Reduced neural synchronization of gamma-band MEG oscillations in first-degree relatives of children with autism

<p>Abstract</p> <p>Background</p> <p>Gamma-band oscillations recorded from human electrophysiological recordings, which may be associated with perceptual binding and neuronal connectivity, have been shown to be altered in people with autism. Transient auditory gamma-band responses, however, have not yet been investigated in autism or in the first-degree relatives of persons with the autism.</p> <p>Methods</p> <p>We measured transient evoked and induced magnetic gamma-band power and inter-trial phase-locking consistency in the magnetoencephalographic recordings of 16 parents of children with autism, 11 adults with autism and 16 control participants. Source space projection was used to separate left and right hemisphere transient gamma-band measures of power and phase-locking.</p> <p>Results</p> <p>Induced gamma-power at 40 Hz was significantly higher in the parent and autism groups than in controls, while evoked gamma-band power was reduced compared to controls. The phase-locking factor, a measure of phase consistency of neuronal responses with external stimuli, was significantly lower in the subjects with autism and the autism parent group, potentially explaining the difference between the evoked and induced power results.</p> <p>Conclusion</p> <p>These findings, especially in first degree relatives, suggest that gamma-band phase consistency and changes in induced versus induced power may be potentially useful endophenotypes for autism, particularly given emerging molecular mechanisms concerning the generation of gamma-band signals.</p

Brain size and brain/intracranial volume ratio in major mental illness

<p>Abstract</p> <p>Background</p> <p>This paper summarizes the findings of a long term study addressing the question of how several brain volume measure are related to three major mental illnesses in a Colorado subject group. It reports results obtained from a large N, collected and analyzed by the same laboratory over a multiyear period, with visually guided MRI segmentation being the primary initial analytic tool.</p> <p>Methods</p> <p>Intracerebral volume (ICV), total brain volume (TBV), ventricular volume (VV), ventricular/brain ratio (VBR), and TBV/ICV ratios were calculated from a total of 224 subject MRIs collected over a period of 13 years. Subject groups included controls (C, N = 89), and patients with schizophrenia (SZ, N = 58), bipolar disorder (BD, N = 51), and schizoaffective disorder (SAD, N = 26).</p> <p>Results</p> <p>ICV, TBV, and VV measures compared favorably with values obtained by other research groups, but in this study did not differ significantly between groups. TBV/ICV ratios were significantly decreased, and VBR increased, in the SZ and BD groups compared to the C group. The SAD group did not differ from C on any measure.</p> <p>Conclusions</p> <p>In this study TBV/ICV and VBR ratios separated SZ and BD patients from controls. Of interest however, SAD patients did not differ from controls on these measures. The findings suggest that the gross measure of TBV may not reliably differ in the major mental illnesses to a degree useful in diagnosis, likely due to the intrinsic variability of the measures in question; the differences in VBR appear more robust across studies. Differences in some of these findings compared to earlier reports from several laboratories finding significant differences between groups in VV and TBV may relate to phenomenological drift, differences in analytic techniques, and possibly the "file drawer problem".</p

Families’ roles in children’s literacy in the UK throughout the 20th century

This paper explores the changing roles of families in children’s developing literacy in the UK in the last century. It discusses how, during this time, understandings of reading and writing have evolved into the more nuanced notion of literacy. Further, in acknowledging changes in written communication practices, and shifting attitudes to reading and writ- ing, the paper sketches out how families have always played some part in the literacy of younger generations; though reading was frequently integral to the lives of many families throughout the past century, we consider in particular the more recent enhancement of children’s literacy through targeted family programmes. The paper considers policy implications for promoting young children’s literacy through work with families

Antipsychotic medication versus psychological intervention versus a combination of both in adolescents with first-episode psychosis (MAPS): a multicentre, three-arm, randomised controlled pilot and feasibility study

Background Evidence for the effectiveness of treatments in early-onset psychosis is sparse. Current guidance for the treatment of early-onset psychosis is mostly extrapolated from trials in adult populations. The UK National Institute for Health and Care Excellence has recommended evaluation of the clinical effectiveness and cost-effectiveness of antipsychotic drugs versus psychological intervention (cognitive behavioural therapy [CBT] and family intervention) versus the combination of these treatments for early-onset psychosis. The aim of this study was to establish the feasibility of a randomised controlled trial of antipsychotic monotherapy, psychological intervention monotherapy, and antipsychotics plus psychological intervention in adolescents with first-episode psychosis. Methods We did a multicentre pilot and feasibility trial according to a randomised, single-blind, three-arm, controlled design. We recruited participants from seven UK National Health Service Trust sites. Participants were aged 14–18 years; help-seeking; had presented with first-episode psychosis in the past year; were under the care of a psychiatrist; were showing current psychotic symptoms; and met ICD-10 criteria for schizophrenia, schizoaffective disorder, or delusional disorder, or met the entry criteria for an early intervention for psychosis service. Participants were assigned (1:1:1) to antipsychotics, psychological intervention (CBT with optional family intervention), or antipsychotics plus psychological intervention. Randomisation was via a web-based randomisation system, with permuted blocks of random size, stratified by centre and family contact. CBT incorporated up to 26 sessions over 6 months plus up to four booster sessions, and family intervention incorporated up to six sessions over 6 months. Choice and dose of antipsychotic were at the discretion of the treating consultant psychiatrist. Participants were followed up for a maximum of 12 months. The primary outcome was feasibility (ie, data on trial referral and recruitment, session attendance or medication adherence, retention, and treatment acceptability) and the proposed primary efficacy outcome was total score on the Positive and Negative Syndrome Scale (PANSS) at 6 months. Primary outcomes were analysed by intention to treat. Safety outcomes were reported according to as-treated status, for all patients who had received at least one session of CBT or family intervention, or at least one dose of antipsychotics. The study was prospectively registered with ISRCTN, ISRCTN80567433. Findings Of 101 patients referred to the study, 61 patients (mean age 16·3 years [SD 1·3]) were recruited from April 10, 2017, to Oct 31, 2018, 18 of whom were randomly assigned to psychological intervention, 22 to antipsychotics, and 21 to antipsychotics plus psychological intervention. The trial recruitment rate was 68% of our target sample size of 90 participants. The study had a low referral to recruitment ratio (around 2:1), a high rate of retention (51 [84%] participants retained at the 6-month primary endpoint), a high rate of adherence to psychological intervention (defined as six or more sessions of CBT; in 32 [82%] of 39 participants in the monotherapy and combined groups), and a moderate rate of adherence to antipsychotic medication (defined as at least 6 consecutive weeks of exposure to antipsychotics; in 28 [65%] of 43 participants in the monotherapy and combined groups). Mean scores for PANSS total at the 6-month primary endpoint were 68·6 (SD 17·3) for antipsychotic monotherapy (6·2 points lower than at randomisation), 59·8 (13·7) for psychological intervention (13·1 points lower than at randomisation), and 62·0 (15·9) for antipsychotics plus psychological intervention (13·9 points lower than at randomisation). A good clinical response at 6 months (defined as ≥50% improvement in PANSS total score) was achieved in four (22%) of 18 patients receiving antipsychotic monotherapy, five (31%) of 16 receiving psychological intervention, and five (29%) of 17 receiving antipsychotics plus psychological intervention. In as-treated groups, serious adverse events occurred in eight [35%] of 23 patients in the combined group, two [13%] of 15 in the antipsychotics group, four [24%] of 17 in the psychological intervention group, and four [80%] of five who did not receive any treatment. No serious adverse events were considered to be related to participation in the trial. Interpretation This trial is the first to show that a head-to-head clinical trial comparing psychological intervention, antipsychotics, and their combination is safe in young people with first-episode psychosis. However, the feasibility of a larger trial is unclear because of site-specific recruitment challenges, and amendments to trial design would be needed for an adequately powered clinical and cost-effectiveness trial that provides robust evidence

A three-arm feasibility randomised controlled trial comparing antipsychotic medication to psychological intervention to a combined treatment in adolescents with first episode psychosis: The Managing Adolescent first episode Psychosis Study (MAPS)

Background: The evidence base for treatments for early-onset psychosis (EOP) is limited and of low quality. Current guidance for the treatment of EOP is mostly extrapolated from trials in adult populations. NICE, in the United Kingdom (UK), make a specific research recommendation for the evaluation of clinical and cost-effectiveness of antipsychotics (AP), versus psychological intervention (cognitive behaviour therapy [CBT] and family intervention), versus combination treatment for EOP. The National Institute for Health Research (NIHR) in the UK commissioned this research to establish feasibility and acceptability of a definitive trial examining these three treatment options. Methods: We conducted a multi-site, Prospective Randomised Open Blinded Evaluation (PROBE) design, feasibility randomised controlled trial (RCT) comparing AP monotherapy with psychological intervention monotherapy (PI) plus a combination of these treatments in 14-18-year olds with a first episode of psychosis. We recruited participants from seven United Kingdom sites. Participants were followed-up at six and 12 months. Cognitive behavioural therapy incorporated up to 26 sessions over 6 months plus up to four booster sessions. Family intervention included up to six sessions over 6 months. Choice and dose of antipsychotic were at the discretion of the treating consultant psychiatrist. The primary outcome was feasibility data (recruitment, retention, acceptability) and the main effectiveness outcome was the Positive and Negative Syndrome Scale (PANSS) total score at 6 months. We conducted a repeated-measures analysis of the proposed primary outcome (PANSS) and the secondary outcome, the Questionnaire about the Process of Recovery (QPR) using a mixed effects model to account for the discrete timing of the follow-up assessments and adjusted for site. Safety outcomes were reported on the basis of as treated status defined as any one session of CBT or any one dose of APs; descriptive statistics are reported for safety outcomes. The study was prospectively registered on 27th February 2017, http://www.isrctn.com/ISRCTN80567433. Findings: 61 patients (aged 14-18 years; mean 16.3, SD 1.3) were recruited from 1st April 2017 to 31st October 2018, 18 were assigned to psychological intervention, 22 to antipsychotics and 21 to the combination. The feasibility of recruitment was unclear, since the trial only recruited 61 of a target of 90 participants. The study had a low referral: randomisation ratio (101:61), high rates of retention (>80%), high rates of adherence for psychological intervention (82.1%) defined as 6 or more sessions of CBT, and moderate rates of adherence for antipsychotic medication (65.1%), defined as 6 or more consecutive weeks of APs. The median number of sessions for CBT for those in the PI arm was 14 (IQR 9, 23) and 15 in the combined arm (IQR 9, 17). Of those in receipt of APs the mean duration that the participant remained on the medication was 31.5 weeks (SD 14.6, minimum 8.7 and maximum 52). There were no serious adverse events considered to be related to the trial. Interpretation: This is the first trial to show that it is safe to conduct a head-to-head clinical trial comparing psychological intervention with antipsychotics and the combination in people in young people with a first-episode psychosis. However, feasibility is unclear due to not meeting the recruitment progression criteria, so amendments to trial design are required in order to conduct an adequately powered clinical and cost effectiveness trial to provide robust evidence

DFT exchange: sharing perspectives on the workhorse of quantum chemistry and materials science

In this paper, the history, present status, and future of density-functional theory (DFT) is informally reviewed and discussed by 70 workers in the field, including molecular scientists, materials scientists, method developers and practitioners. The format of the paper is that of a roundtable discussion, in which the participants express and exchange views on DFT in the form of 302 individual contributions, formulated as responses to a preset list of 26 questions. Supported by a bibliography of 777 entries, the paper represents a broad snapshot of DFT, anno 2022

The diversification and performance of self managed superannuation funds

In this article we examine the diversification and performance of a small preliminary sample of Australian self-managed superannuation (retirement) funds (SMSFs). Using the single index model and traditional (risk-adjusted) performance measures within the context set by modern portfolio theory we find that the SMSFs in our sample exhibit considerable under-diversification. In addition, we find that the SMSFs do not appear to be benefiting from even naive diversification and, unsurprisingly, perform poorly on a risk-adjusted basis vis-à-vis the unmanaged S&P/ASX300 index. This empirical investigation contributes to economists' understanding of the microeconomic structure of this increasingly important component of Australia's retirement income stream

Self managed superannuation funds and the bear market of 2007-2008

[Abstract]: In this paper, we examine the bear market performance of self managed superannuation funds (SMSFs). Previous studies have highlighted some problems with the portfolio construction of SMSFs. This provides a rationale for examining the performance of SMSFs during the recent bear market. Based on data from two independent samples of a total of 141 self managed superannuation funds, two archetype SMSF portfolios are constructed in order to generate insights into the average performance of the funds in the samples. The performance of these funds is compared with (1) the unmanaged market index; and (2) the average returns generated by retail (balanced) superannuation funds. Interestingly, whilst the SMSFs have generated negative returns and problems with the portfolio construction remain, the relative performance of the overall portfolios vis-à-vis the market index and professionally managed funds is reasonably favourable. However, the equity portions of the SMSF portfolios suffer from under-diversification and could be more efficiently constructed

Can self-managed superannuation fund trustees earn the equity risk premium?

The purpose of this paper is to determine whether self-managed superannuation fund (SMSF) trustees earn: the equity risk premium or any premium to the riskless rate of interest. Design/methodology/approach - Using a sample of 100 SMSFs, the average annual returns since inception of the funds in the sample are compared with: the average annual equity risk premium since that time and the average yield of Commonwealth Government Securities since that time. Findings - The investigation reveals: the SMSFs in the sample do not earn the equity risk premium and the SMSFs in the sample did not earn a premium to riskless rate of interest. This leads to the conclusion that the SMSFs have borne risk without commensurate reward. Research limitations/implications - The trustees' rationale for making particular investment decisions and the consistency of the portfolio structures with the risk profiles of the trustees are two areas that may be fruitfully explored in future research. Practical implications - For SMSF trustees, a simple portfolio that divides assets between (unmanaged) index funds and risk-free securities on the basis of trustees' risk aversion may generate better results than the existing portfolios. For policy makers, the relatively poor performance of SMSFs implies that the superannuation system as currently structured may not be generating returns that will maximize retirement incomes. Originality/value - The paper provides the first comparison of SMSF returns with the equity risk premium and the riskless rate of interest measured at appropriate horizons