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Individuals with schizophrenia are at higher risk of physical illnesses, which are a major contributor to their 20-year reduced life expectancy. It is currently unknown what causes the increased risk of physical illness in schizophrenia.
To link genetic data from a clinically ascertained sample of individuals with schizophrenia to anonymised National Health Service (NHS) records. To assess (a) rates of physical illness in those with schizophrenia, and (b) whether physical illness in schizophrenia is associated with genetic liability.
We linked genetic data from a clinically ascertained sample of individuals with schizophrenia (Cardiff Cognition in Schizophrenia participants, n = 896) to anonymised NHS records held in the Secure Anonymised Information Linkage (SAIL) databank. Physical illnesses were defined from the General Practice Database and Patient Episode Database for Wales. Genetic liability for schizophrenia was indexed by (a) rare copy number variants (CNVs), and (b) polygenic risk scores.
Individuals with schizophrenia in SAIL had increased rates of epilepsy (standardised rate ratio (SRR) = 5.34), intellectual disability (SRR = 3.11), type 2 diabetes (SRR = 2.45), congenital disorders (SRR = 1.77), ischaemic heart disease (SRR = 1.57) and smoking (SRR = 1.44) in comparison with the general SAIL population. In those with schizophrenia, carrier status for schizophrenia-associated CNVs and neurodevelopmental disorder-associated CNVs was associated with height (P = 0.015–0.017), with carriers being 7.5–7.7 cm shorter than non-carriers. We did not find evidence that the increased rates of poor physical health outcomes in schizophrenia were associated with genetic liability for the disorder.
This study demonstrates the value of and potential for linking genetic data from clinically ascertained research studies to anonymised health records. The increased risk for physical illness in schizophrenia is not caused by genetic liability for the disorder.
We derive and analyse an energy to model lipid raft formation on biological membranes involving a coupling between the local mean curvature and the local composition. We apply a perturbation method recently introduced by Fritz, Hobbs and the first author to describe the geometry of the surface as a graph over an undeformed Helfrich energy minimising surface. The result is a surface Cahn–Hilliard functional coupled with a small deformation energy. We show that suitable minimisers of this energy exist and consider a gradient flow with conserved Allen–Cahn dynamics, for which existence and uniqueness results are proven. Finally, numerical simulations show that for the long-time behaviour raft-like structures can emerge and stabilise, and their parameter dependence is further explored.
CHD remains one of the leading causes of mortality of children in the United States. There is limited research about the experience of parents from the diagnosis of their child with CHD through the death of their child. A prior study has shown that adults with heart failure go through a series of four transitions: 1) learning the diagnosis, 2) reframing the new normal, 3) taking control of the illness, and 4) understanding death is inevitable. In our qualitative study, we performed semi-structured interviews with parents who have a child die of CHD to determine whether the four transitions in adults apply to parents of children with CHD. We found that these four transitions were present in the parents we interviewed and that there were two novel transitions, one that proceeded the first Jones et al transition (“Prenatal diagnosis”) and one that occurred after the final Jones et al transition (“Adjustment after death”). It is our hope that identification of these six transitions will help better support families of children with CHD.
Schizophrenia is a highly heritable disorder with undetermined neurobiological causes. Understanding the impact on brain anatomy of carrying genetic risk for the disorder will contribute to uncovering its neurobiological underpinnings.
To examine the effect of rare copy number variants (CNVs) associated with schizophrenia on brain cortical anatomy in a sample of unaffected participants from the UK Biobank.
We used regression analyses to compare cortical thickness and surface area (total and across gyri) between 120 unaffected carriers of rare CNVs associated with schizophrenia and 16 670 participants without any pathogenic CNV. A measure of cortical thickness and surface area covariance across gyri was also compared between groups.
Carrier status was associated with reduced surface area (β = −0.020 mm2, P < 0.001) and less robustly with increased cortical thickness (β = 0.015 mm, P = 0.035), and with increased covariance in thickness (carriers z = 0.31 v. non-carriers z = 0.22, P < 0.0005). Associations were mainly present in frontal and parietal areas and driven by a limited number of rare risk alleles included in our analyses (mainly 15q11.2 deletion for surface area and 16p13.11 duplication for thickness covariance).
Results for surface area conformed with previous clinical findings, supporting surface area reductions as an indicator of genetic liability for schizophrenia. Results for cortical thickness, though, argued against its validity as a potential risk marker. Increased structural thickness covariance across gyri also appears related to risk for schizophrenia. The heterogeneity found across the effects of rare risk alleles suggests potential different neurobiological gateways into schizophrenia's phenotype.
This article contributes to conversation analytic research on the formatting of imperative actions by focusing on the English first person imperative let me/lemme X as it appears in a range of naturally occurring interactions. I argue that lemme X is a practice for displacing what was projectably relevant in a given environment in favor of a self-authorized action. This as a result tends to advance the speaker's interests/initiatives. The analysis accounts for speakers’ apparent presumption of permission in unilaterally undertaking their lemme X action by reference to the placement, design, and subsequent orientations to the self-authorized action. The construction is discussed in terms of the distribution of agency and it is suggested that lemme X is particularly suited to advancing activities that favor autonomous action by the speaker and which involve the recipient only minimally. (Conversation analysis, imperatives, directives, English, agency)*
Estuarine habitats are major nurseries for the European flounder Platichthys flesus, with different year classes sharing food and space resources. Hence, an understanding of feeding strategies that optimize resource use and maintain carrying capacity is fundamental for sustainable and successful ecosystem management. The main feeding areas of juvenile European flounder (including 0-group and 1-group age classes) in the Lima estuary (northern Portugal) nursery ground were investigated by integrating stomach content analyses with stable isotopic values (δ13C and δ15N) and fish condition indices (Fulton K and RNA:DNA ratio). The 0-group flounder that were associated with the upstream section of the estuary presented the lowest δ13C value (−25.58 ± 1.86‰), while 1-group flounder exhibited a higher δ13C value (−22.59 ± 2.51‰), indicating use of the more saline areas of the estuary (lower and middle sections). The two age groups did not differ in terms of δ15N (0-group: 13.93 ± 0.29‰; 1-group: 13.50 ± 0.96‰), indicating similar trophic levels. The low salinity upper estuary was the main feeding area of 0-group flounder (74%), while 1-group flounder fed along the estuary both upstream (52%) and downstream (48%). Juvenile flounder showed high individual condition based on the Fulton K index (0-group: 1.05 ± 0.08; 1-group: 1.07 ± 0.05) and RNA:DNA (0-group: 1.70 ± 0.70; 1-group: 1.41 ± 0.47). These indices deal with fish health, and hence indicate nursery habitat quality. It is concluded that in this temperate nursery habitat, different feeding strategies sustained the condition of the European flounder juveniles, compared with other flounder populations.
There is increasing evidence for a neurobiological basis of antisocial personality disorder (ASPD), includinggenetic liability, aberrant serotonergic function, neuropsychological deficits and structural and functional brain abnormalities. However, few functional brain imaging studies have been conducted using tasks of clinically relevant functions such as impulse control and reinforcement processing. Here we report on a study investigating the neural basis of behavioural inhibition and reward sensitivity in ASPD using functional magnetic resonance imaging (fMRI).
17 medication-free male individuals with DSM IV ASPD and 14 healthy controls were included. All subjects were screened for Axis I pathology and substance misuse. Scanner tasks included two block design tasks: one Go/No-Go task and one reward task. Scanning was carried out on a 1.5T Phillips system. Whole brain coverage was achieved using 40 axial slices with 3.5mm spacing a TR of 5 seconds. Data were analysed using SPM5 using random effects models.
Results of the Go/No-Go task confirmed brain activation previously described in the processing of impulse inhibition, namely in the orbitofrontal and dorsolateral prefrontal cortex and the anterior cingulate, and these were enhanced in the PD group. The reward task was associated with BOLD response changes in the reward network in both groups. However, these BOLD responses were reduced in the ASPD group, particularly in prefrontal areas.
Our results further support the notion of prefrontal dysfunction in ASPD. However, contrary to previous studies suggesting “hypofrontality” in this disorder, we found task specific increased and decreased BOLD responses.
Antipsychotics are associated with the polymorphic ventricular tachycardia, Torsade's de pointes, which in worst case can lead to sudden cardiac death. The QTc interval is used as a clinical proxy for Torsade's de pointes. QTc interval is prolonged by monotherapy with antipsychotic, but it is unknown if the QTc interval is prolonged further with antipsychotic polypharmacy.
To investigate the associations between QTc interval and antipsychotic mono- and polypharmaceutical treatment, respectively, in schizophrenic patients.
To learn more about the impact of antipsychotics on the QTc interval.
An observational cohort study of unselected patients with schizophrenia visiting outpatient facilities in the Region of Central Jutland, Denmark. Patients were enrolled from January 2013 through March 2015 with follow-up until June 2015. Data was collected from clinical interviews and clinical case records.
ECGs were available in 58 patients receiving antipsychotic treatment. We observed no difference in average QTc interval for the whole sample of patients receiving monotherapy or polypharmacy (P = 0.29). However, women presented longer QTc-interval on polypharmacy than on monotherapy (P = 0.01).
We recommend an increased focus on monitoring the QTc interval in woman with schizophrenia receiving antipsychotics as polypharmacy.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
As uncertainty remains about whether clinical response influences cognitive function after electroconvulsive therapy (ECT) for depression, we examined the effect of remission status on cognitive function in depressed patients 4 months after a course of ECT.
A secondary analysis was undertaken on participants completing a randomised controlled trial of ketamine augmentation of ECT for depression who were categorised by remission status (MADRS ⩽10 v. >10) 4 months after ECT. Cognition was assessed with self-rated memory and neuropsychological tests of anterograde verbal and visual memory, autobiographical memory, verbal fluency and working memory. Patients were assessed through the study, healthy controls on a single occasion, and compared using analysis of variance.
At 4-month follow-up, remitted patients (N = 18) had a mean MADRS depression score of 3.8 (95% CI 2.2–5.4) compared with 27.2 (23.0–31.5) in non-remitted patients (N = 19), with no significant baseline differences between the two groups. Patients were impaired on all cognitive measures at baseline. There was no deterioration, with some measures improving, 4-months after ECT, at which time remitted patients had significantly improved self-rated memory, anterograde verbal memory and category verbal fluency compared with those remaining depressed. Self-rated memory correlated with category fluency and autobiographical memory at follow-up.
We found no evidence of persistent impairment of cognition after ECT. Achieving remission improved subjective memory and verbal memory recall, but other aspects of cognitive function were not influenced by remission status. Self-rated memory may be useful to monitor the effects of ECT on longer-term memory.
This paper addresses the relative scholarly oversight of the history of public health in Haiti through a close examination of the colonial public health system constructed and operated by the United States (US) during its occupation of Haiti from 1915 to 1934. More than simply documenting a neglected aspect of Caribbean history, the paper offers the US occupation of Haiti as a remarkably clear example of a failed attempt to use a free public health service to cultivate a health conscientiousness among the Haitian citizenry through the aggressive treatment of highly visible ailments such as cataracts and yaws. I argue that the US occupation viewed the success of the Haitian Public Health Service as critical to the generation of a taxable, compliant and trusting citizenry that the colonial state could enter into a contract with. This idealistic programme envisioned by the US occupation was marred by financial mismanagement, racism, delusions of grandeur and contempt for Haitian physicians that resulted in the production of a far more precarious public health service and administrative state than the US occupation had hoped. By the time the Great Depression arrived in 1930 the Haitian Public Health Service was gutted and privatised, having successfully provided the majority of Haitians with free healthcare, yet failed to have persuaded them of the value of being governed by a centralised administrative state.
Background: Insertion of an external ventricular drain (EVD) is performed to treat elevated intracranial pressure. EVD catheters are associated with complications such as EVD catheter infection (ECI), intracranial hemorrhage (ICH) and suboptimal catheter placement. As part of the Canadian Neurosurgery Research Collaborative, we sought to investigate the national rate of such complications and their risk factors. Methods: Prospective study of 273 patients from eight academic Canadian neurosurgery centres Results: Infection rate was 6% and predicted by smaller incisions and not peri-procedure antibiotics, tunneling distance, type of antiseptic used or catheter flushing (p>0.05). The mean duration of EVD was 17.7±3.7 in ECI and ventriculitis group which was significantly higher than in patients without ECI (9.4±8.1) (p=0.045). Although the risk of developing ICH was 9.3%, symptomatic ICH was rare. Pre-procedure pharmacological DVT prophylaxis predicted EVD-related ICH(OR 4.73). The rate of suboptimal catheter location was 31% and predicted by the number of passes (p=0.02), but not image guidance, level of training or catheter placement in an operating room setting (p>0.05). Conclusions: This study reports EVD complication rates and their associated risk factors observed within an academic, multicentre Canadian cohort. This information will help to identify strategies to increase the safety of this common neurosurgical procedure.
Rare copy number variants (CNVs) are associated with risk of neurodevelopmental disorders characterised by varying degrees of cognitive impairment, including schizophrenia, autism spectrum disorder and intellectual disability. However, the effects of many individual CNVs in carriers without neurodevelopmental disorders are not yet fully understood, and little is known about the effects of reciprocal copy number changes of known pathogenic loci.
We aimed to analyse the effect of CNV carrier status on cognitive performance and measures of occupational and social outcomes in unaffected individuals from the UK Biobank.
We called CNVs in the full UK Biobank sample and analysed data from 420 247 individuals who passed CNV quality control, reported White British or Irish ancestry and were not diagnosed with neurodevelopmental disorders. We analysed 33 pathogenic CNVs, including their reciprocal deletions/duplications, for association with seven cognitive tests and four general measures of functioning: academic qualifications, occupation, household income and Townsend Deprivation Index.
Most CNVs (24 out of 33) were associated with reduced performance on at least one cognitive test or measure of functioning. The changes on the cognitive tests were modest (average reduction of 0.13 s.d.) but varied markedly between CNVs. All 12 schizophrenia-associated CNVs were associated with significant impairments on measures of functioning.
CNVs implicated in neurodevelopmental disorders, including schizophrenia, are associated with cognitive deficits, even among unaffected individuals. These deficits may be subtle but CNV carriers have significant disadvantages in educational attainment and ability to earn income in adult life.
Two chondrichthyan assemblages of Late Mississippian/Early Pennsylvanian age are now recognized from the western Grand Canyon of northern Arizona. The latest Serpukhovian Surprise Canyon Formation has yielded thirty-one taxa from teeth and dermal elements, which include members of the Phoebodontiformes, Symmoriiformes, Bransonelliformes, Ctenacanthiformes, Protacrodontoidea, Hybodontiformes, Neoselachii (Anachronistidae), Paraselachii (Gregoriidae, Deeberiidae, Orodontiformes, and Eugeneodontiformes), Petalodontiformes, and Holocephali. The euselachian grade taxa are remarkably diverse with four new taxa recognized here; the Protacrodontidae: Microklomax carrieae new genus new species and Novaculodus billingsleyi new genus new species, and the Anchronistidae: Cooleyella platera new species and Amaradontus santucii new genus new species The Surprise Canyon assemblage also has the youngest occurrence of the elasmobranch Clairina, previously only known from the Upper Devonian. The Surprise Canyon Formation represents a nearshore fluvial infilling of karstic channels, followed by a shallow marine bioherm reef, and finally deeper open water deposition. The early Bashkirian Watahomigi Formation represents open marine deposition and contains only two taxa: a new xenacanthiform, Hokomata parva new genus new species, and the holocephalan Deltodus. The relationship between the Surprise Canyon and Watahomigi chondrichthyan assemblages and other significant coeval chondrichthyan assemblages suggests that there may have been eastern and western distinctions among the Euamerican assemblages during the Serpukhovian due to geographic separation by the formation of Pangea.
Mental disorders may emerge as the result of interactions between observable symptoms. Such interactions can be analyzed using network analysis. Several recent studies have used network analysis to examine eating disorders, indicating a core role of overvaluation of weight and shape. However, no studies to date have applied network models to binge-eating disorder (BED), the most prevalent eating disorder.
We constructed a cross-sectional graphical LASSO network in a sample of 788 individuals with BED. Symptoms were assessed using the Eating Disorders Examination Interview. We identified core symptoms of BED using expected influence centrality.
Overvaluation of shape emerged as the symptom with the highest centrality. Dissatisfaction with weight and overvaluation of weight also emerged as highly central symptoms. On the other hand, behavioral symptoms such as binge eating, eating in secret, and dietary restraint/restriction were less central. The network was stable, allowing for reliable interpretations (centrality stability coefficient = 0.74).
Overvaluation of shape and weight emerged as core symptoms of BED. This trend is consistent with past network analyses of eating disorders more broadly, as well as literature that suggests a primary role of shape and weight concerns in BED. Although DSM-5 diagnostic criteria for BED does not currently include a cognitive criterion related to body image or shape/weight overvaluation, our results provide support for including shape/weight overvaluation as a diagnostic specifier.
The aim of this study was to characterise changes in lean soft tissue (LST) and examine the contributions of energy intake, physical activity and breast-feeding practices to LST changes at 3 and 9 months postpartum. We examined current weight, LST (via dual-energy X-ray absorptiometry), dietary intake (3-d food diary), physical activity (Baecke questionnaire) and breast-feeding practices (3-d breast-feeding diary) in forty-nine women aged 32·9 (sd 3·8) years. Changes in LST varied from −2·51 to +2·50 kg with twenty-nine women gaining LST (1·1 (sd 0·7) kg, P<0·001) and twenty women losing LST (−0·9 (sd 0·8) kg, P<0·001). Energy intake (133 (SD 42) v. 109 (SD 33) kJ/kg, P=0·019) and % kJ from fat at 3 months postpartum was higher in women who gained LST at 9 months postpartum (gained LST=34 (sd 5) % kJ; lost LST=29 (sd 4) % kJ, P=0·002). Women who gained LST reported breast-feeding their infants more frequently (gained LST=8 (sd 3) feeds/d; lost LST=5 (sd 1) feeds/d, P=0·014) and for more time per d (gained LST=115 (sd 78) min/d; lost LST=59 (sd 34) min/d, P=0·016) at 9 months postpartum. Energy intake and % kJ from fat at 3 months were significant predictors of LST gain (β=0·08 (se 0·04) and 0·24 (se 0·09), respectively). This suggests that gain in LST may be associated with more frequent and longer episodes of breast-feeding at 9 months postpartum as well as dietary intake early in the postpartum period.
Background: External ventricular drain (EVD) insertion is a common neurosurgical procedure performed in patients with life-threatening conditions, but can be associated with complications. The objectives of this study are to evaluate data on national practice patterns and complications rates in order to optimize clinical care Methods: The Canadian Neurosurgery Research Collaborative conducted a prospective multi-centre registry of patients undergoing EVD insertions at Canadian residency programs Results: In this interim analysis, 4 sites had recruited 46 patients (mean age: 53.9 years, male:female 2:1). Most EVD insertions occurred outside of the operating theatre, using free-hand technique, and performed by junior neurosurgery residents (R1-R3). The catheter tip was in the ipsilateral frontal horn or body of the lateral ventricle in 76% of cases. Suboptimally placed catheters did not have higher rates of short-term occlusion. EVD-related hemorrhage occurred in 6.5% (3/45) with only 1 symptomatic patient. EVD-related infection occurred in 13% (6/46) at a mean of 6 days and was associated with longer duration of CSF drainage (P=0.039; OR: 1.13) Conclusions: Interim results indicate rates of EVD-related complications may be higher than previously thought. This study will continue to recruit patients to confirm these findings and determine specific risk factors associated with them