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Recent studies have identified DAAO as a probable susceptibility gene for schizophrenia and bipolar disorder. However, little is known about how this gene may affect brain function to increase vulnerability to these disorders.
The present investigation examined the impact of DAAO genotype on brain function in patients with schizophrenia, patients with bipolar I disorder and healthy volunteers.
We tested the hypotheses that the high-risk variant of DAAO would be associated with altered prefrontal function and functional connectivity in schizophrenic and bipolar patients.
We used functional magnetic resonance imaging to measure brain responses during a verbal fluency task in a total of 121 subjects comprising 40 patients with schizophrenia, 33 patients with bipolar I disorder and 48 healthy volunteers. We then used statistical parametric mapping (SPM) and psycho-physiological interaction (PPI) analyses to estimate the main effects of diagnostic group, the main effect of genotype and their interaction on brain activation and functional connectivity.
In schizophrenic patients relative to bipolar patients and controls, the high-risk variant of DAAO was associated with lower deactivation in the left precuneus and greater activation in the right calcarine and posterior cingulate gyrus during task performance. In addiction, these areas expressed altered functional connectivity with the rest of the brain in schizophrenic patients relative to bipolar patients and controls.
Our results suggest that genetic variation in DAAO has a significant impact on brain function and provide preliminary evidence for a disease-specific pattern of gene action in specific brain regions.
To examine the effect of a polymorphism in the Dopamine Transporter (DAT) gene on brain activation during executive function and, for the first time:
1. determine the extent to which this is altered in schizophrenia and
2. use a verbal fluency paradigm.
This is relevant since:
1. DAT plays a key role in the regulation of dopamine, which modulates cortical activation during cognitive tasks and
2. a disruption of dopamine function is a fundamental pathophysiological feature of schizophrenia.
Functional magnetic resonance imaging was used to measure whole-brain responses during overt verbal fluency in 85 subjects: 44 healthy volunteers and 41 DSM-IV schizophrenia patients. Main effects of genotype and diagnostic group on activation and their interaction were estimated using an ANOVA in SPM5.
The 10-repeat allele of the 3'UTR VNTR was associated with greater activation than the 9-repeat allele in the left (Z=4.8; FWEp=0.005) and right (Z=4.2; FWEp=0.057) anterior insula and with decreased activation in the rostral anterior cingulate (Z=4.3 FWEp=0.04) during word generation (versus baseline). These effects were irrespective of diagnostic group but generally more marked in patients. There were also strong trends for groupxgenotype interactions in the left middle frontal gyrus and the left nucleus accumbens. Analysis was controlled for task performance, IQ, antipsychotic medication, psychopathology and demographics.
Cortical function during executive tasks is normally modulated by variation in the DAT gene, effect which is dependent on the brain region. DAT's effect may be altered in schizophrenia patients, which may reflect altered central dopamine function.
Akathisia remains a challenge in routine psychiatric practice, despite the widespread use of second generation antipsychotics (SGAs). This analysis was performed to quantify and qualify clinical characteristics of akathisia in schizophrenia or schizoaffective disorder patients experiencing an acute relapse who were randomized to receive aripiprazole, or placebo in 5 pooled short term trials.
A post hoc analysis of the safety dataset was conducted to assess clinical aspects of akathisia in five 4- or 6-week, double-blind, randomized trials comparing aripiprazole (2, 5, 10, 15, 20, 30 mg/day) to placebo.
A total of 1,635 patients was included in this analysis (aripiprazole: n=1170; placebo: n=465). Akathisia was reported by 9% of the aripiprazole-treated patients and 6% of those receiving placebo. Among those reporting akathisia, more patients receiving aripiprazole (83%, n=86) reported this AE within the first 2 weeks of the trials when compared to placebo (69%, n=20). The mean and median duration of akathisia was generally low in both groups (Mean: aripiprazole=12.5 days and placebo=4.2 days; Median, aripiprazole=5.0 days and placebo=1.5 days). The percentage of patients reporting akathisia at endpoint (BARS Item 4≥2) was similar between aripiprazole- (16%) and placebo-treated patients (14%).
In the aripiprazole and placebo groups, akathisia appeared to occur early in treatment, was time-limited, and was associated with high rates of concomitant benzodiazepine usage. Additionally, most cases of akathisia were reported as mild to moderate and rarely associated with treatment discontinuation.
The heritability of the brain’s structure and function in schizophrenia remains elusive
To assess the influence of genetic and environmental factors on executive function in schizophrenia.
A twin-sibling study of 206 subjects; 163 twins, varying in their zygosity and concordance for schizophrenia, and 43 singletons from sibling clusters varying in their concordance for schizophrenia. We assessed performance and regional brain activation using functional magnetic resonance imaging, during a phonological verbal fluency task.
Patients and their unaffected relatives developed greater activation in the left inferior frontal gyrus, and greater deactivation in the middle temporal gyri bilaterally. These features were maximally evident in subjects with schizophrenia. When the analysis was restricted to the unaffected relatives and healthy controls, a similar pattern was evident. Heritability was greatest in the left hippocampus and the right middle temporal gyrus. Genetic modelling indicated a phenotypic correlation between schizophrenia and increased activity in the inferior frontal gyrus and reduced activity in the left middle temporal gyrus and left hippocampus, which appeared principally due to shared genetic effects.
Both schizophrenia and its familial vulnerability were associated with altered frontal, parahippocampal and temporal activation during verbal fluency. The altered left inferior frontal activity was particularly associated with schizophrenia, while altered left medial temporal and right middle temporal activity were more heritable. The latter was more intimately linked to the genetic risk for schizophrenia, and thus the better candidate intermediate phenotype.
Antipsychotics are the cornerstone of treatment for schizophrenia, but they have limited effectiveness, as most patients require subsequent strategies at some point of their treatment. Despite being widely used, the efficacy of pharmacologic augmentation of antipsychotics is controversial and no combination treatment has been approved for schizophrenia. We conducted a systematic review in PubMed and PsycInfo on June 1st 2015 and a random effects meta-analysis of meta-analyses of short-term, placebo-controlled studies of pharmacological augmentation strategies of antipsychotics in schizophrenia. Methodological quality of meta-analyses was measured using the AMSTAR, plus 6 additional items developed to rate the content quality of the meta-analyzed trials. Out of 3062 publications, we identified 36 eligible augmenting strategies. For total symptom reduction, 25 strategies augmenting antipsychotics and 5 strategies augmenting clozapine were eligible and examined. Eleven strategies were more efficacious than placebo, none of them augmenting clozapine. Significant effect sizes ranged between SMD −1.03 and −0.23. Efficacy was not correlated with the quality of the meta-analyses. Only the meta-analysis for NSAIDs augmentation had a score greater than half of the possible points for content quality. Only antipsychotics, azapirones, antidepressants and lithium were less discontinued than placebo. Serotonin-3-receptor antagonists, lamotrigine, mirtazapine/mianserine, minocycline and estrogens had large effect sizes augmenting antipsychotics. However the quality of the content of most meta-analyses was low. The NSAIDs augmentation meta-analysis had the best content quality, yet with a low effect size for efficacy. The evidence for short-term augmentation strategies of antipsychotics in schizophrenia is inconclusive, due to the limited quality of the available trials.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Currently, propofol, while not perfect, has the most suitable PD and PK characteristics suitable for TIVA. Even for the unenlightened the drug is well established as an induction agent, so it is very likely that you will already have some experience of its use – but this chapter will further elucidate this fascinating drug.
Silphium spp. have garnered interest in Europe as a bioenergy crop and in North America as a perennial oilseed crop. However, very little has been done at this early stage of domestication to characterize wild collections for many key characteristics, including important oilseed traits. The objective of this work was to develop a basic understanding of how biogeography and associated population genetic forces have shaped seed phenotypes in plant collections across the native range of Silphium integrifolium Michx. (Asteraceae: Heliantheae), the primary domestication candidate for oilseed use. A collection of 53 accessions was grown in a common environment in Salina, KS, which is a location well within the native range of the species in central North America. Plants from each collection site were randomly mated by hand to produce seed representative of each accession, and the seeds subjected to seed dimensional trait, oil content and oil composition analyses. Kernel width varied along a latitudinal cline of collection site, while kernel length varied across a longitudinal cline. Palmitic and linoleic acids were inversely correlated with each other and varied along a longitudinal cline of the collection site. The results indicate that accessions collected from more southwesterly sites tended to have larger seed and those from more westerly sites had higher linoleic acid content and lower palmitic and myristic acids, which are all desirable phenotypes for an oilseed Silphium.
Digitaria exilis is an important indigenous cereal in West Africa. The first fonio reference transcriptome was released and became a key tool for developing new molecular markers contributing to a better understanding of its genetic diversity. A total of 126 new putative primer pairs were successfully designed in 37,327 unigenes from the D. exilis transcriptome. Thirty-seven primer pairs were randomly selected and tested for their ability to cross-amplify to related species. Clear amplification patterns were observed on 24 primer pairs. Of these, 71, 74 and 35% showed polymorphism in three species: D. exilis, D. longiflora and D. iburua. The transferability from D. exilis was 96% to D. longiflora and 71% to D. iburua. The new SSR markers confirmed the close genetic proximity of D. exilis with D. longiflora and its stronger genetic difference of D. exilis from D. iburua. These markers will be valuable for completing future knowledge on Digitaria evolutionary history, and for testing gene flows between related species.
This work reports on the synthesis and the main physical and chemical properties of ZnO nanoparticles synthesized by an entirely green Bio-physical-chemical process using natural dye extract from Adansonia digitata leaves as an efficient reduction/oxidizing agent. Their structural and surfaces properties by electron microscopy, X-rays diffraction, Raman and TGA, as well as gas adsorption analysis are reported.
To validate a novel photographic portion guide as a tool to estimate consumption of fish and shrimp. Application of such a validated tool can facilitate accurate individual and community seafood intake assessments and provide meaningful data relative to health benefits and hazard assessment, particularly in response to environmental contamination and disasters.
A photographic fish and shrimp portion guide presenting a stepped range of cooked portion sizes was used by participants to estimate their typical portion sizes. Participants selected their typical portion size from the photographic guide and also from a selection of freshly cooked reference meals. Photographic portions selections were compared with plated reference portions for each participant.
Academic sensory testing laboratory in the USA.
Separate groups of adults (25–64 years) contributed to fish (n 54) and shrimp (n 53) portion size comparison studies.
In the fish study, there was no difference between photographic portion selections (6·59 (sd 2·65) oz (186·8 (sd 75·1) g)) and reference plate selections (7·04 (sd 2·63) oz (199·6 (sd 74·6) g); P=0·384). Similarly in the shrimp study, there was no difference between photographic portion selections (6·88 (sd 3·40) oz (195·0 (sd 96·4) g)) and reference plate selections (6·06 (sd 2·65) oz (171·8 (sd 75·1) g); P=0·159). Photographic portions predicted plated reference portions for both fish and shrimp based on linear regression (P<0·001). Bland–Altman plot analyses showed good agreement between the two methods, <1 oz (<28·3 g) bias, in both fish and shrimp studies.
This validated photographic seafood portion guide provides a utilitarian tool for accurately assessing fish and shrimp intake in a community setting.
Background: The evidence regarding whether co-morbid obsessive compulsive personality disorder (OCPD) is associated with treatment outcomes in obsessive compulsive disorder (OCD) is mixed, with some research indicating that OCPD is associated with poorer response, and some showing that it is associated with improved response. Aims: We sought to explore the role of OCPD diagnosis and the personality domain of conscientiousness on treatment outcomes for exposure and response prevention for OCD. Method: The impact of co-morbid OCPD and conscientiousness on treatment outcomes was examined in a clinical sample of 46 participants with OCD. Results: OCPD diagnosis and scores on conscientiousness were not associated with poorer post-treatment OCD severity, as indexed by Yale-Brown Obsessive Compulsive Scale (YBOCS) scores, although the relative sample size of OCPD was small and thus generalizability is limited. Conclusion: This study found no evidence that OCPD or conscientiousness were associated with treatment outcomes for OCD. Further research with larger clinical samples is required.
A pilot study by 6 Clinical and Translational Science Awards (CTSAs) explored how bibliometrics can be used to assess research influence.
Evaluators from 6 institutions shared data on publications (4202 total) they supported, and conducted a combined analysis with state-of-the-art tools. This paper presents selected results based on the tools from 2 widely used vendors for bibliometrics: Thomson Reuters and Elsevier.
Both vendors located a high percentage of publications within their proprietary databases (>90%) and provided similar but not equivalent bibliometrics for estimating productivity (number of publications) and influence (citation rates, percentage of papers in the top 10% of citations, observed citations relative to expected citations). A recently available bibliometric from the National Institutes of Health Office of Portfolio Analysis, examined after the initial analysis, showed tremendous potential for use in the CTSA context.
Despite challenges in making cross-CTSA comparisons, bibliometrics can enhance our understanding of the value of CTSA-supported clinical and translational research.
Violence against women and girls (VAWG) is an urgent global health problem. Root causes for VAWG include the individual- and family-level factors of alcohol abuse, mental health problems, violence exposure, and related adverse experiences. Few studies in low- and middle-income countries (LMIC) have assessed the effectiveness of psychological interventions for reducing VAWG. This randomized controlled trial, part of the What Works to Prevent Violence Against Women and Girls consortium, examines the effectiveness of a common elements treatment approach (CETA) for reducing VAWG and comorbid alcohol abuse among families in Zambia.
Study participants are families consisting of three persons: an adult woman, her male husband or partner, and one of her children aged 8–17 (if available). Eligibility criteria include experience of moderate-to-severe intimate partner violence by the woman and hazardous alcohol use by her male partner. Family units are randomized to receive CETA or treatment as usual. The primary outcome is VAWG as measured by the Severity of Violence Against Women Scale, assessed along with secondary outcomes at 24 months post-baseline. Interim assessments are also conducted at 4–5 months (following CETA completion) and 12 months post-baseline.
This ongoing trial is one of the first in sub-Saharan Africa to evaluate the use of an evidence-based common elements approach for reducing VAWG by targeting a range of individual- and family-level factors, including alcohol abuse. Results of this trial will inform policy on what interventions work to prevent VAWG in LMIC with local perspectives on scale up and wider implementation.
Perfectionism is a risk and maintaining factor across psychopathology and has been proposed to be a transdiagnostic process. The aim of this study was to examine the reliability and validity of the Clinical Perfectionism Questionnaire (CPQ) in 32 adults (75% female, M age = 35.54 years, SD = 9.71) with a range of psychological disorders, presenting for treatment of clinical perfectionism. There was evidence that the CPQ was correlated with established measures of perfectionism and theoretically related constructs including self-criticism and dichotomous thinking. The CPQ was also able to predict treatment outcome. The internal consistency was not adequate in the current study; however, the sample size was small. Future studies should examine the psychometric properties of the CPQ in a larger sample of individuals with a range of psychological disorders.
Studies from low- and middle-income countries (LMIC) indicate that the use of audio computer-assisted self-interviewing (ACASI) is associated with more accurate reporting of sensitive behaviors (e.g. substance use and sexual risk behaviors) compared with interviewer-administered questionnaires. There is a lack of published information on the process of designing, developing, and implementing ACASI in LMIC. In this paper we describe our experience implementing an ACASI system for use with a population of orphans and vulnerable children in Zambia.
A questionnaire of mental health, substance use, and HIV risk behaviors was converted into an ACASI system, tested in pilot and validity studies, and implemented for use in a randomized controlled trial. Successes, barriers, and challenges associated with each stage in the development and implementation of ACASI are described.
We were able to convert a lengthy and complex survey into an ACASI system that was feasible for use in Zambia. Lessons learned include the importance of: (1) piloting the written and electronic versions; (2) proper and extensive training for study assessors to use ACASI and for those doing voice recordings; and (3) attention to logistics such as appropriate space, internet, and power.
We found that ACASI was feasible and acceptable in Zambia with proper planning, training, and supervision. Given mounting evidence indicating that ACASI provides more accurate self-report data and immediate data download compared with interview-administered measures, it may be an effective and economical alternative for behavioral health research studies in LMIC.
We present the results of two 2.3 μm near-infrared (NIR) radial velocity (RV) surveys to detect exoplanets around 36 nearby and young M dwarfs. We use the CSHELL spectrograph (R ~ 46,000) at the NASA InfraRed Telescope Facility (IRTF), combined with an isotopic methane absorption gas cell for common optical path relative wavelength calibration. We have developed a sophisticated RV forward modeling code that accounts for fringing and other instrumental artifacts present in the spectra. With a spectral grasp of only 5 nm, we are able to reach long-term radial velocity dispersions of ~20–30 m s−1 on our survey targets.