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SPARC is being designed to operate with a normalized beta of
, a normalized density of
and a safety factor of
, providing a comfortable margin to their respective disruption limits. Further, a low beta poloidal
at the safety factor
surface reduces the drive for neoclassical tearing modes, which together with a frozen-in classically stable current profile might allow access to a robustly tearing-free operating space. Although the inherent stability is expected to reduce the frequency of disruptions, the disruption loading is comparable to and in some cases higher than that of ITER. The machine is being designed to withstand the predicted unmitigated axisymmetric halo current forces up to 50 MN and similarly large loads from eddy currents forced to flow poloidally in the vacuum vessel. Runaway electron (RE) simulations using GO+CODE show high flattop-to-RE current conversions in the absence of seed losses, although NIMROD modelling predicts losses of
%; self-consistent modelling is ongoing. A passive RE mitigation coil designed to drive stochastic RE losses is being considered and COMSOL modelling predicts peak normalized fields at the plasma of order
that rises linearly with a change in the plasma current. Massive material injection is planned to reduce the disruption loading. A data-driven approach to predict an oncoming disruption and trigger mitigation is discussed.
Clozapine, an antipsychotic with unique efficacy in treatment-resistant psychosis, is associated with increased susceptibility to infection, including pneumonia.
To investigate associations between clozapine treatment and increased risk of COVID-19 infection in patients with schizophrenia-spectrum disorders who are receiving antipsychotic medications in a geographically defined population in London, UK.
Using information from South London and Maudsley NHS Foundation Trust (SLAM) clinical records, via the Clinical Record Interactive Search system, we identified 6309 individuals who had an ICD-10 diagnosis of schizophrenia-spectrum disorders and were taking antipsychotics at the time of the COVID-19 pandemic onset in the UK. People who were on clozapine treatment were compared with those on any other antipsychotic treatment for risk of contracting COVID-19 between 1 March and 18 May 2020. We tested associations between clozapine treatment and COVID-19 infection, adjusting for gender, age, ethnicity, body mass index (BMI), smoking status and SLAM service use.
Of 6309 participants, 102 tested positive for COVID-19. Individuals who were on clozapine had increased risk of COVID-19 infection compared with those who were on other antipsychotic medication (unadjusted hazard ratio HR = 2.62, 95% CI 1.73–3.96), which was attenuated after adjusting for potential confounders, including clinical contact (adjusted HR = 1.76, 95% CI 1.14–2.72).
These findings provide support for the hypothesis that clozapine treatment is associated with an increased risk of COVID-19 infection. Further research will be needed in other samples to confirm this association. Potential clinical implications are discussed.
Changed spatial configurations at sowing have been investigated as a strategy to minimize interspecific competition and improve the establishment and persistence of multi-species plantings in pastures, but the impact of this practice on the soil microbiome has received almost no previous research attention. Differences in populations of bacteria and fungi in the surface 10 cm of soil in the third year following pasture establishment were quantified using quantitative polymerase chain reaction and terminal restriction fragment length polymorphism methods. Populations were compared on, and between, drill rows sown to either the perennial grass phalaris (Phalaris aquatica L.), perennial legume lucerne (alfalfa; Medicago sativa L.) or the annual legume subterranean clover (Trifolium subterraneum L.). Results showed that soil microbial abundance and diversity were related to plant distribution across the field at the time of sampling and to soil chemical parameters including total carbon (C), mineral nitrogen (N), pH, and available phosphorus (P), potassium (K) and sulfur (S). Despite the 27-month lag since sowing, pasture species remained concentrated around the original drill row with very little colonization of the inter-row area. The abundance and diversity of bacterial and fungal populations were consistently greater under drill rows associated with higher total C concentrations in the surface soil compared with the inter-row areas. Our results showed that the pH and available nutrients were similar between the subterranean clover drill row and the inter-row, suggesting that soil microbial populations were not impacted directly by these soil fertility parameters, but rather were related to the presence or absence of plants. The abundance of bacteria and fungi were numerically lower under phalaris rows compared to rows sown to legumes. The richness and diversity of fungal populations were lowest between rows where lucerne was planted. Possible explanations for this observation include a lower C:N ratio of lucerne roots and/or a lack of fibrous roots at the soil surface compared to the other species, illustrating the influence of contrasting plant types on the soil microflora community. This study highlights the enduring legacy of the drill row on the spatial distribution of plants well into the pasture phase of a cropping rotation and discusses the opportunity to enhance the microbiome of cropping soils on a large scale during the pasture phase by increasing plant distribution across the landscape.
White matter (WM) abnormalities are considered integral to the pathophysiology of Schizophrenia (SZ) and Bipolar Disorder (BD), but there is ongoing uncertainty about the contribution of medication to these findings.
Diffusion Tensor Imaging (DTI) is a neuroimaging technique that provides quantitative indices of the structural and orientational characteristics of WM. These indices include mean diffusivity (MD), which is a directionally averaged measure of the apparent diffusion coefficient, and fractional anisotropy (FA), which summarizes the orientational dependence of diffusivity. We wanted to determine if these indices are affected by antipsychotic medication.
Our aim was to examine the available literature in order to differentiate antipsychotic effects from disorder-specific WM abnormalities on DTI measures.
We conducted a systematic qualitative review of the DTI literature in Bipolar Disorder (BD) and Schizophrenia (SZ), between 1998 and 2010 and included only studies where the relationship between DTI measures and antipsychotic medication was explicitly examined and reported.
We identified 40 studies in SZ and 8 in BD. All studies were cross-sectional and involved relatively small patient samples. 32 studies (80%) did not find any relationship between antipsychotic medication (dose, cumulative exposure) and FA or MD.
Current evidence does not indicate a major impact of antipsychotic treatment on DTI indices of WM integrity. However, the lack of longitudinal, within-subject designs is a major gap in the current literature.
The use of clozapine (CLZ) for treatment-resistant schizophrenia is well established in adults. However, it is seldom used in youth with early onset schizophrenia (EOS) largely because of lack of clarity about its risk benefit ratio. This review synthesises and evaluates available evidence regarding the efficacy and tolerability of CLZ in EOS with the aim to assist clinical decision-making.
We conducted a systematic review of the primary literature on the clinical efficacy and adverse drug reactions (ADRs) observed during CLZ treatment in EOS. We also identified relevant practice guidelines and summarised current guidance.
CLZ showed superior efficacy than other antipsychotics in treating refractory EOS patients; short-term clinical trials suggest an average improvement of 69% on the Brief Psychiatric Rating Scale that was sustained during long-term follow-up (up to 9 years). No fatalities linked to CLZ treatment were reported. Sedation and hypersalivation were the most common complaints, reported by over 90% of patients. Other common ADRs (reported in 10-60% of patients) were enuresis, constipation, weight gain, and non-specific EEG changes. Less common ADRs (reported in 10-30% of patients) were akathisia, tachycardia and changes in blood pressure. Neutropenia was reported in 6–15% of cases but was usually transient while agranulocytosis was rare (< 0.1%). Seizures were also uncommon (< 3%). Metabolic changes were relatively common (8–22%) but emergent diabetes was not frequently observed (< 6%). Overall the rate of discontinuation was low (3–6%). Current guidelines recommend the use of CLZ in EOS patients who have failed to respond to two adequate trials with different antipsychotics and provide detailed schedules of assessments to evaluate and assess potential ADRs both prior to initiation and throughout CLZ treatment.
Available data although limited in terms of number of studies are consistent in demonstrating that CLZ is effective and generally safe in the treatment of refractory EOS provided patients are regularly monitored
The aim of this study was to audit the effectiveness of individual psychodynamic psychotherapy and group therapy in a London psychotherapy service.
The data between January 2002 and July 2012 were reviewed. Of 255 profiles with an End-of-therapy form, 121 (47.45%) patients provided analyzable data at initial assessment and last session. Data was extracted on sociodemographic and mental health characteristics, responses on End-of-Therapy form, and item scores on CORE-OM on each time of measurement.
Patients who terminated prematurely did not differ from those who completed on most of the patient characteristics despite age (t=2.16, p< 0.05), risk to harm others (t=2.93, p< 0.01), percentage of attendance (t=-3.51, p< 0.01), unplanned ending (X2=30.68, p< 0.05), contextual factors (ts ranging from -2.56 to -4.84, ps< 0.05) and benefits of therapy (ts ranging from 5.29-16.18, ps< 0.05). Results indicated that IPP is effective, with a significant difference on CORE-OM (All Mann-Whitney Us range from 2697.50—4253.50, all ps< 0.001) and risk assessment (All Mann-Whitney Us range from 3161.00—3706.50, all ps< 0.001) between initial assessment and last session. However, GT patients demonstrated a significant improvement in risk assessment (All Mann-Whitney Us range from 9.00—20.50, all ps< 0.01).
Our findings further substantiate the effectiveness of IPP. Yet, it is premature to conclude that GT is not as effective as IPP due to small sample size in this study. In fact, this audit was more difficult to carry out than anticipated due to client and data attrition. Recommendations for future audit are discussed.
The use of clozapine (CLZ) for treatment-resistant schizophrenia is well established in adults. However, it is seldom used in children and adolescents with early onset schizophrenia (EOS) largely because of lack of clarity about its risk benefit ratio. This review synthesises and evaluates available evidence regarding the efficacy and tolerability of CLZ in EOS with the aim to assist clinical decision-making.
We conducted a systematic review of the primary the literature on the clinical efficacy and adverse drug reactions (ADRs) observed during CLZ treatment in EOS. We also identified relevant practice guidelines and summarised current guidance.
CLZ showed superior efficacy than other antipsychotics in treating refractory EOS patients; short-term clinical trials suggest an average improvement of 69% on the Brief Psychiatric Rating Scale that was sustained during long-term follow-up. No fatalities linked to CLZ treatment were reported. Sedation and hypersalivation were the most common complaints (90% of patients). Other common ADRs (10-60% of patients) were enuresis, constipation, weight gain, and non-specific EEG changes. Neutropenia was reported in 6-15% while agranulocytosis was rare. Seizures were also uncommon. Metabolic changes were relatively common (8-22%). Overall the rate of discontinuation was low (3-6%). Current guidelines recommend the use of CLZ in treatment-resistant EOS patients and provide detailed schedule of assessments to evaluate and assess potential ADRs both prior to initiation and throughout CLZ treatment.
Available data is consistent in demonstrating that CLZ is effective and generally safe in the treatment of refractory EOS provided patients are regularly monitored.
Compared to the general population, people with schizophrenia have a substantially higher risk of premature mortality which translates into a 10–15 year reduction in life expectancy. The aim of this investigation was to determine if symptoms (including aggression, hallucinations or delusions, and depression) or the environmental and functional status of people with schizophrenia contribute to the high mortality risk observed in this patient group.
We identified cases of schizophrenia, aged ≥15 years in a large secondary mental healthcare case register linked to national mortality tracing. We modelled the effect of specific symptoms, activities of daily living (ADLs), living conditions, occupational and recreational activities (Health of the Nation Outcome Scale [HoNOS] subscales) on all-cause mortality over a 4-year observation period (2007-10) using Cox regression.
We identified 4270 schizophrenia cases (170 deaths) in the observation period. After controlling for a broad range of covariates, mortality was not significantly associated with hallucinations and delusions or overactive-aggressive behaviour, but was associated with subclinical depression (adjusted HR 1.5; 95% CI 1.1-2.2) and ADL impairment (adjusted HR 1.8; 95% CI 1.2-2.9).
Severity of symptoms, such as delusions and hallucinations, was less important in predicting mortality than subclinical depression and difficulties carrying out activities of daily living. The overall picture appears to be one where the highest all-cause mortality risk is in service users who are least visible to clinical teams.
Internet-delivered treatments for depression have proved successful, with supported programs offering the potential for improved adherence and outcomes. Internet interventions are particularly interesting in the context of increasing access to interventions, and delivering interventions population-wide.
Investigate the potential feasibility and effectiveness of an online intervention for depression in the community.
Establish the effectiveness of a supported online delivered cognitive behavioural intervention for symptoms of depression in adults in the community.
The study was a randomized controlled trial of an 8-module internet-delivered cognitive behavioral therapy (iCBT) program for adults with depressive symptoms (n = 96) compared to a waiting-list control group (n = 92). Participants received weekly support from a trained supporter. The primary outcome was depressive symptoms as measured by the Beck Depression Inventory (BDI-II). The program was made available nationwide from an established and recognized charity for depression.
For the treatment group, post-treatment effect sizes reported were large for the primary outcome measure (d = 0.91). The between-group effects were moderate to large and statistically significant for the primary outcomes (d = 0.50) favoring the treatment group. Gains were maintained at 6-month follow-up.
The study has demonstrated the efficacy of the online delivered space from depression treatment. Participants demonstrated reliable and statistically significant changes in symptoms from pre- to post-intervention. The study supports a model for delivering online depression interventions population-wide using trained supporters.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Associations between childhood abuse and various psychotic illnesses in adulthood are commonly reported. We aim to examine associations between several reported childhood adverse events (sexual abuse, physical abuse, emotional abuse, neglect and interpersonal loss) among adults with diagnosed psychotic disorders and clinical and psychosocial outcomes.
Within a large epidemiological study, the 2010 Australian National Survey of Psychosis (Survey of High Impact Psychosis, SHIP), we used logistic regression to model childhood adverse events (any and specific types) on 18 clinical and psychosocial outcomes.
Eighty percent of SHIP participants (1466/1825) reported experiencing adverse events in childhood (sexual abuse, other types of abuse and interpersonal loss). Participants reporting any form of childhood adversity had higher odds for 12/18 outcomes we examined. Significant associations were observed with all psychosocial outcomes (social dysfunction, victimisation, offending and homelessness within the previous 12 months, and definite psychosocial stressor within 12 months of illness onset), with the strongest association for homelessness (odds ratio (OR) = 2.82). Common across all adverse event types was an association with lifetime depression, anxiety and a definite psychosocial stressor within 12 months of illness onset. When adverse event types were non-hierarchically coded, sexual abuse was associated with 11/18 outcomes, other types of abuse 13/18 and, interpersonal loss occurring in the absence of other forms of abuse was associated with fewer of the clinical and psychosocial outcomes, 4/18. When adverse events types were coded hierarchically (to isolate the effect of interpersonal loss in the absence of abuse), interpersonal loss was associated with lower odds of self-reproach (OR = 0.70), negative syndrome (OR = 0.75) and victimisation (OR = 0.82).
Adverse childhood experiences among people with psychosis are common, as are subsequent psychosocial stressors. Mental health professionals should routinely enquire about all types of adversities in this group and provide effective service responses. Childhood abuse, including sexual abuse, may contribute to subsequent adversity, poor psychosocial functioning and complex needs among people with psychosis. Longitudinal research to better understand these relationships is needed, as are studies which evaluate the effectiveness of preventative interventions in high-risk groups.
Trends in detention under the Mental Health Act 1983 in two major London secondary mental healthcare providers were explored using patient-level data in a historical cohort study between 2007–2008 and 2016–2017. An increase in the number of detention episodes initiated per fiscal year was observed at both sites. The rise was accompanied by an increase in the number of active patients; the proportion of active patients detained per year remained relatively stable. Findings suggest that the rise in the number of detentions reflects the rise of the number of people receiving secondary mental healthcare.
Iron deficiency is common in pregnant and lactating women and is associated with reduced cognitive development of the offspring. Since iron affects lipid metabolism, the availability of fatty acids, particularly the polyunsaturated fatty acids required for early neural development, was investigated in the offspring of female rats fed iron-deficient diets during gestation and lactation. Subsequent to the dams giving birth, one group of iron-deficient dams was recuperated by feeding an iron-replete diet. Dams and neonates were killed on postnatal days 1, 3 and 10, and the fatty acid composition of brain and stomach contents was assessed by gas chromatography. Changes in the fatty acid profile on day 3 became more pronounced on day 10 with a decrease in the proportion of saturated fatty acids and a compensatory increase in monounsaturated fatty acids. Long-chain polyunsaturated fatty acids in the n-6 family were reduced, but there was no change in the n-3 family. The fatty acid profiles of neonatal brain and stomach contents were similar, suggesting that the change in milk composition may be related to the changes in the neonatal brain. When the dams were fed an iron-sufficient diet at birth, the effects of iron deficiency on the fatty acid composition of lipids in both dam’s milk and neonates’ brains were reduced. This study showed an interaction between maternal iron status and fatty acid composition of the offspring’s brain and suggests that these effects can be reduced by iron repletion of the dam’s diet at birth.
Common mental health problems affect a quarter of the population. Online cognitive–behavioural therapy (CBT) is increasingly used, but the factors modulating response to this treatment modality remain unclear.
This study aims to explore the demographic and clinical predictors of response to one-to-one CBT delivered via the internet.
Real-world clinical outcomes data were collected from 2211 NHS England patients completing a course of CBT delivered by a trained clinician via the internet. Logistic regression analyses were performed using patient and service variables to identify significant predictors of response to treatment.
Multiple patient variables were significantly associated with positive response to treatment including older age, absence of long-term physical comorbidities and lower symptom severity at start of treatment. Service variables associated with positive response to treatment included shorter waiting times for initial assessment and longer treatment durations in terms of the number of sessions.
Knowledge of which patient and service variables are associated with good clinical outcomes can be used to develop personalised treatment programmes, as part of a quality improvement cycle aiming to drive up standards in mental healthcare. This study exemplifies translational research put into practice and deployed at scale in the National Health Service, demonstrating the value of technology-enabled treatment delivery not only in facilitating access to care, but in enabling accelerated data capture for clinical research purposes.
Declaration of interest
A.C., S.B., V.T., K.I., S.F., A.R., A.H. and A.D.B. are employees or board members of the sponsor. S.R.C. consults for Cambridge Cognition and Shire. Keywords: Anxiety disorders; cognitive behavioural therapies; depressive disorders; individual psychotherapy
Serious mental illness (SMI, including schizophrenia, schizoaffective disorder, and bipolar disorder) is associated with worse general health. However, admissions to general hospitals have received little investigation. We sought to delineate frequencies of and causes for non-psychiatric hospital admissions in SMI and compare with the general population in the same area.
Records of 18 380 individuals with SMI aged ⩾20 years in southeast London were linked to hospitalisation data. Age- and gender-standardised admission ratios (SARs) were calculated by primary discharge diagnoses in the 10th edition of the World Health Organization International Classification of Diseases (ICD-10) codes, referencing geographic catchment data.
Commonest discharge diagnosis categories in the SMI cohort were urinary conditions, digestive conditions, unclassified symptoms, neoplasms, and respiratory conditions. SARs were raised for most major categories, except neoplasms for a significantly lower risk. Hospitalisation risks were specifically higher for poisoning and external causes, injury, endocrine/metabolic conditions, haematological, neurological, dermatological, infectious and non-specific (‘Z-code’) causes. The five commonest specific ICD-10 diagnoses at discharge were ‘chronic renal failure’ (N18), a non-specific code (Z04), ‘dental caries’ (K02), ‘other disorders of the urinary system’ (N39), and ‘pain in throat and chest’ (R07), all of which were higher than expected (SARs ranging 1.57–6.66).
A range of reasons for non-psychiatric hospitalisation in SMI is apparent, with self-harm, self-neglect and/or reduced healthcare access, and medically unexplained symptoms as potential underlying explanations.
Mitochondrial dysfunction and resulting changes in adiposity have been observed in the offspring of animals fed a high fat (HF) diet. As iron is an important component of the mitochondria, we have studied the offspring of female rats fed complete (Con) or iron-deficient (FeD) rations for the duration of gestation to test for similar effects. The FeD offspring were ~12% smaller at weaning and remained so because of a persistent reduction in lean tissue mass. The offspring were fed a complete (stock) diet until 52 weeks of age after which some animals from each litter were fed a HF diet for a further 12 weeks. The HF diet increased body fat when compared with animals fed the stock diet, however, prenatal iron deficiency did not change the ratio of fat:lean in either the stock or HF diet groups. The HF diet caused triglyceride to accumulate in the liver, however, there was no effect of prenatal iron deficiency. The activity of the mitochondrial electron transport complexes was similar in all groups including those challenged with a HF diet. HF feeding increased the number of copies of mitochondrial DNA and the prevalence of the D-loop mutation, however, neither parameter was affected by prenatal iron deficiency. This study shows that the effects of prenatal iron deficiency differ from other models in that there is no persistent effect on hepatic mitochondria in aged animals exposed to an increased metabolic load.
This study examined the response of forage crops to composted dairy waste (compost) applied at low rates and investigated effects on soil health. The evenness of spreading compost by commercial machinery was also assessed. An experiment was established on a commercial dairy farm with target rates of compost up to 5 t ha−1 applied to a field containing millet [Echinochloa esculenta (A. Braun) H. Scholz] and Pasja leafy turnip (Brassica hybrid). A pot experiment was also conducted to monitor the response of a legume forage crop (vetch; Vicia sativa L.) on three soils with equivalent rates of compost up to 20 t ha−1 with and without ‘additive blends’ comprising gypsum, lime or other soil treatments. Few significant increases in forage biomass were observed with the application of low rates of compost in either the field or pot experiment. In the field experiment, compost had little impact on crop herbage mineral composition, soil chemical attributes or soil fungal and bacterial biomass. However, small but significant increases were observed in gravimetric water content resulting in up to 22.4 mm of additional plant available water calculated in the surface 0.45 m of soil, 2 years after compost was applied in the field at 6 t ha−1 dried (7.2 t ha−1 undried), compared with the nil control. In the pot experiment, where the soil was homogenized and compost incorporated into the soil prior to sowing, there were significant differences in mineral composition in herbage and in soil. A response in biomass yield to compost was only observed on the sandier and lower fertility soil type, and yields only exceeded that of the conventional fertilizer treatment where rates equivalent to 20 t ha−1 were applied. With few yield responses observed, the justification for applying low rates of compost to forage crops and pastures seems uncertain. Our collective experience from the field and the glasshouse suggests that farmers might increase the response to compost by: (i) increasing compost application rates; (ii) applying it prior to sowing a crop; (iii) incorporating the compost into the soil; (iv) applying only to responsive soil types; (v) growing only responsive crops; and (vi) reducing weed burdens in crops following application. Commercial machinery incorporating a centrifugal twin disc mechanism was shown to deliver double the quantity of compost in the area immediately behind the spreader compared with the edges of the spreading swathe. Spatial variability in the delivery of compost could be reduced but not eliminated by increased overlapping, but this might represent a potential 20% increase in spreading costs.