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Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.
Methods
T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).
Results
PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).
Conclusions
PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.
To improve early intervention and personalise treatment for individuals early on the psychosis continuum, a greater understanding of symptom dynamics is required. We address this by identifying and evaluating the movement between empirically derived attenuated psychotic symptomatic substates—clusters of symptoms that occur within individuals over time.
Methods
Data came from a 90-day daily diary study evaluating attenuated psychotic and affective symptoms. The sample included 96 individuals aged 18–35 on the psychosis continuum, divided into four subgroups of increasing severity based on their psychometric risk of psychosis, with the fourth meeting ultra-high risk (UHR) criteria. A multilevel hidden Markov modelling (HMM) approach was used to characterise and determine the probability of switching between symptomatic substates. Individual substate trajectories and time spent in each substate were subsequently assessed.
Results
Four substates of increasing psychopathological severity were identified: (1) low-grade affective symptoms with negligible psychotic symptoms; (2) low levels of nonbizarre ideas with moderate affective symptoms; (3) low levels of nonbizarre ideas and unusual thought content, with moderate affective symptoms; and (4) moderate levels of nonbizarre ideas, unusual thought content, and affective symptoms. Perceptual disturbances predominantly occurred within the third and fourth substates. UHR individuals had a reduced probability of switching out of the two most severe substates.
Conclusions
Findings suggest that individuals reporting unusual thought content, rather than nonbizarre ideas in isolation, may exhibit symptom dynamics with greater psychopathological severity. Individuals at a higher risk of psychosis exhibited persistently severe symptom dynamics, indicating a potential reduction in psychological flexibility.
Digital Mental Health Interventions (DMHIs) that meet the definition of a medical device are regulated by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK. The MHRA uses procedures that were originally developed for pharmaceuticals to assess the safety of DMHIs. There is recognition that this may not be ideal, as is evident by an ongoing consultation for reform led by the MHRA and the National Institute for Health and Care Excellence.
Aims
The aim of this study was to generate an experts’ consensus on how the medical regulatory method used for assessing safety could best be adapted for DMHIs.
Method
An online Delphi study containing three rounds was conducted with an international panel of 20 experts with experience/knowledge in the field of UK digital mental health.
Results
Sixty-four items were generated, of which 41 achieved consensus (64%). Consensus emerged around ten recommendations, falling into five main themes: Enhancing the quality of adverse events data in DMHIs; Re-defining serious adverse events for DMHIs; Reassessing short-term symptom deterioration in psychological interventions as a therapeutic risk; Maximising the benefit of the Yellow Card Scheme; and Developing a harmonised approach for assessing the safety of psychological interventions in general.
Conclusion
The implementation of the recommendations provided by this consensus could improve the assessment of safety of DMHIs, making them more effective in detecting and mitigating risk.
Visual deficits are common after stroke and are powerful predictors for the chronic functional outcome. However, while basic visual field and recognition deficits are relatively easy to assess with standardized methods, selective deficits in visual primitives, such as shape or motion, are harder to identify, as they often require a symmetrical bilateral posterior lesion in order to provoke full field deficits. We aimed to investigate the prevalence and co-occurrence of hemifield “mid-range” visual deficits. In addition, we looked at the repercussions of these mid-range deficits on higher-order visual cognitive functions, such as visuoconstruction and memory. At a more theoretical level, we investigated whether associations between deficits in 'mid-range’ visual functions and deficits in higher-order visual cognitive functions are in line with a hierarchical, two-pathway model of the visual brain.
Participants and Methods:
In 220 stroke patients and a healthy control group (N=49), we assessed the perception of colour (isoluminant stimuli in the red-green range), shape (Efron shapes), location (dot in a circle), orientation (lines at different angles), contrast (bars with converging grey-level differences), texture (from Brodatz grayscale texture album) and correlated motion (different percentages of dots moving in the same direction). All tasks started with a fixation dot presented at the centre of the screen. After one second, a target stimulus was presented on the horizontal midline at either 5° to the left or at 5° to the right side of the fixation. Then, after 1.5 seconds, two response items appeared in addition to the target stimulus for three seconds. To control for eye movements, we used an eye-tracker to present the target in a gaze contingent fashion. Thus, the target always remained in the correct retinal position independent of eye movements. In a subset of 182 ischemic stroke patients, we also assessed visuoconstruction (Copy Rey-Complex Figure Test), visual emotion recognition (FEEST test) and visual memory (Doors-test).
Results:
The results showed that deficits in motion-perception were most prevalent (26%), followed by colour (22%), texture (22%), location (21%), orientation (18%), contrast (14%), shape (14%) and glossiness (13%). 63% of the stroke patients showed one or more mid-range visual deficits. Overlap of deficits was small; they mostly occurred in isolation or co-occurred with only one or two other deficits. Impairments in mid-range visual functions could not predict performance on higher-order visual cognitive tasks. Impaired visuoconstruction and visual memory were only modestly predicted by a worse location perception. Impaired emotion perception was modestly predicted by a worse orientation perception. In addition, double dissociations were found: there were patients with selective deficits in 'mid-range’ visual functions without higher-order visual deficits and vice versa.
Conclusions:
First, deficits in “mid-range” visual functions are very prevalent. Since we found no strong patterns of co-occurrences, we suggest that an assessment of deficits at this level of visual processing requires screening the full range of visual functions. Second, the relationship between mid-range visual tasks and higher-order visual cognitive tasks is weak. Finally, our findings are not supportive of the hierarchical, two-pathway model but more in line with an alternative patchwork model.
A third nationally representative serosurvey was performed to study the changes in Toxoplasma gondii (T. gondii) seroprevalence in the Netherlands over a 20-year time span and to identify and confirm risk factors for acquired toxoplasmosis. This cross-sectional study (conducted in 2016/2017) was designed similarly to the previous two studies (1995/1996 and 2006/2007) and included a questionnaire and serum sampling among Dutch residents. Factors associated with seropositivity for T. gondii were determined using multivariable analysis of the questionnaire-derived data. The earlier observed decrease in T. gondii seroprevalence between 1995/1996 and 2006/2007 (from 40.5% to 26.0%) did not continue into 2016/2017 (29.9%). Similarly to the previous studies, the seroprevalence increased with age and varied among regions. In all studies, higher T. gondii seropositivity was associated with increasing age, lower educational level, not living in the Southeast, and eating raw or semi-cooked pork. The incidence of congenital toxoplasmosis was estimated at 1.3/1000 (95% CI 0.9–1.8) live-born children in 2017. As the seroprevalence of T. gondii in the Netherlands did not decrease over the last decade, an increase in public health awareness is needed and prevention measures may need to be taken to achieve a further reduction in T. gondii infections in the Netherlands.
Arctic mining has a bad reputation because the extractive industry is often responsible for a suite of environmental problems. Yet, few studies explore the gap between untouched tundra and messy megaproject from a historical perspective. Our paper focuses on Advent City as a case study of the emergence of coal mining in Svalbard (Norway) coupled with the onset of mining-related environmental change. After short but intensive human activity (1904–1908), the ecosystem had a century to respond, and we observe a lasting impact on the flora in particular. With interdisciplinary contributions from historical archaeology, archaeozoology, archaeobotany and botany, supplemented by stable isotope analysis, we examine 1) which human activities initially asserted pressure on the Arctic environment, 2) whether the miners at Advent City were “eco-conscious,” for example whether they showed concern for the environment and 3) how the local ecosystem reacted after mine closure and site abandonment. Among the remains of typical mining infrastructure, we prioritised localities that revealed the subtleties of long-term anthropogenic impact. Significant pressure resulted from landscape modifications, the import of non-native animals and plants, hunting and fowling, and the indiscriminate disposal of waste material. Where it was possible to identify individual inhabitants, these shared an economic attitude of waste not, want not, but they did not hold the environment in high regard. Ground clearances, animal dung and waste dumps continue to have an effect after a hundred years. The anthropogenic interference with the fell field led to habitat creation, especially for vascular plants. The vegetation cover and biodiversity were high, but we recorded no exotic or threatened plant species. Impacted localities generally showed a reduction of the natural patchiness of plant communities, and highly eutrophic conditions were unsuitable for liverworts and lichens. Supplementary isotopic analysis of animal bones added data to the marine reservoir offset in Svalbard underlining the far-reaching potential of our multi-proxy approach. We conclude that although damaging human–environment interactions formerly took place at Advent City, these were limited and primarily left the visual impact of the ruins. The fell field is such a dynamic area that the subtle anthropogenic effects on the local tundra may soon be lost. The fauna and flora may not recover to what they were before the miners arrived, but they will continue to respond to new post-industrial circumstances.
Episodic memory is impaired in Alzheimer’s disease (AD) dementia but thought to be relatively spared in behavioral variant frontotemporal dementia (bvFTD). This view is challenged by evidence of memory impairment in bvFTD. This study investigated differences in recognition memory performance between bvFTD and AD.
Method:
We performed a retrospective analysis on the recognition trial of the Rey Auditory Verbal Learning Test in patients with bvFTD (n = 85), AD (n = 55), and control participants (n = 59). Age- and education-adjusted between-group analysis was performed on the total score and indices of discriminative ability and response bias. Correlations between recognition and measures of memory, language, executive functioning, and construction were examined.
Results:
Patients with AD had a significantly lower total recognition score than patients with bvFTD (control 28.8 ± 1.5; bvFTD 24.8 ± 4.5; AD 23.4 ± 3.6, p < .01). Both bvFTD and AD had worse discriminative ability than controls (A’ control 0.96 ± 0.03; bvFTD 0.87 ± 0.03; AD 0.84 ± 0.10, p < .01), but there was no difference in response bias (B” control 0.9 ± 0.2; bvFTD 1.6 ± 1.47; AD 1.4± 1.4, p < .01). AD had worse discriminability than bvFTD (p < .05). Discriminability was associated with memory for both patient groups (median correlation coefficient r = .34) and additionally associated with language (r = .31), but not executive functioning (r = −.03) in bvFTD. Response bias was unrelated to other cognitive functions (r = −.02).
Conclusions:
Discriminability, but not response bias, differentiated patients with bvFTD from AD. The presence of an impaired discrimination index suggests a “pure” (recognition) memory deficit in bvFTD.
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.
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.
This article synthesises the results of a large international study on primary care (PC), the QUALICOPC study.
Background:
Since the Alma Ata Declaration, strengthening PC has been high on the policy agenda. PC is associated with positive health outcomes, but it is unclear how care processes and structures relate to patient experiences.
Methods:
Survey data were collected during 2011–2013 from approximately 7000 PC physicians and 70 000 patients in 34, mainly European, countries. The data on the patients are linked to data on the PC physicians within each country and analysed using multilevel modelling.
Findings:
Patients had more positive experiences when their PC physician provided a broader range of services. However, a broader range of services is also associated with higher rates of hospitalisations for uncontrolled diabetes, but rates of avoidable diabetes-related hospitalisations were lower in countries where patients had a continuous relationship with PC physicians. Additionally, patients with a long-term relationship with their PC physician were less likely to attend the emergency department. Capitation payment was associated with more positive patient experiences. Mono- and multidisciplinary co-location was related to improved processes in PC, but the experiences of patients visiting multidisciplinary practices were less positive. A stronger national PC structure and higher overall health care expenditures are related to more favourable patient experiences for continuity and comprehensiveness. The study also revealed inequities: patients with a migration background reported less positive experiences. People with lower incomes more often postponed PC visits for financial reasons. Comprehensive and accessible care processes are related to less postponement of care.
Conclusions:
The study revealed room for improvement related to patient-reported experiences and highlighted the importance of core PC characteristics including a continuous doctor–patient relationship as well as a broad range of services offered by PC physicians.
Child maltreatment has been associated with various cumulative risk factors. However, little is known about the extent to which genetic and environmental factors contribute to individual differences between parents in perpetrating child maltreatment. To estimate the relative contribution of genetic and environmental factors to perpetrating maltreatment we used a parent-based extended family design. Child-reported perpetrated maltreatment was available for 556 parents (283 women) from 63 families. To explore reporter effects (i.e., child perspective on maltreatment), child reports were compared to multi-informant reports. Based on polygenic model analyses, most of the variance related to the perpetration of physical abuse and emotional neglect was explained by common environmental factors (physical abuse: c2 = 59%, SE = 12%, p = .006; emotional neglect: c2 = 47%, SE = 8%, p < .001) whereas genetic factors did not significantly contribute to the model. For perpetrated emotional abuse, in contrast, genetic factors did significantly contribute to perpetrated emotional abuse (h2 = 33%, SE = 8%, p < .001), whereas common environment factors did not. Multi-informant reports led to similar estimates of genetic and common environmental effects on all measures except for emotional abuse, where a multi-informant approach yielded higher estimates of the common environmental effects. Overall, estimates of unique environment, including measurement error, were lower using multi-informant reports. In conclusion, our findings suggest that genetic pathways play a significant role in perpetrating emotional abuse, while physical abuse and emotional neglect are transmitted primarily through common environmental factors. These findings imply that interventions may need to target different mechanisms dependings on maltreatment type.
A narrow bridge of floating ice that connected the Wilkins Ice Shelf, Antarctica, to two confining islands eventually collapsed in early April 2009. In the month preceding the collapse, we observed deformation of the ice bridge by means of satellite imagery and from an in situ GPS station. TerraSAR-X images (acquired in stripmap mode) were used to compile a time series. The ice bridge bent most strongly in its narrowest part (westerly), while the northern end (near Charcot Island) shifted in a northeasterly direction. In the south, the ice bridge experienced compressive strain parallel to its long axis. GPS position data were acquired a little south of the narrowest part of the ice bridge from 19 January 2009. Analysis of these data showed both cyclic and monotonic components of motion. Meteorological data and re-analysis of the output of weather-prediction models indicated that easterly winds were responsible for the cyclic motion component. In particular, wind stress on the rough ice melange that occupied the area to the east exerted significant pressure on the ice bridge. The collapse of the ice bridge began with crack formation in the southern section parallel to the long axis of the ice bridge and led to shattering of the southern part. Ultimately, the narrowest part, only 900 m wide, ruptured. The formation of many small icebergs released energy of >125 ×106 J.
Multi-decade observing campaigns of the globular clusters 47 Tucanae and M15 have led to an outstanding number of discoveries. Here, we report on the latest results of the long-term observations of the pulsars in these two clusters. For most of the pulsars in 47 Tucanae we have measured, among other things, their higher-order spin period derivatives, which have in turn provided stringent constraints on the physical parameters of the cluster, such as its distance and gravitational potential. For M15, we have studied the relativistic spin precession effect in PSR B2127+11C. We have used full-Stokes observations to model the precession effect, and to constrain the system geometry. We find that the visible beam of the pulsar is swiftly moving away from our line of sight and may very soon become undetectable. On the other hand, we expect to see the opposite emission beam sometime between 2041 and 2053.
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.
Method
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.
Results
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.
Conclusions
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.
This paper reviews strategies and methods to improve accuracies of genomic predictions from the perspective of a numerically small population. Improvements are realized by influencing one or both of the main factors: (1) improve or increase genomic connections to phenotypic records in training data. (2) Models and strategies to focus genomic predictions on markers closer to the causative variants. Combining populations into a joint reference population results in high improvements when combining populations of the same breed and diminishes as the genetic distance between populations increases. For distantly related breeds sophisticated Bayesian variable selection models in combination with denser markers sets or functional subsets of markers is needed. This is expected to be further improved by the efficient use of sequence information. In addition predictions can be improved by the use of phenotypes of genotyped and non-genotyped cows directly. For a small population the optimal approach will combine the above components.
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.
Method
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.
Results
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.
Conclusion
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.
This textbook presents in a unified manner the fundamentals of both continuous and discrete versions of the Fourier and Laplace transforms. These transforms play an important role in the analysis of all kinds of physical phenomena. As a link between the various applications of these transforms the authors use the theory of signals and systems, as well as the theory of ordinary and partial differential equations. The book is divided into four major parts: periodic functions and Fourier series, non-periodic functions and the Fourier integral, switched-on signals and the Laplace transform, and finally the discrete versions of these transforms, in particular the Discrete Fourier Transform together with its fast implementation, and the z-transform. This textbook is designed for self-study. It includes many worked examples, together with more than 120 exercises, and will be of great value to undergraduates and graduate students in applied mathematics, electrical engineering, physics and computer science.
It is unclear how the course of maternal depressive symptoms affects child development. We modelled trajectories of maternal depressive symptoms from mid-pregnancy to 3 years after childbirth to better determine their associations with child problem behaviour.
Method
Mother–child dyads (n = 4167) participated in a population-based prospective cohort in The Netherlands. Depressive symptoms were assessed with the Brief Symptom Inventory during pregnancy and at 2, 6 and 36 months postnatally. When children were 3 years old, problem behaviour was assessed with the Child Behaviour Checklist completed by each parent. A group-based modelling technique was used to model trajectories of maternal depressive symptoms and to examine their association with child problem behaviour. The added value of trajectory modelling was determined with successive linear regressions.
Results
We identified four trajectories of maternal depressive symptoms; ‘no’ (34%), ‘low’ (54%), ‘moderate’ (11%) and ‘high’ (1.5%). Child problem behaviour varied as a function of maternal trajectory membership. Whether rated by mother or father, children of mothers assigned to higher trajectories had significantly more problem behaviours than children of mothers assigned to lower trajectories. The model including trajectories had additive predictive value over a model relying only on a summed repeated measure of severity and a predefined chronicity variable.
Conclusions
Depending on their course, maternal depressive symptoms have different effects on child problem behaviour. More information is gained by studying trajectories of symptoms, than only predefined measures of severity and chronicity. Moreover, trajectories can help identifying clinically depressed mothers who are possible candidates for early interventions.