Mapping degeneration of the visual system in long-term follow-up after childhood hemispherectomy - A series of four cases

OBJECTIVE: Although hemidisconnection surgery may eliminate or reduce seizure activity in patients with epilepsy, there are visual, cognitive and motor deficits which affect patients' function post-operatively, with varying severity and according to pathology. Consequently, there is a need to map microstructural changes over long time periods and develop/apply methods that work with legacy data. METHODS: In this study, we applied the novel single shell 3-Tissue method to data from a cohort of 4 patients who were scanned 20-years following childhood hemidisconnection surgery and presented with variable clinical outcomes. We have successfully reconstructed tractography of the whole visual pathway from single shell diffusion data with reduced number of gradient directions. RESULTS: All patients presented with degeneration of the visual system characterised by low fractional anisotropy and high mean diffusivity. There were no apparent microstructural differences between both optic nerves that could explain the different level of visual function across patients. However, we provide evidence suggesting an association between the level of visual function and DTI metrics within the remaining components of the visual system, particularly the optic tract, of the contralateral hemisphere post-surgery. SIGNIFICANCE: We believe this study suggests that diffusion MRI can be used to monitor the integrity of the visual system following hemispherectomy and if extended to larger cohorts and a greater number of time-points, including pre-surgically, can provide a clearer picture of the natural history of visual system degeneration. This knowledge may in turn help to identify patients at greatest risk of poor visual outcomes that might benefit from rehabilitation therapies

The impact of SARS-CoV-2 vaccination in Dravet Syndrome: A UK survey

Background: The COVID-19 pandemic led to the urgent need for accelerated vaccine development. Approved vaccines have proved to be safe and well tolerated across millions of people in the general population. Dravet Syndrome (DS) is a severe, early onset, developmental and epileptic encephalopathy. Vaccination is a precipitating factor for seizures. Whilst there is no evidence that vaccine-precipitated seizures lead to adverse outcomes in people with DS, fear surrounding vaccination can remain for caregivers of people with DS, in some cases resulting in rejection of recommended vaccinations, leaving individuals more vulnerable to the relevant infections. A greater understanding of the safety profile of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in this vulnerable group will help provide guidance for caregivers and clinicians when considering vaccination. / Methods: A cross‐sectional survey regarding COVID-19 and SARS-CoV-2 vaccine, in people with DS, was conducted by Dravet Syndrome UK (DSUK). Concomitantly, a review of individuals with DS who had recently received the SARS-CoV-2 vaccine, and who are resident at the Chalfont Centre for Epilepsy (CCE), or attend epilepsy clinics at the National Hospital for Neurology and Neurosurgery (NHNN), was undertaken. / Results: 38 people completed the DSUK survey. 37% of caregivers reported being concerned about someone with DS receiving the SARS-CoV-2 vaccine; with some reporting that they would decline a vaccine when offered. 77% had not received any advice from a health care professional about the SARS-CoV-2 vaccination. 18/38 were eligible for SARS-CoV-2 vaccination, of whom nine had received their first vaccine dose. Combining the results of the DSUK survey and the review of individuals monitored at CCE or NHNN, fifteen people with DS had received their first dose of the SARS-CoV-2 vaccine. 11/15 (73%) reported at least one side effect, the most common being fatigue (6/15; 40%) and fever (6/15; 40%). Three individuals (20%) reported an increase in seizure frequency after the first vaccine dose. No increase in seizure frequency or duration was reported after the second dose. / Conclusion: Overall, these results suggest that SARS-CoV-2 vaccines are safe and well tolerated in individuals with DS, as they are in most people without DS. In most people with DS, SARS-CoV-2 vaccine does not appear to be associated with an increase in the frequency or duration of seizures, even in those who develop fever post-vaccination. Many caregivers are concerned about a person with DS receiving a SARS-CoV-2 vaccine, with some reporting that they would decline a SARS-CoV-2 vaccine when offered. It is crucial that healthcare professionals are proactive in providing accurate information regarding the risks and benefits of vaccination in this population, given the potential for serious outcomes from infection

A review of tennis racket performance parameters

The application of advanced engineering to tennis racket design has influenced the nature of the sport. As a result, the International Tennis Federation has established rules to limit performance, with the aim of protecting the nature of the game. This paper illustrates how changes to the racket affect the player-racket system. The review integrates engineering and biomechanical issues related to tennis racket performance, covering the biomechanical characteristics of tennis strokes, tennis racket performance, the effect of racket parameters on ball rebound and biomechanical interactions. Racket properties influence the rebound of the ball. Ball rebound speed increases with frame stiffness and as string tension decreases. Reducing inter-string contacting forces increases rebound topspin. Historical trends and predictive modelling indicate swingweights of around 0.030–0.035 kg/m2 are best for high ball speed and accuracy. To fully understand the effect of their design changes, engineers should use impact conditions in their experiments, or models, which reflect those of actual tennis strokes. Sports engineers, therefore, benefit from working closely with biomechanists to ensure realistic impact conditions

A Dynamical Analysis of the Suitability of Prehistoric Spheroids from the Cave of Hearths as Thrown Projectiles

Spheroids are ball-shaped stone objects found in African archaeological sites dating from 1.8 million years ago (Early Stone Age) to at least 70,000 years ago (Middle Stone Age). Spheroids are either fabricated or naturally shaped stones selected and transported to places of use making them one of the longest-used technologies on record. Most hypotheses about their use suggest they were percussive tools for shaping or grinding other materials. However, their size and spherical shape make them potentially useful as projectile weapons, a property that, uniquely, humans have been specialised to exploit for millions of years. Here we show (using simulations of projectile motions resulting from human throwing) that 81% of a sample of spheroids from the late Acheulean (Bed 3) at the Cave of Hearths, South Africa afford being thrown so as to inflict worthwhile damage to a medium-sized animal over distances up to 25 m. Most of the objects have weights that produce optimal levels of damage from throwing, rather than simply being as heavy as possible (as would suit other functions). Our results show that these objects were eminently suitable for throwing, and demonstrate how empirical research on behavioural tasks can inform and constrain our theories about prehistoric artefacts

Why Moral Expertise Needs Moral Theory

Discussions of the nature or possibility of moral expertise have largely proceeded in atheoretical terms, with little attention paid to whether moral expertise depends on theoretical knowledge of morality. Here I argue that moral expertise is more theory-dependent than is commonly recognized: Moral expertise consists, at least in part, in knowledge of the correct or best moral theory, and second, that knowledge of moral theory is essential to moral experts dispensing expert counsel to non-experts. Moral experts would not be moral experts absent knowledge of moral theory, nor could they play the testimonial role we would expect them to play in moral inquiry and deliberation absent such knowledg

Continuation for thin film hydrodynamics and related scalar problems

This chapter illustrates how to apply continuation techniques in the analysis of a particular class of nonlinear kinetic equations that describe the time evolution through transport equations for a single scalar field like a densities or interface profiles of various types. We first systematically introduce these equations as gradient dynamics combining mass-conserving and nonmass-conserving fluxes followed by a discussion of nonvariational amendmends and a brief introduction to their analysis by numerical continuation. The approach is first applied to a number of common examples of variational equations, namely, Allen-Cahn- and Cahn-Hilliard-type equations including certain thin-film equations for partially wetting liquids on homogeneous and heterogeneous substrates as well as Swift-Hohenberg and Phase-Field-Crystal equations. Second we consider nonvariational examples as the Kuramoto-Sivashinsky equation, convective Allen-Cahn and Cahn-Hilliard equations and thin-film equations describing stationary sliding drops and a transversal front instability in a dip-coating. Through the different examples we illustrate how to employ the numerical tools provided by the packages auto07p and pde2path to determine steady, stationary and time-periodic solutions in one and two dimensions and the resulting bifurcation diagrams. The incorporation of boundary conditions and integral side conditions is also discussed as well as problem-specific implementation issues

Red and Processed Meat and Colorectal Cancer Incidence: Meta-Analysis of Prospective Studies

The evidence that red and processed meat influences colorectal carcinogenesis was judged convincing in the 2007 World Cancer Research Fund/American Institute of Cancer Research report. Since then, ten prospective studies have published new results. Here we update the evidence from prospective studies and explore whether there is a non-linear association of red and processed meats with colorectal cancer risk

A randomized controlled trial investigation of a non-stimulant in attention deficit hyperactivity disorder (ACTION): Rationale and design

<p>Abstract</p> <p>Background</p> <p>The ACTION study (<it>Attention deficit hyperactivity disorder Controlled Trial Investigation Of a Non-stimulant) </it>is a multi-center, double-blind, randomized cross-over trial of the non-stimulant medication, Atomoxetine, in children and adolescents with attention deficit hyperactivity disorder (ADHD). The primary aims are to examine the efficacy of atomoxetine for improving cognition and emotional function in ADHD and whether any improvements in these outcomes are more pronounced in participants with comorbid anxiety; and to determine if changes in these outcomes after atomoxetine are more reliable than changes in diagnostic symptoms of ADHD. This manuscript will describe the methodology and rationale for the ACTION study.</p> <p>Methods</p> <p>Children and adolescents aged 6 - 17 y with ADHD will be enrolled. Clinical interview and validated scales will be used to confirm diagnosis and screen for exclusion criteria, which include concurrent stimulant use, and comorbid psychiatric or neurological conditions other than anxiety. Three assessment sessions will be conducted over the 13-week study period: Session 1 (Baseline, pre-treatment), Session 2 (six weeks, atomoxetine or placebo), and Session 3 (13 weeks, cross-over after one-week washout period). The standardized touch-screen battery, "IntegNeuro™", will be used to assess cognitive and emotional function. The primary measure of response will be symptom ratings, while quality of life will be a secondary outcome. Logistic regression will be used to determine predictors of treatment response, while repeated measures of analysis will determine any differences in effect of atomoxetine and placebo.</p> <p>Results</p> <p>The methodology for the ACTION study has been detailed.</p> <p>Conclusions</p> <p>The ACTION study is the first controlled trial to investigate the efficacy of atomoxetine using objective cognitive and emotional function markers, and whether these objective measures predict outcomes with atomoxetine in ADHD with and without comorbid anxiety. First enrollment was in March 2008. The outcomes of this study will be a significant step towards a 'personalized medicine' (and therefore a more efficient) approach to ADHD treatment.</p> <p>Trial registration</p> <p>Australian and New Zealand Clinical Trials Registry <a href="http://www.anzctr.org.au/ANZCTRN12607000535471.aspx">ANZCTRN12607000535471</a>.</p

Common polygenic variation in coeliac disease and confirmation of ZNF335 and NIFA as disease susceptibility loci

Coeliac disease (CD) is a chronic immune-mediated disease triggered by the ingestion of gluten. It has an estimated prevalence of approximately 1% in European populations. Specific HLA-DQA1 and HLA-DQB1 alleles are established coeliac susceptibility genes and are required for the presentation of gliadin to the immune system resulting in damage to the intestinal mucosa. In the largest association analysis of CD to date, 39 non-HLA risk loci were identified, 13 of which were new, in a sample of 12 014 individuals with CD and 12 228 controls using the Immunochip genotyping platform. Including the HLA, this brings the total number of known CD loci to 40. We have replicated this study in an independent Irish CD case–control population of 425 CD and 453 controls using the Immunochip platform. Using a binomial sign test, we show that the direction of the effects of previously described risk alleles were highly correlated with those reported in the Irish population, (P=2.2 × 10−16). Using the Polygene Risk Score (PRS) approach, we estimated that up to 35% of the genetic variance could be explained by loci present on the Immunochip (P=9 × 10−75). When this is limited to non-HLA loci, we explain a maximum of 4.5% of the genetic variance (P=3.6 × 10−18). Finally, we performed a meta-analysis of our data with the previous reports, identifying two further loci harbouring the ZNF335 and NIFA genes which now exceed genome-wide significance, taking the total number of CD susceptibility loci to 42