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Pellet injection is currently the primary candidate for achieving efficient plasma fuelling, one of the key issues for steady-state operation in large fusion devices. In this paper, pellet injection experiments are performed for several magnetic configurations of the TJ-II stellarator. The aim of this study is to increase the understanding of the role played by rational surfaces in plasmoid drift and deposition profiles in stellarators. The analysis of experimentally observed plasmoid drifts is supported by simulations of such cases made with the HPI2 code. Plasmoid drift is found to be significantly reduced, as in tokamaks, in the vicinity of rational surfaces. This is attributed to the fact that plasmoid external charge reconnection lengths are shorter near rational surfaces, resulting in a more effective damping of the plasmoid drift. Although the effect of plasmoid external currents on the drift is expected to be negligible in stellarators, compared with those caused by plasmoid internal currents, the effect observed in TJ-II is clearly measurable. In addition, simulations show that enhanced drift reductions near rational surfaces lead to significantly different deposition profiles for the magnetic configurations included in this study. This implies that it should be possible to select the magnetic configurations to obtain more efficient pellet fuelling.
Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.
Aims
To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
Method
This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.
Results
The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.
Conclusions
Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
The evolution of glaciers and ice sheets depends on processes in the subglacial environment. Shear seismicity along the ice–bed interface provides a window into these processes. Such seismicity requires a rapid loss of strength that is typically ascribed to rate-weakening friction, i.e., decreasing friction with sliding or sliding rate. Many friction experiments have investigated glacial materials at the temperate conditions typical of fast flowing glacier beds. To our knowledge, however, these studies have all found rate-strengthening friction. Here, we investigate the possibility that rate-weakening rock-on-rock friction between sediments frozen to the bottom of the glacier and the underlying water-saturated sediments or bedrock may be responsible for subglacial shear seismicity along temperate glacier beds. We test this ‘entrainment-seismicity hypothesis’ using targeted laboratory experiments and simple models of glacier sliding, seismicity and sediment entrainment. These models suggest that sediment entrainment may be a necessary but not sufficient condition for the occurrence of basal shear seismicity. We propose that stagnation at the Whillans Ice Stream, West Antarctica may be caused by the growth of a frozen fringe of entrained sediment in the ice stream margins. Our results suggest that basal shear seismicity may indicate geomorphic activity.
Background Attention-deficit/hyperactivity disorder (ADHD) is among the most common psychiatric disorders of childhood that often persists into adulthood and old age. Yet ADHD is currently underdiagnosed and undertreated in many European countries, leading to chronicity of symptoms and impairment, due to lack of, or ineffective treatment, and higher costs of illness.
Methods The European Network Adult ADHD and the Section for Neurodevelopmental Disorders Across the Lifespan (NDAL) of the European Psychiatric Association (EPA), aim to increase awareness and knowledge of adult ADHD in and outside Europe. This Updated European Consensus Statement aims to support clinicians with research evidence and clinical experience from 63 experts of European and other countries in which ADHD in adults is recognized and treated.
Results Besides reviewing the latest research on prevalence, persistence, genetics and neurobiology of ADHD, three major questions are addressed: (1) What is the clinical picture of ADHD in adults? (2) How should ADHD be properly diagnosed in adults? (3) How should adult ADHDbe effectively treated?
Conclusions ADHD often presents as a lifelong impairing condition. The stigma surrounding ADHD, mainly due to lack of knowledge, increases the suffering of patients. Education on the lifespan perspective, diagnostic assessment, and treatment of ADHD must increase for students of general and mental health, and for psychiatry professionals. Instruments for screening and diagnosis of ADHD in adults are available, as are effective evidence-based treatments for ADHD and its negative outcomes. More research is needed on gender differences, and in older adults with ADHD.
Established methods of recruiting population controls for case–control studies to investigate gastrointestinal disease outbreaks can be time consuming, resulting in delays in identifying the source or vehicle of infection. After an initial evaluation of using online market research panel members as controls in a case–control study to investigate a Salmonella outbreak in 2013, this method was applied in four further studies in the UK between 2014 and 2016. We used data from all five studies and interviews with members of each outbreak control team and market research panel provider to review operational issues, evaluate risk of bias in this approach and consider methods to reduce confounding and bias. The investigators of each outbreak reported likely time and cost savings from using market research controls. There were systematic differences between case and control groups in some studies but no evidence that conclusions on the likely source or vehicle of infection were incorrect. Potential selection biases introduced by using this sampling frame and the low response rate are unclear. Methods that might reduce confounding and some bias should be balanced with concerns for overmatching. Further evaluation of this approach using comparisons with traditional methods and population-based exposure survey data is recommended.
We present preliminary results from two parallel programs to search for new substellar companions to nearby, young M-stars and to characterize the atmospheres of known planetary mass and temperature substellar companions. For the M-star survey, we are analyzing high angular resolution archival data on systems within 15pc, complementing a subset with well-determined young ages based on measurements of several age indicators. The results include stellar and substellar companion candidates, which we are currently pursuing with follow-up second epoch images. The characterization component of the project involves using LBT LMIRCam and MMT ARIES direct imaging and spectroscopy data to investigate the atmospheres of known young substellar companions with masses overlapping the planetary regime. These atmospheric studies will represent an analogous comparison to the atmospheres of young imaged planets, and provide a means to fundamentally test evolutionary models, enhancing our understanding of the overall substellar population.
We sought to explain seasonality and other aspects of Campylobacter jejuni epidemiology by integrating population genetic and epidemiological analysis in a large 3-year longitudinal, two-centre, population-based study. Epidemiological information was collected for 1505 isolates, which were multilocus sequence-typed. Analyses compared pathogen population structure between areas, over time, and between clinical presentations. Pooled analysis was performed with published international datasets. Subtype association with virulence was not observed. UK sites had nearly identical C. jejuni populations. A clade formed by ST45 and ST283 clonal complexes showed a summer peak. This clade was common in a Finnish dataset but not in New Zealand and Australian collections, countries with less marked seasonality. The UK, New Zealand and Australian collections were otherwise similar. These findings map to known in-vitro differences of this clade. This identifies a target for studies to elucidate the drivers of the summer peak in human C. jejuni infection.
The antibody responses of 8 cattle experimentally infected with Onchocerca ochengi to 18 recombinant O. volvulus antigens
were measured by ELISA. In addition to establishing antigenic cross-reactivity between the species, the dynamics of
antigen-specific responses were examined to assess how the recognition of the antigens compared to the known stage-specificity of expression. Six cattle responded to all of the antigens and 2 animals responded to all but 1. The dynamics
of the recognition of 4 antigens (B20, MOv-2, MOv-14 and OvNHR2 02E1) were characterized by rapid seroconversion
following infection. Antibody levels to 2 antigens (Ov7 and OvALT-1) increased gradually over the course of infection.
Antibody levels to 4 antigens (OvTPX-2, OvL3Chitinase, Ov103 and Ov9m) reached maximum levels coincident with
the onset of patency. The levels to 3 antigens (OvProalf C50, OvAldolase, Ov39) varied little over the course of infection.
Responses to antigens with functional similarities (OvSOD1, OvSOD2 and OvSOD3 or OvGST1 and OvGST2) showed
comparable temporal profiles. This study demonstrates the high degree of immunological cross-reactivity between the
antigens of O. volvulus and O. ochengi. The immunogenicity of antigens varied over the course of infection in an antigen-specific manner, which not always reflected developmentally regulated expression of the corresponding gene, possibly
owing to cross-reactive epitopes on distinct parasite products.
Renal concentrating capacity following 18 hours of fluid deprivation was measured in 75 patients receiving prophylactic lithium therapy, and in 30 affectively ill subjects receiving other drugs. The lithium-treated patients had significantly lower urine osmolality and higher serum osmolality than the control subjects. Older subjects, patients maintained at higher serum lithium levels and those with a history of previous neurotoxicity showed the most impairment. Ten patients with urine osmolalities of less than 700 mOsm/l following this test were investigated further. Inulin and para-amino hippurate (PAH) clearance rates were determined and the effect of a subpressor challenge of dopamine on these measures was observed. Half of the patients showed some reduction in inulin and PAH clearance, which was greatest in those patients who had been taking lithium for over 10 years. However, all of the patients tested showed the expected increase in renal blood flow and sodium and water excretion in response to dopamine. Six additional patients had clearance estimations made before starting lithium treatment which were repeated after a period of 3–6 months on the drug. No consistent changes in haemodynamics were observed.
Lithium clearly reduces renal concentrating capacity, but other measures of renal tubular function were well preserved in patients receiving long-term therapy. Glomerular function may be slightly reduced in patients taking lithium for long periods. The results show that prophylactic lithium treatment does not affect renal cortical function adversely in the majority of patients, but impaired renal concentrating ability is a common accompaniment.
The normal flora of cockroaches (Periplaneta americana) was determined over a period of 24 days prior to substituting water with 1% Formalin for drinking water. During the first 4 days of treatment the normal flora was significantly reduced and by the fifth day, when the cockroaches became diarrhoeic, no bacteria, fungi, or viruses could be detected by the methods used.
Skin infections are highly prevalent in many Australian Aboriginal communities. This study aimed to determine the prevalence of group A streptococcus (GAS) and Staphylococcus aureus in skin sores of Indigenous people living in an urban setting. We undertook a cross-sectional study of 173 children and youths attending the Wuchopperen Clinic (Cairns) for treatment of skin infections. Participants were interviewed using a structured questionnaire, and a skin lesion swab obtained. The median age was 5·3 years, with 42% identifying themselves as Torres Strait Islanders and 34% as Aboriginal. Impetigo (65%) was the most frequent diagnosis reported followed by scabies (19%); 79% of the lesions had erythema and 70% had exudate. Of 118 lesions, 114 were positive for pathogenic bacteria, with GAS isolated in 84 cases and S. aureus in 92; both these species were recovered from 63 lesions. Significant diversity of emm-types of GAS was associated with skin lesions in Indigenous patients (22 emm-types identified). Fifteen of the 92 S. aureus isolates were suggestive of being community-acquired on the basis of antimicrobial susceptibility profile and nine of these strains were co-cultured from nine lesions. These results have implications for future changes of antibiotic policies for the treatment of skin infections in this population.
Eighteen children with hemiplegia, mean age 8 years 5 months, underwent gait analysis and musculoskeletal modelling using specially designed software. The maximum lengths of the hamstrings were determined for each child walking in and out of an ankle–foot orthosis (AFO). The muscles were deemed to be short if shorter than the normal average –1SD. In bare feet 8 participants had short medial hamstrings with a higher proportion of these in the less involved individuals. All participants showed an increase in maximum hamstring length when wearing an AFO. In all but one child this was sufficient to restore hamstring length to within normal limits. These finding suggest that hamstring pathology in hemiplegic gait is usually secondary to more distal lower limb pathology.
Evidence exists for an association between aggression and schizophrenia. Although the aetiology of aggression is multifactorial, three studies have reported associations between polymorphisms of the catechol-O-methyltransferase (COMT) gene and aggression in schizophrenia.
Aims
To replicate these findings in a larger sample using the Overt Aggression Scale (OAS).
Method
A sample of 180 people with DSM–IV schizophrenia were rated for aggression using the OAS. Kruskal–Wallis and contingency table analyses were applied to the OAS results.
Results
The high-activity homozygotes showed significantly higher scores of aggression, whereas the heterozygotes showed significantly lower scores. The odds ratio for aggression for the high-activity homozygotes was 2.07 (95% Cl=1.03–4.15), whereas that for the heterozygotes was 0.54 (95% CI=0. 30–1.00).
Conclusions
The high-activity COMT homozygote confers a higher risk of recorded aggression in schizophrenia. Heterozygotes had a significantly lower risk, which may represent an example of heterosis/heterozygote advantage.
The triennial report of Commission 19 was composed from the contributions of its members. Space does not permit a listing of their names, but their contributions are sincerely appreciated. Unfortunately because of limited space it is also not possible to provide in this report the extensive list of publication of the Commission members. The list of publications is however available on the Commission 19 web site at maia.usno.navy.mil/iauc19.
Dihydrohpoamide acetyl transferase (E2), a catalytic and structural component of a multienzyme complex that catalyzes the oxidative decarboxylation of pyruvate, forms the central core to which the other components are bound. We have utilized protein engineering and 3-D electron microscopy to study the structural organization of the largest multienzyme complex known (Mr ∼ 107). The structures of the truncated 60-mer core (tE2) and complexes of the tE2 associated with a binding protein (BP), and the BP associated with its dihydrohpoamide dehydrogenase (BP'E3) and the intact E2 associated with BP and the pyruvate dehydrogenase (E1) were determined (Figs. 1 and 2). The tE2 core is a pentagonal dodecahedron consisting of 20 cone-shaped trimers interconnected by 30 bridges.
Previous studies have given rise to the generally accepted belief that BP and BP'E3 components are bound on the outside of the E2 scaffold and that E1 is similarly bound to the core in variable positions by flexible tethers.