Editorial perspective: Leaving the baby in the bathwater in neurodevelopmental research

Neurodevelopmental conditions are characterised by differences in the way children interact with the people and environments around them. Despite extensive investigation, attempts to uncover the brain mechanisms that underpin neurodevelopmental conditions have yet to yield any translatable insights. We contend that one key reason is that psychologists and cognitive neuroscientists study brain function by taking children away from their environment, into a controlled lab setting. Here, we discuss recent research that has aimed to take a different approach, moving away from experimental control through isolation and stimulus manipulation, and towards approaches that embrace the measurement and targeted interrogation of naturalistic, user-defined and complex, multivariate datasets. We review three worked examples (of stress processing, early activity level in ADHD and social brain development in autism) to illustrate how these new approaches might lead to new conceptual and translatable insights into neurodevelopment

Parsing eye-tracking data of variable quality to provide accurate fixation duration estimates in infants and adults

Researchers studying infants’ spontaneous allocation of attention have traditionally relied on hand-coding infants’ direction of gaze from videos; these techniques have low temporal and spatial resolution and are labor intensive. Eye-tracking technology potentially allows for much more precise measurement of how attention is allocated at the subsecond scale, but a number of technical and methodological issues have given rise to caution about the quality and reliability of high temporal resolution data obtained from infants. We present analyses suggesting that when standard dispersal-based fixation detection algorithms are used to parse eye-tracking data obtained from infants, the results appear to be heavily influenced by interindividual variations in data quality. We discuss the causes of these artifacts, including fragmentary fixations arising from flickery or unreliable contact with the eyetracker and variable degrees of imprecision in reported position of gaze. We also present new algorithms designed to cope with these problems by including a number of new post hoc verification checks to identify and eliminate fixations that may be artifactual. We assess the results of our algorithms by testing their reliability using a variety of methods and on several data sets. We contend that, with appropriate data analysis methods, fixation duration can be a reliable and stable measure in infants. We conclude by discussing ways in which studying fixation durations during unconstrained orienting may offer insights into the relationship between attention and learning in naturalistic settings

New LISA dynamics feedback control scheme: Common-mode isolation of test mass control and probes of test-mass acceleration

The Drag-Free and Attitude Control System is a central element of LISA technology, ensuring the very high dynamic stability of spacecraft and test masses required in order to reach the sensitivity that gravitational wave astronomy in space requires. Applying electrostatic forces on test-masses is unavoidable but should be restricted to the minimum necessary to keep the spacecraft-test masses system in place, while granting the optimal quality of test-mass free-fall. To realise this, we propose a new test-mass suspension scheme that applies forces and torques only in proportion to any differential test mass motion observed, and we demonstrate that the new scheme significantly mitigates the amount of suspension forces and torques needed to control the whole system. The mathematical method involved allows us to derive a new observable measuring the differential acceleration of test masses projected on the relevant sensitive axes, which will have important consequences for LISA data calibration, processing and analysis

The LISA PathFinder DMU and Radiation Monitor

The LISA PathFinder DMU (Data Management Unit) flight model was formally accepted by ESA and ASD on 11 February 2010, after all hardware and software tests had been successfully completed. The diagnostics items are scheduled to be delivered by the end of 2010. In this paper we review the requirements and performance of this instrumentation, specially focusing on the Radiation Monitor and the DMU, as well as the status of their programmed use during mission operations, on which work is ongoing at the time of writing.Comment: 11 pages, 7 figures, prepared for the Proceedings of the 8th International LISA Symposium, Classical and Quantum Gravit

Epidemiology of Acromegaly: Review of population studies

Acromegaly is a rare condition necessitating large population studies for the generation of reliable epidemiological data. In this review, we systematically analysed the epidemiological profile of this condition based on recently published population studies from various geographical areas. The total prevalence ranges between 2.8 and 13.7 cases per 100,000 people and the annual incidence rates range between 0.2 and 1.1 cases/100,000 people. The median age at diagnosis is in the fifth decade of life with a median diagnostic delay of 4.5–5 years. Acral enlargement and coarse facial features are the most commonly described clinical manifestations. At the time of detection, most of the tumors are macroadenomas possibly relating to diagnostic delays and posing challenges in the surgical management. Increased awareness of acromegaly amongst the medical community is of major importance aiming to reduce the adverse sequelae of late diagnosis and treatment, improve patient outcomes and, hopefully, reduce the burden on the health care system

3DLigandSite: Structure-based prediction of protein-ligand binding sites

3DLigandSite is a web tool for the prediction of ligand-binding sites in proteins. Here, we report a significant update since the first release of 3DLigandSite in 2010. The overall methodology remains the same, with candidate binding sites in proteins inferred using known binding sites in related protein structures as templates. However, the initial structural modelling step now uses the newly available structures from the AlphaFold database or alternatively Phyre2 when AlphaFold structures are not available. Further, a sequence-based search using HHSearch has been introduced to identify template structures with bound ligands that are used to infer the ligand-binding residues in the query protein. Finally, we introduced a machine learning element as the final prediction step, which improves the accuracy of predictions and provides a confidence score for each residue predicted to be part of a binding site. Validation of 3DLigandSite on a set of 6416 binding sites obtained 92% recall at 75% precision for non-metal binding sites and 52% recall at 75% precision for metal binding sites. 3DLigandSite is available at https://www.wass-michaelislab.org/3dligandsite. Users submit either a protein sequence or structure. Results are displayed in multiple formats including an interactive Mol* molecular visualization of the protein and the predicted binding sites

Limits of 'patient-centredness'; valuing contextually specific communication patterns

Context Globally, doctor–patient communication is becoming synonymous with high-quality health care in the 21st century. However, what is meant by ‘good communication’ and whether there is consensus internationally remain unclear. Objectives Here, we characterise understandings of ‘good communication’ in future doctors from medical schools in three contextually contrasting continents. Given locally specific socio-cultural influences, we hypothesised that there would be a lack of global consensus on what constitutes ‘good communication’. Methods A standardised two-phase methodology was applied in turn to each of three medical schools in the UK, Egypt and India (n = 107 subjects), respectively, in which students were asked: ‘What is good communication?’ Phase I involved exploratory focus groups to define preliminary themes (mean number of participants per site: 17). Phase II involved thematic confirmation and expansion in one-to-one semi-structured interviews (mean number of participants per site: 18; mean hours of dialogue captured per site: 55). Findings were triangulated and analysed using grounded theory. Results The overarching theme that emerged from medical students was that ‘good communication’ requires adherence to certain ‘rules of communication’. A shared rule that doctors must communicate effectively despite perceived disempowerment emerged across all sites. However, contradictory culturally specific rules about communication were identified in relation to three major domains: family; gender, and emotional expression. Egyptian students perceived emotional aspects of Western doctors’ communication strikingly negatively, viewing these doctors as problematically cold and unresponsive. Conclusions Contradictory perceptions of ‘good communication’ in future doctors are found cross-continentally and may contribute to prevalent cultural misunderstandings in medicine. The lack of global consensus on what defines good communication challenges prescriptively taught Western ‘patient-centredness’ and questions assumptions about international transferability. Health care professionals must be educated openly about flexible, context-specific communication patterns so that they can avoid cultural incompetence and tailor behaviours in ways that optimise therapeutic outcomes wherever they work around the globe

Automatic classification of ICA components from infant EEG using MARA.

Automated systems for identifying and removing non-neural ICA components are growing in popularity among EEG researchers of adult populations. Infant EEG data differs in many ways from adult EEG data, but there exists almost no specific system for automated classification of source components from paediatric populations. Here, we adapt one of the most popular systems for adult ICA component classification for use with infant EEG data. Our adapted classifier significantly outperformed the original adult classifier on samples of naturalistic free play EEG data recorded from 10 to 12-month-old infants, achieving agreement rates with the manual classification of over 75% across two validation studies (n = 44, n = 25). Additionally, we examined both classifiers' ability to remove stereotyped ocular artifact from a basic visual processing ERP dataset compared to manual ICA data cleaning. Here, the new classifier performed on level with expert manual cleaning and was again significantly better than the adult classifier at removing artifact whilst retaining a greater amount of genuine neural signal operationalised through comparing ERP activations in time and space. Our new system (iMARA) offers developmental EEG researchers a flexible tool for automatic identification and removal of artifactual ICA components

Proliferation, bcl-2 expression and angiogenesis in pituitary adenomas: relationship to tumour behaviour

The prediction of pituitary tumour behaviour, in terms of response to treatment from which can be derived optimal management strategies, is a challenge that has been approached using several different means. Angiogenesis in other tumour types has been shown to be correlated with poor response to treatment and tumour recurrence. The aim of this paper is to assess the role of measurements of cell proliferation and angiogenesis in predicting pituitary tumour behaviour. The proliferative capacity of the tumour was assessed using the Ki-67 labelling index (LI) while bcl-2 expression was used to assess anti-apoptotic pathways. The microvessel density (MVD) was assessed using antibodies to CD31 and factor VIII-related antigen, and with biotinylated ulex europaeus agglutinin I. There was no difference between Ki-67 LI and MVD of functionless tumours that recurred and those that did not, but bcl-2 expression was significantly lower in tumours that subsequently regrew. Macroprolactinomas had significantly higher LI than microprolactinomas and than all other tumours. Cell proliferation and angiogenesis were not related, showing that both processes are under different control mechanisms in pituitary tumours. In contrast there was a positive relationship between markers of angiogenesis and bcl-2 expression in prolactinomas, GH-secreting tumours and non-recurrent functionless tumours with higher levels of bcl-2 expression being found in the more vascular tumours. These findings may suggest that angiogenesis is related to the ability of tumour cells to survive rather than their proliferative activity. © 2000 Cancer Research Campaig