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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.
The global loss of biodiversity is one of the most important challenges facing humanity, and a multi-faceted strategy is needed to address the size and complexity of this problem. This paper draws on scholarship from the philosophy of science and environmental ethics to help address one aspect of this challenge: namely, the question of how to frame biodiversity loss in a compelling manner. The paper shows that the concept of biodiversity, like many scientific concepts, is value-laden in the sense that it tends to support some ethical or social values over others. Specifically, in comparison with other potential concepts, the biodiversity concept is tied more closely to the notion that nature has intrinsic value than to the idea that nature is valuable instrumentally or relationally. Thus, alternative concepts could prove helpful for communicating about biodiversity loss with those who emphasize different value systems. The paper briefly discusses five concepts that illustrate the potential for using different concepts in different contexts. Going forward, conservationists would do well to recognize the values embedded in their language choices and work with social scientists to develop a suite of concepts that can motivate the broadest swath of people to promote conservation.
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.
Both scientists and philosophers of science have recently emphasized the importance of promoting transparency in science. For scientists, transparency is a way to promote reproducibility, progress, and trust in research. For philosophers of science, transparency can help address the value-ladenness of scientific research in a responsible way. Nevertheless, the concept of transparency is a complex one. Scientists can be transparent about many different things, for many different reasons, on behalf of many different stakeholders. This paper proposes a taxonomy that clarifies the major dimensions along which approaches to transparency can vary. By doing so, it provides several insights that philosophers and other science studies scholars can pursue. In particular, it helps address common objections to pursuing transparency in science, it clarifies major forms of transparency, and it suggests avenues for further research on this topic.
The aim of this study was to review microbiology results from testing >2500 raw drinking milk and dairy products made with unpasteurised milk examined in England between 2013 and 2019. Samples were collected as part of incidents of contamination, investigation of infections or as part of routine monitoring and were tested using standard methods for a range of both pathogens and hygiene indicators. Results from testing samples of raw cow's milk or cheese made from unpasteurised milk for routine monitoring purposes were overall of better microbiological quality than those collected during incident or investigations of infections. Results from routine monitoring were satisfactory for 62% of milks, 82% of cream, 100% of ice-cream, 51% of butter, 63% of kefir and 79% of cheeses, with 5% of all samples being considered potentially hazardous. Analysis of data from cheese demonstrated a significant association between increasing levels of indicator Escherichia coli with elevated levels of coagulase positive staphylococci and decreased probability of isolation of Shiga toxin-producing E. coli. These data highlight the public health risk associated with these products and provide further justification for controls applied to raw drinking milk and dairy products made with unpasteurised milk.
Evidence suggests that dietary intake of UK children is currently suboptimal. It is therefore imperative to identify effective and sustainable methods of improving dietary habits and knowledge in this population, whilst also promoting the value of healthiness of food products beyond price. Schools are ideally placed to influence children's knowledge and health, and Project Daire, in partnership with schools, food industry partners and stakeholders, aims to improve children's knowledge of, and interest in, food to improve health, wellbeing and educational attainment.
Daire is a randomised-controlled, factorial design trial evaluating two interventions. In total, n = 880 Key Stage (KS) 1 and 2 pupils have been recruited from 18 primary schools in the North West of Northern Ireland and will be randomised to one of four 6-month intervention arms: i) ‘Engage’, ii) ‘Nourish’, iii) ‘Engage’ and ‘Nourish’ and iv) Delayed. ‘Engage’ is an age-appropriate, cross-curricular educational intervention on food, agriculture, science and careers linked to the current curriculum. ‘Nourish’ is an intervention aiming to alter schools’ food environments and increase exposure to local foods. Study outcomes include food knowledge, attitudes, trust, diet, behaviour, health and wellbeing and will be collected at baseline and six months. Qualitative data on teacher/pupil opinions will also be collected. The intervention phase is currently ongoing. We present baseline results from our involvement and food attitudes measure from all participating schools. Results were compared by Key Stage and sex using Pearson Chi-Squared test.
Baseline results from our food involvement and attitudes measure are presented for n = 880 KS1 (n = 454) and KS2 (n = 426) pupils. KS1 pupils were more likely to always or sometimes help with food shopping (89.0%) whilst KS2 pupils were more likely to always or sometimes help with food preparation (69.0%). A higher proportion of KS1 pupils reported liking to try new foods (66.1%) and that it was important that food looked (64.5%), tasted (71.1%) and smelled good (60.6%) compared with KS2 children (P < 0.01). Girls were more likely to always or sometimes help with food shopping (96.2%) and preparation (73%) when compared with boys; whilst a higher proportion of girls reported they liked to try new foods (48.2%) and that it was important that food looked (68%) smelled (50.5%) and tasted (71.8%) good compared with boys (P < 0.01).
Results suggest that involvement in food preparation and shopping, willingness to try new foods and attitudes towards food presentation varied by KS and sex in this cohort.
Around 30% of individuals with schizophrenia remain symptomatic and significantly impaired despite antipsychotic treatment and are considered to be treatment resistant. Clinicians are currently unable to predict which patients are at higher risk of treatment resistance.
To determine whether genetic liability for schizophrenia and/or clinical characteristics measurable at illness onset can prospectively indicate a higher risk of treatment-resistant psychosis (TRP).
In 1070 individuals with schizophrenia or related psychotic disorders, schizophrenia polygenic risk scores (PRS) and large copy number variations (CNVs) were assessed for enrichment in TRP. Regression and machine-learning approaches were used to investigate the association of phenotypes related to demographics, family history, premorbid factors and illness onset with TRP.
Younger age at onset (odds ratio 0.94, P = 7.79 × 10−13) and poor premorbid social adjustment (odds ratio 1.64, P = 2.41 × 10−4) increased risk of TRP in univariate regression analyses. These factors remained associated in multivariate regression analyses, which also found lower premorbid IQ (odds ratio 0.98, P = 7.76 × 10−3), younger father's age at birth (odds ratio 0.97, P = 0.015) and cannabis use (odds ratio 1.60, P = 0.025) increased the risk of TRP. Machine-learning approaches found age at onset to be the most important predictor and also identified premorbid IQ and poor social adjustment as predictors of TRP, mirroring findings from regression analyses. Genetic liability for schizophrenia was not associated with TRP.
People with an earlier age at onset of psychosis and poor premorbid functioning are more likely to be treatment resistant. The genetic architecture of susceptibility to schizophrenia may be distinct from that of treatment outcomes.
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.
Background: Electroconvulsive therapy (ECT) involves the induction of a generalized seizure with an electrical current and has been used worldwide when treating medically refractory psychiatric illness. Here we describe a patient with no prior history or risk factors for epilepsy who developed temporal lobe epilepsy after chronic treatment of ECT. Methods: A 16-year-old right-handed boy with severe refractory depression received ECT treatment every 10 days for 8 months. Six months into his ECT treatment, the patient developed seizures and was admitted to a pediatric epilepsy monitoring unit. Results: Initial clinical events included lightheadedness, diaphoresis, and nausea with associated kaleidoscopic vision changes. Seizures progressed to confusion, fear and paranoia by the time the patient was admitted for monitoring. Long-term video EEG captured many focal seizures with impaired awareness, all originating from both temporal lobes. MRI was normal. ECT was terminated and the patient started on carbamazepine. He has been seizure free for the past 2 years on medication Conclusions: While rare, we present a case of a patient with no prior risk factors for epilepsy who developed temporal lobe epilepsy after chronic ECT treatment. Although ECT is an indispensable treatment for many medically refractory psychiatric illnesses, we suggest caution in young patient undergoing ECT.
Background: Diffusion-tensor imaging (DTI) tractography is commonly used in neurosurgical practice, but is largely limited to the preoperative setting. This is due primarily to image degradation caused by susceptibility artifact when conventional single-shot (SS) echo-planar imaging DTI is acquired for open cranial, surgical position intraoperative DTI (iDTI). A novel, artifact-resistant, readout-segmented (RS) DTI has not yet been evaluated in the intraoperative MRI (iMRI) environment. Our objective was to evaluate the performance of RS-DTI versus SS-DTI for intraoperative white matter imaging. Methods: Pre- and intraoperative 3T, T1-weighted and DTI (RS-iDTI and SS-iDTI) in 22 adults undergoing intraaxial iMRI resections (low-grade glioma: 14, 64%; high-grade glioma: 7, 32%; cortical dysplasia: 1). Regional susceptibility artifact, anatomical deviation relative to T1WI, and tractographic output were compared between iDTI sequences. Results: RS-iDTI resulted in less regional susceptibility artifact and mean anatomic deviation (RS-iDTI: 2.7±0.2 mm versus SS-iDTI 7.5±0.4 mm; p<0.0001). Tractographic failure occurred in 8/22 (36%) patients for SS-iDTI whereas RS-iDTI permitted successful reconstruction in 4 of these 8. Maximal tractographic differences between DTI sequences were substantial (mean 9.7±5.7 mm). Conclusions: Readout-segmented EPI enables higher quality and more accurate DTI for surgically relevant tractography of major white matter tracts in intraoperative, open cranium, neurosurgical applications at 3T.
Introduction: Simulation is becoming widely adopted across medical disciplines and by different medical professionals. For medical students, emergency medicine simulation has been shown to increase knowledge, confidence and satisfaction. At the University of Ottawa Skills and Simulation Centre, third-year medical students participate in simulated scenarios common to Emergency Medicine (EM) as part of their mandatory EM clerkship rotation. This study aims to evaluate simulation as part of the EM clerkship rotation by assessing changes in student confidence following a simulation session. Methods: In groups of seven, third year medical students at the University of Ottawa completed simulation sessions of the following: Status Asthmaticus, Status Epilepticus, Urosepsis and Breaking Bad News. Student confidence with each topic was assessed before and after simulation with a written survey. Confidence scores pre- and post-simulation were compared with the Wilcoxon signed rank test. Results: Forty-eight third years medical students in their core EM clerkship rotation, between September 2017 and August 2018 participated in this study. Medical student confidence with diagnosis of status asthmaticus (N = 44, p = 0.0449) and status epilepticus (N = 45, p = 0.0011) increased significantly following simulation, whereas confidence with diagnosis of urosepsis was unchanged (N = 45, p = 0.0871). Treatment confidence increased significantly for status asthmaticus (N = 47, p = 0.0009), status epilepticus (N = 48, p = 0.0005) and urosepsis (N = 48, p < 0.0001). Confidence for breaking bad news was not significantly changed after simulation (N = 47, p = 0.0689). Conclusion: Simulation training in our EM clerkship rotation significantly increased the confidence of medical students for certain common EM presentations, but not for all. Further work will aim to understand why some simulation scenarios did not improve confidence, and look to improve existing scenarios.
Introduction: Learners, ether medical students or residents, often provide the initial assessment of patients visiting the Emergency Department (ED). Their involvement in ED patient care has been shown to increase length of stay, time to disposition decision, utilization of imaging and admission rates. It is unclear, however, if learners have an impact on the rate of short-term unscheduled return visits. The objective of this study was to determine if the involvement of learners in ED visits increases the rate of short-term unscheduled return visits. Methods: This study was a retrospective analysis of ED visit data at a single tertiary care center over a one-year period. Short-term unscheduled return visits (return visits) were defined as ED visits presenting within 72 hours of discharge from an initial non-admit ED visit and resulting in an admission to an inpatient unit on the second visit. The primary outcome was the rate of return visits for each staff physician, with and without learners involved during the initial visit. The secondary outcome assessed the interaction of level of training (medical student year 3, 4, resident year 1, 2, etc.) on return visit rates. For the primary outcome, statistical analysis was with a Wilcoxon Matched Pairs test; staff alone vs with learners. A Kruskal-Wallis test was used to compare learner level of training. Results: Return visits accounted for 1858 (1.09%) of all visits (N = 172494) to this tertiary care ED over the one-year study period. Return visits were statistically more likely when learners were involved in the initial ED visit (1.16%, CI 0.12), compared to initial visits seen by staff physicians alone (0.88%, CI 0.09) (p < 0.0001). Return rates were statistically higher for PGY2 (1.67% CI 0.35) and PGY3 (1.66% CI 0.28) residents compared to staff physicians alone (p < 0.0001). There was no difference in return visit rates between staff physicians and third year medical students (1.07% CI 0.27), fourth year medical students (1.21% CI 0.37), PGY1 (1.42% CI 0.22), PGY4 (1.23% CI 0.54) or PGY5 (1.33% CI 0.49) residents. Conclusion: This study demonstrated that the involvement of learners in ED patient assessments increased the rate of short-term unscheduled return visits. Moreover, return visit rates were highest for PGY2 and PGY3 residents. Further work is needed to understand the factors that contribute to this phenomenon.
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.
Identifying characteristics of individuals at greatest risk for prolonged grief disorder (PGD) can improve its detection and elucidate the etiology of the disorder. The Safe Passage Study, a study of women at high risk for sudden infant death syndrome (SIDS), prospectively examined the psychosocial functioning of women while monitoring their healthy pregnancies. Mothers whose infants died of SIDS were followed in bereavement.
Pre-loss data were collected from 12 000 pregnant mothers and analyzed for their associations with grief symptoms and PGD in 50 mothers whose infants died from SIDS, from 2 to 48 months after their infant's death, focusing on pre-loss risk factors of anxiety, depression, alcohol use, maternal age, the presence of other living children in the home, and previous child loss.
The presence of any four risk factors significantly predicted PGD for 24 months post-loss (p < 0.003); 2–3 risk factors predicted PGD for 12 months (p = 0.02). PGD rates increased in the second post-loss year, converging in all groups to approximately 40% by 3 years. Pre-loss depressive symptoms were significantly associated with PGD. Higher alcohol intake and older maternal age were consistently positively associated with PGD. Predicted risk scores showed good discrimination between PGD and no PGD 6–24 months after loss (C-statistic = 0.83).
A combination of personal risk factors predicted PGD in 2 years of bereavement. There is a convergence of risk groups to high rates at 2–3 years, marked by increased PGD rates in mothers at low risk. The risk factors showed different effects on PGD.
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.
Light sheet fluorescence microscopy (LSFM) allows for high-resolution three-dimensional imaging with minimal photo-damage. By viewing the sample from different directions, different regions of large specimens can be imaged optimally. Moreover, owing to their good spatial resolution and high signal-to-noise ratio, LSFM data are well suited for image deconvolution. Here we present the Huygens Fusion and Deconvolution Wizard, a unique integrated solution for restoring LSFM images, and show that improvements in signal and resolution of 1.5 times and higher are feasible.
The Arizona Department of Health Services identified unusually high levels of influenza activity and severe complications during the 2015–2016 influenza season leading to concerns about potential increased disease severity compared with prior seasons. We estimated state-level burden and severity to compare across three seasons using multiple data sources for community-level illness, hospitalisation and death. Severity ratios were calculated as the number of hospitalisations or deaths per community case. Community influenza-like illness rates, hospitalisation rates and mortality rates in 2015–2016 were higher than the previous two seasons. However, ratios of severe disease to community illness were similar. Arizona experienced overall increased disease burden in 2015–2016, but not increased severity compared with prior seasons. Timely estimates of state-specific burden and severity are potentially feasible and may provide important information during seemingly unusual influenza seasons or pandemic situations.
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