Is gender equality in brain damage ‘progress’ for women and sport?

This commentary sits within a context of growing cultural concern over brain damage that occurs in many of the Western world’s most popular, profitable and prized sports. After laying out evidence demonstrating this point, we discuss the increasing inclusion of women within sports which involve regular and routinised brain injuries. We problematise this apparent ‘progress’ with the title of our commentary. In particular, rather than offering some simplified yes/no answer, we argue that in light of the five decades of social scientific scholarship documenting the various harms produced by performance impact sports, working toward gender equality in brain damage is a nonsensical outcome. So, while there is clear evidence from academic gender studies that progress has been made toward tackling issues of exclusion and various forms of discrimination against women and girls in performance sport spaces, there has not been concomitant progress made in tackling the ways bodies and brains are often broken down, damaged and sometimes destroyed during participation in such sports. We do not suggest that consenting adults should be prohibited from enjoying impact sports and our aim with this commentary is not driven by a paternalistic, patriarchal belief which reflects historical notions around sportswomen being the ‘fairer’ sex, nor that responses to sport-acquired brain injury should be sex- or gender-specific. Rather, we conclude by suggesting that the emerging science on sport-acquired brain injuries should serve as an important inflection point to those leaders, organisers, practitioners and scholars working in this area to reconsider how we imagine, promote and structure sport - for everyone

Biallelic mutations in neurofascin cause neurodevelopmental impairment and peripheral demyelination.

Axon pathfinding and synapse formation are essential processes for nervous system development and function. The assembly of myelinated fibres and nodes of Ranvier is mediated by a number of cell adhesion molecules of the immunoglobulin superfamily including neurofascin, encoded by the NFASC gene, and its alternative isoforms Nfasc186 and Nfasc140 (located in the axonal membrane at the node of Ranvier) and Nfasc155 (a glial component of the paranodal axoglial junction). We identified 10 individuals from six unrelated families, exhibiting a neurodevelopmental disorder characterized with a spectrum of central (intellectual disability, developmental delay, motor impairment, speech difficulties) and peripheral (early onset demyelinating neuropathy) neurological involvement, who were found by exome or genome sequencing to carry one frameshift and four different homozygous non-synonymous variants in NFASC. Expression studies using immunostaining-based techniques identified absent expression of the Nfasc155 isoform as a consequence of the frameshift variant and a significant reduction of expression was also observed in association with two non-synonymous variants affecting the fibronectin type III domain. Cell aggregation studies revealed a severely impaired Nfasc155-CNTN1/CASPR1 complex interaction as a result of the identified variants. Immunofluorescence staining of myelinated fibres from two affected individuals showed a severe loss of myelinated fibres and abnormalities in the paranodal junction morphology. Our results establish that recessive variants affecting the Nfasc155 isoform can affect the formation of paranodal axoglial junctions at the nodes of Ranvier. The genetic disease caused by biallelic NFASC variants includes neurodevelopmental impairment and a spectrum of central and peripheral demyelination as part of its core clinical phenotype. Our findings support possible overlapping molecular mechanisms of paranodal damage at peripheral nerves in both the immune-mediated and the genetic disease, but the observation of prominent central neurological involvement in NFASC biallelic variant carriers highlights the importance of this gene in human brain development and function

Does the aldosterone: renin ratio predict the efficacy of spironolactone over bendroflumethiazide in hypertension? A clinical trial protocol for RENALDO (RENin-ALDOsterone) study

<p>Background: High blood pressure is an important determinant of cardiovascular disease risk. Treated hypertensives do not attain a risk level equivalent to normotensives. This may be a consequence of suboptimal blood pressure control to which indiscriminate use of antihypertensive drugs may contribute. Indeed the recent ALLHAT[1]study suggests that thiazides should be given first to virtually all hypertensives. Whether this is correct or whether different antihypertensive therapies should be targeted towards different patients is a major unresolved issue, which we address in this study.</p> <p>The measurement of the ratio of aldosterone: renin is used to identify hypertensive subjects who may respond well to treatment with the aldosterone antagonist spironolactone. It is not known if subjects with a high ratio have aldosteronism or aldosterone-sensitive hypertension is debated but it is important to know whether spironolactone is superior to other diuretics such as bendroflumethiazide in this setting.</p> <p>Methods/design: The study is a double-blind, randomised, crossover, controlled trial that will randomise 120 hypertensive subjects to 12 weeks treatment with spironolactone 50 mg once daily and 12 weeks treatment with bendroflumethiazide 2.5 mg once daily. The 2 treatment periods are separated by a 2-week washout period. Randomisation is stratified by aldosterone: renin ratio to include equal numbers of subjects with high and low aldosterone: renin ratios.</p> <p>Primary Objective – To test the hypothesis that the aldosterone: renin ratio predicts the antihypertensive response to spironolactone, specifically that the effect of spironolactone 50 mg is greater than that of bendroflumethiazide 2.5 mg in hypertensive subjects with high aldosterone: renin ratios.</p> <p>Secondary Objectives – To determine whether bendroflumethiazide induces adverse metabolic abnormalities, especially in subjects with high aldosterone: renin ratios and if baseline renin measurement predicts the antihypertensive response to spironolactone and/or bendrofluazide.</p> <p>Discussion: The numerous deleterious effects of hypertension dictate the need for a systematic approach for its treatment. In spite of various therapies, resistant hypertension is widely prevalent. Among various factors, primary aldosteronism is an important cause of resistant hypertension and is now more commonly recognised. More significantly, hypertensives with primary aldosteronism are also exposed to various other deleterious effects of excess aldosterone. Hence treating hypertension with specific aldosterone antagonists may be a better approach in this group of patients. It may lead on to better blood pressures with fewer medications.</p&gt

Expanding the genetic heterogeneity of intellectual disability

Intellectual disability (ID) is a common morbid condition with a wide range of etiologies. The list of monogenic forms of ID has increased rapidly in recent years thanks to the implementation of genomic sequencing techniques. In this study, we describe the phenotypic and genetic findings of 68 families (105 patients) all with novel ID-related variants. In addition to established ID genes, including ones for which we describe unusual mutational mechanism, some of these variants represent the first confirmatory disease-gene links following previous reports (TRAK1, GTF3C3, SPTBN4 and NKX6-2), some of which were based on single families. Furthermore, we describe novel variants in 14 genes that we propose as novel candidates (ANKHD1, ASTN2, ATP13A1, FMO4, MADD, MFSD11, NCKAP1, NFASC, PCDHGA10, PPP1R21, SLC12A2, SLK, STK32C and ZFAT). We highlight MADD and PCDHGA10 as particularly compelling candidates in which we identified biallelic likely deleterious variants in two independent ID families each. We also highlight NCKAP1 as another compelling candidate in a large family with autosomal dominant mild intellectual disability that fully segregates with a heterozygous truncating variant. The candidacy of NCKAP1 is further supported by its biological function, and our demonstration of relevant expression in human brain. Our study expands the locus and allelic heterogeneity of ID and demonstrates the power of positional mapping to reveal unusual mutational mechanisms

Pore-space structure and average dissolution rates: A simulation study

We study the influence of the pore-space geometry on sample-averaged dissolution rates in millimeter-scale carbonate samples undergoing reaction-controlled mineral dissolution upon the injection of a CO2 -saturated brine. The representation of the pore space is obtained directly from micro-CT images with a resolution of a few microns. Simulations are performed with a particle tracking approach on images of three porous rocks of increasing pore-space complexity: a bead pack, a Ketton oolite, and an Estaillades limestone. Reactive transport is simulated with a hybrid approach that combines a Lagrangian method for transport and reaction with the Eulerian flow field obtained by solving the incompressible Navier-Stokes equations directly on the voxels of three-dimensional images. Particle advection is performed with a semianalytical streamline method and diffusion is simulated via a random walk. Mineral dissolution is defined in terms of the particle flux through the pore-solid interface, which can be related analytically to the batch (intrinsic) reaction rate. The impact of the flow heterogeneity on reactive transport is illustrated in a series of simulations performed at different flow rates. The average dissolution rates depend on both the heterogeneity of the sample and on the flow rate. The most heterogeneous rock may exhibit a decrease of up to two orders of magnitude in the sample-averaged reaction rates in comparison with the batch rate. Furthermore, we provide new insights for the dissolution regime that would be traditionally characterized as uniform. In most cases, at the pore-scale, dissolution preferentially enlarges fast-flow channels which greatly restricts the effective surface available for reaction

Visualization and deep-learning-based malware variant detection using OpCode-level features

Malicious software (malware) is a major threat to the systems and networks’ security. Although anti-malware products are used to protect systems and networks against malware attacks, obfuscated malware that is capable of evading analysis and detection by anti-malware software have become prevalent. Therefore, how to detect and remove obfuscated malware from the systems has become a major concern. In this research work, we propose a semi-supervised approach that integrates deep learning, feature engineering, image transformation and processing techniques for obfuscated malware detection. We validated the proposed approach through experiments and compared it with existing approaches. With 99.12% accuracy in detecting obfuscated malware detection, the proposed approach substantially outperformed the other approaches