Cognitive strengths in first episode psychosis: a thematic analysis of clinicians' perspectives.

BACKGROUND: Cognitive deficits are associated with poor functional outcomes in individuals recovering from a first episode of psychosis (FEP). Existing treatments that target cognitive deficits in FEP may enhance cognitive function, but improvements to real-world functioning are less consistent. Furthermore, these treatments may not adequately address the personal recovery goals of young people attending FEP services. A novel cognitive strengths-based approach may overcome these shortcomings. METHODS: This qualitative study used semi-structured interviews to explore clinicians' (N = 12) perspectives toward the potential development of a cognitive strengths-based assessment or treatment in FEP. The interviews were analysed using thematic analysis. RESULTS: Five higher-order themes emerged: (1) pro-strengths attitude despite unfamiliarity and minimal use, (2) default to a cognitive deficit lens, (3) potential benefits of a cognitive strengths approach, (4) potential risks and barriers, and (5) considerations for successful implementation. While clinicians acknowledged their current deficit approach, they supported implementing a cognitive strengths assessment or treatment and highlighted their potential benefits for the personal recovery needs of young people with FEP. CONCLUSIONS: These findings suggest that a deficit-focused approach to cognitive function amongst clinicians may be common practice in FEP services. Nevertheless, a cognitive strengths approach was viewed favourably by clinicians and may represent a novel method of supporting personal recovery. Thus, the design and implementation of a cognitive strengths approach may be worthwhile. Future exploration of other stakeholder perspectives, such as young people with FEP, is essential.

Levetiracetam versus phenytoin for second-line treatment of convulsive status epilepticus in children (ConSEPT): an open-label, multicentre, randomised controlled trial.

BACKGROUND: Phenytoin is the current standard of care for second-line treatment of paediatric convulsive status epilepticus after failure of first-line benzodiazepines, but is only effective in 60% of cases and is associated with considerable adverse effects. A newer anticonvulsant, levetiracetam, can be given more quickly, is potentially more efficacious, and has a more tolerable adverse effect profile. We aimed to determine whether phenytoin or levetiracetam is the superior second-line treatment for paediatric convulsive status epilepticus. METHODS: ConSEPT was an open-label, multicentre, randomised controlled trial conducted in 13 emergency departments in Australia and New Zealand. Children aged between 3 months and 16 years, with convulsive status epilepticus that failed first-line benzodiazepine treatment, were randomly assigned (1:1) using a computer-generated permuted block (block sizes 2 and 4) randomisation sequence, stratified by site and age (≤5 years, >5 years), to receive 20 mg/kg phenytoin (intravenous or intraosseous infusion over 20 min) or 40 mg/kg levetiracetam (intravenous or intraosseous infusion over 5 min). The primary outcome was clinical cessation of seizure activity 5 min after the completion of infusion of the study drug. Analysis was by intention to treat. This trial is registered with the Australian and New Zealand Clinical Trials Registry, number ACTRN12615000129583. FINDINGS: Between March 19, 2015, and Nov 29, 2017, 639 children presented to participating emergency departments with convulsive status epilepticus; 127 were missed, and 278 did not meet eligibility criteria. The parents of one child declined to give consent, leaving 233 children (114 assigned to phenytoin and 119 assigned to levetiracetam) in the intention-to-treat population. Clinical cessation of seizure activity 5 min after completion of infusion of study drug occurred in 68 (60%) patients in the phenytoin group and 60 (50%) patients in the levetiracetam group (risk difference -9·2% [95% CI -21·9 to 3·5]; p=0·16). One participant in the phenytoin group died at 27 days because of haemorrhagic encephalitis; this death was not thought to be due to the study drug. There were no other serious adverse events. INTERPRETATION: Levetiracetam is not superior to phenytoin for second-line management of paediatric convulsive status epilepticus. FUNDING: Health Research Council of New Zealand, A+ Trust, Emergency Medicine Foundation, Townsville Hospital Private Practice Fund, Eric Ormond Baker Charitable Fund, and Princess Margaret Hospital Foundation.

Exploring Spacer Arm Structures for Designs of Asymmetric Sulfoxide-Containing MS-Cleavable Cross-Linkers.

Cross-linking mass spectrometry (XL-MS) has become a powerful structural tool for defining protein-protein interactions (PPIs) and elucidating architectures of large protein assemblies. To advance XL-MS studies, we have previously developed a series of sulfoxide-containing MS-cleavable cross-linkers to facilitate the detection and identification of cross-linked peptides using multistage mass spectrometry (MSn). While current sulfoxide-based cross-linkers are effective for in vivo and in vitro XL-MS studies at the systems-level, new reagents are still needed to help expand PPI coverage. To this end, we have designed and synthesized six variable-length derivatives of disuccinimidyl sulfoxide (DSSO) to better understand the effects of spacer arm modulation on MS-cleavability, fragmentation characteristics, and MS identification of cross-linked peptides. In addition, the impact on cross-linking reactivity was evaluated. Moreover, alternative MS2-based workflows were explored to determine their feasibility for analyzing new sulfoxide-containing cross-linked products. Based on the results of synthetic peptides and a model protein, we have further demonstrated the robustness and predictability of sulfoxide chemistry in designing MS-cleavable cross-linkers. Importantly, we have identified a unique asymmetric design that exhibits preferential fragmentation of cross-links over peptide backbones, a desired feature for MSn analysis. This work has established a solid foundation for further development of sulfoxide-containing MS-cleavable cross-linkers with new functionalities.

PREDICT prioritisation study: establishing the research priorities of paediatric emergency medicine physicians in Australia and New Zealand.

BACKGROUND: The Paediatric Research in Emergency Departments International Collaborative (PREDICT) performs multicentre research in Australia and New Zealand. Research priorities are difficult to determine, often relying on individual interests or prior work. OBJECTIVE: To identify the research priorities of paediatric emergency medicine (PEM) specialists working in Australia and New Zealand. METHODS: Online surveys were administered in a two-stage, modified Delphi study. Eligible participants were PEM specialists (consultants and senior advanced trainees in PEM from 14 PREDICT sites). Participants submitted up to 3 of their most important research questions (survey 1). Responses were collated and refined, then a shortlist of refined questions was returned to participants for prioritisation (survey 2). A further prioritisation exercise was carried out at a PREDICT meeting using the Hanlon Process of Prioritisation. This determined the priorities of active researchers in PEM including an emphasis on the feasibility of a research question. RESULTS: One hundred and six of 254 (42%) eligible participants responded to survey 1 and 142/245 (58%) to survey 2. One hundred and sixty-eight (66%) took part in either or both surveys. Two hundred forty-six individual research questions were submitted in survey 1. Survey 2 established a prioritised list of 35 research questions. Priority topics from both the Delphi and Hanlon process included high flow oxygenation in intubation, fluid volume resuscitation in sepsis, imaging in cervical spine injury, intravenous therapy for asthma and vasopressor use in sepsis. CONCLUSION: This prioritisation process has established a list of research questions, which will inform multicentre PEM research in Australia and New Zealand. It has also emphasised the importance of the translation of new knowledge.

A multicentre randomised controlled trial of levetiracetam versus phenytoin for convulsive status epilepticus in children (protocol): Convulsive Status Epilepticus Paediatric Trial (ConSEPT) - a PREDICT study.

BACKGROUND: Convulsive status epilepticus (CSE) is the most common life-threatening childhood neurological emergency. Despite this, there is a lack of high quality evidence supporting medication use after first line benzodiazepines, with current treatment protocols based solely on non-experimental evidence and expert opinion. The current standard of care, phenytoin, is only 60% effective, and associated with considerable adverse effects. A newer anti-convulsant, levetiracetam, can be given faster, is potentially more efficacious, with a more tolerable side effect profile. The primary aim of the study presented in this protocol is to determine whether intravenous (IV) levetiracetam or IV phenytoin is the better second line treatment for the emergency management of CSE in children. METHODS/DESIGN: 200 children aged between 3 months and 16 years presenting to 13 emergency departments in Australia and New Zealand with CSE, that has failed to stop with first line benzodiazepines, will be enrolled into this multicentre open randomised controlled trial. Participants will be randomised to 40 mg/kg IV levetiracetam infusion over 5 min or 20 mg/kg IV phenytoin infusion over 20 min. The primary outcome for the study is clinical cessation of seizure activity five minutes following the completion of the infusion of the study medication. Blinded confirmation of the primary outcome will occur with the primary outcome assessment being video recorded and assessed by a primary outcome assessment team blinded to treatment allocation. Secondary outcomes include: Clinical cessation of seizure activity at two hours; Time to clinical seizure cessation; Need for rapid sequence induction; Intensive care unit (ICU) admission; Serious adverse events; Length of Hospital/ICU stay; Health care costs; Seizure status/death at one-month post discharge. DISCUSSION: This paper presents the background, rationale, and design for a randomised controlled trial comparing levetiracetam to phenytoin in children presenting with CSE in whom benzodiazepines have failed. This study will provide the first high quality evidence for management of paediatric CSE post first-line benzodiazepines. TRIAL REGISTRATION: Prospectively registered with the Australian and New Zealand Clinical Trial Registry (ANZCTR): ACTRN12615000129583 (11/2/2015). UTN U1111-1144-5272. ConSEPT protocol version 4 (12/12/2014).

Bell's palsy in children: Current treatment patterns in Australia and New Zealand. A PREDICT study.

AIM: The aetiology and clinical course of Bell's palsy may be different in paediatric and adult patients. There is no randomised placebo controlled trial (RCT) to show effectiveness of prednisolone for Bell's palsy in children. The aim of the study was to assess current practice in paediatric Bell's palsy in Australia and New Zealand Emergency Departments (ED) and determine the feasibility of conducting a multicentre RCT within the Paediatric Research in Emergency Departments International Collaborative (PREDICT). METHODS: A retrospective analysis of ED medical records of children less than 18 years diagnosed with Bell's palsy between 1 January, 2012 and 31 December, 2013 was performed. Potential participants were identified from ED information systems using Bell's palsy related search terms. Repeat presentations during the same illness were excluded but relapses were not. Data on presentation, diagnosis and management were entered into an online data base (REDCap). RESULTS: Three hundred and twenty-three presentations were included from 14 PREDICT sites. Mean age at presentation was 9.0 (SD 5.0) years with 184 (57.0%) females. Most (238, 73.7%) presented to ED within 72 h of symptoms, 168 (52.0%) had seen a doctor prior. In ED, 218 (67.5%) were treated with steroids. Prednisolone was usually prescribed for 9 days at around 1 mg/kg/day, with tapering in 35.7%. CONCLUSION: Treatment of Bell's palsy in children presenting to Australasian EDs is varied. Prednisolone is commonly used in Australasian EDs, despite lack of high-level paediatric evidence. The study findings confirm the feasibility of an RCT of prednisolone for Bell's palsy in children.

Nasolacrimal duct screening to minimize post-cataract surgery endophthalmitis.

BACKGROUND: To examine unrecognized nasolacrimal duct obstruction as a risk factor for developing endophthalmitis post-cataract surgery in order to assess the value of preoperative lacrimal system screening. DESIGN: Prospective case-control study. PARTICIPANTS: A random sample of patients undergoing phacoemulsification cataract surgery (control group) and a consecutive series of patients admitted to our hospital with post-cataract surgery endophthalmitis. METHODS: We compared the rate of nasolacrimal duct obstruction in the control group versus the endophthalmitis series. Both groups underwent nasolacrimal duct syringing with normal saline on the ipsilateral side to the surgery. A standard macro-dacryocystogram was performed to confirm for obstruction detected on syringing. MAIN OUTCOME MEASURES: Nasolacrimal duct obstruction rate. RESULTS: Forty-four eyes from 39 patients were included in this study: 34 eyes from 29 patients formed the control group and 10 eyes from 10 patients formed the endophthalmitis group. A higher rate of nasolacrimal duct obstruction was found among patients who developed endophthalmitis post-cataract in comparison with the control group, on both nasolacrimal duct syringing (50.0% vs. 11.8%; P = 0.018) and macro-dacryocystogram (20.0% vs. 2.9%, P = 0.125). Two out of the three patients with radiologically confirmed nasolacrimal duct obstruction reported a long history of epiphora. CONCLUSION: The higher rates of obstruction on nasolacrimal duct syringing and macro-dacryocystogram among patients who developed endophthalmitis suggest that nasolacrimal duct obstruction is a significant risk factor for postoperative endophthalmitis. We recommend routine screening for symptoms and examination of the lacrimal system prior to cataract surgery.

iPhone applications for eye care professionals: a review of current capabilities and concerns.

PURPOSE: To quantitatively review and categorize the eye care-related iPhone(®) (Apple(®), Cupertino, CA) applications ("apps") currently available, evaluate qualified professional involvement in app development, and suggest future needs in this emerging area of mobile health. MATERIALS AND METHODS: The Apple iTunes(®) store was searched for iPhone eye care-themed apps using the general terms "ophthalmology," "ophthalmologist," "optometry," "optometrist," "eye care," and "ocular," in addition to terms based on the Centers for Disease Control and Prevention's common eye conditions. Data collected from each app included publication date, target audience, category of app, estimated number of downloads, average user rating, and documented involvement of qualified professionals. RESULTS: In total, 182 apps were identified. The majority of apps lacked community user ratings and had 3,000 or fewer downloads (84% and 69%, respectively). Consistent with other medical specialties, only 37% of apps had documented qualified professional involvement in their development. When stratified by intended audience, 52% and 44% of apps designed for ophthalmologists and optometrists, respectively, had professional input, compared with 31% for non-eye care clinicians and 21% for the general public. CONCLUSIONS: Smartphone apps are likely to become of increasingly greater relevance to the modern eye care professional with tremendous versatility in daily practice. However, despite the rapid emergence of eye care apps, a low level of qualified professional involvement in app development and a lack of peer review after publishing remain. There is a clear need for evidence-based principles and standards of app development to be adopted in this emerging area.

Colloidal and interfacial properties of spray dried pulse protein-blueberry polyphenol particles in model dispersion systems.

The phytochemical composition and physicochemical attributes of polyphenol-enriched protein particle ingredients produced with pulse proteins (e.g. chickpea protein, pea protein, and a chickpea-pea protein blend) and polyphenols recovered from wild blueberry pomace were investigated for colloidal and interfacial properties. Anthocyanins were the major polyphenol fraction (27.74-36.47 mg C3G/g) of these polyphenol-rich particles (44.95-62.08 mg GAE/g). Dispersions of pea protein-polyphenol particles showed a superior phase stability before and after heat treatment compared to the chickpea pea protein-polyphenol system. This observation was independent of the added amount of NaCl in the dispersion. In general, at quasi equilibrium state, pulse protein-polyphenol particles and parental pulse protein ingredients showed similar oil-water interfacial tension. However, pea protein-polyphenol particles demonstrated a reduced diffusion-driven oil-water interfacial adsorption rate constant compared to the parental pea protein ingredient. Overall, the obtained results suggest application potential of pea protein-polyphenol particles as a functional food/beverage ingredient.

Cognitive health treatment priorities and preferences among young people with mental illness: The your mind, your choice survey.

AIM: Cognitive impairments negatively impact the everyday functioning of young people with mental illness. However, no previous study has asked young people (1) how much of a priority cognitive functioning is within mental health treatment, and (2) what types of cognition-focused treatments are most appealing. The current study aimed to address these questions. METHODS: Your Mind, Your Choice was a survey-based study involving an Australian sample of young people who were receiving mental health treatment. The survey asked participants to (1) provide demographic and mental health history, (2) rate the importance of 20 recovery domains, including cognition, when receiving mental health treatment, (3) share their experiences of cognitive functioning, and (4) rate their likelihood of trying 14 different behavioural, biochemical, and physical treatments that may address cognitive functioning. RESULTS: Two-hundred and forty-three participants (Mage = 20.07, SD = 3.25, range = 15-25, 74% female) completed the survey. Participants reported that addressing cognitive functioning in mental health care was very important (M = 76.33, SD = 20.7, rated on a scale from 0 = not important to 100 = extremely important), ranking cognition among their top six treatment needs. Seventy percent of participants reported experiencing cognitive difficulties, but less than one-third had received treatment for these difficulties. Compensatory training, sleep interventions and psychoeducation were ranked as treatments that participants were most likely to try to support their cognitive functioning. CONCLUSIONS: Young people with mental ill-health commonly experience cognitive difficulties and would like this to be a focus of treatment; however, this need is often unmet and should be a focus of research and implementation.

Psychological Predictors of Mental Health Difficulties After Pediatric Concussion.

Children often experience mental health difficulties after a concussion. Yet, the extent to which a concussion precipitates or exacerbates mental health difficulties remains unclear. This study aimed to examine psychological predictors of mental health difficulties after pediatric concussion. Children (5 to <18 years of age, M = 11.7, SD = 3.3) with concussion were recruited in a single-site longitudinal prospective cohort study conducted at a tertiary children's hospital (n = 115, 73.9% male). The primary outcomes included internalizing (anxious, depressed, withdrawn behaviors), externalizing (risk-taking, aggression, attention difficulties), and total mental health problems, as measured by the Child Behavior Checklist at 2 weeks (acute) and 3 months (post-acute) after concussion. Predictors included parents' retrospective reports of premorbid concussive symptoms (Post-Concussion Symptom Inventory; PCSI), the child and their family's psychiatric history, child-rated perfectionism (Adaptive-Maladaptive Perfectionism Scale), and child-rated resilience (Youth Resilience Measure). Higher premorbid PCSI ratings consistently predicted acute and post-acute mental health difficulties. This relationship was significantly moderated by child psychiatric history. Furthermore, pre-injury learning difficulties, child psychiatric diagnoses, family psychiatric history, lower resilience, previous concussions, female sex, and older age at injury were associated with greater mental health difficulties after concussion. Pre-injury factors accounted for 23.4-39.9% of acute mental health outcomes, and 32.3-37.8% of post-acute mental health outcomes. When acute mental health was factored into the model, a total of 47.0-68.8% of variance was explained by the model. Overall, in this sample of children, several pre-injury demographic and psychological factors were observed to predict mental health difficulties after a concussion. These findings need to be validated in future research involving larger, multi-site studies that include a broader cohort of children after concussion.

Validating cognitive screening in young people with first-episode psychosis: The CogScreen protocol.

AIM: Cognitive impairments are a core feature of first-episode psychosis (FEP) and one of the strongest predictors of long-term psychosocial functioning. Cognition should be assessed and treated as part of routine clinical care for FEP. Cognitive screening offers the opportunity to rapidly identify and triage those in most need of cognitive support. However, there are currently no validated screening measures for young people with FEP. CogScreen is a hybrid effectiveness-implementation study which aims to evaluate the classification accuracy (relative to a neuropsychological assessment as a reference standard), test-retest reliability and acceptability of two cognitive screening tools in young people with FEP. METHODS: Participants will be 350 young people (aged 12-25) attending primary and specialist FEP treatment centres in three large metropolitan cities (Adelaide, Sydney, and Melbourne) in Australia. All participants will complete a cross-sectional assessment over two sessions including two cognitive screening tools (Screen for Cognitive Impairment in Psychiatry and Montreal Cognitive Assessment), a comprehensive neuropsychological assessment battery, psychiatric and neurodevelopmental assessments, and other supplementary clinical measures. To determine the test-retest reliability of the cognitive screening tools, a subset of 120 participants will repeat the screening measures two weeks later. RESULTS: The protocol, rationale, and hypotheses for CogScreen are presented. CONCLUSIONS: CogScreen will provide empirical evidence for the validity and reliability of two cognitive screening tools when compared to a comprehensive neuropsychological assessment. The screening measures may later be incorporated into clinical practice to assist with rapid identification and treatment of cognitive deficits commonly experienced by young people with FEP.

Early Changes in Tumor-Naive Cell-Free Methylomes and Fragmentomes Predict Outcomes in Pembrolizumab-Treated Solid Tumors.

Early kinetics of circulating tumor DNA (ctDNA) in plasma predict response to pembrolizumab but typically requires sequencing of matched tumor tissue or fixed gene panels. We analyzed genome-wide methylation and fragment-length profiles using cell-free methylated DNA immunoprecipitation and sequencing (cfMeDIP-seq) in 204 plasma samples from 87 patients before and during treatment with pembrolizumab from a pan-cancer phase II investigator-initiated trial (INSPIRE). We trained a pan-cancer methylation signature using independent methylation array data from The Cancer Genome Atlas to quantify cancer-specific methylation (CSM) and fragment-length score (FLS) for each sample. CSM and FLS are strongly correlated with tumor-informed ctDNA levels. Early kinetics of CSM predict overall survival and progression-free survival, independently of tumor type, PD-L1, and tumor mutation burden. Early kinetics of FLS are associated with overall survival independently of CSM. Our tumor-naïve mutation-agnostic ctDNA approach integrating methylomics and fragmentomics could predict outcomes in patients treated with pembrolizumab. SIGNIFICANCE: Analysis of methylation and fragment length in plasma using cfMeDIP-seq provides a tumor-naive approach to measure ctDNA with results comparable with a tumor-informed bespoke ctDNA. Early kinetics within the first weeks of treatment in methylation and fragment quantity can predict outcomes with pembrolizumab in patients with various advanced solid tumors. This article is featured in Selected Articles from This Issue, p. 897.

Examining post-concussion white matter change in a pediatric sample.

Diffusion-Weight Imaging (DWI) is increasingly used to explore a range of outcomes in pediatric concussion, particularly the neurobiological underpinnings of symptom recovery. However, the DWI findings within the broader pediatric concussion literature are mixed, which can largely be explained by methodological heterogeneity. To address some of these limitations, the aim of the present study was to utilize internationally- recognized criteria for concussion and a consistent imaging timepoint to conduct a comprehensive, multi-parametric survey of white matter microstructure after concussion. Forty-three children presenting with concussion to the emergency department of a tertiary level pediatric hospital underwent neuroimaging and were classified as either normally recovering (n = 27), or delayed recovering (n = 14) based on their post-concussion symptoms at 2 weeks post-injury.We combined multiple DWI metrics across four modeling approaches using Linked Independent Component Analysis (LICA) to extract several independent patterns of covariation in tissue microstructure present in the study cohort. Our analysis did not identify significant differences between the symptomatic and asymptomatic groups and no component significantly predicted delayed recovery. If white matter microstructure changes are implicated in delayed recovery from concussion, these findings, alongside previous work, suggest that current diffusion techniques are insufficient to detect those changes at this time.

Primary cardiac arrest following sport or exertion in children presenting to an emergency department: chest compressions and early defibrillation can save lives, but is intravenous epinephrine always appropriate?

OBJECTIVES: The objective of this study was to describe the characteristics and outcome of pediatric patients presenting to an emergency department (ED) following out-of-hospital primary cardiac arrest (OHPCA), to determine if long-term survival is influenced by specific resuscitation interventions. METHODS: This was a prospective observational study of cases of OHPCA during sport or exertion in young patients presenting to an ED over a 5-year period. Cases were identified from a resuscitation database, which documented patient demographics, nature of event, emergency treatment, response times, and clinical progress. These data were analyzed to determine outcomes. RESULTS: Nine children were identified who presented following OHPCA during the study period. The mean age was 10.7 (±4.2) years. All were subsequently diagnosed with an underlying primary cardiac disorder. Six patients (66.6%) survived to make a full recovery. All patients who survived had received early chest compressions (within 5 minutes) and early defibrillation (within 10 minutes). The initial cardiac arrest rhythm in all survivors had been an electrically cardiovertable rhythm. Five (83%) of the 6 survivors did not receive epinephrine during resuscitation. CONCLUSIONS: The importance of early chest compressions and defibrillation in collapsed young athletes is highlighted in this report. These interventions can result in full long-term neurological recovery. Use of epinephrine in these patients may be dangerous. We suggest that special consideration should be given to this subgroup of patients in the development of future resuscitation guidelines.

Treatments for objective and subjective cognitive functioning in young people with depression: Systematic review of current evidence.

AIM: Cognitive deficits are recognized features of depressive disorders in youth aged 12-25. These deficits are distressing, predict functional impairment and limit the effectiveness of psychological therapies. Cognitive enhancement using behavioural, biochemical or physical treatments may be useful in young people with depression, but studies have not been synthesized. The aim was to systematically review the evidence for treatments for objective and subjective cognitive functioning, and their acceptability and functional outcomes in people aged 12-25 with depression. METHOD: Three electronic databases were searched for articles using pre-specified criteria. Pharmacological treatments were not eligible. Risk of bias was rated using the Cochrane Collaboration's revised risk-of-bias tool. Dual full-text article screening, data extraction and quality ratings were completed. RESULTS: Twelve studies were included for review (median participant age: 20.39 years), five of which were randomized-controlled trials (RCTs). Sample sizes were generally small (median = 23; range: 9-46). Eight studies investigated behavioural treatments including aerobic exercise, cognitive training and education or strategy-based methods. Four studies examined repetitive transcranial magnetic brain stimulation (rTMS). Most behavioural treatments revealed preliminary evidence of improved cognitive function in youth depression. Consent rates were greatest for exercise- and education-based approaches, which may indicate higher acceptability levels. Findings from rTMS trials were mixed, with only half showing cognitive improvement. Functional outcomes were reported by three behavioural treatment trials and one rTMS trial, with functional improvement reported only in the former. Some concern of risk of bias was found in each RCT. CONCLUSION: Behavioural treatments, such as exercise, cognitive training and education/strategy-focused techniques, show encouraging results and appear to be acceptable methods of addressing cognitive deficits in youth depression based on participation rates. Brain stimulation and biochemical treatments (e.g., nutrient-based treatment) require further investigation.

Intelligence trajectories in individuals at ultra-high risk for psychosis: An 8-year longitudinal analysis.

Cognitive impairment is a well-documented predictor of transition to a full-threshold psychotic disorder amongst individuals at ultra-high risk (UHR) for psychosis. However, less is known about whether change in cognitive functioning differs between those who do and do not transition. Studies to date have not examined trajectories in intelligence constructs (e.g., acquired knowledge and fluid intelligence), which have demonstrated marked impairments in individuals with schizophrenia. This study aimed to examine intelligence trajectories using longitudinal data spanning an average of eight years, where some participants completed assessments over three time-points. Participants (N = 139) at UHR for psychosis completed the Wechsler Abbreviated Scale of Intelligence (WASI) at each follow-up. Linear mixed-effects models mapped changes in WASI Full-Scale IQ (FSIQ) and T-scores on Vocabulary, Similarities, Block Design, and Matrix Reasoning subtests. The sample showed stable and improving trajectories for FSIQ and all subtests. There were no significant differences in trajectories between those who did and did not transition to psychosis and between individuals with good and poor functional outcomes. However, although not significant, the trajectories of the acquired knowledge subtests diverged between transitioned and non-transitioned individuals (ß = -0.12, 95 % CI [-0.29, 0.05] for Vocabulary and ß = -0.14, 95 % CI [-0.33, 0.05] for Similarities). Overall, there was no evidence for long-term deterioration in intelligence trajectories in this UHR sample. Future studies with a larger sample of transitioned participants may be needed to explore potential differences in intelligence trajectories between UHR transition groups and other non-psychosis outcomes.

Effects of omega-3 polyunsaturated fatty acid supplementation on cognitive functioning in youth at ultra-high risk for psychosis: secondary analysis of the NEURAPRO randomised controlled trial.

BACKGROUND: Cognitive impairments are well-established features of psychotic disorders and are present when individuals are at ultra-high risk for psychosis. However, few interventions target cognitive functioning in this population. AIMS: To investigate whether omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation improves cognitive functioning among individuals at ultra-high risk for psychosis. METHOD: Data (N = 225) from an international, multi-site, randomised controlled trial (NEURAPRO) were analysed. Participants were given omega-3 supplementation (eicosapentaenoic acid and docosahexaenoic acid) or placebo over 6 months. Cognitive functioning was assessed with the Brief Assessment of Cognition in Schizophrenia (BACS). Mixed two-way analyses of variance were computed to compare the change in cognitive performance between omega-3 supplementation and placebo over 6 months. An additional biomarker analysis explored whether change in erythrocyte n-3 PUFA levels predicted change in cognitive performance. RESULTS: The placebo group showed a modest greater improvement over time than the omega-3 supplementation group for motor speed (ηp2 = 0.09) and BACS composite score (ηp2 = 0.21). After repeating the analyses without individuals who transitioned, motor speed was no longer significant (ηp2 = 0.02), but the composite score remained significant (ηp2 = 0.02). Change in erythrocyte n-3 PUFA levels did not predict change in cognitive performance over 6 months. CONCLUSIONS: We found no evidence to support the use of omega-3 supplementation to improve cognitive functioning in ultra-high risk individuals. The biomarker analysis suggests that this finding is unlikely to be attributed to poor adherence or consumption of non-trial n-3 PUFAs.

The cell-free DNA methylome captures distinctions between localized and metastatic prostate tumors.

Metastatic prostate cancer remains a major clinical challenge and metastatic lesions are highly heterogeneous and difficult to biopsy. Liquid biopsy provides opportunities to gain insights into the underlying biology. Here, using the highly sensitive enrichment-based sequencing technology, we provide analysis of 60 and 175 plasma DNA methylomes from patients with localized and metastatic prostate cancer, respectively. We show that the cell-free DNA methylome can capture variations beyond the tumor. A global hypermethylation in metastatic samples is observed, coupled with hypomethylation in the pericentromeric regions. Hypermethylation at the promoter of a glucocorticoid receptor gene NR3C1 is associated with a decreased immune signature. The cell-free DNA methylome is reflective of clinical outcomes and can distinguish different disease types with 0.989 prediction accuracy. Finally, we show the ability of predicting copy number alterations from the data, providing opportunities for joint genetic and epigenetic analysis on limited biological samples.

Charge Transfer Screening and Energy Level Alignment at Complex Organic-Inorganic Interfaces: A Tractable Ab Initio GW Approach.

Complex organic-inorganic interfaces are important for device and sensing applications. Charge transfer doping is prevalent in such applications and can affect the interfacial energy level alignments (ELA), which are determined by many-body interactions. We develop an approximate ab initio many-body GW approach that can capture many-body interactions due to interfacial charge transfer. The approach uses significantly less resources than a regular GW calculation but gives excellent agreement with benchmark GW calculations on an F4TCNQ/graphene interface. We find that many-body interactions due to charge transfer screening result in gate-tunable F4TCNQ HOMO-LUMO gaps. We further predict the ELA of a large system of experimental interest-4,4'-bis(dimethylamino)bipyridine (DMAP-OED) on monolayer MoS2, where charge transfer screening results in an ∼1 eV reduction of the molecular HOMO-LUMO gap. Comparison with a two-dimensional electron gas model reveals the importance of explicitly considering the intraband transitions in determining the charge transfer screening in organic-inorganic interface systems.