Background: Adverse effects and risks associated with glucocorticoid (GC) treatment are frequently encountered in immune-mediated neuromuscular disorders. However, significant variability exists in the management of these complications. Our aim was to establish international consensus guidance on the management of GC-related complications in neuromuscular disorders. Methods: An international task force of 15 experts was assembled to develop clinical recommendations for managing GC-related complications in neuromuscular patients. The RAND/UCLA Appropriateness Method (RAM) was employed to formulate consensus guidance statements. Initial statements were drafted following a comprehensive literature review and were refined based on anonymous expert feedback, with up to three rounds of email voting to achieve consensus. Results: Consensus was reached on statements addressing general patient care, monitoring during GC therapy, osteoporosis prevention, vaccinations, infection screening, and prophylaxis for Pneumocystis jiroveci pneumonia. A multidisciplinary approach to managing GC-related complications was highlighted as a key recommendation. Conclusions: This represents the first consensus guidance in the neurological literature on GC complications, and offer clinicians structured guidance on mitigating and managing common adverse effects associated with both short- and long-term GC use. They also provide a foundation for future debate, quality improvement, research work in this area.

A period of the life course where optimal nutrition and food security are crucial for the life-long health and wellbeing of women/birthing parents and infants is preconception, pregnancy, and infancy.(1) It is estimated that nearly one in every four households with pre-school children (0-4 years) experience food insecurity (FI) in the UK.(2) Yet, we lack an evidence-base exploring experiences of FI in this life course stage.(3,4) This study aimed to explore women’s experiences of food insecurity during and after pregnancy, including its influence on infant feeding decisions.

This study was ethically approved (Ref No: LRS/DP-23/24-39437) and pre-registered on OSF Registries (https://osf.io/9hn6r). Semi-structured mixed format individual interviews were conducted between November 2023 and February 2024. Pregnant individuals, those who had given birth ≤12 months ago, ≥18 years old, food insecure, residing in South London and with recourse to public funds were recruited through purposive sampling. The topic guide was informed by FI, pregnancy and postpartum related literature and piloted (n = 2). Interviews were audiorecorded and professionally transcribed. Demographic data was summarised using SPSS. Inductive thematic analysis was used to analyse the data and was completed using NVivo.

Eleven food insecure participants (2 pregnant, 9 new mothers; 2 White European, 9 Black African/Caribbean/British women) participated in the study. Six women were 0-6 months postpartum, and 3 women were between 6-12 months postpartum. The preliminary findings are represented by three themes: 1) A dichotomy: knowing vs affording, 2) Adaptive food coping strategies, and 3) Infant feeding practices. Participants shared detailed accounts of valuing a healthy diet and adapting food practices, yet they still were unable to meet their dietary needs and desires during and after pregnancy. Participants described worry around breastmilk supply; quality and quantity. Complimentary feeding was also identified as a source of worry. “She is still breastfeeding fully. I don’t want to change to milk, which maybe, sometimes, I might not be able to afford it…I won’t stop until she is 1.”Whilst the cost of formula feeding was a driver of a more severe experience of FI.

Policy and practice recommendations include enhancing local breastfeeding support to address FI specific concerns around breastmilk supply and at national level, advocating for greater support for adequate healthy food provision and for a price cap on infant formula. Future interventions must support maternal mental health given the high cognitive stress identified with living with FI during and after pregnancy. Further high-quality research is needed 1) amongst asylum seekers and refugees and non-English speakers who may also experience FI, and 2) exploring cultural influences on breastfeeding and the relationship with FI.

Single-particle cryogenic electron microscopy (cryo-EM) is an imaging technique capable of recovering the high-resolution three-dimensional (3D) structure of biological macromolecules from many noisy and randomly oriented projection images. One notable approach to 3D reconstruction, known as Kam’s method, relies on the moments of the two-dimensional (2D) images. Inspired by Kam’s method, we introduce a rotationally invariant metric between two molecular structures, which does not require 3D alignment. Further, we introduce a metric between a stack of projection images and a molecular structure, which is invariant to rotations and reflections and does not require performing 3D reconstruction. Additionally, the latter metric does not assume a uniform distribution of viewing angles. We demonstrate the uses of the new metrics on synthetic and experimental datasets, highlighting their ability to measure structural similarity.

Principal component analysis (PCA) plays an important role in the analysis of cryo-electron microscopy (cryo-EM) images for various tasks such as classification, denoising, compression, and ab initio modeling. We introduce a fast method for estimating a compressed representation of the 2-D covariance matrix of noisy cryo-EM projection images affected by radial point spread functions that enables fast PCA computation. Our method is based on a new algorithm for expanding images in the Fourier–Bessel basis (the harmonics on the disk), which provides a convenient way to handle the effect of the contrast transfer functions. For $ N $ images of size $ L\times L $, our method has time complexity $ O\left({NL}^3+{L}^4\right) $ and space complexity $ O\left({NL}^2+{L}^3\right) $. In contrast to previous work, these complexities are independent of the number of different contrast transfer functions of the images. We demonstrate our approach on synthetic and experimental data and show acceleration by factors of up to two orders of magnitude.

A microswimmer placed inside of a passive lamellar vesicle can hydrodynamically induce directed motion of the vesicle so long as fluid is permitted to pass through the vesicle's surface. With an interest in understanding the underlying theoretical mechanism responsible for this directed motion, we study the low Reynolds number fluid mechanics of a reduced system in which a spherical squirming particle is encapsulated inside of a rigid porous spherical container (membrane). We create a theoretical model for this system and obtain two exact analytical solutions to the Stokes equations which describe the motion of the squirmer and container under porous and non-porous container descriptions. Fluid flow through the container's surface is described using a model similar to Darcy's law where proportionality constants, $R_{\parallel }$ and $R_{\perp }$, parameterize the container's resistance to permeable flow parallel and normal to the container's surface. We numerically simulate trajectories of the squirmer–container system by reformulating the fluid mechanics problem as a coupled set of second kind boundary integral equations (BIEs). This system of BIEs is solved numerically using a Galerkin boundary element discretization on graphics processing units enabled with NVIDIA's Compute Unified Device Architecture. We obtain excellent agreement between the analytical and numerical solutions for the concentric geometry. Trajectories of pusher squirmers show earlier radial spread towards the container's surface, whereas puller squirmers tend to move radially inwards, towards the container's centre. Both the squirmer type (pusher, puller, neutral) and container resistance parameters heavily influence net container motion and early squirmer dynamics.

The identity, richness, and abundance of true flies (Diptera) from the nests of three cavity-nesting raptors (Aves) were investigated in northern Nova Scotia, Canada. After fledging, flies were extracted from the nest material using Berlese funnels within an emergence chamber. Thirty-one species/morphospecies from 14 families were collected, including eight new records for Nova Scotia and two new records for eastern North America.

This guidance paper from the European Psychiatric Association (EPA) aims to provide evidence-based recommendations on early intervention in clinical high risk (CHR) states of psychosis, assessed according to the EPA guidance on early detection. The recommendations were derived from a meta-analysis of current empirical evidence on the efficacy of psychological and pharmacological interventions in CHR samples. Eligible studies had to investigate conversion rate and/or functioning as a treatment outcome in CHR patients defined by the ultra-high risk and/or basic symptom criteria. Besides analyses on treatment effects on conversion rate and functional outcome, age and type of intervention were examined as potential moderators. Based on data from 15 studies (n = 1394), early intervention generally produced significantly reduced conversion rates at 6- to 48-month follow-up compared to control conditions. However, early intervention failed to achieve significantly greater functional improvements because both early intervention and control conditions produced similar positive effects. With regard to the type of intervention, both psychological and pharmacological interventions produced significant effects on conversion rates, but not on functional outcome relative to the control conditions. Early intervention in youth samples was generally less effective than in predominantly adult samples. Seven evidence-based recommendations for early intervention in CHR samples could have been formulated, although more studies are needed to investigate the specificity of treatment effects and potential age effects in order to tailor interventions to the individual treatment needs and risk status.

The aim of this guidance paper of the European Psychiatric Association is to provide evidence-based recommendations on the early detection of a clinical high risk (CHR) for psychosis in patients with mental problems. To this aim, we conducted a meta-analysis of studies reporting on conversion rates to psychosis in non-overlapping samples meeting any at least any one of the main CHR criteria: ultra-high risk (UHR) and/or basic symptoms criteria. Further, effects of potential moderators (different UHR criteria definitions, single UHR criteria and age) on conversion rates were examined. Conversion rates in the identified 42 samples with altogether more than 4000 CHR patients who had mainly been identified by UHR criteria and/or the basic symptom criterion ‘cognitive disturbances’ (COGDIS) showed considerable heterogeneity. While UHR criteria and COGDIS were related to similar conversion rates until 2-year follow-up, conversion rates of COGDIS were significantly higher thereafter. Differences in onset and frequency requirements of symptomatic UHR criteria or in their different consideration of functional decline, substance use and co-morbidity did not seem to impact on conversion rates. The ‘genetic risk and functional decline’ UHR criterion was rarely met and only showed an insignificant pooled sample effect. However, age significantly affected UHR conversion rates with lower rates in children and adolescents. Although more research into potential sources of heterogeneity in conversion rates is needed to facilitate improvement of CHR criteria, six evidence-based recommendations for an early detection of psychosis were developed as a basis for the EPA guidance on early intervention in CHR states.

Terrestrial plant macrofossils from the sedimentary record of Lake Suigetsu, Japan, provide the only quasi-continuous direct atmospheric record of radiocarbon (14C) covering the last 50 ka cal BP (Bronk Ramsey et al. 2012). Since then, new high precision data have become available on U-Th dated speleothems from Hulu Cave China, covering the same time range (Cheng et al. 2018). In addition, an updated varve-based chronology has also been published for the 2006 core from Lake Suigetsu (SG06) based on extended microscopic analysis of the sediments and improved algorithms for interpolation (Schlolaut et al. 2018). Here we reanalyze the radiocarbon dataset from Suigetsu based on the new varve counting information and the constraints imposed by the speleothem data. This enables the new information on the calendar age scale of the Suigetsu dataset to be used in the construction of the consensus IntCal calibration curve. Comparison of the speleothem and plant macrofossil records provides insight into the mechanisms underlying the incorporation of carbon into different types of record and the relative strengths of different types of archive for calibration purposes.

At Guy's King's and St Thomas’ School of Medicine, a unique initiative is the Psychiatry Early Experience Programme (PEEP), which allows students to shadow psychiatry trainees at work several times a year. The students’ attitudes towards psychiatry and the scheme are regularly assessed and initial results are already available.

A computational study was performed both of a single agglomerate and of the collision of two agglomerates in a shear flow. The agglomerates were extracted from a direct numerical simulation of a turbulent agglomeration process, and had the loosely packed fractal structure typical of agglomerate structures formed in turbulent agglomeration processes. The computation was performed using a discrete-element method for adhesive particles with four-way coupling, accounting both for forces between the fluid and the particles (and vice versa) as well as force transmission directly between particles via particle collisions. In addition to understanding and characterizing the particle dynamics, the study focused on illuminating the fluid flow field induced by the agglomerate in the presence of a background shear and the effect of collisions on this particle-induced flow. Perhaps the most interesting result of the current work was the observation that the flow field induced by a particle agglomerate rotating in a shear flow has the form of two tilted vortex rings with opposite-sign circulation. These rings are surrounded by a sea of stretched vorticity from the background shear flow. The agglomerate rotates in the shear flow, but at a slower rate than the ambient fluid elements. In the computations with two colliding agglomerates, we observed cases resulting in agglomerate merger, bouncing and fragmentation. However, the bouncing cases were all observed to also result in an exchange of particles between the two colliding agglomerates, so that they were influenced both by elastic rebound of the agglomerate structures as well as by tearing away of particulate matter between the agglomerates. Overall, the problems of agglomerate–flow interaction and of the collision of two agglomerates in a shear flow are considerably richer in physical phenomena and more complex than can be described by the common approximation that represents each agglomerate by an ‘equivalent sphere’.

Polyphenol oxidase (PPO) in red clover (RC) has been shown to reduce both lipolysis and proteolysis in silo and implicated (in vitro) in the rumen. However, all in vivo comparisons have compared RC with other forages, typically with lower levels of PPO, which brings in other confounding factors as to the cause for the greater protection of dietary nitrogen (N) and C18 polyunsaturated fatty acids (PUFA) on RC silage. This study compared two RC silages which when ensiled had contrasting PPO activities (RC+ and RC−) against a control of perennial ryegrass silage (PRG) to ascertain the effect of PPO activity on dietary N digestibility and PUFA biohydrogenation. Two studies were performed the first to investigate rumen and duodenal flow with six Hereford×Friesian steers, prepared with rumen and duodenal cannulae, and the second investigating whole tract N balance using six Holstein-Friesian non-lactating dairy cows. All diets were offered at a restricted level based on animal live weight with each experiment consisting of two 3×3 Latin squares using big bale silages ensiled in 2010 and 2011, respectively. For the first experiment digesta flow at the duodenum was estimated using a dual-phase marker system with ytterbium acetate and chromium ethylenediaminetetraacetic acid as particulate and liquid phase markers, respectively. Total N intake was higher on the RC silages in both experiments and higher on RC− than RC+. Rumen ammonia-N reflected intake with ammonia-N per unit of N intake lower on RC+ than RC−. Microbial N duodenal flow was comparable across all silage diets with non-microbial N higher on RC than the PRG with no difference between RC+ and RC−, even when reported on a N intake basis. C18 PUFA biohydrogenation was lower on RC silage diets than PRG but with no difference between RC+ and RC−. The N balance trial showed a greater retention of N on RC+ over RC−; however, this response is likely related to the difference in N intake over any PPO driven protection. The lack of difference between RC silages, despite contrasting levels of PPO, may reflect a similar level of protein-bound-phenol complexing determined in each RC silage. Previously this complexing has been associated with PPOs protection mechanism; however, this study has shown that protection is not related to total PPO activity.