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Implementation of genome-scale sequencing in clinical care has significant challenges: the technology is highly dimensional with many kinds of potential results, results interpretation and delivery require expertise and coordination across multiple medical specialties, clinical utility may be uncertain, and there may be broader familial or societal implications beyond the individual participant. Transdisciplinary consortia and collaborative team science are well poised to address these challenges. However, understanding the complex web of organizational, institutional, physical, environmental, technologic, and other political and societal factors that influence the effectiveness of consortia is understudied. We describe our experience working in the Clinical Sequencing Evidence-Generating Research (CSER) consortium, a multi-institutional translational genomics consortium.
A key aspect of the CSER consortium was the juxtaposition of site-specific measures with the need to identify consensus measures related to clinical utility and to create a core set of harmonized measures. During this harmonization process, we sought to minimize participant burden, accommodate project-specific choices, and use validated measures that allow data sharing.
Identifying platforms to ensure swift communication between teams and management of materials and data were essential to our harmonization efforts. Funding agencies can help consortia by clarifying key study design elements across projects during the proposal preparation phase and by providing a framework for data sharing data across participating projects.
In summary, time and resources must be devoted to developing and implementing collaborative practices as preparatory work at the beginning of project timelines to improve the effectiveness of research consortia.
Psychiatric services providing care for patients and their families confronted with a first psychotic episode need to be sensitive towards patients’ and families’ preferences. Ten patients, ten family members and ten professional caregivers composed a list of 42 preferences in the treatment for a first psychotic episode. In total 99 patients, 100 family members and 263 professional caregivers evaluated these preferences, thus producing an order of priorities. There appears to be considerable agreement among the groups of respondents regarding their top ten priorities, especially concerning information on diagnosis and medication. However, we found important differences between groups of respondents. The results suggest that in psychiatric services great attention should be given to psycho-education and early outpatient intervention.
Impairment of insight in psychotic disorder is associated with adverse impact in treatment compliance, outcome and social functioning although its underlying mechanisms are still unknown. Social cognition and more specifically Theory of mind have been proposed to be correlated to insight. However, the relationship between both factors is still not well defined.
To study the association between social cognition and insight into mental illness in individuals with early psychosis included in the first episode of psychosis program of Hospital del Mar.
From the 94 patients included in the first psychotic episode program between January 2011 and January 2016, thirty-eight patients were evaluated six months after the episode. The three initial items of SUMD (Scale Unawareness of Mental Disorder) were used to measure insight and MSCEIT (Mayer-Salovey-Caruso Emotional Intelligence Test) was used to assess social cognition. Linear correlation analysis by Pearson correlation was conducted.
Insight results of SUMD six months after the first episode of psychosis were significantly associated with several subsections of MSCEIT, such as experiential area total punctuation (r = –0.574; P = 0.025), emotional facilitation section (r = –0.633; P = 0.011) and the facial emotion perception task (r = –0.572; P = 0.026).
Results suggest an association between insight and emotional perception and facilitation performance in first episode patients, which may suggest a role of social cognition in psychosis insight impairment. Further research to better define the participation of social cognition in insight into psychosis alteration is mandatory to understand the etiology of insight, define treatment targets and consequently improve the disorder prognosis.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Surface melt on the coastal Antarctic ice sheet (AIS) determines the viability of its ice shelves and the stability of the grounded ice sheet, but very few in situ melt rate estimates exist to date. Here we present a benchmark dataset of in situ surface melt rates and energy balance from nine sites in the eastern Antarctic Peninsula (AP) and coastal Dronning Maud Land (DML), East Antarctica, seven of which are located on AIS ice shelves. Meteorological time series from eight automatic and one staffed weather station (Neumayer), ranging in length from 15 months to almost 24 years, serve as input for an energy-balance model to obtain consistent surface melt rates and energy-balance results. We find that surface melt rates exhibit large temporal, spatial and process variability. Intermittent summer melt in coastal DML is primarily driven by absorption of shortwave radiation, while non-summer melt events in the eastern AP occur during föhn events that force a large downward directed turbulent flux of sensible heat. We use the in situ surface melt rate dataset to evaluate melt rates from the regional atmospheric climate model RACMO2 and validate a melt product from the QuikSCAT satellite.
Our understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity.
This study included 1985 individuals with schizophrenia from 17 research groups around the world contributing to the ENIGMA Schizophrenia Working Group. Cortical thickness values were obtained from T1-weighted structural brain scans using FreeSurfer. A meta-analysis across sites was conducted over effect sizes from a model predicting cortical thickness by negative symptom score (harmonized Scale for the Assessment of Negative Symptoms or Positive and Negative Syndrome Scale scores).
Meta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (βstd = −0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged.
Using an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in schizophrenia.
Early trauma is linked to higher symptom levels in bipolar and psychotic disorders, but the translating mechanisms are not well understood. This study examines whether the relationship between early emotional abuse and depressive symptoms is mediated by metacognitive beliefs about thoughts being uncontrollable/dangerous, and whether this pathway extends to influence positive symptoms.
Patients (N = 261) with psychotic or bipolar disorders were assessed for early trauma experiences, metacognitive beliefs, and current depression/anxiety and positive symptoms. Mediation path analyses using ordinary least-squares regressions tested if the effect of early emotional abuse on depression/anxiety was mediated by metacognitive beliefs, and if the effect of early emotional abuse on positive symptoms was mediated by metacognitive beliefs and depression/anxiety.
Metacognitive beliefs about thoughts being uncontrollable/dangerous significantly mediated the relationship between early emotional abuse and depression/anxiety. Metacognitive beliefs and depression/anxiety significantly mediated the relationship between early emotional abuse and positive symptoms. The models explained a moderate amount of the variance in symptoms (R2 = 0.21–0.29).
Our results indicate that early emotional abuse is relevant to depression/anxiety and positive symptoms in bipolar and psychotic disorders, and suggest that metacognitive beliefs could play a role in an affective pathway to psychosis. Metacognitive beliefs could be relevant treatment targets with regards to depression/anxiety and positive symptoms in bipolar and psychotic disorders.
Current ultra-high-risk (UHR) criteria appear insufficient to predict imminent onset of first-episode psychosis, as a meta-analysis showed that about 20% of patients have a psychotic outcome after 2 years. Therefore, we aimed to develop a stage-dependent predictive model in UHR individuals who were seeking help for co-morbid disorders.
Baseline data on symptomatology, and environmental and psychological factors of 185 UHR patients (aged 14–35 years) participating in the Dutch Early Detection and Intervention Evaluation study were analysed with Cox proportional hazard analyses.
At 18 months, the overall transition rate was 17.3%. The final predictor model included five variables: observed blunted affect [hazard ratio (HR) 3.39, 95% confidence interval (CI) 1.56–7.35, p < 0.001], subjective complaints of impaired motor function (HR 5.88, 95% CI 1.21–6.10, p = 0.02), beliefs about social marginalization (HR 2.76, 95% CI 1.14–6.72, p = 0.03), decline in social functioning (HR 1.10, 95% CI 1.01–1.17, p = 0.03), and distress associated with suspiciousness (HR 1.02, 95% CI 1.00–1.03, p = 0.01). The positive predictive value of the model was 80.0%. The resulting prognostic index stratified the general risk into three risk classes with significantly different survival curves. In the highest risk class, transition to psychosis emerged on average ⩾8 months earlier than in the lowest risk class.
Predicting a first-episode psychosis in help-seeking UHR patients was improved using a stage-dependent prognostic model including negative psychotic symptoms (observed flattened affect, subjective impaired motor functioning), impaired social functioning and distress associated with suspiciousness. Treatment intensity may be stratified and personalized using the risk stratification.
Tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) may be associated with lower heart rate variability (HRV), a condition associated with increased mortality risk. We aimed to investigate the association between TCAs, SSRIs and HRV in a population-based study.
In the prospective Rotterdam Study cohort, up to five electrocardiograms (ECGs) per participant were recorded (1991–2012). Two HRV variables were studied based on 10-s ECG recordings: standard deviation of normal-to-normal RR intervals (SDNN) and root mean square of successive RR interval differences (RMSSD). We compared the HRV on ECGs recorded during use of antidepressants with the HRV on ECGs recorded during non-use of any antidepressant. Additionally, we analysed the change in HRV on consecutive ECGs. Those who started or stopped using antidepressants before the second ECG were compared with non-users on two ECGs.
We included 23 647 ECGs from 11 729 participants (59% women, mean age 64.6 years at baseline). Compared to ECGs recorded during non-use of antidepressants (n = 22 971), SDNN and RMSSD were lower in ECGs recorded during use of TCAs (n = 296) and SSRIs (n = 380). Participants who started using TCAs before the second ECG had a decrease in HRV and those who stopped had an increase in HRV compared to consistent non-users (p < 0.001). Starting or stopping SSRIs was not associated with HRV changes.
TCAs were associated with a lower HRV in all analyses, indicating a real drug effect. For SSRIs the results are mixed, indicating a weaker association, possibly due to other factors.
We internally validated previously published rates of remission, continuation and incidence of broadly defined eating disorders during pregnancy in the Norwegian Mother and Child Cohort (MoBa) at the Norwegian Institute of Public Health.
A total of 77 267 pregnant women enrolled at 17 weeks gestation between 2001 and 2009 were split into a training sample (n = 41 243) from the version 2 dataset and a validation sample (n = 36 024) from the version 5 dataset who were not in the original study. Internal validation of original rate models involved fitting a calibration model to compare model parameters between the two samples and bootstrap estimates of bias in the entire version 5 dataset.
Remission, continuation and incidence estimates remained stable. Pre-pregnancy prevalence estimates in the validation sample were: anorexia nervosa (AN; 0.1%), bulimia nervosa (BN; 1.0%), binge eating disorder (BED; 3.3%) and eating disorder not otherwise specified-purging disorder (EDNOS-P; 0.1%). In early pregnancy, estimates were: BN (0.2%), BED (4.8%) and EDNOS-P (<0.01%). Incident BN and EDNOS-P during pregnancy were rare. The highest rates were for full or partial remission for BN and EDNOS-P and continuation for BED.
We validated previously estimated rates of remission, continuation and incidence of eating disorders during pregnancy. Eating disorders, especially BED, during pregnancy were relatively common, occurring in nearly one in every 20 women. Pregnancy was a window of remission from BN but a window of vulnerability for BED. Training to detect eating disorders by obstetricians/gynecologists and interventions to enhance pregnancy and neonatal outcomes warrant attention.
The aim of this study was to determine the potential association between housing type and multiple drug resistance (MDR) in Escherichia coli and Enterococcus faecalis isolates recovered from 283 laying-hen flocks. In each flock, a cloacal swab from four hens was collected and produced 1102 E. coli and 792 E. faecalis isolates. Broth microdilution was used to test susceptibility to antimicrobials. Country and housing type interacted differently with the MDR levels of both species. In the E. coli model, housing in a raised-floor system was associated with an increased risk of MDR compared to the conventional battery system [odds ratio (OR) 2·12, 95% confidence interval (CI) 1·13–3·97)]. In the E. faecalis model the MDR levels were lower in free-range systems than in conventional battery cages (OR 0·51, 95% CI 0·27–0·94). In Belgium, ceftiofur-resistant E. coli isolates were more numerous than in the other countries.
Trap crops are a plausible control strategy for the wheat stem sawfly (WSS), Cephus cinctus Norton (Hymenoptera: Cephidae), especially in alternate wheat−fallow cropping systems. Identifying the most suitable winter wheat (Triticum aestivum L., Poaceae) cultivars is necessary to further improve the effectiveness of winter wheat trap crops. We compared cultivars suitable for cultivation in Montana to identify those that exhibit the greatest potential as trap crops. To accomplish this we used nine winter wheat cultivars to analyze plant characteristics that influence the oviposition behavior of the WSS: stem height, stem diameter, rate of plant development, and emission of the WSS attractant (Z)-3-hexenyl acetate. Data on sawfly-induced stem cutting collected from these cultivars in field nurseries were analyzed to evaluate the potential of each cultivar to attract sawflies. Based on these criteria, five cultivars with good potential as trap crops are ‘Norstar’, ‘Neeley’, ‘Morgan’, ‘Rampart’, and ‘BigSky’. More data from laboratory preference tests and detailed measurement of semiochemical production from these cultivars are required for selecting optimal cultivars for trap-cropping.