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Performance monitoring entails rapid error detection to maintain task performance. Impaired performance monitoring is a candidate pathophysiological process in psychotic disorders, which may explain the broader deficit in executive function and its known associations with negative symptoms and poor functioning. The current study models cross-sectional pathways bridging neurophysiological measures of performance monitoring with executive function, symptoms, and functioning.
Data were from the 20-year assessment of the Suffolk County Mental Health Project. Individuals with psychotic disorders (N = 181) were originally recruited from inpatient psychiatric facilities. Data were also collected from a geographically and demographically matched group with no psychosis history (N = 242). Neural measures were the error-related negativity (ERN) and error positivity (Pe). Structural equation modeling tested mediation pathways.
Blunted ERN and Pe in the clinical cohort related to impaired executive function (r = 0.26–0.35), negative symptom severity (r = 0.17–0.25), and poor real-world functioning (r = 0.17–0.19). Associations with executive function were consistent across groups. Multiple potential pathways were identified in the clinical cohort: reduced ERN to inexpressivity was mediated by executive function (β = 0.10); reduced Pe to global functioning was mediated by executive function and avolition (β = 0.10).
This supports a transdiagnostic model of psychotic disorders by which poor performance monitoring contributes to impaired executive function, which contributes to negative symptoms and poor real-world functioning. If supported by future longitudinal research, these pathways could inform the development of targeted interventions to address cognitive and functional deficits that are central to psychotic disorders.
To evaluate long-term treatment with ziprasidone versus haloperidol (up to 196 weeks), as assessed by PANSS negative score and and its association with quality-of-life (QLS).
The study included two treatment periods: (i) a 40-week, randomized, double-blind phase comparing ziprasidone (ZIP 80-160 mg/d given BID, N=227; ZIP 80-120 mg/d given QD, N=221) versus haloperidol (HAL 5-20 mg/d, N=151), followed by (ii) a 3-year, double-blind extension phase on the same double-blind medications (ZIP BID N=72, ZIP QD N=67, and HAL N=47, respectively). We adapted the Andreasen et al. approach to define negative symptom remission based on attainment of a score ≤3 (mild or less) for at least 6 months on all 7 PANSS negative symptom items. MMRM and GEE models were applied to analyze mean changes in PANSS negative, negative symptom remission rate, and QLS scores over time.
In the 40-week core study, ziprasidone was associated with greater improvement in efficacy and QLS outcomes than haloperidol, but the differences were not statistically significant (p>0.05). However, MMRM analysis of PANSS negative and QLS scores over 196 weeks demonstrated differential treatment effects favoring ziprasidone (80-160 mg/d BID vs. haloperidol) (all p<0.05). Ziprasidone-treated subjects (given BID) were significantly more likely to achieve negative symptom remission (46%) than haloperidol-treated (32%) subjects (p<0.05) during the continuation phase; while ziprasidone given QD (46%) showed a trend to enhanced remission (p<0.08).
These findings support the potential for enhanced social and functional outcomes during long-term treatment with an atypical antipsychotic agent.
Data related to brain function may have the potential to improve the reliability and validity of assessments for the aetiologically and clinically heterogeneous syndrome of attention-deficit/hyperactivity disorder (ADHD). This study investigated associations between questionnaire assessments of behavioural features of adults with ADHD and an aspect of neurocognitive performance which has been reported to be impaired in adults with ADHD.
Fifty-nine adult patients with a DSM-IV diagnosis of ADHD, and their informants, completed questionnaires related to aspects of severity of ADHD. Associations were examined between questionnaire ratings and performance on a computer-administered task of spatial working memory (SWM).
Correlations between ratings of ADHD and SWM indicated moderate but significant correlations for patients' ratings, but not for informants' ratings. Also, patients who reported a past history of ‘self-harm’ (N = 33) had a significantly worse mean performance on both measures of SWM (p = 0.004, 0.003).
The results indicate that aspects of impulsivity, i.e. self-ratings of ‘emotive’ behaviour (involving rapid response to stimuli and marked reactivity of mood) and of past ‘self-harm’, show relatively strong associations with SWM performance in adults selected on the basis of an ADHD diagnosis. A profile of neurocognitive performances may have a role in the assessment of ADHD.
Lack of insight in schizophrenia is frequently associated with deficits in self-assessment of cognitive and functional abilities, as well as quality of life outcomes.
The aim of this analysis was to evaluate the impact of treatment-related improvement in illness awareness on changes in cognition and functional outcomes in a double-blind, controlled study.
Clinically unstable patients with schizophrenia (N=488) were randomized to once-daily, fixed dose treatment with lurasidone 80 mg (LUR 80), lurasidone 160 mg (LUR 160), quetiapine XR 600 mg (QXR) or placebo (PBO), followed by a 12-month, double-blind extension. Impairment of insight (G12 ‘lack of judgment and insight’), cognitive performance, quality of well-being (QWB scale), and UPSA-B were assessed at baseline, week-6 and month-6 of extension (32 weeks). Mixed effects model was applied.
PANSS insight scores were significantly improved for all treatment groups compared to placebo after 6 weeks. Improvement in insight at week-32 was significantly greater in subjects treated with lurasidone compared with quetiapine XR. Improved insight at week-6 was a significant mediator for the effect of LUR160 (vs. placebo) on neurocognitive composite score (p<0.05), UPSA-B total score (p<0.05), and QWB (p<0.05) at week-6. Improved insight was significantly associated with increase in UPSA-B score and health-related quality of life at weeks 19 and 32.
Improvement in insight at week-32 was significantly greater in subjects treated with lurasidone compared with quetiapine XR. Our findings suggest treatment-related improvement in illness awareness had significant impact on cognition and functional outcomes in a doubleblind, controlled study.
Diet modifies the risk of colorectal cancer (CRC), and inconclusive evidence suggests that yogurt may protect against CRC. We analysed the data collected from two separate colonoscopy-based case–control studies. The Tennessee Colorectal Polyp Study (TCPS) and Johns Hopkins Biofilm Study included 5446 and 1061 participants, respectively, diagnosed with hyperplastic polyp (HP), sessile serrated polyp, adenomatous polyp (AP) or without any polyps. Multinomial logistic regression models were used to derive OR and 95 % CI to evaluate comparisons between cases and polyp-free controls and case–case comparisons between different polyp types. We evaluated the association between frequency of yogurt intake and probiotic use with the diagnosis of colorectal polyps. In the TCPS, daily yogurt intake v. no/rare intake was associated with decreased odds of HP (OR 0·54; 95 % CI 0·31, 0·95) and weekly yogurt intake was associated with decreased odds of AP among women (OR 0·73; 95 % CI 0·55, 0·98). In the Biofilm Study, both weekly yogurt intake and probiotic use were associated with a non-significant reduction in odds of overall AP (OR 0·75; 95 % CI 0·54, 1·04) and (OR 0·72; 95 % CI 0·49, 1·06) in comparison with no use, respectively. In summary, yogurt intake may be associated with decreased odds of HP and AP and probiotic use may be associated with decreased odds of AP. Further prospective studies are needed to verify these associations.
Sub-acute ruminal acidosis (SARA) can reduce the production efficiency and impair the welfare of cattle, potentially in all production systems. The aim of this study was to characterise measurable postmortem observations from divergently managed intensive beef finishing farms with high rates of concentrate feeding. At the time of slaughter, we obtained samples from 19 to 20 animals on each of 6 beef finishing units (119 animals in total) with diverse feeding practices, which had been subjectively classified as being high risk (three farms) or low risk (three farms) for SARA on the basis of the proportions of barley, silage and straw in the ration. We measured the concentrations of histamine, lipopolysaccharide (LPS), lactate and other short-chain fatty acids (SCFAs) in ruminal fluid, LPS and SCFA in caecal fluid. We also took samples of the ventral blind sac of the rumen for histopathology, immunohistopathology and gene expression. Subjective assessments were made of the presence of lesions on the ruminal wall, the colour of the lining of the ruminal wall and the shape of the ruminal papillae. Almost all variables differed significantly and substantially among farms. Very few pathological changes were detected in any of the rumens examined. The animals on the high-risk diets had lower concentrations of SCFA and higher concentrations of lactate and LPS in the ruminal fluid. Higher LPS concentrations were found in the caecum than the rumen but were not related to the risk status of the farm. The diameters of the stratum granulosum, stratum corneum and of the vasculature of the papillae, and the expression of the gene TLR4 in the ruminal epithelium were all increased on the high-risk farms. The expression of IFN-γ and IL-1β and the counts of cluster of differentiation 3 positive and major histocompatibility complex class two positive cells were lower on the high-risk farms. High among-farm variation and the unbalanced design inherent in this type of study in the field prevented confident assignment of variation in the dependent variables to individual dietary components; however, the CP percentage of the total mixed ration DM was the factor that was most consistently associated with the variables of interest. Despite the strong effect of farm on the measured variables, there was wide inter-animal variation.
Associations between childhood abuse and various psychotic illnesses in adulthood are commonly reported. We aim to examine associations between several reported childhood adverse events (sexual abuse, physical abuse, emotional abuse, neglect and interpersonal loss) among adults with diagnosed psychotic disorders and clinical and psychosocial outcomes.
Within a large epidemiological study, the 2010 Australian National Survey of Psychosis (Survey of High Impact Psychosis, SHIP), we used logistic regression to model childhood adverse events (any and specific types) on 18 clinical and psychosocial outcomes.
Eighty percent of SHIP participants (1466/1825) reported experiencing adverse events in childhood (sexual abuse, other types of abuse and interpersonal loss). Participants reporting any form of childhood adversity had higher odds for 12/18 outcomes we examined. Significant associations were observed with all psychosocial outcomes (social dysfunction, victimisation, offending and homelessness within the previous 12 months, and definite psychosocial stressor within 12 months of illness onset), with the strongest association for homelessness (odds ratio (OR) = 2.82). Common across all adverse event types was an association with lifetime depression, anxiety and a definite psychosocial stressor within 12 months of illness onset. When adverse event types were non-hierarchically coded, sexual abuse was associated with 11/18 outcomes, other types of abuse 13/18 and, interpersonal loss occurring in the absence of other forms of abuse was associated with fewer of the clinical and psychosocial outcomes, 4/18. When adverse events types were coded hierarchically (to isolate the effect of interpersonal loss in the absence of abuse), interpersonal loss was associated with lower odds of self-reproach (OR = 0.70), negative syndrome (OR = 0.75) and victimisation (OR = 0.82).
Adverse childhood experiences among people with psychosis are common, as are subsequent psychosocial stressors. Mental health professionals should routinely enquire about all types of adversities in this group and provide effective service responses. Childhood abuse, including sexual abuse, may contribute to subsequent adversity, poor psychosocial functioning and complex needs among people with psychosis. Longitudinal research to better understand these relationships is needed, as are studies which evaluate the effectiveness of preventative interventions in high-risk groups.
Autism spectrum disorder (ASD) and schizophrenia (SCZ) are separate neurodevelopmental disorders that are both characterized by difficulties in social cognition and social functioning. Due to methodological confounds, the degree of similarity in social cognitive impairments across these two disorders is currently unknown. This study therefore conducted a comprehensive comparison of social cognitive ability in ASD and SCZ to aid efforts to develop optimized treatment programs.
In total, 101 individuals with ASD, 92 individuals with SCZ or schizoaffective disorder, and 101 typically developing (TD) controls, all with measured intelligence in the normal range and a mean age of 25.47 years, completed a large battery of psychometrically validated social cognitive assessments spanning the domains of emotion recognition, social perception, mental state attribution, and attributional style.
Both ASD and SCZ performed worse than TD controls, and very few differences were evident between the two clinical groups, with effect sizes (Cohen's d) ranging from 0.01 to 0.34. For those effects that did reach statistical significance, such as greater hostility in the SCZ group, controlling for symptom severity rendered them non-significant, suggesting that clinical distinctions may underlie these social cognitive differences. Additionally, the strength of the relationship between neurocognitive and social cognitive performance was of similar, moderate size for ASD and SCZ.
Findings largely suggest comparable levels of social cognitive impairment in ASD and SCZ, which may support the use of existing social cognitive interventions across disorders. However, future work is needed to determine whether the mechanisms underlying these shared impairments are also similar or if these common behavioral profiles may emerge via different pathways.
We have observed the G23 field of the Galaxy AndMass Assembly (GAMA) survey using the Australian Square Kilometre Array Pathfinder (ASKAP) in its commissioning phase to validate the performance of the telescope and to characterise the detected galaxy populations. This observation covers ~48 deg2 with synthesised beam of 32.7 arcsec by 17.8 arcsec at 936MHz, and ~39 deg2 with synthesised beam of 15.8 arcsec by 12.0 arcsec at 1320MHz. At both frequencies, the root-mean-square (r.m.s.) noise is ~0.1 mJy/beam. We combine these radio observations with the GAMA galaxy data, which includes spectroscopy of galaxies that are i-band selected with a magnitude limit of 19.2. Wide-field Infrared Survey Explorer (WISE) infrared (IR) photometry is used to determine which galaxies host an active galactic nucleus (AGN). In properties including source counts, mass distributions, and IR versus radio luminosity relation, the ASKAP-detected radio sources behave as expected. Radio galaxies have higher stellar mass and luminosity in IR, optical, and UV than other galaxies. We apply optical and IR AGN diagnostics and find that they disagree for ~30% of the galaxies in our sample. We suggest possible causes for the disagreement. Some cases can be explained by optical extinction of the AGN, but for more than half of the cases we do not find a clear explanation. Radio sources aremore likely (~6%) to have an AGN than radio quiet galaxies (~1%), but the majority of AGN are not detected in radio at this sensitivity.
Background: In Alberta in 2016 more people died from an opioid overdose than from motor vehicle crashes. Naloxone is an opioid antagonist - it can reverse an opioid overdose for a period of 30 to 60 minutes. Naloxone kits are available free at emergency departments and community organizations around the province with training provided at the point of pickup. It is possible that training may be refused or may be forgotten and people are often left to rely solely on the instructions included in the kit. Human centred design can improve the way people interact with overdose instructions. Aim Statement: This study will measure the effectiveness and usefulness of prototype community naloxone kit instructions over a six month period of time (2018) in Calgary and Edmonton with the aim to use human centred design principles to improve the way people interpret emergency overdose response directions. Measures & Design: Information design experts engaged people with lived experience to provide a process map outlining the current role that educational materials and instructions for community naloxone kits play in responding to an opioid overdose. Alberta Health Services (AHS) Human Factors, in collaboration with AHS harm reduction developed the protocol and administered pre- and post-questionnaire and specific ‘performance checkpoints’ intended to measure effectiveness and usefulness. A simulated overdose including a mannequin, injection trainer and anatomical paper diagram was designed and a community naloxone kit with instructions setting was provided. Participants were recruited through harm reduction nurses with pre-existing clinical relationships (experienced group), family and friends of people who use opioids and general public (non-experienced) through the University of Alberta Faculty of Art and Design. Evaluation/Results: A total of 30 voluntary participants provided their informed consent and engaged in a simulated overdose scenario using a set of prototype instructions developed by a professional information designer. Through repeated data sampling, the following points were observed and will be integrated in the next iteration of design: It isn't clear to people what opioids are. It isn't clear to people that giving a dose of naloxone will not harm a person, especially if they have not overdosed. Almost none of the participants called 911. People seem to read pictures and text equally in the non-experienced group, but in the experienced group, typically read the pictures. Many participants stated that they knew how to do rescue breaths, but did not perform them correctly. Performing the procedure is a not the same as being asked about how to perform the procedure. Discussion/Impact: Even with new instructional prototypes, many participants identified components that were unclear or confusing. The experienced group made less mistakes than the non-experienced group. They seemed to be more invested or interested in saving a friend's life. These instructions will go through another round of design to incorporate feedback from end users. The final product will be part of a larger provincial emergency medicine initiative that includes participant led design and education around emergency response in opioid overdose settings.
While dialectical behaviour therapy (DBT) appears efficacious in reducing suicidal and self-harming behaviour, it is unclear whether DBT reduces emotion regulation (ER) difficulties, a purported mechanism of change of treatment. This review aims to investigate and evaluate the current evidence to understand the effectiveness of DBT in improving ER difficulties. A qualitative synthesis of studies investigating the effectiveness of DBT on self-reported ER difficulties as measured by the Difficulties in Emotion Regulation Scale (DERS) was performed, identifying eligible studies using PsycINFO, PubMed, MEDLINE and EMBASE databases. Fourteen studies were identified. Current evidence indicates that DBT does not show consistent benefits relative to existing psychological treatments in improving ER difficulties. The literature is compromised by significant methodological limitations increasing risk of bias across study outcomes. Furthermore, high variability across DBT programs and a lack of investigation regarding adherence and participant engagement within interventions was observed. Further research is needed in order to conclude regarding the effectiveness of DBT in improving ER difficulties. Consistent use of active treatment conditions, greater standardisation of DBT-based interventions, in addition to further examination of participant engagement level in DBT-based interventions in the long term may assist understanding as to whether DBT improves ER difficulties.
Virtue epistemology is among the dominant influences in mainstream epistemology today. An important commitment of one strand of virtue epistemology – responsibilist virtue epistemology – is that it must provide regulative normative guidance for good thinking. Recently, a number of virtue epistemologists (most notably Baehr) have held that virtue epistemology not only can provide regulative normative guidance, but moreover that we should reconceive the primary epistemic aim of all education as the inculcation of the intellectual virtues. Baehr's picture contrasts with another well-known position – that the primary aim of education is the promotion of critical thinking. In this paper – that we hold makes a contribution to both philosophy of education and epistemology and, a fortiori, epistemology of education – we challenge this picture. We outline three criteria that any putative aim of education must meet and hold that it is the aim of critical thinking, rather than the aim of instilling intellectual virtue, that best meets these criteria. On this basis, we propose a new challenge for intellectual virtue epistemology, next to the well-known empirically driven ‘situationist challenge’. What we call the ‘pedagogical challenge’ maintains that the intellectual virtues approach does not have available a suitably effective pedagogy to qualify the acquisition of intellectual virtue as the primary aim of education. This is because the pedagogic model of the intellectual virtues approach (borrowed largely from exemplarist thinking) is not properly action-guiding. Instead, we hold that, without much further development in virtue-based theory, logic and critical thinking must still play the primary role in the epistemology of education.
This article considers the problem of testing for an explosive bubble in financial data in the presence of time-varying volatility. We propose a sign-based variant of the Phillips, Shi, and Yu (2015, International Economic Review 56, 1043–1077) test. Unlike the original test, the sign-based test does not require bootstrap-type methods to control size in the presence of time-varying volatility. Under a locally explosive alternative, the sign-based test delivers higher power than the original test for many time-varying volatility and bubble specifications. However, since the original test can still outperform the sign-based one for some specifications, we also propose a union of rejections procedure that combines the original and sign-based tests, employing a wild bootstrap to control size. This is shown to capture most of the power available from the better performing of the two tests. We also show how a sign-based statistic can be used to date the bubble start and end points. An empirical illustration using Bitcoin price data is provided.