Antenatal corticosteroids are given to pregnant people at risk of preterm birth to reduce newborn morbidity, including respiratory distress syndrome. However, there has been concern surrounding potential adverse effects on subsequent generations. Animal studies have demonstrated endocrine and metabolic changes in those exposed to corticosteroids in utero (F1) and in the second generation (F2). We aimed to assess the effects of parental antenatal corticosteroid exposure on health of the second generation (F2) of Auckland Steroid Trial (AST) participants. In the AST, women (F0) expected to birth between 24 and 36 weeks’ gestation were randomised to betamethasone or placebo. When their children (F1) were 50 years old, they and their children (F2) were followed up with a self-report questionnaire and data linkage. The primary outcome for this analysis was body mass index (BMI) z-score in the F2 generation. Secondary outcomes included respiratory, cardiovascular, neurodevelopmental, mental and general health, and social outcomes. Of the 213 F2 participants, 144 had BMI data available. There was no difference in BMI z-score between participants whose parent was exposed to betamethasone versus placebo (mean (SD) 0.63 (1.45), N = 77 vs 0.41 (1.28), N = 67, adjusted mean difference (95% confidence interval) = 0.16 (-0.37, 0.69)). There was no evidence of a difference in rates of overweight, diabetes, respiratory disease, cardiometabolic risk factors, neurodevelopmental difficulties, mental health difficulties and social outcomes between parental betamethasone versus placebo exposure groups, but confidence intervals were wide. These findings are reassuring regarding the intergenerational safety of antenatal corticosteroids.

An assessment of systemic inflammation and nutritional status may form the basis of a framework to examine the prognostic value of cachexia in patients with advanced cancer. The objective of the study was to examine the prognostic value of the Global Leadership Initiative on Malnutrition criteria, including BMI, weight loss (WL) and systemic inflammation (as measured by the modified Glasgow Prognostic Score (mGPS)), in advanced cancer patients. Three criteria were examined in a combined cohort of patients with advanced cancer, and their relationship with survival was examined using Cox regression methods. Data were available on 1303 patients. Considering BMI and the mGPS, the 3-month survival rate varied from 74 % (BMI > 28 kg/m2) to 61 % (BMI < 20 kg/m2) and from 84 % (mGPS 0) to 60 % (mGPS 2). Considering WL and the mGPS, the 3-month survival rate varied from 81 % (WL ± 2·4 %) to 47 % (WL ≥ 15 %) and from 93 % (mGPS 0) to 60 % (mGPS 2). Considering BMI/WL grade and mGPS, the 3-month survival rate varied from 86 % (BMI/WL grade 0) to 59 % (BMI/WL grade 4) and from 93 % (mGPS 0) to 63 % (mGPS 2). When these criteria were combined, they better predicted survival. On multivariate survival analysis, the most highly predictive factors were BMI/WL grade 3 (HR 1·454, P = 0·004), BMI/WL grade 4 (HR 2·285, P < 0·001) and mGPS 1 and 2 (HR 1·889, HR 2·545, all P < 0·001). In summary, a high BMI/WL grade and a high mGPS as outlined in the BMI/WL grade/mGPS framework were consistently associated with poorer survival of patients with advanced cancer. It can be readily incorporated into the routine assessment of patients.

Annual bluegrass is a troublesome weed in turfgrass, with reported resistance to at least 12 herbicide sites of action. The mitotic-inhibiting herbicide pronamide has both preemergence and postemergence activity on susceptible annual bluegrass populations. Previous studies suggest that postemergence activity may be compromised due to lack of root uptake, as well as target-site- and translocation-based mechanisms. Research was conducted to determine the effects of spray droplet spectra on spray coverage and control of annual bluegrass with pronamide, flazasulfuron, and a mixture of pronamide plus flazasulfuron. Herbicides were delivered to annual bluegrass plants having two to three leaves via five different spray spectra based on volume median diameters (VMD) of 200, 400, 600, 800, and 1,000 µm. Fluorescent tracer dye was added to each treatment solution to quantify the effects of herbicide and spray droplet spectra on herbicide deposition. In another experiment, the efficacy of 0.58, 1.16, and 2.32 kg pronamide ha−1; 0.022, 0.044, and 0.088 kg flazasulfuron ha−1, or a combination of the two, were assessed in iteration with droplet spectrum sprays of 400 and 1,000 µm on two pronamide-resistant and two pronamide-susceptible annual bluegrass populations. Spray droplet spectrum affected the deposition of pronamide and flazasulfuron, applied alone and in combination. Pronamide foliar deposition decreased with increasing droplet spectra. Pronamide efficacy was affected by droplet spectrum, with the largest (1,000 µm) exhibiting improved control. Flazasulfuron efficacy and pronamide plus flazasulfuron efficacy were not affected by droplet spectra. Pronamide plus flazasulfuron mixture controlled all four populations more effectively than pronamide alone, regardless of droplet spectra. A mixture of pronamide plus flazasulfuron applied with relatively large droplets may be optimal for annual bluegrass control, which offers valuable insights for optimizing herbicide application and combatting herbicide resistance. However, applications in this controlled-growth pot study may not mimic conditions in which thatch and turfgrass canopy limit the soil deposition of pronamide.

The mitotic-inhibiting herbicide pronamide controls susceptible annual bluegrass (Poa annua L.) pre- and postemergence, but in some resistant populations, postemergence activity is compromised, hypothetically due to a target-site mutation, lack of root uptake, or an unknown resistance mechanism. Three suspected pronamide-resistant (LH-R, SC-R, and SL-R) and two pronamide-susceptible (BS-S and HH-S) populations were collected from Mississippi golf courses. Dose–response experiments were conducted to confirm and quantify pronamide resistance, as well as resistance to flazasulfuron and simazine. Target sites known to confer resistance to mitotic-inhibiting herbicides were sequenced, as were target sites for herbicides inhibiting acetolactate synthase (ALS) and photosystem II (PSII). Pronamide absorption and translocation were investigated following foliar and soil applications. Dose–response experiments confirmed pronamide resistance of LH-R, SC-R, and SL-R populations, as well as instances of multiple resistance to ALS- and PSII-inhibiting herbicides. Sequencing of the α-tubulin gene confirmed the presence of a mutation that substituted isoleucine for threonine at position 239 (Thr-239-Ile) in LH-R, SC-R, SL-R, and BS-S populations. Foliar application experiments failed to identify differences in pronamide absorption and translocation between the five populations, regardless of harvest time. All populations had limited basipetal translocation—only 3% to 13% of the absorbed pronamide—across harvest times. Soil application experiments revealed that pronamide translocation was similar between SC-R, SL-R, and both susceptible populations across harvest times. The LH-R population translocated less soil-applied pronamide than susceptible populations at 24, 72, and 168 h after treatment, suggesting that reduced acropetal translocation may contribute to pronamide resistance. This study reports three new pronamide-resistant populations, two of which are resistant to two modes of action (MOAs), and one of which is resistant to three MOAs. Results suggest that both target site– and translocation-based mechanisms may be associated with pronamide resistance. Further research is needed to confirm the link between pronamide resistance and the Thr-239-Ile mutation of the α-tubulin gene.

This article is a clinical guide which discusses the “state-of-the-art” usage of the classic monoamine oxidase inhibitor (MAOI) antidepressants (phenelzine, tranylcypromine, and isocarboxazid) in modern psychiatric practice. The guide is for all clinicians, including those who may not be experienced MAOI prescribers. It discusses indications, drug-drug interactions, side-effect management, and the safety of various augmentation strategies. There is a clear and broad consensus (more than 70 international expert endorsers), based on 6 decades of experience, for the recommendations herein exposited. They are based on empirical evidence and expert opinion—this guide is presented as a new specialist-consensus standard. The guide provides practical clinical advice, and is the basis for the rational use of these drugs, particularly because it improves and updates knowledge, and corrects the various misconceptions that have hitherto been prominent in the literature, partly due to insufficient knowledge of pharmacology. The guide suggests that MAOIs should always be considered in cases of treatment-resistant depression (including those melancholic in nature), and prior to electroconvulsive therapy—while taking into account of patient preference. In selected cases, they may be considered earlier in the treatment algorithm than has previously been customary, and should not be regarded as drugs of last resort; they may prove decisively effective when many other treatments have failed. The guide clarifies key points on the concomitant use of incorrectly proscribed drugs such as methylphenidate and some tricyclic antidepressants. It also illustrates the straightforward “bridging” methods that may be used to transition simply and safely from other antidepressants to MAOIs.

Pompe disease results from lysosomal acid α-glucosidase deficiency, which leads to cardiomyopathy in all infantile-onset and occasional late-onset patients. Cardiac assessment is important for its diagnosis and management. This article presents unpublished cardiac findings, concomitant medications, and cardiac efficacy and safety outcomes from the ADVANCE study; trajectories of patients with abnormal left ventricular mass z score at enrolment; and post hoc analyses of on-treatment left ventricular mass and systolic blood pressure z scores by disease phenotype, GAA genotype, and “fraction of life” (defined as the fraction of life on pre-study 160 L production-scale alglucosidase alfa). ADVANCE evaluated 52 weeks’ treatment with 4000 L production-scale alglucosidase alfa in ≥1-year-old United States of America patients with Pompe disease previously receiving 160 L production-scale alglucosidase alfa. M-mode echocardiography and 12-lead electrocardiography were performed at enrolment and Week 52. Sixty-seven patients had complete left ventricular mass z scores, decreasing at Week 52 (infantile-onset patients, change −0.8 ± 1.83; 95% confidence interval −1.3 to −0.2; all patients, change −0.5 ± 1.71; 95% confidence interval −1.0 to −0.1). Patients with “fraction of life” <0.79 had left ventricular mass z score decreasing (enrolment: +0.1 ± 3.0; Week 52: −1.1 ± 2.0); those with “fraction of life” ≥0.79 remained stable (enrolment: −0.9 ± 1.5; Week 52: −0.9 ± 1.4). Systolic blood pressure z scores were stable from enrolment to Week 52, and no cohort developed systemic hypertension. Eight patients had Wolff–Parkinson–White syndrome. Cardiac hypertrophy and dysrhythmia in ADVANCE patients at or before enrolment were typical of Pompe disease. Four-thousand L alglucosidase alfa therapy maintained fractional shortening, left ventricular posterior and septal end-diastolic thicknesses, and improved left ventricular mass z score.

Trial registry: ClinicalTrials.gov Identifier: NCT01526785 https://clinicaltrials.gov/ct2/show/NCT01526785.

Social Media Statement: Post hoc analyses of the ADVANCE study cohort of 113 children support ongoing cardiac monitoring and concomitant management of children with Pompe disease on long-term alglucosidase alfa to functionally improve cardiomyopathy and/or dysrhythmia.

Impairments in retrieving event-level, specific autobiographical memories, termed overgeneral memory (OGM), are recognised as a feature of clinical depression. A previous meta-analytic review assessing how OGM predicts the course of subsequent depressive symptoms showed small effects for correlations and regression analyses when baseline depressive symptoms were controlled for. We aimed to update this study and examine whether their findings replicate given the decade of research that has been published since. A systematic literature review using the same eligibility criteria as the previous meta-analysis led to a doubling of eligible studies (32 v. 15). The results provided more precise estimates of effect sizes, and largely support the finding that OGM predicts the course of depressive symptoms. The effects were generally small, but significantly larger among clinical samples, compared to studies with non-clinical samples. There was some evidence that higher age was associated with stronger effects, and longer follow-up was associated with weaker effects. The findings on other moderating variables that were analysed were mixed. Continued research into this modifiable cognitive process may help to provide an avenue to better understand and treat highly prevalent and impactful depressive disorders.

Approximately, 1.7 million individuals in the United States have been infected with SARS-CoV-2, the virus responsible for the novel coronavirus disease-2019 (COVID-19). This has disproportionately impacted adults, but many children have been infected and hospitalised as well. To date, there is not much information published addressing the cardiac workup and monitoring of children with COVID-19. Here, we share the approach to the cardiac workup and monitoring utilised at a large congenital heart centre in New York City, the epicentre of the COVID-19 pandemic in the United States.

We apply two methods to estimate the 21-cm bispectrum from data taken within the Epoch of Reionisation (EoR) project of the Murchison Widefield Array (MWA). Using data acquired with the Phase II compact array allows a direct bispectrum estimate to be undertaken on the multiple redundantly spaced triangles of antenna tiles, as well as an estimate based on data gridded to the uv-plane. The direct and gridded bispectrum estimators are applied to 21 h of high-band (167–197 MHz; z = 6.2–7.5) data from the 2016 and 2017 observing seasons. Analytic predictions for the bispectrum bias and variance for point-source foregrounds are derived. We compare the output of these approaches, the foreground contribution to the signal, and future prospects for measuring the bispectra with redundant and non-redundant arrays. We find that some triangle configurations yield bispectrum estimates that are consistent with the expected noise level after 10 h, while equilateral configurations are strongly foreground-dominated. Careful choice of triangle configurations may be made to reduce foreground bias that hinders power spectrum estimators, and the 21-cm bispectrum may be accessible in less time than the 21-cm power spectrum for some wave modes, with detections in hundreds of hours.

A suite of experimentally deformed single-crystal pyrite samples has been investigated using electron backscatter diffraction (EBSD). Single crystals were loaded parallel to <100> or <110> and deformed at a strain rate of 10-5 s-1, confining pressure of 300 MPa and temperatures of 600°C and 700°C. Although geometrically (Schmid factor) the {001}<100> slip system should not be activated in <100> loaded samples, lattice rotation and boundary trace analyses of the distorted crystals indicate this slip system is easier to justify. Determination of 75 MPa as the critical resolved shear stress (CRSS) for {001}<100> activation, in the <110> loaded crystals, suggests a crystal misalignment of ~5—15° in the <100> loaded crystals would be sufficient to activate the {001}<100> slip system. Therefore, {001}<100> is considered the dominant slip system in all of the single-crystal pyrite samples studied. Slip-system analysis of the experimentally deformed polycrystalline pyrite aggregates is consistent with the single-crystal findings, with the exception that {001}<11̄> also appears to be important, although less common than the {001}<100> slip system. The lack of crystal preferred orientation (CPO) development in the polycrystalline pyrite aggregates can be accounted for by the presence of two independent symmetrically equivalent slip systems more than satisfying the von Mises criterion.

We present techniques developed to calibrate and correct Murchison Widefield Array low-frequency (72–300 MHz) radio observations for polarimetry. The extremely wide field-of-view, excellent instantaneous (u, v)-coverage and sensitivity to degree-scale structure that the Murchison Widefield Array provides enable instrumental calibration, removal of instrumental artefacts, and correction for ionospheric Faraday rotation through imaging techniques. With the demonstrated polarimetric capabilities of the Murchison Widefield Array, we discuss future directions for polarimetric science at low frequencies to answer outstanding questions relating to polarised source counts, source depolarisation, pulsar science, low-mass stars, exoplanets, the nature of the interstellar and intergalactic media, and the solar environment.