Inherited cavernous malformations of the central nervous system: clinical and genetic features in 19 Swiss families

Cavernous malformations (CCMs) are benign, well-circumscribed, and mulberry-like vascular malformations that may be found in the central nervous system in up to 0.5% of the population. Cavernous malformations can be sporadic or inherited. The common symptoms are epilepsy, hemorrhages, focal neurological deficits, and headaches. However, CCMs are often asymptomatic. The familiar form is associated with three gene loci, namely 7q21-q22 (CCM1), 7p13-p15 (CCM2), and 3q25.2-q27 (CCM3) and is inherited as an autosomal dominant trait with incomplete penetrance. The CCM genes are identified as Krit 1 (CCM1), MGC4607 (CCM2), and PDCD10 (CCM3). Here, we present the clinical and genetic features of CCMs in 19 Swiss families. Furthermore, surgical aspects in such families are also discusse

The SAVEMEDCOASTS-2 webGIS: The Online Platform for Relative Sea Level Rise and Storm Surge Scenarios up to 2100 for the Mediterranean Coasts

Here we show the SAVEMEDCOASTS-2 web-based geographic information system (webGIS) that supports land planners and decision makers in considering the ongoing impacts of Relative Sea Level Rise (RSLR) when formulating and prioritizing climate-resilient adaptive pathways for the Mediterranean coasts. The webGIS was developed within the framework of the SAVEMEDCOASTS and SAVEMEDCOASTS-2 projects, funded by the European Union, which respond to the need to protect people and assets from natural disasters along the Mediterranean coasts that are vulnerable to the combined effects of Sea Level Rise (SLR) and Vertical Land Movements (VLM). The geospatial data include available or new high-resolution Digital Terrain Models (DTM), bathymetric data, rates of VLM, and multi-temporal coastal flooding scenarios for 2030, 2050, and 2100 with respect to 2021, as a consequence of RSLR. The scenarios are derived from the 5th Assessment Report (AR5) provided by the Intergovernmental Panel on Climate Change (IPCC) and encompass different Representative Concentration Pathways (RCP2.6 and RCP8.5) for climate projections. The webGIS reports RSLR scenarios that incorporate the temporary contribution of both the highest astronomical tides (HAT) and storm surges (SS), which intensify risks to the coastal infrastructure, local community, and environment

Cytosine deaminase base editing to restore COL7A1 in dystrophic epidermolysis bullosa human:murine skin model

Recessive dystrophic epidermolysis bullosa (RDEB) is a debilitating blistering skin disorder caused by loss-of-function mutations in COL7A1 encoding type VII collagen (C7), the main component of anchoring fibrils (AFs) at the dermal-epidermal junction (DEJ). Although conventional gene therapy approaches through viral vectors have been tested in pre-clinical and clinical trials, they are limited by transgene size constraints and only support unregulated gene expression. Genome editing could potentially overcome some of these limitations, and CRISPR/Cas9 has already been applied in research studies to restore COL7A1 expression. Delivery of suitable repair templates for repair of DNA cleaved by Cas9 is still major challenge, and alternative base editing strategies may offer corrective solutions for certain mutations. We demonstrate highly targeted and efficient cytidine deamination and molecular correction of a defined RDEB mutation (c.425A>G) leading to restoration of full-length C7 protein expression in primary human fibroblasts and iPSCs. C7 basement membrane expression and skin architecture were restored with de novo AFs identified by electron microscopy in base edited human RDEB grafts recovered from immunodeficient mice. The results demonstrate the potential and promise of emerging base editing technologies in tackling inherited disorders with well-defined single nucleotide mutations

â-thalassemia and gonadal axis: a cross-sectional, clinical study in a Greek population

ABSTRACT â-thalassemia (â-thal) is characterized by disturbances of the reproductive system. The aim of the present study was: 1) to assess the hypothalamic pituitary -gonadal axis in patients with â-thal in relation to their phenotype and 2) to determine prognostic features of current gonadal status. We studied 135 patients (67 males and 68 females) with â-thal through history, physical examination, spermiograms and GnRH test. These patients were divided into â-thal major (51 males and 62 females) and â-thal intermedia phenotypes (16 males and 6 females). Male patients with â-thal major were subdivided into three groups a) eugonadal (35%, Tanners stage V, normal testicular volume, normal spermiograms, normal basal and stimulated hormone values), b) patients with hypogonadotrophic hypogonadism (HH) of late onset (24%, Tanners stage II-V, low-normal testicular volume, abnormal spermiograms, normal basal gonadotrophin values and abnormal response to GnRH test) and c) patients with HH of early onset (41%, Tanners stage I, small testicular volume, abnormal spermiograms, abnormal basal and stimulated hormone values). Female patients with â-thal major were subdivided into: a) eugonadal (32%, Tanners stage V, regular menstruation, normal basal and stimulated hormone values), b) patients with hypogonadotrophic hypogonadism (HH) of late onset (34%, Tanners stage II-V, secondary amenorrhea, subnormal basal and stimulated gonadotrophin values) and c) patients with HH of early onset (34%, Tanners stage I, primary amenorrhea, subnormal basal and stimulated hormone values). Patients with â-thal intermedia were subdivided into eugonadal (75% of males -33% of females) and hypogonadal (25% of males -67% of females). Current gonadal status could not be predicted by means of transfusion or chelation parameters. In conclusion, â-thal patients could be eugonadal or develop early or late onset HH. â-thal intermedia patients have a more favorable profile than â-thal major individuals. Current gonadal status of â-thal patients cannot be predicted by means of history, clinical or laboratory parameters

An appropriate tool for entrepreneurial learning in SMEs? The case of the 20Twenty Leadership Programme

The 20Twenty Leadership Programme was developed by Cardiff Metropolitan University as an executive education programme to be delivered within South Wales to small businesses. It is funded by the European Social Fund (ESF) and administered by the Welsh European Funding Office and has the key aim of developing SME’s growth potential via a range of leadership and management skills, including a focus on ‘soft’ skills. The focus of this paper is to place the 20Twenty Leadership Programme within the wider context of entrepreneurship policy and SME training initiatives in particular, and then to examine the rationale and delivery methods of the Programme in relation to these. It also reflects on the Programme’s success (or otherwise) to date where possible. Finally, the paper seeks to suggest fruitful areas of further research both in terms of the 20Twenty Leadership Programme itself, but also with regard to evaluation in relation to other parallel programmes, and to SME training initiatives more generally

Status of Turbulence Modeling for Hypersonic Propulsion Flowpaths

This report provides an assessment of current turbulent flow calculation methods for hypersonic propulsion flowpaths, particularly the scramjet engine. Emphasis is placed on Reynolds-averaged Navier-Stokes (RANS) methods, but some discussion of newer meth- ods such as Large Eddy Simulation (LES) is also provided. The report is organized by considering technical issues throughout the scramjet-powered vehicle flowpath including laminar-to-turbulent boundary layer transition, shock wave / turbulent boundary layer interactions, scalar transport modeling (specifically the significance of turbulent Prandtl and Schmidt numbers) and compressible mixing. Unit problems are primarily used to conduct the assessment. In the combustor, results from calculations of a direct connect supersonic combustion experiment are also used to address the effects of turbulence model selection and in particular settings for the turbulent Prandtl and Schmidt numbers. It is concluded that RANS turbulence modeling shortfalls are still a major limitation to the accuracy of hypersonic propulsion simulations, whether considering individual components or an overall system. Newer methods such as LES-based techniques may be promising, but are not yet at a maturity to be used routinely by the hypersonic propulsion community. The need for fundamental experiments to provide data for turbulence model development and validation is discussed

AR AND CHAMBER MUSIC: MUSICAL KALEIDOSCOPE

DIGI-ORCH is a research project with objectives, on one hand, to design and develop "smart" brochures for concerts and educational programs of the State Conservatory of Thessaloniki (Greece), and, on the other, to develop an innovative system for the visualization of information on smart mobile devices (smartphones and tablets). The application of Augmented Reality (AR) provides free access to the information and content of the above concerts and educational programs, combining the information of a robust data server and an easy-to-use user interface of the smart device in real-time.The pilot implementation of the system in real conditions took place at the beginning of December 2022, in an event held at the facilities of the State Conservatory of Thessaloniki. The event was an evening of Chamber Music entitled Musical Kaleidoscope, with the internationally acclaimed artists Simos Papanas (violin), Dimos Goundaroulis (violoncello), and Vassilis Varvaresos (piano). They performed the Piano Trio no. 3 in G minor, Robert Schumann's opus 110, and the Piano Trio no. 2 in E flat major, Op. 100 D. 929 by Franz Schubert. The concert was attended by over 150 attendees.The paper will present the chaîne-operatoire of the development of the system, from the acquisition of raw data (text, video, image, and sound) to the methodology used to produce the "smart" event brochure and the AR application for the above concert. Essentially, this large amount of information that cannot be assessed by a regular printed concert brochure is included in the smart system and displayed on the mobile device when the user locates the appropriate AR patterns on the surface of the analog concert poster and/or on the pages of the brochure.This information comprised of ie. additional text and images about the composers and their musical projects, about the musicians of the concert (e.g. biographies), their interviews and rehearsals (video) before the concert, information about the State Conservatory of Thessaloniki (text, video, image, and sound), 3D models of musical instruments, 360° of the concert space, etc. diverse multimedia material.</p