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The nature and degree of cognitive impairments in schizoaffective disorder is not well established. The aim of this meta-analysis was to characterise cognitive functioning in schizoaffective disorder and compare it with cognition in schizophrenia and bipolar disorder. Schizoaffective disorder was considered both as a single category and as its two diagnostic subtypes, bipolar and depressive disorder.
Following a thorough literature search (468 records identified), we included 31 studies with a total of 1685 participants with schizoaffective disorder, 3357 with schizophrenia and 1095 with bipolar disorder. Meta-analyses were conducted for seven cognitive variables comparing performance between participants with schizoaffective disorder and schizophrenia, and between schizoaffective disorder and bipolar disorder.
Participants with schizoaffective disorder performed worse than those with bipolar disorder (g = −0.30) and better than those with schizophrenia (g = 0.17). Meta-analyses of the subtypes of schizoaffective disorder showed cognitive impairments in participants with the depressive subtype are closer in severity to those seen in participants with schizophrenia (g = 0.08), whereas those with the bipolar subtype were more impaired than those with bipolar disorder (g = −0.23) and less impaired than those with schizophrenia (g = 0.29). Participants with the depressive subtype had worse performance than those with the bipolar subtype but this was not significant (g = 0.25, p = 0.05).
Cognitive impairments increase in severity from bipolar disorder to schizoaffective disorder to schizophrenia. Differences between the subtypes of schizoaffective disorder suggest combining the subtypes of schizoaffective disorder may obscure a study's results and hamper efforts to understand the relationship between this disorder and schizophrenia or bipolar disorder.
Measurements of a variety of physical properties of muscle tissue have been proposed as objective tests for meat tenderness. We have attempted to single out a specific physical factor, namely tensile stress, and to determine its effect on the ultrastructure of raw and cooked muscle tissue. Extension of this approach to the other physical factors involved in mastication will hopefully establish the structural factors important to meat tenderness.
The bovine semitendenosus muscle (eye round) was obtained either commercially or excised from a carcass aged under controlled conditions for 10 days. Small strips (¼” x ¼” x 1-½”), raw and cooked at 90°C, were subjected to tensile stress and then fixed in glutaraldehyde. A motorized minitensile stage (Fig. 1), designed to be small enough to operate within the SEM, stressed the muscle samples while viewed by a stereomicroscope and simultaneously monitored with a closed circuit TV system. Identical areas of samples subjected to tensile stress could be observed in both the light and scanning electron microscopes (Fig. 2).
The dendrite morphologies of the cast nickel-based superalloy CMSX-4® (CMSX-4® is registered trademarks of the Cannon-Muskegon Corporation) and the austenitic stainless steel HP microalloy have been obtained via an automated serial-sectioning process which allows three-dimensional (3D) microstructural characterization. The dendrite arm spacing, volume fraction of segregation, and fraction of porosity have been determined. This technique not only increases the depth, scope, and level of detailed microstructural characterization but also delivers microstructural data for modeling and simulation.
It is not clear to what extent associations between schizophrenia, cannabis use and cigarette use are due to a shared genetic etiology. We, therefore, examined whether schizophrenia genetic risk associates with longitudinal patterns of cigarette and cannabis use in adolescence and mediating pathways for any association to inform potential reduction strategies.
Associations between schizophrenia polygenic scores and longitudinal latent classes of cigarette and cannabis use from ages 14 to 19 years were investigated in up to 3925 individuals in the Avon Longitudinal Study of Parents and Children. Mediation models were estimated to assess the potential mediating effects of a range of cognitive, emotional, and behavioral phenotypes.
The schizophrenia polygenic score, based on single nucleotide polymorphisms meeting a training-set p threshold of 0.05, was associated with late-onset cannabis use (OR = 1.23; 95% CI = 1.08,1.41), but not with cigarette or early-onset cannabis use classes. This association was not mediated through lower IQ, victimization, emotional difficulties, antisocial behavior, impulsivity, or poorer social relationships during childhood. Sensitivity analyses adjusting for genetic liability to cannabis or cigarette use, using polygenic scores excluding the CHRNA5-A3-B4 gene cluster, or basing scores on a 0.5 training-set p threshold, provided results consistent with our main analyses.
Our study provides evidence that genetic risk for schizophrenia is associated with patterns of cannabis use during adolescence. Investigation of pathways other than the cognitive, emotional, and behavioral phenotypes examined here is required to identify modifiable targets to reduce the public health burden of cannabis use in the population.
OBJECTIVES/GOALS: HIV-specific CD8+ T-cells play a critical role in partially controlling viral replication in infected-individuals, but ultimately fail to eliminate infection. Enhancing these T-cell responses through lymphocyte engineering approaches has the potential as a novel therapy capable of achieving durable control or eradication of infection. METHODS/STUDY POPULATION: IL-15 Superagonist (IL-15SA) potently supports the in vivo persistence and antiviral activity of adoptively transferred CD8+ T-cells. The Deep-PrimingTM technology platform, developed by Torque, allows for loading of immunomodulators onto the surface of T-cells via electrostatic ‘nanogels’, which slowly release to deliver sustained autocrine immune stimulation without the harmful effects of systemic exposure. Here, we investigate the impact of IL-15SA Deep-Priming on HIV-specific CD8+ T-cells in a humanized mouse model of HIV infection. Humanized mice were generated by engrafting NOD-scid-IL2Rgnull mice with memory CD4+ T-cells isolated from an ARV-suppressed HIV+ donor. An autologous HIV-specific Cytotoxic T-Lymphocyte (CTL) clone was isolated, and killing potential confirmed. Four weeks post humanization, mice were infected with HIV and received an infusion of unmodified HIV-Specific CTLs, or IL-15SA Deep-Primed HIV-specific CTLs (CTL-DP). T-cell numbers and plasma viral loads were quantified weekly by flow cytometry and qRT-PCR. RESULTS/ANTICIPATED RESULTS: Mice receiving unmodified CTLs trended toward reduced viral loads compared to the No Treatment condition, while mice receiving CTL-DP saw significant, 2-Log10 reductions in VL (p < 0.01). At 41 days post-infection 100% (5/5) of the No Treatment, 66.7% (4/6) of the CTL treatment, and 16.7% (1/6) of CTL-DP treatment mice had detectable viremia. IL-15SA Deep-Priming increased CTL expansion and persistence in peripheral blood which correlated with improved CD4+T-cell preservation. DISCUSSION/SIGNIFICANCE OF IMPACT: Here we demonstrate the first in vivo analysis of IL-15SA Deep-Priming of HIV-Specific CTLs. These data suggest that Deep-Priming of patient T-cells can enhance in vivo function and persistence, leading to improved viral suppression; a significant advancement in the field of HIV cure research. CONFLICT OF INTEREST DESCRIPTION: Austin Boesch, Thomas Andresen, and Douglas Jones are employees of Torque. Darrell Irvine is a co-founder of Torque and Chairman of Torque’s Scientific Advisory Board.
Introduction: Medical record review (MRR) studies are commonly used in Emergency Medicine (EM) research. It is not always clear how sample size calculations are reported, or the methods by which they were derived. This scoping review sought to examine reporting and justification of MRR sample sizes from the EM literature. Methods: Using Web of Science, we identified the top ten journals, based on impact factor rating in 2018, within the field of Emergency Medicine. Journals were excluded if they were not in English or did not include sufficient articles for analysis. Within each of these ten selected journals, we searched for chart reviews and related terms: "medical record", "outpatient record", "inpatient record", "clinical record", and "nursing note". From this search subset, five articles were randomly selected from each journal. Data about sample size and sample size selection were extracted and analyzed by two reviewers independently for each article. Results: Of the 50 articles randomly selected, 48 articles were retrospective MRRs and two articles were prospective MRRs. 78% (39 articles) chose sample size based on availability, 14% (seven articles) chose sample size based on power calculations, 4% (two articles) chose sample size based on a previous study's methodology, and 4% (two articles) did not give details on sample size selection. Conclusion: While some emergency medicine MRRs based sample size selection on power or previous studies, the vast majority are based on availability with study-specific exclusion/inclusion criteria. This may indicate they are using a smaller sample size than necessary to be sufficiently powered to assess their end goal. More work is required to determine the effect of this on outcomes and interpretability of results, as well as which method is most accurate and efficient.
Teams are an integral part of organizations; however, changes in the nature of work – including increases in globalization, the scale and complexity of problems, and the capabilities of technology – have fundamentally altered the nature of teams. In this chapter, we delineate three important changes to the nature of teams: (1) complex organizational challenges are requiring complex and fluid patterns of teamwork; (2) teams are being assembled and led by members as well as managers; and (3) technology is increasingly interwoven with teamwork. In reference to these changes, we provide recommendations for future research and management of teams.
To investigate the feasibility, and patient/psychiatrist acceptability, of an SMS text messaging system reminding patients receiving quetiapine to take their medication.
8-12(mean:9.4) week, non-interventional, psychiatrist assessed, pilot study of 27 outpatients receiving quetiapine (mean age[range]: 35.3[19-57] years). Patients were asked to reply to SMS messages sent twice daily to their cellular phone to remind them to take their medication (morning) and enquire about their well-being (evening). Patients' response (morning-yes/no; evening-positive/negative/neutral) was monitored by psychiatrists (n=7) via a website, and subsequently used to assess technical feasibility. Psychiatrists rated acceptability and feasibility of the system by completing case report forms (CRFs). Data are from the LOCF population.
Patients responded to 77% (compliance) of the 5,000 SMS messages sent (84% correctly, 13% inaccurately, 3% responded late [eg, day after]). 7/27 patients withdrew prematurely. The most common benefits expressed by patients were that they felt cared for (n=11/21) and were reminded to take their medication (n=7/21). Psychiatrists' ratings of the system improved over time, with SMS compliance and increased patient contact seen as the most valuable aspects. At study end, CRF data showed psychiatrists felt the system was valuable to 19/22 patients, 16/24 patients remained compliant with the system and 16/22 patients felt the frequency of SMS messages was acceptable. There was a strong correlation between patients giving positive well-being responses and SMS compliance (R Pearson=0.72, p<0.001).
The high levels of SMS compliance and benefits expressed by patients and psychiatrists support a larger-scale assessment of this system.
Psychiatry in the UK has longstanding recruitment problems (1). Evidence suggests the positive effects of clinical attachments on attitudes towards psychiatry are often transient (2). We therefore created the Psychiatry Early Experience Programme (PEEP) where year 1 medical students are paired with psychiatry trainees and shadow them at work. Students will ideally remain in PEEP throughout medical school, providing consistent exposure to psychiatry and a broad experience of its subspecialties.
1. To present PEEP
2. To assess:
a. Students’ baseline attitudes to psychiatry
b. PEEPs’ impact on students’ attitudes to psychiatry
A prospective survey based cohort study of King’s College London medical students.
PEEP started in 2013. In this cohort all students that signed up were accepted.
Students’ attitudes towards psychiatry were assessed on recruitment using the ATP-30 questionnaire (3), and will be re-assessed annually.
127 students were recruited. Attitudes were positive overall. 73% listed psychiatry in their top three specialities. 95.3% agreed or strongly agreed that ‘psychiatric illness deserves at least as much attention as physical illness.’ 84.3% disagreed or strongly disagreed that ‘at times it is hard to think of psychiatrists as equal to other doctors.’
Baseline attitudes to psychiatry were positive. By March 2015 we aim to collect and analyse data on students’ attitudes after one year in PEEP. Through on-ongoing analysis of this and future cohorts, we aim to assess the impact of PEEP on improving attitudes to psychiatry and whether this will ultimately improve recruitment.
There has been increasing interest in the association between childhood trauma and psychosis. Proposals for potential mechanisms involved include affective dysregulation and appraisals of threat, yet few large-scale clinical studies exist in affective psychosis.
We hypothesise that within bipolar disorder (BD), childhood events will show a significant association with psychosis, and in particular with symptoms driven by dysregulation of mood or with a persecutory content.
2019 participants were recruited as part of our programme of research into the genetic and non-genetic determinants of BD (www.bdrn.org). Data on lifetime ever presence of psychosis and specific psychotic symptoms were determined by detailed structured interview with case note review. Childhood events were recorded after self-report questionnaire and case note information.
There was no relationship between childhood events, or childhood abuse, and psychosis per se. Childhood events were not associated with increased risk of persecutory or other delusions. Significant associations were found between childhood abuse and auditory hallucinations, strongest between sexual abuse and mood congruent or abusive voices. These relationships remain significant after controlling for lifetime ever cannabis misuse.
Within affective disorder, the relationship between childhood events and psychosis appears to be relatively symptom-specific. It is possible that the pathways leading to psychotic symptoms differ, with delusions and non-hallucinatory symptoms being influenced less by childhood or early environmental experience.
1. Upthegrove R, Chard C, Jones, L, Gordon –Smith K, Forty L, Jones I and Craddock N. Adverse Childhood Events and Psychosis in Bipolar Affective Disorder. BJPsych In press BJP/2014/152611
There are limited amount of studies comparing time trends of incidence and risk factors of psychosis.
To compare time trends of incidence of psychosis in two population samples.
To study 1) onset age and cumulative incidence of psychoses in two Northern Finland Birth Cohorts (NFBC), 2) changes in type of diagnosis and risk factors.
The NFBC 1966 (N=12,058) and NFBC 1986 (N=9,432) are prospective cohorts of the two provinces of Finland with the live born children followed since pregnancy. The data for psychosis and risk factors were collected from variety of nationwide registers and earlier collected data of the NFBCs. The follow-up time was in both cohorts in average 26.5 years.
Proportion of all psychoses was higher in NFBC 1986 than in the NFBC 1966 (1.81% vs 1.0%). There were more affective psychoses in NFBC 1986 (0.5% vs 0.1%), but incidence of schizophrenia was the same (0.4%) in both cohorts. The age of onset was lower in NFBC 1986 than in NFBC 1966 and majority of this cases were females. Only parental psychosis was a significant risk factor predicting psychosis (Hazard Ratios >3.0) in both cohorts.
In conclusion, two birth cohorts within 20 years covering altogether about 40 years showed changes in terms of incidence, age of onset, and type of psychosis.
The effects of long-term antipsychotic medication on cognition in schizophrenia are unclear (Husa A.P. et al., Schizophr. Res. 2014).
Understanding how long-term antipsychotic treatment affects cognition is crucial for the development of safe, evidence-based treatment of schizophrenia.
To analyse the association between cumulative lifetime antipsychotic dose and cognition in schizophrenia at age 43 years in a general population sample.
Sixty (33 males) schizophrenia spectrum subjects from the Northern Finland Birth Cohort 1966 were assessed at age 43 years by California Verbal Learning Test, Visual Object Learning Test, Abstraction Inhibition and Working Memory task, Verbal fluency, Visual series, Vocabulary, Digit Span and Matrix reasoning. Cumulative lifetime antipsychotic dose-years were collected from treatment records and interviews. A factor analysis based on the cognitive tests resulted in one cognitive factor. The association between this cognitive composite score and antipsychotic dose-years was analysed by linear regression.
Higher lifetime antipsychotic dose-years were statistically significantly associated with poorer cognitive composite score at age 43 years (B=-0.32, p>0.001), also when adjusted for gender, onset age, remission and number of hospital treatment days (B=-0.42, p=0.008).
To our knowledge, this is the first report of an association between cumulative lifetime antipsychotic dose and cognition in midlife in schizophrenia. Based on this data, the use of high antipsychotic doses may relate to poorer cognitive functioning in schizophrenia after twenty years of illness. These results do not support the view that antipsychotics prevent cognitive decline or promote cognitive recovery in schizophrenia.
Our aim was to investigate how age of achieving early motor developmental milestones differ among subjects with and without a history of parental psychosis and whether parental psychosis may alter the effects of the age of achievement on the risk of schizophrenia.
The study sample comprised 10,307 individuals from the prospective Northern Finland Birth Cohort 1966. A total of 139 (1.3%) cohort members suffered from schizophrenia by the age of 46 years. Out of them 19 (13.7%) had a parent with a history of psychosis, while among the non-psychotic cohort members this figure was 524 (5.2%).
Out of eight different motor milestones investigated, parental psychosis associated (p>0.05) with later learning of holding head up, grabbing object, and walking without support. In the parental psychosis group, significant risk factors for schizophrenia included later learning of holding head up and touching thumb with index finger. In the non-parental psychosis group risk estimates were lower and statistical significant milestones were different i.e. turning over, sitting without support, standing up, standing and walking without support. Interactions between parental psychosis and touching thumb with index finger and walking without support was found.
Although parental psychosis associated with delays in motor milestones in the first year of life, it does not explain the association between late achievement of motor milestones and later risk for schizophrenia
Stress and reward processing are two of the principal mechanisms involved in the modulation of homeostasis in the body. According to neurobiological research, these two mechanisms overlap in the cortico-striatal-limbic circuit, which can be disrupted due to chronic stress and substance abuse. Stress is primarily modulated by the hypothalamic-pituitary-adrenal (HPA) axis, from which cortisol is an end-product.
The aim of the study was to investigate the effects of chronic stimulant abuse on the cortico-striatal limbic circuit. This was examined by relating cortisol levels with grey matter volume in brain structures associated with addiction and stress.
We hypothesised that stimulant-dependent individuals show increased cortisol levels and abnormalities in the corticostriatal- limbic circuit. We further hypothesised relationships between altered grey matter volume and increased cortisol levels in the patients.
Twenty-two stimulant-dependent individuals and 21 healthy volunteers (matched for age and gender) underwent an assessment session and structural MRI brain scan. Cortisol was assessed in saliva and blood plasma. Mood, impulsivity and compulsivity were measured by clinical instruments.
Stimulant-dependent individuals showed higher levels of cortisol in both saliva and blood, which were associated with distinct alterations in grey matter volume in fronto-limbic structures. Plasma cortisol was positively correlated with the duration of cocaine use. No relationships were found with current mood, trait-impulsivity and drug-related compulsivity.
The relationships observed between cortisol and fronto-limbic structures may, in part, be explained by HPA axis dysfunction and its downstream effects on brain structures involved in stress modulation in stimulant-dependent individuals.
A clearer understanding of the ebb and flow of depression and suicidal thinking in the early phase of psychosis, and how this relates to other symptom dimensions, is essential for developing interventions to reduce risk. The studies presented here investigate whether depression and suicidal thinking are predictable, how they relate to the early course of psychotic symptoms and develop over time.
92 patients with first episode psychosis recruited from the Birmingham Early Intervention Service completed measures of depression, including an prodromal depression, psotove and negative symptoms, self-harm, duration of untreated psychosis, insight and illness appraisals. Follow up took place over 12 months.
Depression occurred in 80% of patients at one or more phase of illness; a combination of depression and suicidal thinking was present in 63%. Depression in the prodromal phase was the most significant predictor of future depression and acts of selfharm. Post psychotic depression unheralded by previous depressive episodes was rare. Depression and suicidal thinking in the acute and post psychotic phases is associated with higher levels of loss and shame, and subordination to persecutors and malevolent voices.
Depression early in the emergence of a psychosis is fundamental to the development of future depression and suicidal thinking, and related to the personal significance and impact of positive symptom dimensions. Efforts to predict and reduce depression and self-harm in psychosis may need to target this early phase to reduce later risk.