While clozapine has risks, relative risk of fatality is overestimated. The UK pharmacovigilance programme is efficient, but comparisons with other drugs can mislead because of reporting variations. Clozapine actually lowers mortality, partly by reducing schizophrenia-related suicides, but preventable deaths still occur. Clozapine should be used earlier and more widely, but there should be better monitoring and better management of toxicity.

NASA’s all-sky survey mission, the Transiting Exoplanet Survey Satellite (TESS), is specifically engineered to detect exoplanets that transit bright stars. Thus far, TESS has successfully identified approximately 400 transiting exoplanets, in addition to roughly 6 000 candidate exoplanets pending confirmation. In this study, we present the results of our ongoing project, the Validation of Transiting Exoplanets using Statistical Tools (VaTEST). Our dedicated effort is focused on the confirmation and characterisation of new exoplanets through the application of statistical validation tools. Through a combination of ground-based telescope data, high-resolution imaging, and the utilisation of the statistical validation tool known as TRICERATOPS, we have successfully discovered eight potential super-Earths. These planets bear the designations: TOI-238b (1.61$^{+0.09} _{-0.10}$ R$_\oplus$), TOI-771b (1.42$^{+0.11} _{-0.09}$ R$_\oplus$), TOI-871b (1.66$^{+0.11} _{-0.11}$ R$_\oplus$), TOI-1467b (1.83$^{+0.16} _{-0.15}$ R$_\oplus$), TOI-1739b (1.69$^{+0.10} _{-0.08}$ R$_\oplus$), TOI-2068b (1.82$^{+0.16} _{-0.15}$ R$_\oplus$), TOI-4559b (1.42$^{+0.13} _{-0.11}$ R$_\oplus$), and TOI-5799b (1.62$^{+0.19} _{-0.13}$ R$_\oplus$). Among all these planets, six of them fall within the region known as ‘keystone planets’, which makes them particularly interesting for study. Based on the location of TOI-771b and TOI-4559b below the radius valley we characterised them as likely super-Earths, though radial velocity mass measurements for these planets will provide more details about their characterisation. It is noteworthy that planets within the size range investigated herein are absent from our own solar system, making their study crucial for gaining insights into the evolutionary stages between Earth and Neptune.

Hydrothermal synthesis experiments were conducted to study the transition from smectite to corrensite. A mixture of oxides with the bulk composition of corrensite—Na0.4(Si6.4Al1.6)(Mg7.8Al1.2)-O20(OH)10—was sealed in platinum capsules with 29–37 wt. % water. One set of samples was treated in cold-seal vessels at 500°C and 2 kbar for durations of 2, 3, 6, 12, and 24 h; the other set was treated at 350°C and 2 kbar for periods of 12 to 89 d. X-ray diffraction patterns (XRD) of oriented aggregates from treated products were obtained from ethylene glycol-solvated and air-dried preparations. Samples were also heated to 350°C either in a calibrated muffle furnace, removed and quickly placed in a nitrogen filled chamber on the diffractometer, or were heated at 350°C by using a calibrated heating stage mounted on the diffractometer.

Initial mineral assemblages at both temperatures contained only saponite and serpentine. In experiments at 500°C, saponite transformed to corrensite within 6 h; in experiments at 350°C, the transformation occurred as early as 22 d. Increased experiment times at both temperatures produced increasing amounts of well-crystallized corrensite, as indicated by several well-defined XRD peaks. No evidence of a randomly interstratified chlorite-smectite (C-S) precursor to corrensite was found. The identification of pure smectite, as opposed to highly-expanded randomly interstratified C-S, was possible only when clays were dehydrated on a heating stage on the diffractometer.

These results call for a new examination of hydrothermally-altered basalt that has been reported to contain randomly interstratified C-S as an intermediate step in the reaction of smectite to corrensite or chlorite. These results also strengthen the view held by increasing numbers of investigators that corrensite should be regarded as a single phase, not as a mixed-layered phyllosilicate.

We present a method for tracking radio-tagged pebbles and cobbles through subglacial meltwater channels under shallow temperate glaciers. Natural particles tagged with active radio transmitters were injected directly into a large subglacial channel 300 m up-glacier from the terminus of the Glacier d'Otemma, Switzerland. A roving antenna was developed to localise tagged particles planimetrically in subglacial and proglacial channel reaches (350 and 150 m long, respectively) using a probabilistic technique, delivering records of the change in particle location and transport distance over time with uncertainty. The roving antenna had a ±5−15 m planimetric precision, a 75% particle localisation rate and operated at a maximum ice depth of 47 m. Additionally, stationary supraglacial and proglacial antennas continuously monitored the passage of tagged particles through consecutive reaches of the channel, constraining the timing of particle transport events. The proglacial antenna system had a 98.1% detection rate and was operational to 0.89 m water depth during testing. Roving and stationary antenna records were combined to create a transport distance model for each particle, which may be used in conjunction with hydraulic data to investigate the kinematics of particle motion. When applied at scale in future studies, this method may be used to reveal the mechanisms and timescales of coarse sediment export from Alpine glaciers.

The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery (WCPCCS) will be held in Washington DC, USA, from Saturday, 26 August, 2023 to Friday, 1 September, 2023, inclusive. The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery will be the largest and most comprehensive scientific meeting dedicated to paediatric and congenital cardiac care ever held. At the time of the writing of this manuscript, The Eighth World Congress of Pediatric Cardiology and Cardiac Surgery has 5,037 registered attendees (and rising) from 117 countries, a truly diverse and international faculty of over 925 individuals from 89 countries, over 2,000 individual abstracts and poster presenters from 101 countries, and a Best Abstract Competition featuring 153 oral abstracts from 34 countries. For information about the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery, please visit the following website: [www.WCPCCS2023.org]. The purpose of this manuscript is to review the activities related to global health and advocacy that will occur at the Eighth World Congress of Pediatric Cardiology and Cardiac Surgery.

Acknowledging the need for urgent change, we wanted to take the opportunity to bring a common voice to the global community and issue the Washington DC WCPCCS Call to Action on Addressing the Global Burden of Pediatric and Congenital Heart Diseases. A copy of this Washington DC WCPCCS Call to Action is provided in the Appendix of this manuscript. This Washington DC WCPCCS Call to Action is an initiative aimed at increasing awareness of the global burden, promoting the development of sustainable care systems, and improving access to high quality and equitable healthcare for children with heart disease as well as adults with congenital heart disease worldwide.

The transition from DSM-IV to DSM-5 relaxed diagnostic criteria for anorexia nervosa and bulimia nervosa, and recognised a third eating disorder, binge eating disorder. However, a large proportion of cases remain in the ill-defined category of ‘other specified feeding and eating disorders’. We sought to investigate the utility of a proposed solution to classify this group further, subdividing based on the dominant clinical feature: binge eating/purging or restraint. Cluster analysis failed to identify clusters in a treatment-seeking sample based on symptoms of restraint, binge eating, purging and over-evaluation of shape and weight. Further investigation of this highly heterogeneous group is required.

Patients with single-ventricle CHD undergo a series of palliative surgeries that culminate in the Fontan procedure. While the Fontan procedure allows most patients to survive to adulthood, the Fontan circulation can eventually lead to multiple cardiac complications and multi-organ dysfunction. Care for adolescents and adults with a Fontan circulation has begun to transition from a primarily cardiac-focused model to care models, which are designed to monitor multiple organ systems, and using clues from this screening, identify patients who are at risk for adverse outcomes. The complexity of care required for these patients led our centre to develop a multidisciplinary Fontan Management Programme with the primary goals of earlier detection and treatment of complications through the development of a cohesive network of diverse medical subspecialists with Fontan expertise.

Diets varying in SFA and MUFA content can impact glycaemic control; however, whether underlying differences in genetic make-up can influence blood glucose responses to these dietary fatty acids is unknown. We examined the impact of dietary oils varying in SFA/MUFA content on changes in blood glucose levels (primary outcome) and whether these changes were modified by variants in the stearoyl-CoA desaturase (SCD) gene (secondary outcome). Obese men and women participating in the randomised, crossover, isoenergetic, controlled-feeding Canola Oil Multicenter Intervention Trial II consumed three dietary oils for 6 weeks, with washout periods of ˜6 weeks between each treatment. Diets studied included a high SFA/low MUFA Control oil (36·6 % SFA/28·2 % MUFA), a conventional canola oil (6·2 % SFA/63·1 % MUFA) and a high-oleic acid canola oil (5·8 % SFA/74·7 % MUFA). No differences in fasting blood glucose were observed following the consumption of the dietary oils. However, when stratified by SCD genotypes, significant SNP-by-treatment interactions on blood glucose response were found with additive models for rs1502593 (P = 0·01), rs3071 (P = 0·02) and rs522951 (P = 0·03). The interaction for rs3071 remained significant (P = 0·005) when analysed with a recessive model, where individuals carrying the CC genotype showed an increase (0·14 (sem 0·09) mmol/l) in blood glucose levels with the Control oil diet, but reductions in blood glucose with both MUFA oil diets. Individuals carrying the AA and AC genotypes experienced reductions in blood glucose in response to all three oils. These findings identify a potential new target for personalised nutrition approaches aimed at improving glycaemic control.

A retrospective study was conducted to describe the impact of a molecular assay to detect the most common carbapenemase genes in carbapenem-resistant Enterobacterales isolates recovered in culture. Carbapenemases were detected in 69% of isolates, and assay results guided treatment modifications or epidemiologic investigation in 20% and 4% of cases, respectively.

Across the globe, the implementation of quality improvement science and collaborative learning has positively affected the care and outcomes for children born with CHD. These efforts have advanced the collective expertise and performance of inter-professional healthcare teams. In this review, we highlight selected quality improvement initiatives and strategies impacting the field of cardiovascular care and describe implications for future practice and research. The continued leveraging of technology, commitment to data transparency, focus on team-based practice, and recognition of cultural norms and preferences ensure the success of sustainable models of global collaboration.

Fatty acid ethanolamides (FAE), a group of lipid mediators derived from long-chain fatty acids (FA), mediate biological activities including activation of cannabinoid receptors, stimulation of fat oxidation and regulation of satiety. However, how circulating FAE levels are influenced by FA intake in humans remains unclear. The objective of the present study was to investigate the response of six major circulating FAE to various dietary oil treatments in a five-period, cross-over, randomised, double-blind, clinical study in volunteers with abdominal obesity. The treatment oils (60 g/12 552 kJ per d (60 g/3000 kcal per d)) provided for 30 d were as follows: conventional canola oil, high oleic canola oil, high oleic canola oil enriched with DHA, flax/safflower oil blend and corn/safflower oil blend. Two SNP associated with FAE degradation and synthesis were studied. Post-treatment results showed overall that plasma FAE levels were modulated by dietary FA and were positively correlated with corresponding plasma FA levels; minor allele (A) carriers of SNP rs324420 in gene fatty acid amide hydrolase produced higher circulating oleoylethanolamide (OEA) (P=0·0209) and docosahexaenoylethanolamide (DHEA) levels (P=0·0002). In addition, elevated plasma DHEA levels in response to DHA intake tended to be associated with lower plasma OEA levels and an increased gynoid fat mass. In summary, data suggest that the metabolic and physiological responses to dietary FA may be influenced via circulating FAE. Genetic analysis of rs324420 might help identify a sub-population that appears to benefit from increased consumption of DHA and oleic acid.

Ludwig’s Bustard Neotis ludwigii is globally ‘Endangered’ because of a projected population decline resulting from high collision mortality on power lines throughout its southern African range. Population monitoring is key to the effective conservation of threatened species, but there are no population trend data to confirm the impact of this mortality. We repeated extensive road and aerial census counts of Ludwig’s Bustards and other large terrestrial birds, previously conducted in the late 1980s, across the Karoo, South Africa. An aerial survey gave similar density patterns to a concurrent road count, suggesting that road counts are an adequate method for censusing Ludwig’s Bustards. In common with the 1980s surveys, there was a strong seasonal effect in the Succulent Karoo, with Ludwig’s Bustards abundant in winter and rare in summer. There was no evidence of a corresponding decline in the Nama Karoo in winter, but this probably relates to reduced detectability in the Nama Karoo in summer as there is evidence for large proportions of the population migrating between biomes. No relationship was found between the numbers of Ludwig’s Bustards and rainfall, perhaps because of larger scale rainfall patterns in the Karoo and/or because the species is not strictly nomadic. Compared with the 1980s, Ludwig’s Bustards were more strongly associated with transformed lands, which have increased marginally on road count transects. Using Distance, the current South African population is estimated at 114,000 (95% CI 87,000-148,000) birds, with no evidence for a population decline over the past two decades. Numbers of Blue Cranes Anthropoides paradiseus increased since the 1980s, corresponding with other data supporting this trend, but numbers of Karoo Korhaan Eupodotis vigorsii, Southern Black Korhaan Afrotis afra and Blue Korhaan E. caerulescens all decreased, raising concerns about the conservation status of these resident bustard species.

The present randomised parallel study assessed the impact of adding MUFA to a dietary portfolio of cholesterol-lowering foods on the intravascular kinetics of apoAI- and apoB-containing lipoproteins in subjects with dyslipidaemia. A sample of sixteen men and postmenopausal women consumed a run-in stabilisation diet for 4 weeks. Subjects were then randomly assigned to an experimental dietary portfolio either high or low in MUFA for another 4 weeks. MUFA substituted 13·0 % of total energy from carbohydrate (CHO) in the high-MUFA dietary portfolio. Lipoprotein kinetics were assessed after the run-in and portfolio diets using a primed, constant infusion of [2H3]leucine and multicompartmental modelling. The high-MUFA dietary portfolio resulted in higher apoAI pool size (PS) compared with the low-MUFA dietary portfolio (15·9 % between-diet difference, P= 0·03). This difference appeared to be mainly attributable to a reduction in apoAI fractional catabolic rate (FCR) after the high-MUFA diet ( − 5·6 %, P= 0·02 v. pre-diet values), with no significant change in production rate. The high-MUFA dietary portfolio tended to reduce LDL apoB100 PS compared with the low-MUFA dietary portfolio ( − 28·5 % between-diet difference, P= 0·09), predominantly through an increase in LDL apoB100 FCR (23·2 % between-diet difference, P= 0·04). These data suggest that adding MUFA to a dietary portfolio of cholesterol-lowering foods provides the added advantage of raising HDL primarily through a reduction in HDL clearance rate. Replacing CHO with MUFA in a dietary portfolio may also lead to reductions in LDL apoB100 concentrations primarily by increasing LDL clearance rate, thus potentiating further the well-known cholesterol-lowering effect of this diet.