Detecting carotid stenosis from skin vibrations using Laser Doppler Vibrometry - An in vitro proof-of-concept.

Early detection of asymptomatic carotid stenosis may help identifying individuals at risk of stroke. We explore a new method based on laser Doppler vibrometry (LDV) which could allow the non-contact detection of stenosis from neck skin vibrations due to stenosis-induced flow disturbances. Experimental fluid dynamical tests were performed with water on a severely stenosed patient-specific carotid bifurcation model. Measurements were taken under various physiological flow regimes both in a compliant and stiff-walled version of the model, at 1 to 4 diameters downstream from the stenosis. An inter-arterial pressure catheter was positioned as reference. Increasing flow led to corresponding increase in power spectral density (PSD) of pressure and LDV recordings in the 0-500 Hz range. The stiff model lead to higher PSD. PSD of the LDV signal was less dependent on the downstream measurement location than pressure. The strength of the association between PSD and flow level, model material and measuring location was highest in the 0-50 Hz range, however useful information was found up to 200 Hz. This proof-of-concept suggests that LDV has the potential to detect stenosis-induced disturbed flow. Further computational and clinical validation studies are ongoing to assess the sensitivity and specificity of the technique for clinical screening.EU H2020 644798 gran

Finding a cure for tuberous sclerosis complex: from genetics through to targeted drug therapies

Tuberous sclerosis complex (TSC) is a rare, autosomal dominant genetic condition caused by a mutation in either the TSC1 or TSC2 gene. Phenotypically, this leads to aberrant cell growth and the formation of benign tumors called hamartomas in multiple organs. Understanding the mechanisms of pathology that are caused through the presence of disease causing mutations is a real hurdle for many rare genetic disorders; a limiting factor that restricts knowledge of the disease and any hope of a future cure. Through the discovery of the TSC1 and TSC2 genes and the signaling pathways responsible for the pathology of TSC, a new drug target called mechanistic target of rapamycin complex 1 (mTORC1) was discovered. Rapamycin, an mTORC1 inhibitor, is now the only pharmacological therapy approved for the treatment of TSC. This chapter summarizes the success story of TSC and explores the future possibilities of finding a cure

The SHAMISEN recommendations on preparedness and health surveillance of populations affected by a radiation accident

This paper, the last in the Special Issue (SI) on the SHAMISEN project, presents an overview of the SHAMISEN Recommendations for Preparedness and Health Surveillance of Populations Affected by a Radiation Accident. The recommendations are based on the lessons learnt from previous nuclear accidents, and the engagement activities with different stakeholder groups, described in the other papers of this SI. The SHAMISEN project developed a total of 28 recommendations. They include general recommendations, applicable across all phases of an accident, and specific recommendations for each of the three main phases: preparedness, early and intermediate, and long-term recovery. The recommendations are subdivided by topic: health surveillance, epidemiological studies, dose reconstruction, evacuation, and training of and communication with health personnel and other actors involved in liaising with affected populations. Each recommendation is divided into 3 sections - why, how and who - thus providing background and concrete advice as to how each SHAMISEN recommendation should be implemented and by whom. It is notable that many recommendations are also applicable to other disaster types, including the current SARS-CoV-2 pandemic.SHAMISEN was supported by the EURATOM (European Atomic Energy Community) program of the European Commission in the framework of the OPERRA (Open Project for the European Radiation Research Area) project (FP7 grant agreement No. 604984)

Genome-wide association analysis identifies a meningioma risk locus at 11p15.5

BackgroundMeningiomas are adult brain tumors originating in the meningeal coverings of the brain and spinal cord, with significant heritable basis. Genome-wide association studies (GWAS) have previously identified only a single risk locus for meningioma, at 10p12.31.MethodsTo identify a susceptibility locus for meningioma, we conducted a meta-analysis of 2 GWAS, imputed using a merged reference panel from the 1000 Genomes Project and UK10K data, with validation in 2 independent sample series totaling 2138 cases and 12081 controls.ResultsWe identified a new susceptibility locus for meningioma at 11p15.5 (rs2686876, odds ratio = 1.44, P = 9.86 × 10-9). A number of genes localize to the region of linkage disequilibrium encompassing rs2686876, including RIC8A, which plays a central role in the development of neural crest-derived structures, such as the meninges.ConclusionsThis finding advances our understanding of the genetic basis of meningioma development and provides additional support for a polygenic model of meningioma