandemic, the frequency of in-person contacts was significantly reduced compared with that in the previous year (ß coefficient: -5829.6 contacts, 95% CI -6919.5 to -4739.6, p<0.001), while the frequency of remote contacts significantly increased (ß coefficient: 3338.5 contacts, 95% CI 3074.4 to 3602.7, p<0.001). Rates of remote consultation were lower in older adults than in working age adults, children and adolescents. Despite this change in the type of patient contact, antipsychotic and mood stabiliser prescribing remained at similar levels. CONCLUSIONS: The COVID-19 pandemic has been associated with a marked increase in remote consultation, particularly among younger patients. However, there was no evidence that this has led to changes in psychiatric prescribing. Nevertheless, further work is needed to ensure that older patients are able to access mental healthcare remotely.

Using Natural Language Processing on Electronic Health Records to Enhance Detection and Prediction of Psychosis Risk.

BACKGROUND: Using novel data mining methods such as natural language processing (NLP) on electronic health records (EHRs) for screening and detecting individuals at risk for psychosis. METHOD: The study included all patients receiving a first index diagnosis of nonorganic and nonpsychotic mental disorder within the South London and Maudsley (SLaM) NHS Foundation Trust between January 1, 2008, and July 28, 2018. Least Absolute Shrinkage and Selection Operator (LASSO)-regularized Cox regression was used to refine and externally validate a refined version of a five-item individualized, transdiagnostic, clinically based risk calculator previously developed (Harrell's C = 0.79) and piloted for implementation. The refined version included 14 additional NLP-predictors: tearfulness, poor appetite, weight loss, insomnia, cannabis, cocaine, guilt, irritability, delusions, hopelessness, disturbed sleep, poor insight, agitation, and paranoia. RESULTS: A total of 92 151 patients with a first index diagnosis of nonorganic and nonpsychotic mental disorder within the SLaM Trust were included in the derivation (n = 28 297) or external validation (n = 63 854) data sets. Mean age was 33.6 years, 50.7% were women, and 67.0% were of white race/ethnicity. Mean follow-up was 1590 days. The overall 6-year risk of psychosis in secondary mental health care was 3.4 (95% CI, 3.3-3.6). External validation indicated strong performance on unseen data (Harrell's C 0.85, 95% CI 0.84-0.86), an increase of 0.06 from the original model. CONCLUSIONS: Using NLP on EHRs can considerably enhance the prognostic accuracy of psychosis risk calculators. This can help identify patients at risk of psychosis who require assessment and specialized care, facilitating earlier detection and potentially improving patient outcomes.

Implementing Precision Psychiatry: A Systematic Review of Individualized Prediction Models for Clinical Practice.

BACKGROUND: The impact of precision psychiatry for clinical practice has not been systematically appraised. This study aims to provide a comprehensive review of validated prediction models to estimate the individual risk of being affected with a condition (diagnostic), developing outcomes (prognostic), or responding to treatments (predictive) in mental disorders. METHODS: PRISMA/RIGHT/CHARMS-compliant systematic review of the Web of Science, Cochrane Central Register of Reviews, and Ovid/PsycINFO databases from inception until July 21, 2019 (PROSPERO CRD42019155713) to identify diagnostic/prognostic/predictive prediction studies that reported individualized estimates in psychiatry and that were internally or externally validated or implemented. Random effect meta-regression analyses addressed the impact of several factors on the accuracy of prediction models. FINDINGS: Literature search identified 584 prediction modeling studies, of which 89 were included. 10.4% of the total studies included prediction models internally validated (n = 61), 4.6% models externally validated (n = 27), and 0.2% (n = 1) models considered for implementation. Across validated prediction modeling studies (n = 88), 18.2% were diagnostic, 68.2% prognostic, and 13.6% predictive. The most frequently investigated condition was psychosis (36.4%), and the most frequently employed predictors clinical (69.5%). Unimodal compared to multimodal models (ß = .29, P = .03) and diagnostic compared to prognostic (ß = .84, p < .0001) and predictive (ß = .87, P = .002) models were associated with increased accuracy. INTERPRETATION: To date, several validated prediction models are available to support the diagnosis and prognosis of psychiatric conditions, in particular, psychosis, or to predict treatment response. Advancements of knowledge are limited by the lack of implementation research in real-world clinical practice. A new generation of implementation research is required to address this translational gap.

Transdiagnostic individualized clinically-based risk calculator for the automatic detection of individuals at-risk and the prediction of psychosis: external replication in 2,430,333 US patients.

The real-world impact of psychosis prevention is reliant on effective strategies for identifying individuals at risk. A transdiagnostic, individualized, clinically-based risk calculator to improve this has been developed and externally validated twice in two different UK healthcare trusts with convincing results. The prognostic performance of this risk calculator outside the UK is unknown. All individuals who accessed primary or secondary health care services belonging to the IBM® MarketScan® Commercial Database between January 2015 and December 2017, and received a first ICD-10 index diagnosis of nonorganic/nonpsychotic mental disorder, were included. According to the risk calculator, age, gender, ethnicity, age-by-gender, and ICD-10 cluster diagnosis at index date were used to predict development of any ICD-10 nonorganic psychotic disorder. Because patient-level ethnicity data were not available city-level ethnicity proportions were used as proxy. The study included 2,430,333 patients with a mean follow-up of 15.36 months and cumulative incidence of psychosis at two years of 1.43%. There were profound differences compared to the original development UK database in terms of case-mix, psychosis incidence, distribution of baseline predictors (ICD-10 cluster diagnoses), availability of patient-level ethnicity data, follow-up time and availability of specialized clinical services for at-risk individuals. Despite these important differences, the model retained accuracy significantly above chance (Harrell's C = 0.676, 95% CI: 0.672-0.679). To date, this is the largest international external replication of an individualized prognostic model in the field of psychiatry. This risk calculator is transportable on an international scale to improve the automatic detection of individuals at risk of psychosis.

Core Formation and Geophysical Properties of Mars.

The chemical and physical properties of the interiors of terrestrial planets are largely determined during their formation and differentiation. Modeling a planet's formation provides important insights into the properties of its core and mantle, and conversely, knowledge of those properties may constrain formational narratives. Here, we present a multi-stage model of Martian core formation in which we calculate core-mantle equilibration using parameterizations from high pressure-temperature metal-silicate partitioning experiments. We account for changing core-mantle boundary (CMB) conditions, composition-dependent partitioning, and partial equilibration of metal and silicate, and we evolve oxygen fugacity (fO2) self-consistently. The model successfully reproduces published meteorite-based estimates of most elemental abundances in the bulk silicate Mars, which can be used to estimate core formation conditions and core composition. This composition implies that the primordial material that formed Mars was significantly more oxidized (0.9-1.4 log units below the iron-wüstite buffer) than that of the Earth, and that core-mantle equilibration in Mars occurred at 42-60% of the evolving CMB pressure. On average, at least 84% of accreted metal and at least 40% of the mantle were equilibrated in each impact, a significantly higher degree of metal equilibration than previously reported for the Earth. In agreement with previous studies, the modeled Martian core is rich in sulfur (18-19 wt%), with less than one weight percent O and negligible Si. We have used these core and mantle compositions to produce physical models of the present-day Martian interior and evaluate the sensitivity of core radius to crustal thickness, mantle temperature, core composition, core temperature, and density of the core alloy. Trade-offs in how these properties affect observable physical parameters like planetary mass, radius, moment of inertia, and tidal Love number k2 define a range of likely core radii: 1620-1870 km. Seismic velocity profiles for several combinations of model parameters have been used to predict seismic body-wave travel times and planetary normal mode frequencies. These results may be compared to forthcoming Martian seismic data to further constrain core formation conditions and geophysical properties.