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The epilepsies are devastating neurological disorders for which progress developing effective new therapies has slowed over recent decades, primarily due to the complexity of the brain at all scales. This reality has shifted the focus of experimental and clinical practice toward complex systems approaches to overcoming current barriers. Organized by scale from genes to whole brain, the chapters of this book survey the theoretical underpinnings and use of network and dynamical systems approaches to interpreting and modeling experimental and clinical data in epilepsy. The emphasis throughout is on the value of the non-trivial, and often counterintuitive, properties of complex systems, and how to leverage these properties to elaborate mechanisms of epilepsy and develop new therapies. In this essential book, readers will learn key concepts of complex systems theory applied across multiple scales and how each of these scales connects to epilepsy.
Bustards comprise a highly threatened family of birds and, being relatively fast, heavy fliers with very limited frontal visual fields, are particularly susceptible to mortality at powerlines. These infrastructures can also displace them from immediately adjacent habitat and act as barriers, fragmenting their ranges. With geographically ever wider energy transmission and distribution grids, the powerline threat to bustards is constantly growing. Reviewing the published and unpublished literature up to January 2021, we found 2,774 records of bustard collision with powerlines, involving 14 species. Some studies associate powerline collisions with population declines. To avoid mortalities, the most effective solution is to bury the lines; otherwise they should be either routed away from bustard-frequented areas, or made redundant by local energy generation. When possible, new lines should run parallel to existing structures and wires should preferably be as low and thick as possible, with minimal conductor obstruction of vertical airspace, although it should be noted that these measures require additional testing. A review of studies finds limited evidence that ‘bird flight diverters’ (BFDs; devices fitted to wires to induce evasive action) achieve significant reductions in mortality for some bustard species. Nevertheless, dynamic BFDs are preferable to static ones as they are thought to perform more effectively. Rigorous evaluation of powerline mortalities, and effectiveness of mitigation measures, need systematic carcass surveys and bias corrections. Whenever feasible, assessments of displacement and barrier effects should be undertaken. Following best practice guidelines proposed with this review paper to monitor impacts and mitigation could help build a reliable body of evidence on best ways to prevent bustard mortality at powerlines. Research should focus on validating mitigation measures and quantifying, particularly for threatened bustards, the population effects of powerline grids at the national scale, to account for cumulative impacts on bustards and establish an equitable basis for compensation measures.
Variation exists in the timing of surgery for balanced complete atrioventricular septal defect repair. We sought to explore associations between timing of repair and resource utilisation and clinical outcomes in the first year of life.
In this retrospective single-centre cohort study, we included patients who underwent complete atrioventricular septal defect repair between 2005 and 2019. Patients with left or right ventricular outflow tract obstruction and major non-cardiac comorbidities (except trisomy 21) were excluded. The primary outcome was days alive and out of the hospital in the first year of life.
Included were 79 infants, divided into tertiles based on age at surgery (1st = 46 to 137 days, 2nd = 140 – 176 days, 3rd = 178 – 316 days). There were no significant differences among age tertiles for days alive and out of the hospital in the first year of life by univariable analysis (tertile 1, median 351 days; tertile 2, 348 days; tertile 3, 354 days; p = 0.22). No patients died. Fewer post-operative ICU days were used in the oldest tertile relative to the youngest, but days of mechanical ventilation and hospitalisation were similar. Clinical outcomes after repair and resource utilisation in the first year of life were similar for unplanned cardiac reinterventions, outpatient cardiology clinic visits, and weight-for-age z-score at 1 year.
Age at complete atrioventricular septal defect repair is not associated with important differences in clinical outcomes or resource utilisation in the first year of life.
Trained neural networks are promising tools to analyze the ever-increasing amount of scientific image data, but it is unclear how to best customize these networks for the unique features in transmission electron micrographs. Here, we systematically examine how neural network architecture choices affect how neural networks segment, or pixel-wise separate, crystalline nanoparticles from amorphous background in transmission electron microscopy (TEM) images. We focus on decoupling the influence of receptive field, or the area of the input image that contributes to the output decision, from network complexity, which dictates the number of trainable parameters. For low-resolution TEM images which rely on amplitude contrast to distinguish nanoparticles from background, we find that the receptive field does not significantly influence segmentation performance. On the other hand, for high-resolution TEM images which rely on both amplitude and phase-contrast changes to identify nanoparticles, receptive field is an important parameter for increased performance, especially in images with minimal amplitude contrast. Rather than depending on atom or nanoparticle size, the ideal receptive field seems to be inversely correlated to the degree of nanoparticle contrast in the image. Our results provide insight and guidance as to how to adapt neural networks for applications with TEM datasets.
Understanding the structure of materials is crucial for engineering devices and materials with enhanced performance. Four-dimensional scanning transmission electron microscopy (4D-STEM) is capable of mapping nanometer-scale local crystallographic structure over micron-scale field of views. However, 4D-STEM datasets can contain tens of thousands of images from a wide variety of material structures, making it difficult to automate detection and classification of structures. Traditional automated analysis pipelines for 4D-STEM focus on supervised approaches, which require prior knowledge of the material structure and cannot describe anomalous or deviant structures. In this article, a pipeline for engineering 4D-STEM feature representations for unsupervised clustering using non-negative matrix factorization (NMF) is introduced. Each feature is evaluated using NMF and results are presented for both simulated and experimental data. It is shown that some data representations more reliably identify overlapping grains. Additionally, real space refinement is applied to identify spatially distinct sample regions, allowing for size and shape analysis to be performed. This work lays the foundation for improved analysis of nanoscale structural features in materials that deviate from expected crystallographic arrangement using 4D-STEM.
Good quality parenting in early childhood is reliably associated with positive mental and physical health over the lifespan.
The hypothesis that early parenting quality has significant long-term financial benefits has not been previously tested.
Design: Longitudinal study with follow-up from 2012 to 2016; UK multicentre study cohort. Participants: 174 young people drawn from 2 samples, one at moderate risk of poor outcomes and one at high risk, assessed aged 4–6 years then followed up in early adolescence (mean age 12.1 years). Measures: The primary outcome was total costs: health, social care, extra school support, out-of-home placements and family-born expenditure, determined through semistructured economic interviews. Early parenting quality was independently assessed through direct observation of parent–child interaction.
Costs were lower for youths exposed to more sensitive parenting (most sensitive quartile mean £1,619, least sensitive quartile mean £21,763; p < .001). Costs were spread across personal family expenditure and education, health, social and justice services. The cost difference remained significant after controlling for several potential confounders. These included demographic variables (family poverty, parental education); exposure to child abuse; and child/young person variables including level of antisocial behaviour in both childhood and adolescence, IQ and attachment security.
This study is the first showing that more sensitive early parental care predicts lower costs to society many years later, independent of poverty, child and youth antisocial behaviour levels and IQ. The findings provide novel evidence for the public health impact of early caregiving quality and likely financial benefits of improving it.
We investigated the efficacy and complication profile of intranasal dexmedetomidine for transthoracic echocardiography sedation in patients with single ventricle physiology and shunt-dependent pulmonary blood flow during the high-risk interstage period.
A single-centre, retrospective review identified interstage infants who received dexmedetomidine for echocardiography sedation. Baseline and procedural vitals were reported. Significant adverse events related to sedation were defined as an escalation in care or need for any additional/increased inotropic support to maintain pre-procedural haemodynamics. Minor adverse events were defined as changes from baseline haemodynamics that resolved without intervention. To assess whether sedation was adequate, echocardiogram reports were reviewed for completeness.
From September to December 2020, five interstage patients (age 29–69 days) were sedated with 3 mcg/kg intranasal dexmedetomidine. The median sedation onset time and duration time was 24 minutes (range 12–43 minutes) and 60 minutes (range 33–60 minutes), respectively. Sedation was deemed adequate in all patients as complete echocardiograms were accomplished without a rescue dose. When compared to baseline, three (60%) patients had a >10% reduction in heart rate, one (20%) patient had a >10% reduction in oxygen saturations, and one (20%) patient had a >30% decrease in blood pressure. Amongst all patients, no significant complications occurred and haemodynamic changes from baseline did not result in need for intervention or interruption of study.
Intranasal dexmedetomidine may be a reasonable option for echocardiography sedation in infants with shunt-dependent single ventricle heart disease, and further investigation is warranted to ensure efficacy and safety in an outpatient setting.
This chapter addresses how stakeholders of scientific research can assess whether research is compliant with the scientific method and then promote useful scientific research to improve products, services, processes, methods, and decision-making. We address stakeholders in sections for universities, scientific journals, governments, regulators and courts, and media and interested individuals.
The invitation for those nominating candidates for the Nobel Prize in economics, the “Sveriges Riksbank Prize in Economic Sciences in Memory of Alfred Nobel,” described the award of the prize as being “based solely on scientific merit.” No criteria for judging scientific merit were provided, but nominators were directed to “consider origin and gender” of the nominees. Without clear criteria for the award, to what extent can one be confident that the prize was based on the scientific merit of the findings?
Gerd Gigerenzer, Director of the Max Planck Institute for Human Development, commented on reading papers in the Journal of Experimental Psychology from the 1920s and 1930s. He observed that “This was professionally a most depressing experience, but not because these articles were methodologically mediocre. On the contrary, many of them make today’s research pale in comparison with their diversity of methods and statistics” (Gigerenzer, 2000, p. 296).
We believe that the primary role of a scientist is to make discoveries that can help to improve peoples’ lives, whether directly such as through the discovery of a vaccine against a disease or indirectly such as through the invention of a procedure that can improve efficiency or lead to better decisions. In this chapter, we provide practical advice on how to identify important problems, how to choose which important problems to research, how to design a study, how to collect data, and how to analyze them.
We intend that our checklist provides a common understanding among all stakeholders in science of what the scientific method entails. To that end, we describe it in terms that are simple and commonly understood.