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The southeastern United States represents one of the richest collections of aquatic biodiversity worldwide; however, many of these taxa are under an increasing threat of imperilment, local extirpation, or extinction. The pearl darter Percina aurora is a small-bodied freshwater fish endemic to the Pearl and Pascagoula river systems of Mississippi and Louisiana (USA). The last collected specimen from the Pearl River drainage was taken in 1973, and it now appears that populations in this system are likely extirpated. This reduced the historical range of this species by approximately 50%, ultimately resulting in federal protection under the US Endangered Species Act in 2017. To better understand the current distribution and general biology of extant populations, we analyzed data collected from a series of surveys conducted in the Pascagoula River drainage from 2000 to 2016. Pearl darters were captured at relatively low abundance (2.4 ± 4.0 ind. per collection) from 57% of 308 collections. We identified strong relationships between local habitat variables and occurrence and catch-per-unit-effort (CPUE) of pearl darters. Pearl darters were frequently encountered and in greater abundance in depositional areas characterized by low-velocity habitats and finer substrates. Patterns of occurrence and CPUE were spatiotemporally variable across years; however, repeated collections from a subset of localities collected across a decade or more indicated long-term persistence and stability, suggesting population resilience throughout the Pascagoula River drainage.

Objective: to determine whether patients with fibromyalgia [FMS], treated in a tertiary care setting, got worse over time, remained the same, or got better. Methods: Validated self-report questionnaires and checklists were sent at two-year intervals to patients who were screened for entry into a six-month FMS treatment program. Patients were divided into subgroups based on whether they finished the program or did not enter or finish. They were followed for up to nine years. Results: The subgroup that finished the six-month program had lower Fibromyalgia Impact Questionnaire and Beck Depression Inventory and higher Quality of Life Scale scores over time than the subgroup that did not enter the program or finish. The Fibromyalgia Impact Questionnaire scores of program finishers were significantly lower at three to four years [P = .031] and seven to nine years [P = .001]. Beck Depression Inventory scores were significantly lower at three to four years [P = .047]. The Quality of Life Scale scores were not significantly different at any measurement. Over the survey period, a majority of the total group rated their FMS symptoms and physical abilities as better than when they were pretested for the program. Up to 35 per cent had periods of time without symptoms and nearly 50 per cent rated their general health as good or excellent. A majority of patients whether they finished the program or not took medications for sleep, exercised, and used relaxation and self-talk coping strategies. Use of both pain medications and anti-depressants increased over the course of the study. Conclusions: Patients treated in a comprehensive program had consistently lower FMS impact, depression, pain, and fatigue scores over time. Patients who did not enter or complete the program were as likely take sleep medication, exercise or use self-management techniques over time but did not perceive themselves to be doing as well as those who completed the program. [ABSTRACT FROM AUTHOR]

Objectives: To characterize and compare the demographics, symptom profiles, pain coping strategies, and quality of life in three age groups of women with fibromyalgia [FMS].Methods: Self-report questionnaires, including the Fibromyalgia Impact Questionnaire [FIQ], Beck Depression Inventory, Coping Strategies Questionnaire, and Quality of Life Scale, were filled out by 343 consecutive women who were participating in FMS treatment programs. Patients were divided into three age groups for purposes of data analysis.Results: The youngest age group had their symptoms for a significantly shorter period of time than the middle age and older age groups. Tender point pain score, the FIQ physical functioning and well-being items, and perceived ability to decrease pain were significantly worse for the youngest age group when compared to the other two groups. The youngest group had significantly higher catastrophizing scores and lower duality of life than the oldest age group. Discriminant function analysis between the youngest and oldest groups revealed that a combination of six variables: length of symptoms, quality of life, tender point pain score, morning tiredness, behavioral activity strategies, and a pain control/rational thinking factor were 84% accurate in classifying these patients into their original groups. When length of symptoms was excluded, the remaining five variables were 79% accurate in classifying the patients.Conclusions: Young women with FMS perceive the severity of FMS to he higher and respond with more distress than older women with FMS. This finding is largely independent of' symptom length. [ABSTRACT FROM AUTHOR]

This article offers an overview on the founding of the American College of Life Underwriters. At the turn of the twentieth century, the substantial growth in the volume of life insurance written brought a widespread appreciation of the fundamental role which life insurance--with its new lines of coverage--had come to play in economic and social life in the U.S. These facts convinced some of the leaders in the field that, in view of the rapidly developing new uses of life insurance, more definitive attention should be given to improving the preparation of the life underwriter. In order to meet these conditions, it was felt that some form of specialized education was required. From 1913 to 1914, a beginning in life insurance education was made. The subject was not only emphasized, it became the theme of the National Association of Life Underwriters convention in Cincinnati, Ohio in September 1914. In January 1927, the Board of Trustees of the National Association of Life Underwriters formally approved the creation of the American College of Life Underwriters, with the view of establishing a professional standard of higher education in life underwriting--a standard that would include not only a study of life insurance, but of the allied subjects and general fields of knowledge with which a career life underwriter should of necessity be acquainted in order to render advice and service to the insuring public.

In the past two decades, significant progress has been made in the development of polygenic scores (PGSs). One specific application of PGSs is the development and potential use of pharmacogenomic- scores (PGx-scores) to identify patients who can benefit from a specific medication or are likely to experience side effects. This systematic review comprehensively evaluates published PGx-score studies in psychiatry and provides insights into their potential clinical use and avenues for future development. A systematic literature search was conducted across PubMed, EMBASE, and Web of Science databases until 22 August 2023. This review included fifty-three primary studies, of which the majority (69.8%) were conducted using samples of European ancestry. We found that over 90% of PGx-scores in psychiatry have been developed based on psychiatric and medical diagnoses or trait variants, rather than pharmacogenomic variants. Among these PGx-scores, the polygenic score for schizophrenia (PGS SCZ ) has been most extensively studied in relation to its impact on treatment outcomes (32 publications). Twenty (62.5%) of these studies suggest that individuals with higher PGS SCZ have negative outcomes from psychotropic treatment - poorer treatment response, higher rates of treatment resistance, more antipsychotic-induced side effects, or more psychiatric hospitalizations, while the remaining studies did not find significant associations. Although PGx-scores alone accounted for at best 5.6% of the variance in treatment outcomes (in schizophrenia treatment resistance), together with clinical variables they explained up to 13.7% (in bipolar lithium response), suggesting that clinical translation might be achieved by including PGx-scores in multivariable models. In conclusion, our literature review found that there are still very few studies developing PGx-scores using pharmacogenomic variants. Research with larger and diverse populations is required to develop clinically relevant PGx-scores, using biology-informed and multi-phenotypic polygenic scoring approaches, as well as by integrating clinical variables with these scores to facilitate their translation to psychiatric practice., (© 2024. The Author(s).)

Background and Hypothesis: The clinical-high-risk (CHR) approach was developed to prevent psychosis through the detection of psychosis risk. CHR services are transdiagnostic in nature, therefore the appropriate management of comorbidity is a central part of care. Differential diagnosis is particularly challenging across 3 common comorbidities, schizotypal personality disorder (SPD), autism spectrum disorder (ASD), and borderline personality disorder (BPD). Phenomenological research indicates a disturbance of "basic self" may differentiate between these commonly comorbid disorders and can be captured by Huber's basic symptoms (BS) concept. We investigated whether BS vary across these disorders and may inform differential diagnosis in young person's meeting CHR criteria., Study Design: A total of 685 participants meeting CHR criteria from the NAPLS-3 cohort completed the COGDIS items of the schizophrenia proneness instrument, a measure of BS, as well as the structured interview for DSM-5 (SCID-5). A logistic regression model was used to investigate the variation of COGDIS across SPD, ASD, and BPD, while controlling for age and SIPs positive severity., Study Results: Meeting COGDIS criteria was positively associated with SPD (OR = 1.72, CI = [1.31-2.28], P  = .001) but not ASD nor BPD., Conclusions: Our results indicate that "basic self-disturbance" as indicated by COGDIS differs across SPD, ASD, and BPD. COGDIS may be useful to inform the management of comorbidities in CHR services, by providing insight into subtle subjective experiences that may benefit from disorder-specific interventions., (© The Author(s) 2024. Published by Oxford University Press on behalf of the University of Maryland's school of medicine, Maryland Psychiatric Research Center.)

Understanding the entropy production of systems strongly coupled to thermal baths is a core problem of both quantum thermodynamics and mesoscopic physics. While many techniques exist to accurately study entropy production in such systems, they typically require a microscopic description of the baths, which can become numerically intractable to study for large systems. Alternatively an open-systems approach can be employed with all the nuances associated with various levels of approximation. Recently, the mesoscopic leads approach has emerged as a powerful method for studying such quantum systems strongly coupled to multiple thermal baths. In this method, a set of discretized lead modes, each locally damped, provide a Markovian embedding. Here we show that this method proves extremely useful to describe entropy production of a strongly coupled open quantum system. We show numerically, for both noninteracting and interacting setups, that a system coupled to a single bath exhibits a thermal fixed point at the level of the embedding. This allows us to use various results from the thermodynamics of quantum dynamical semigroups to infer the nonequilibrium thermodynamics of the strongly coupled, non-Markovian central systems. In particular, we show that the entropy production in the transient regime recovers the well-established microscopic definitions of entropy production with a correction that can be computed explicitly for both the single- and multiple-lead cases.

Background: Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N = 2064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II., Results: We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism., Conclusions: Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II., (© 2024. The Author(s).)

Clozapine is effective in up to 50 % of patients resistant to other antipsychotics. Its use is restricted to third-line due to adverse effects which include myocarditis. Australia reports the highest incidence of clozapine-associated myocarditis (CAM) in the context of pharmacovigilance and relatively rapid titration. An audit of patients commenced on clozapine within the Central Adelaide Local Health Network (CALHN) between 2012 and 2015 found an incidence of 8.6 %. We present here a case series from a follow up audit considering titration relevant risk factors for CAM. We reviewed anecdotal cases and data from all hospital-based commencements of clozapine across CALHN for the period July 2021 to June 2022 using pharmacy and medical record databases. We identified 5 cases of CAM and all had risk factors impacting on clozapine metabolism, including rapid titration, elevated baseline CRP, Asian ethnicity and concomitant treatment with inhibitors of clozapine metabolism. While personalisation of clozapine treatment needs further investigation in prospective trials, slower titration to lower targets for risk groups may not impact on hospital length of stay and has the potential to significantly reduce the burden of adverse events. Australian manufacturer approved titration rates exceed those recommended for personalised dosing and may not be safe for patients with risk factors. Early clozapine levels at week two could identify slow metabolisers for dose adjustment. Closer ties between psychiatrists and cardiologists are critical for the development of protocols for safely maintaining clozapine treatment during low level cardiac inflammation and to support safe rechallenge., Competing Interests: Declaration of competing interest SRC has participated in advisory and educational boards and received speaker's fees from Janssen- Cilag, Lundbeck, Otsuka, and Servier; research funding from Janssen-Cilag, Lundbeck, Otsuka, and Gilead; and data sharing from Viatris Australia. All other authors report no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Up to 1/2 of outpatients prescribed clozapine may be partially/fully non-adherent, based on therapeutic drug monitoring (TDM). Three indices for measuring partial/full non-adherence are proposed a: 1) clozapine concentration/dose (C/D) ratio which drops to half or more of what is expected in the patient; 2) clozapine/norclozapine ratio that becomes inverted; and 3) clozapine concentration that becomes non-detectable., Methods: These 3 proposed indices are based on a literature review and 17 cases of possible non-adherence from 3 samples: 1) an inpatient study in a Chinese hospital, 2) an inpatient randomized clinical trial in a United States hospital, and 3) and a Uruguayan outpatient study., Results: The first index of non-adherence is a clozapine C/D ratio which is less than half the ratio corresponding to the patient's specific ancestry group and sex-smoking subgroup. Knowing the minimum therapeutic dose of the patient based on repeated TDM makes it much easier to establish non-adherence. The second index is inverted clozapine/norclozapine ratios in the absence of alternative explanations. The third index is undetectable concentrations. By using half-lives, the chronology of the 3 indices of non-adherence was modeled in two patients: 1) the clozapine C/D ratio dropped to ≥1/2 of what is expected from the patient (around day 2); 2) the clozapine/norclozapine ratio became inverted (around day 3); and 3) the clozapine concentration became undetectable by the laboratory (around days 9-11)., Conclusion: Prospective studies should further explore these proposed clozapine indices in average patients, poor metabolizers (3 presented) and ultrarapid metabolizers (2 presented)., Competing Interests: Declaration of competing interest GS has received speaker/consultation fees from HLS Therapeutics and Thermo Fisher. AEAY has received speaker/advisory board fees from Janssen, Abdi İbrahim Otsuka and Nobel, and has received investigator fees from Janssen. CBE received honoraria for conferences from Forum pour la formation médicale, Janssen-Cilag, Lundbeck, Otsuka, Sandoz, Servier, Sunovion, Sysmex Suisse AG, Takeda, Vifor-Pharma, and Zeller in the past 3 years. SRC received speaker/consultation fees from: Janssen-Cilag, Lundbeck, Otsuka and Servier and research funding from Janssen-Cilag, Lundbeck, Otsuka and Gilead. SHK has received research grants from Janssen and Dongwha. JGL has consulted/spoken on behalf of Saladax Biomedical. RMP has received speaker/consultation fees from Eisai, HLS Therapeutics, Jansen, Lundbeck, and Otsuka. HT has received grants from Daiichi Sankyo and Novartis Pharma; speaker's fees from EA. Pharma, Eisai, Kyowa, Janssen, Lundbeck, Meiji Seika Pharma, MSD, Otsuka, Sumitomo Pharma, Takeda, and Yoshitomiyakuhin; and consulting fees from Janssen, Mitsubishi Tanabe Pharma, Ono, and Sumitomo Pharma. CUC has been a consultant and/or advisor to or has received honoraria from: AbbVie, Acadia, Alkermes, Allergan, Angelini, Aristo, Boehringer-Ingelheim, Cardio Diagnostics, Cerevel, CNX Therapeutics, Compass Pathways, Darnitsa, Denovo, Gedeon Richter, Hikma, Holmusk, IntraCellular Therapies, Janssen/J&J, Karuna, LB Pharma, Lundbeck, MedAvante-ProPhase, MedInCell, Merck, Mindpax, Mitsubishi Tanabe Pharma, Mylan, Neurocrine, Newron, Noven, Novo Nordisk, Otsuka, Pharmabrain, PPD Biotech, Recordati, Relmada, Reviva, Rovi, Seqirus, SK Life Science, Sunovion, Sun Pharma, Supernus, Takeda, Teva, and Viatris. He provided expert testimony for Janssen and Otsuka. He served on a Data Safety Monitoring Board for Compass Pathways, Denovo, Lundbeck, Relmada, Reviva, Rovi, Supernus, and Teva. He has received grant support from Janssen and Takeda. He received royalties from UpToDate and is also a stock option holder of Cardio Diagnostics, Mindpax, LB Pharma and Quantic. In the last 3 years, the remaining authors report no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

Competing Interests: Declaration of competing interest SRC has participated in advisory and educational boards and received speaker's fees from Janssen- Cilag, Lundbeck, Otsuka, and Servier; research funding from Janssen-Cilag, Lundbeck, Otsuka, and Gilead; and data sharing from Viatris Australia. All other authors report no conflicts of interest.

During weak induction (from smoking and/or valproate co-prescription), clozapine ultrarapid metabolizers (UMs) need very high daily doses to reach the minimum therapeutic concentration of 350 ng/ml in plasma; clozapine UMs need clozapine doses higher than: 1) 900 mg/day in patients of European/African ancestry, or 2) 600 mg/day in those of Asian ancestry. Published clozapine UMs include 10 males of European/African ancestry, mainly assessed with single concentrations. Five new clozapine UMs (two of European and three of Asian ancestry) with repeated assessments are described. A US double-blind randomized trial included a 32-year-old male smoking two packages/day with a minimum therapeutic dose of 1,591 mg/day from a single TDM during open treatment of 900 mg/day. In a Turkish inpatient study, a 30-year-old male smoker was a possible clozapine UM needing a minimum therapeutic dose of 1,029 mg/day estimated from two trough steady-state concentrations on 600 mg/day. In a Chinese study, three possible clozapine UMs (all male smokers) were identified. The clozapine minimum therapeutic dose estimated with trough steady-state concentrations >150 ng/ml was: 1) 625 mg/day, based on a mean of 20 concentrations in Case 3; 2) 673 mg/day, based on a mean of 4 concentrations in Case 4; and 3) 648 mg/day, based on a mean of 11 concentrations in Case 5. Based on these limited studies, clozapine UMs during weak induction may account for 1-2% of clozapine-treated patients of European ancestry and <1% of those of Asian ancestry. A clozapine-to-norclozapine ratio <0.5 should not be used to identify clozapine UMs., Competing Interests: Declaration of competing interest GS has received speaker/consultation fees from HLS Therapeutics and Thermo Fisher. SRC received speaker/consultation fees from: Janssen-Cilag, Lundbeck, Otsuka and Servier and research funding from Janssen-Cilag, Lundbeck, Otsuka and Gilead. SH Kim has received research grants from Janssen and Dongwha. HT has received grants from Daiichi Sankyo and Novartis Pharma; speaker's fees from EA. Pharma, Eisai, Kyowa, Janssen, Lundbeck, Meiji Seika Pharma, MSD, Otsuka, Sumitomo Pharma, Takeda, and Yoshitomiyakuhin; and consulting fees from Janssen, Mitsubishi Tanabe Pharma, Ono, and Sumitomo Pharma. CUC has been a consultant and/or advisor to or has received honoraria from: AbbVie, Acadia, Alkermes, Allergan, Angelini, Aristo, Boehringer-Ingelheim, Cardio Diagnostics, Cerevel, CNX Therapeutics, Compass Pathways, Darnitsa, Denovo, Gedeon Richter, Hikma, Holmusk, IntraCellular Therapies, Janssen/J&J, Karuna, LB Pharma, Lundbeck, MedAvante-ProPhase, MedInCell, Merck, Mindpax, Mitsubishi Tanabe Pharma, Mylan, Neurocrine, Newron, Noven, Novo Nordisk, Otsuka, Pharmabrain, PPD Biotech, Recordati, Relmada, Reviva, Rovi, Seqirus, SK Life Science, Sunovion, Sun Pharma, Supernus, Takeda, Teva, and Viatris. He provided expert testimony for Janssen and Otsuka. He served on a Data Safety Monitoring Board for Compass Pathways, Denovo, Lundbeck, Relmada, Reviva, Rovi, Supernus, and Teva. He has received grant support from Janssen and Takeda. He received royalties from UpToDate and is also a stock option holder of Cardio Diagnostics, Mindpax, LB Pharma and Quantic. In the last 3 years, the remaining authors report no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Study Design: Systematic Review and Meta-Analysis., Objective: Identify the incidence, mechanism of injury, investigations, management, and outcomes of Vertebral Artery Injury (VAI) after cervical spine trauma., Methods: A systematic review and meta-analysis were conducted in accordance with the PRISMA guidelines (PROSPERO-ID CRD42021295265). Three databases were searched (PubMed, SCOPUS, Google Scholar, CINAHL PLUS). Incidence of VAI, investigations to diagnose (Computed Tomography Angiography, Digital Subtraction Angiography, Magnetic Resonance Angiography), stroke incidence, and management paradigms (conservative, antiplatelets, anticoagulants, surgical, endovascular treatment) were delineated. Incidence was calculated using pooled proportions random effects meta-analysis., Results: A total of 44 studies were included (1777 patients). 20-studies (n = 503) included data on trauma type; 75.5% (n = 380) suffered blunt trauma and 24.5% (n = 123) penetrating. The overall incidence of VAI was .95% (95% CI 0.65-1.29). From the 16 studies which reported data on outcomes, 8.87% (95% CI 5.34- 12.99) of patients with VAI had a posterior stroke. Of the 33 studies with investigation data, 91.7% (2929/3629) underwent diagnostic CTA; 7.5% (242/3629) underwent MRA and 3.0% (98/3629) underwent DSA. Management data from 20 papers (n = 475) showed 17.9% (n = 85) undergoing conservative therapy, anticoagulation in 14.1% (n = 67), antiplatelets in 16.4% (n = 78), combined therapy in 25.5% (n = 121) and the rest (n = 124) managed using surgical and endovascular treatments., Conclusion: VAI in cervical spine trauma has an approximate posterior circulation stroke risk of 9%. Optimal management paradigms for the prevention and management of VAI are yet to be standardized and require further research., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

This article describes the rationale, aims, and methodology of the Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ). This is the largest international collaboration to date that will develop algorithms to predict trajectories and outcomes of individuals at clinical high risk (CHR) for psychosis and to advance the development and use of novel pharmacological interventions for CHR individuals. We present a description of the participating research networks and the data processing analysis and coordination center, their processes for data harmonization across 43 sites from 13 participating countries (recruitment across North America, Australia, Europe, Asia, and South America), data flow and quality assessment processes, data analyses, and the transfer of data to the National Institute of Mental Health (NIMH) Data Archive (NDA) for use by the research community. In an expected sample of approximately 2000 CHR individuals and 640 matched healthy controls, AMP SCZ will collect clinical, environmental, and cognitive data along with multimodal biomarkers, including neuroimaging, electrophysiology, fluid biospecimens, speech and facial expression samples, novel measures derived from digital health technologies including smartphone-based daily surveys, and passive sensing as well as actigraphy. The study will investigate a range of clinical outcomes over a 2-year period, including transition to psychosis, remission or persistence of CHR status, attenuated positive symptoms, persistent negative symptoms, mood and anxiety symptoms, and psychosocial functioning. The global reach of AMP SCZ and its harmonized innovative methods promise to catalyze the development of new treatments to address critical unmet clinical and public health needs in CHR individuals., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

Background: Multimodal modeling that combines biological and clinical data shows promise in predicting transition to psychosis in individuals who are at ultra-high risk. Individuals who transition to psychosis are known to have deficits at baseline in cognitive function and reductions in gray matter volume in multiple brain regions identified by magnetic resonance imaging., Methods: In this study, we used Cox proportional hazards regression models to assess the additive predictive value of each modality-cognition, cortical structure information, and the neuroanatomical measure of brain age gap-to a previously developed clinical model using functioning and duration of symptoms prior to service entry as predictors in the Personal Assessment and Crisis Evaluation (PACE) 400 cohort. The PACE 400 study is a well-characterized cohort of Australian youths who were identified as ultra-high risk of transitioning to psychosis using the Comprehensive Assessment of At Risk Mental States (CAARMS) and followed for up to 18 years; it contains clinical data (from N = 416 participants), cognitive data (n = 213), and magnetic resonance imaging cortical parameters extracted using FreeSurfer (n = 231)., Results: The results showed that neuroimaging, brain age gap, and cognition added marginal predictive information to the previously developed clinical model (fraction of new information: neuroimaging 0%-12%, brain age gap 7%, cognition 0%-16%)., Conclusions: In summary, adding a second modality to a clinical risk model predicting the onset of a psychotic disorder in the PACE 400 cohort showed little improvement in the fit of the model for long-term prediction of transition to psychosis., (Copyright © 2023 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Hidradenitis suppurativa (HS) is a chronic, inflammatory skin condition that causes pain and discomfort in various body regions. This review explores the comparative effectiveness of two surgical techniques, namely, surgical deroofing and carbon dioxide laser therapy, in managing symptomatic HS, particularly in patients with Hurley stage I-III disease. We conducted a systematic literature search on PubMed and ClinicalTrials.gov. The clinical evidence suggests that surgical deroofing and carbon dioxide laser treatment are effective strategies for managing symptomatic HS. However, a comprehensive analysis of 1,120 patients indicates a higher recurrence rate with surgical deroofing. Further investigation into short-term and long-term follow-up data revealed comparable recurrence-free rates within 12 months post-procedure. Beyond 12 months, carbon dioxide laser treatment exhibited slightly higher recurrence-free rates, which necessitate more extensive studies for validation due to the limited sample size. In addition, surgical deroofing demonstrated quicker healing times, while carbon dioxide laser therapy showcased varying timelines, with primary closure after laser excision presenting a two-week healing time. Both procedures reported high patient satisfaction, emphasizing the need for personalized treatment decisions. Therefore, further research is essential to evaluate the efficacy of each treatment modality considering individual patient profiles and disease severity. It will benefit individuals affected by HS, leading to better health outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Clark et al.)

Individual and societal factors influencing the formation of long-term recreational exercise habits during the transition from adolescence to young adulthood are not well explored. Using data from the Longitudinal Survey of Australian Youth (LSAY), a population-representative cohort study of Young People followed from age 15 to 25, we aimed to (1) model longitudinal recreational exercise trajectories from age 16 to 24, (2) examine predictors at age 15 of entering these trajectories, and (3) explore the association between the trajectories and health, mental health and educational achievement outcomes measured at the final study wave (age 25). Self-reported recreational exercise frequency data from 9353 LSAY participants were analysed using group-based trajectory modelling. We modelled the evolution of two patterns of recreational exercise behaviour: daily exercise, as per public health guidelines (Model 1); and at least once weekly exercise (Model 2). Model 1 trajectories were guideline-adherent exercisers (17.9% of the sample), never guideline exercisers (27.5%), guideline drop-outs (15.2%) and towards guideline (39.4%); Model 2 trajectories were weekly exercise (69.5% of the sample), decreasing (17.4%), increasing (4.8%), and infrequent (8.3%). For both models, at age 15, trajectory membership was predicted by gender, self-efficacy, time spent participating in sport, time spent watching TV, parental socioeconomic status, and academic literacy. At age 25, people in the guideline-adherent exerciser trajectory (model 1) reported better general health relative to other trajectories, Those in the weekly exerciser trajectory (model 2) had better general health and reduced rates of psychological distress, were happier with life and were more optimistic for the future relative to participants in less than weekly trajectory groups. Exercise-promoting interventions for Young People should specifically address the needs of females, people with low self-efficacy, reluctant exercisers, higher academic achievers, and those experiencing socioeconomic disadvantage., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Morgan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Lithium is the gold standard treatment for bipolar disorder (BD). However, its mechanism of action is incompletely understood, and prediction of treatment outcomes is limited. In our previous multi-omics study of the Pharmacogenomics of Bipolar Disorder (PGBD) sample combining transcriptomic and genomic data, we found that focal adhesion, the extracellular matrix (ECM), and PI3K-Akt signaling networks were associated with response to lithium. In this study, we replicated the results of our previous study using network propagation methods in a genome-wide association study of an independent sample of 2039 patients from the International Consortium on Lithium Genetics (ConLiGen) study. We identified functional enrichment in focal adhesion and PI3K-Akt pathways, but we did not find an association with the ECM pathway. Our results suggest that deficits in the neuronal growth cone and PI3K-Akt signaling, but not in ECM proteins, may influence response to lithium in BD., (© 2024. The Author(s).)

Background: Clozapine is associated with the risk of serious neutropenia. However, this risk might decrease over time, meaning that indefinite absolute neutrophil count (ANC) monitoring could be unnecessary. We aimed to determine the epidemiology and timing of clozapine-associated neutropenia outcomes, to investigate variables that might contribute to the odds of neutropenia, and to determine risk of competing neutropenic events during clozapine treatment., Methods: We performed a retrospective analysis of the Australian and New Zealand Viatris Pharmacovigilance system (one of two monitoring databases for these two countries) between June 6, 1990, and Oct 25, 2022. Patients were excluded from analysis if they commenced clozapine before 1990, did not have a haematology test within 2 weeks of commencement date, or had no follow-up. We measured minor neutropenia (ANC 1·0-1·5 × 10 9 per L) and serious neutropenia (ANC <1·0 × 10 9 per L) leading to cessation of clozapine within 6 weeks of the neutropenic event. We determined the rates of minor and serious neutropenia and calculated odds ratios (ORs) for the likelihood of neutropenia leading to cessation. For serious neutropenia leading to cessation, we used time-to-event to calculate rolling weekly averages and to perform competing risk analysis of outcomes using Cox proportional hazards models and a Fine-Gray subdistribution hazards regression model. For the subset of data where information on previous clozapine use was available, we did an analysis for participants who did and did not have previous clozapine exposure., Findings: We included 26 630 people, with 2·6 million ANC values. Within the total cohort, 17 585 people (66%) were male, 9025 (33·9%) female, and 20 (0·1%) other gender, and the mean age was 36·1 years (SD 13·7). We did not have data on race or ethnicity. Of the 26 630 people taking clozapine, 1146 (4·3%) had minor neutropenia, 313 (1·2%) had serious neutropenia leading to cessation, and 223 (0·8%) had serious neutropenia unrelated to clozapine without cessation. In people with no previous exposure to clozapine (n=15 973), the cumulative incidence of serious neutropenia leading to cessation was 0·9% at 18 weeks and 1·4% at 2 years; the weekly incidence rate for serious neutropenia leading to cessation peaked at 9 weeks (0·128%) and fell to a rolling average weekly incidence of 0·001% by 2 years. For minor neutropenia, the cumulative incidence was 1·7% at 18 weeks and 3·5% at 2 years; the weekly incidence rate peaked at 9 weeks (0·218%) and fell to a stable rolling average of 0·01%. The median time to a serious neutropenic event leading to cessation was 17 weeks (IQR 9·96-102). Previous clozapine exposure reduced the risk of serious neutropenia leading to cessation (OR 0·19, 95% CI 0·12-0·31; p <0·0001)., Interpretation: Most serious neutropenia leading to clozapine cessation occurs within 18 weeks of treatment and becomes negligible after 2 years. Weekly haematological monitoring after the first 18 weeks could be safely reduced to once every 4 weeks and ceased after 2 years unless clinically indicated. Clozapine retrial after interruption with 2 cumulative years of unremarkable testing might not require further haematological monitoring. A serious neutropenia ANC threshold of ≤1·0 × 10 9 per L could be used in more jurisdictions., Funding: None., Competing Interests: Declaration of interests NW has received speaker fees from Ostuka, Lundbeck, and Janssen. SRC has received grants and served as consultant, adviser, or Continuing Medical Education speaker for the following entities: Otsuka Australia, Lundbeck Australia, Janssen-Cilag Australia, and Servier Australia. SK reports receiving speaker fees from Lundbeck. KN, NM, SE-P, HM, and DS declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental health disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li + PGS ) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li + PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi + Gen: N = 2367) and replicated in the combined PsyCourse (N = 89) and BipoLife (N = 102) studies. The associations of Li + PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P < 0.05. Li + PGS was positively associated with lithium treatment response in the ConLi + Gen cohort, in both the categorical (P = 9.8 × 10 - 12 , R 2  = 1.9%) and continuous (P = 6.4 × 10 - 9 , R 2  = 2.6%) outcomes. Compared to bipolar patients in the 1 st decile of the risk distribution, individuals in the 10 th decile had 3.47-fold (95%CI: 2.22-5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P = 3.9 × 10 - 4 , R 2  = 0.9%), but not for the continuous outcome (P = 0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li + PGS may be useful in the development of pharmacogenomic testing strategies by enabling a classification of bipolar patients according to their response to treatment., (© 2023. The Author(s).)

Objective: Major depressive disorder (MDD) remains difficult to treat, with many patients resistant to existing treatments or experiencing relapse. Cognitive dysfunction is associated with more severe clinical outcomes. Vortioxetine has shown efficacy in remediating depression-associated cognitive impairment. Anti-inflammatory augmentation of antidepressants is a new strategy in treating depression and has not previously been assessed for effects on cognition in depression., Methods: Exploratory analyses were performed on secondary outcome cognitive data from the PREDDICT parallel-group, randomized, double-blind, placebo-controlled trial at the University of Adelaide (Australia). Participants (N = 119) with MDD (validated with Mini-International Neuropsychiatric Interview for DSM-IV ) were treated with vortioxetine and celecoxib or vortioxetine and placebo for 6 weeks between December 2017 and April 2020. Measures included objective cognition composite scores (Choice Reaction Time, N-Back, Digit Symbol Substitution Test, Trail Making Task Part B), subjective cognition scores (Perceived Deficits Questionnaire), and global cognition composite scores (combined objective and subjective scores) derived from the THINC integrated tool (THINC-it). High-sensitivity C-reactive protein (hsCRP) measured at baseline and week 6 was tested for a predictive relationship with cognitive outcomes., Results: Cognition composite scores demonstrated improvement by week 6 in both treatment groups. However, there was no significant interaction between change over time and treatment group. HsCRP did not have a significant relationship with any tested cognition measures., Conclusions: Both treatment groups showed a reduction in depression-associated cognitive impairment. No superior clinical effect was reported for the add-on celecoxib group. HsCRP was modulated by neither vortioxetine nor add-on celecoxib., Trial Registration: ANZCTR identifier: ACTRN12617000527369., (© Copyright 2023 Physicians Postgraduate Press, Inc.)

Background: The efficacy of digital meditation is well established. However, the extent to which the benefits remain after 12 weeks in real-world settings remains unknown. Additionally, findings related to dosage and practice habits have been mixed, and the studies were conducted on small and homogeneous samples and used a limited range of analytical procedures and meditation techniques. Findings related to the predictors of adherence are also lacking and may help inform future meditators and meditation programs on how to best structure healthy sustainable practices., Objective: This study aimed to measure outcome change across a large and globally diverse population of meditators and meditations in their naturalistic practice environments, assess the dose-response relationships between practice habits and outcome change, and identify predictors of adherence., Methods: We used ecological momentary assessment to assess participants' well-being over a 14-month period. We engineered outcomes related to the variability of change over time (equanimity) and recovery following a drop in mood (resilience) and established the convergent and divergent validity of these outcomes using a validated scale. Using linear mixed-effects and generalized additive mixed-effects models, we modeled outcome changes and patterns of dose-response across outcomes. We then used logistic regression to study the practice habits of participants in their first 30 sessions to derive odds ratios of long-term adherence., Results: Significant improvements were observed in all outcomes (P<.001). Generalized additive mixed models revealed rapid improvements over the first 50-100 sessions, with further improvements observed until the end of the study period. Outcome change corresponded to 1 extra day of improved mood for every 5 days meditated and half-a-day-faster mood recovery compared with baseline. Overall, consistency of practice was associated with the largest outcome change (4-7 d/wk). No significant differences were observed across session lengths in linear models (mood: P=.19; equanimity: P=.10; resilience: P=.29); however, generalized additive models revealed significant differences over time (P<.001). Longer sessions (21-30 min) were associated with the largest magnitude of change in mood from the 20th session onward and fewer sessions to recovery (increased resilience); midlength sessions (11-20 min) were associated with the largest decreases in recovery; and mood stability was similar across session lengths (equanimity). Completing a greater variety of practice types was associated with significantly greater improvements across all outcomes. Adhering to a long-term practice was best predicted by practice consistency (4-7 d/wk), a morning routine, and maintaining an equal balance between interoceptive and exteroceptive meditations., Conclusions: Long-term real-world digital meditation practice is effective and associated with improvements in mood, equanimity, and resilience. Practice consistency and variety rather than length best predict improvement. Long-term sustainable practices are best predicted by consistency, a morning routine, and a practice balanced across objects of focus that are internal and external to the body., (©Micah Cearns, Scott R Clark. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 19.09.2023.)

Low-grade inflammation is considered as a pathophysiological mechanism in a subtype of patients with major depressive disorder (MDD). Anti-inflammatory drugs have shown efficacy in treating MDD. However, it remains unclear how to identify suitable patients for anti-inflammatory treatment of depression. This study investigates the predictive value of pre-treatment high-sensitivity C-Reactive Protein (hsCRP) stratification on the outcome of celecoxib augmentation of vortioxetine. The PREDDICT study was conducted as a randomized, double-blind, placebo-controlled 6-week trial on augmentation of vortioxetine with celecoxib between December 2017 and April 2020 at the University of Adelaide (Australia). The present analysis focusses on the question of whether the pre-treatment hsCRP measurement and stratification of patients to depression with inflammation (hsCRP >3 mg/L) or without inflammation (hsCRP ≤3 mg/L) has an impact on the outcome of anti-inflammatory treatment with celecoxib. A total of n = 119 mostly treatment-resistant MDD patients with moderate to severe symptomatology were recruited in the trial. There was no effect of treatment group (celecoxib or placebo), pre-treatment hsCRP strata (with/without inflammation), or interaction between the two terms on treatment outcome. The results of the current analysis do not support the hypothesis that pre-treatment hsCRP level is predictive for response to anti-inflammatory treatment with celecoxib in MDD patients. Further research is needed to identify appropriate biomarkers for the prediction of anti-inflammatory treatment outcome in depression. CLINICAL TRIALS REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12617000527369p. Registered on 11 April 2017, http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12617000527369p., (© 2023 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.)

The concept of anomalous self-experience, also termed Self-Disorder, has attracted both clinical and research interest, as empirical studies suggest such experiences specifically aggregate in and are a core feature of schizophrenia spectrum disorders. A comprehensive neurophenomenological understanding of Self-Disorder may improve diagnostic and therapeutic practice. This systematic review aims to evaluate anatomical, physiological, and neurocognitive correlates of Self-Disorder (SD), considered a core feature of Schizophrenia Spectrum Disorders (SSDs), towards developing a neurophenomenological understanding. A search of the PubMed database retrieved 285 articles, which were evaluated for inclusion using PRISMA guidelines. Non-experimental studies, studies with no validated measure of Self-Disorder, or those with no physiological variable were excluded. In total, 21 articles were included in the review. Findings may be interpreted in the context of triple-network theory and support a core dysfunction of signal integration within two anatomical components of the Salience Network (SN), the anterior insula and dorsal anterior cingulate cortex, which may mediate connectivity across both the Default Mode Network (DMN) and Fronto-Parietal Network (FPN). We propose a theoretical Triple-Network Model of Self-Disorder characterized by increased connectivity between the Salience Network (SN) and the DMN, increased connectivity between the SN and FPN, decreased connectivity between the DMN and FPN, and increased connectivity within both the DMN and FPN. We go on to describe translational opportunities for clinical practice and provide suggestions for future research.

Purpose/background: A recent article in this journal presented a US perspective regarding the modernization of clozapine prescription and proposed an escape from the long shadow cast by agranulocytosis., Methods: Here, an international group of collaborators discusses a point of view complementary to the US view by focusing on worldwide outcomes of clozapine usage that may be uneven in terms of frequency of clozapine adverse drug reactions., Findings/results: Studies from the Scandinavian national registries (Finland and Denmark) did not find increased mortality in clozapine patients or any clear evidence of the alleged toxicity of clozapine. Data on clozapine-associated fatal outcomes were obtained from 2 recently published pharmacovigilance studies and from the UK pharmacovigilance database. A pharmacovigilance study focused on physician reports to assess worldwide lethality of drugs from 2010 to 2019 found 968 clozapine-associated fatal outcomes in the United Kingdom. Moreover, the United Kingdom accounted for 55% (968 of 1761) of worldwide and 90% (968 of 1073) of European fatal clozapine-associated outcomes. In a pharmacovigilance study from the UK database (from 2008 to 2017), clozapine was associated with 383 fatal outcomes/year including all reports from physicians and nonphysicians. From 2018 to 2021, UK clozapine-associated fatal outcomes increased to 440/year., Implications/conclusions: The interpretation of fatal outcomes in each country using pharmacovigilance databases is limited and only allows gross comparisons; even with those limitations, the UK data seem concerning. Pneumonia and myocarditis may be more important than agranulocytosis in explaining the uneven distribution of fatal outcomes in clozapine patients across countries., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Study Objectives: To assess the association between psychotropic medications and sleep microstructure in large community-based cohorts of older people., Methods: We analyzed overnight polysomnograms of 381 women from the Study of Osteoporotic Fractures (SOF) and 2,657 men from the Osteoporotic Fractures in Men Sleep Study (MrOS), who either used no psychotropic medication (n = 2,819), only benzodiazepines (n = 112), or only selective serotonin reuptake inhibitors (SSRI) (n = 107). Sleep microstructure (cyclic alternating pattern, CAP) was compared between the no medication group and psychotropic medication groups using the Mann-Whitney U test. Significant differences were investigated using multivariable linear regression adjusted for confounders., Results: CAP rate, arousal index, apnea-hypopnea index, and the frequency of slow, low-amplitude electroencephalography activation phases were significantly lower in MrOS participants using benzodiazepines than participants not taking psychotropic medication. SSRI users in MrOS experienced no altered sleep microstructure compared to those with no psychotropic use. SOF participants using benzodiazepines did not show similar associations with sleep microstructure. However, SSRI users from SOF had a significantly higher frequency of rapid, high-amplitude electroencephalography activation phases (A2 + 3) and periodic limb-movement index than participants not taking psychotropic medication. Multivariable linear regression adjusted for demographic, lifestyle, mood disorders, and health variables indicated additional significant associations between benzodiazepine usage and CAP rate and A2 + 3 index, respectively, in older men, and between CAP rate and SSRI usage in older women., Conclusions: We identified significant associations between sleep microstructure and psychotropic drugs in MrOS and SOF, highlighting the importance of comprehensive sleep analysis, including CAP. Our results may improve understanding of the differences in sleep-wake mechanisms based on psychotropic usage., Clinical Trial Registration: Registry: ClinicalTrials.gov; Title: Outcomes of Sleep Disorders in Older Men; Identifier: NCT00070681; URL: https://clinicaltrials.gov/ct2/show/record/NCT00070681., Citation: Hartmann S, Parrino L, Ensrud K, et al. Association between psychotropic medication and sleep microstructure: evidence from large population studies. J Clin Sleep Med . 2023;19(3):581-589., (© 2023 American Academy of Sleep Medicine.)

Introduction: Lateral lumbar fusion via the trans-psoas approach is popular in adult deformity reconstruction. To overcome its limitations (neurological damage to the plexus and lack of applicability to the lumbosacral junction), a modified anterior-to-psoas (ATP) approach has been described and used., Research Question: To investigate the results of ATP lumbar and lumbosacral fusion, in a cohort of adult patients treated with combined anteroposterior approaches for adult spinal deformity (ASD)., Materials and Methods: ASD patients surgically treated at two tertiary spinal centres were followed up. Forty patients were treated with combined ATP and posterior surgery: 11 with open lumbar lateral interbody-fusions (lumbotomy LLIF) and 29 with lesser invasive oblique lateral interbody-fusions (OLIF). Preoperative demographics, aetiology, clinical characteristics, and spinopelvic parameters were comparable between the two cohorts., Results: At a minimum 2-year follow-up, both cohorts showed significant improvements in patient reported outcome measures (PROMs), i.e. Visual Analogue Scale and Core Outcome Measures Index, as well as radiological parameters, with no significant differences based on the type of surgical approach. No significant differences were found in major (P ​= ​0.457) and minor (P ​= ​0.071) complications between the two cohorts., Discusson and Conclusion: Anterolateral lumbar interbody fusions, whether performed via a direct or oblique approach, proved to be safe and effective adjuvants to posterior surgery in patients with ASD. No significant complication differences were noted between techniques. In addition, the anterior-to-psoas approaches limited the risks of post-operative pseudoarthrosis by providing solid anterior support to lumbar and lumbosacral segments, demonstrating a positive impact on PROMS., Competing Interests: Simon Clark and Marco Teli declare signed affiliations to Medtronic UK for educational purposes. The other authors have no relevant financial or non-financial interests to disclose., (© 2023 The Authors.)

Introduction: The UK Biobank cognitive assessment data has been a significant resource for researchers looking to investigate predictors and modifiers of cognitive abilities and associated health outcomes in the general population. Given the diverse nature of this data, researchers use different approaches - from the use of a single test to composing the general intelligence score, g , across the tests. We argue that both approaches are suboptimal - one being too specific and the other one too general - and suggest a novel multifactorial solution to represent cognitive abilities., Methods: Using a combined Exploratory Factor (EFA) and Exploratory Structural Equation Modeling Analyses (ESEM) we developed a three-factor model to characterize an underlying structure of nine cognitive tests selected from the UK Biobank using a Cattell-Horn-Carroll framework. We first estimated a series of probable factor solutions using the maximum likelihood method of extraction. The best solution for the EFA-defined factor structure was then tested using the ESEM approach with the aim of confirming or disconfirming the decisions made., Results: We determined that a three-factor model fits the UK Biobank cognitive assessment data best. Two of the three factors can be assigned to fluid reasoning (Gf) with a clear distinction between visuospatial reasoning and verbal-analytical reasoning . The third factor was identified as a processing speed (Gs) factor., Discussion: This study characterizes cognitive assessment data in the UK Biobank and delivers an alternative view on its underlying structure, suggesting that the three factor model provides a more granular solution than g that can further be applied to study different facets of cognitive functioning in relation to health outcomes and to further progress examination of its biological underpinnings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ciobanu, Stankov, Ahmed, Heathcote, Clark and Aidman.)

Introduction: The ability to perform optimally under pressure is critical across many occupations, including the military, first responders, and competitive sport. Despite recognition that such performance depends on a range of cognitive factors, how common these factors are across performance domains remains unclear. The current study sought to integrate existing knowledge in the performance field in the form of a transdisciplinary expert consensus on the cognitive mechanisms that underlie performance under pressure., Methods: International experts were recruited from four performance domains [(i) Defense; (ii) Competitive Sport; (iii) Civilian High-stakes; and (iv) Performance Neuroscience]. Experts rated constructs from the Research Domain Criteria (RDoC) framework (and several expert-suggested constructs) across successive rounds, until all constructs reached consensus for inclusion or were eliminated. Finally, included constructs were ranked for their relative importance., Results: Sixty-eight experts completed the first Delphi round, with 94% of experts retained by the end of the Delphi process. The following 10 constructs reached consensus across all four panels (in order of overall ranking): (1) Attention; (2) Cognitive Control-Performance Monitoring; (3) Arousal and Regulatory Systems-Arousal; (4) Cognitive Control-Goal Selection, Updating, Representation, and Maintenance; (5) Cognitive Control-Response Selection and Inhibition/Suppression; (6) Working memory-Flexible Updating; (7) Working memory-Active Maintenance; (8) Perception and Understanding of Self-Self-knowledge; (9) Working memory-Interference Control, and (10) Expert-suggested-Shifting., Discussion: Our results identify a set of transdisciplinary neuroscience-informed constructs, validated through expert consensus. This expert consensus is critical to standardizing cognitive assessment and informing mechanism-targeted interventions in the broader field of human performance optimization., Competing Interests: VM was employed by Mindflex Group Ltd. JG is a stockholder in MAP Biotech Pty Ltd. SC has received speakers fees Janssen-Cilag Australia, Lundbeck Otsuka Australia, Servier Australia; Investigator Initiated research funding Janssen-Cilag Australia; Lundbeck Otsuka Australia; Advisory Boards Lundbeck Otsuka Australia. AT has received research funding from BHP, Rio Tinto, and Shell. SD is a Member of the Board of Advisors Eisai Australia Pty Ltd. MY has received payments in relation to court-, expert witness-, and/or expert review-reports. JD was employed by Florida Maxima Corporation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Albertella, Kirkham, Adler, Crampton, Drummond, Fogarty, Gross, Zaichkowsky, Andersen, Bartone, Boga, Bond, Brunyé, Campbell, Ciobanu, Clark, Crane, Dietrich, Doty, Driskell, Fahsing, Fiore, Flin, Funke, Gatt, Hancock, Harper, Heathcote, Heaton, Helsen, Hussey, Jackson, Khemlani, Killgore, Kleitman, Lane, Loft, MacMahon, Marcora, McKenna, Meijen, Moulton, Moyle, Nalivaiko, O’Connor, O’Conor, Patton, Piccolo, Ruiz, Schücker, Smith, Smith, Sobrino, Stetz, Stewart, Taylor, Tucker, van Stralen, Vickers, Visser, Walker, Wiggins, Williams, Wong, Aidman and Yücel.)

Understanding the genomic architecture and molecular mechanisms of cognitive functioning in healthy individuals is critical for developing tailored interventions to enhance cognitive functioning, as well as for identifying targets for treating impaired cognition. There has been substantial progress in uncovering the genetic composition of the general cognitive ability (g). However, there is an ongoing debate whether executive functioning (EF)-another key predictor of cognitive health and performance, is separable from general g. To provide an analytical review on existing findings on genetic influences on the relationship between g and EF, we re-analysed a subset of genome-wide association studies (GWAS) from the GWAS catalogue that used measures of g and EF as outcomes in non-clinical populations. We identified two sets of single nucleotide polymorphisms (SNPs) associated with g (1,372 SNPs across 12 studies), and EF (300 SNPs across 5 studies) at p<5x10-6. A comparative analysis of GWAS-identified g and EF SNPs in high linkage disequilibrium (LD), followed by pathway enrichment analyses suggest that g and EF are overlapping but separable at genetic variant and molecular pathway levels, however more evidence is required to characterize the genetic overlap/distinction between the two constructs. While not without limitations, these findings may have implications for navigating further research towards translatable genetic findings for cognitive remediation, enhancement, and augmentation., Competing Interests: The authors have declared that no competing interests exist.

Over the last decade, there has been an irreversible shift from hydrocarbon exploration towards carbon storage, low-carbon energy generation and hydrogen exploration. Whilst basin modelling techniques may be used to predict the migration of hydrocarbons through sedimentary basins on geological timescales, there remains little understanding of how fluids behave at the basin scale on present-day timescales. We apply the Darcy flow equation to present an algorithm to determine the basin-scale mobilities and maximum vertical velocity, [Formula: see text], of CO[Formula: see text], methane, hydrogen and hydrocarbons with depth for sandstone and carbonate. [Formula: see text] for CO[Formula: see text] and methane are on scales of m/year, whilst values for hydrocarbon fluids are an order of magnitude smaller than for other fluids. Our results indicate that the fluid mobility of subsurface CO[Formula: see text] may be sensitive to surface and near-surface temperature variations. [Formula: see text] for hydrogen is approximately 2-10 times greater than hydrocarbon fluids, yielding important consequences for the future use of basin modelling software for determining hydrogen migration for exploration and storage., (© 2022. The Author(s).)

Time series data from environmental monitoring stations are often analysed with machine learning methods on an individual basis, however recent advances in the machine learning field point to the advantages of incorporating multiple related time series from the same monitoring network within a 'global' model. This approach provides the opportunity for larger training data sets, allows information to be shared across the network, leading to greater generalisability, and can overcome issues encountered in the individual time series, such as small datasets or missing data. We present a case study involving the analysis of 165 time series from groundwater monitoring wells in the Namoi region of Australia. Analyses of the multiple time series using a variety of different aggregations are compared and contrasted (with single time series, subsets, and all of the time series together), using variations of the multilayer perceptron (MLP), self-organizing map (SOM), long short-term memory (LSTM), and a recently developed LSTM extension (DeepAR) that incorporates autoregressive terms and handles multiple time series. The benefits, in terms of prediction performance, of these various approaches are investigated, and challenges such as differing measurement frequencies and variations in temporal patterns between the time series are discussed. We conclude with some discussion regarding recommendations and opportunities associated with using networks of environmental data to help inform future resource-related decision making.

Background: No biological treatment has been firmly established for the at-risk stage of psychotic disorder. In this study we aim to test if subthreshold psychotic symptoms can be effectively treated with cannabidiol (CBD), a non-psychoactive compound of the plant Cannabis sativa. The question has taken on increased importance in the wake of evidence questioning both the need and efficacy of specific pharmacological interventions in the ultra-high risk (UHR) for psychosis group., Methods: Three-arm randomized controlled trial of 405 patients (135 per arm) aged 12-25 years who meet UHR for psychosis criteria. The study includes a 6-week lead-in phase during which 10% of UHR individuals are expected to experience symptom remission. Participants will receive CBD (per oral) at doses 600 or 1000 mg per day (fixed schedule) for 12 weeks. Participants in the third arm of the trial will receive matching placebo capsules. Primary outcome is severity of positive psychotic symptoms as measured by the Comprehensive Assessment of At-Risk Mental States at 12 weeks. We hypothesize that CBD will be significantly more effective than placebo in improving positive psychotic symptoms in UHR patients. All participants will also be followed up 6 months post baseline to evaluate if treatment effects are sustained., Conclusion: This paper reports on the rationale and protocol of the Cannabidiol for At Risk for psychosis Youth (CanARY) study. This study will test CBD for the first time in the UHR phase of psychotic disorder., (© 2021 John Wiley & Sons Australia, Ltd.)