From gene to therapy in spinal and bulbar muscular atrophy: Are we there yet?

Abnormal polyglutamine expansions in the androgen receptor (AR) cause a muscular condition, known as Kennedy's disease or spinal and bulbar muscular atrophy (SBMA). The disease is transmitted in an X-linked fashion and is clinically characterized by weakness, atrophy and fasciculations of the limb and bulbar muscles as a result of a toxic gain-of-function of the mutant protein. Notably, affected males also show signs of androgen insensitivity, such as gynaecomastia and reduced fertility. The characterization of the natural history of the disease, the increasing understanding of the mechanism of pathogenesis and the elucidation of the functions of normal and mutant AR have offered a momentum for developing a rational therapeutic strategy for this disease. In this special issue on androgens and AR functions, we will review the molecular, biochemical, and cellular mechanisms underlying the pathogenesis of SBMA. We will discuss recent advances on therapeutic approaches and opportunities for this yet incurable disease, ranging from androgen deprivation, to gene silencing, to an expanding repertoire of peripheral targets, including muscle. With the advancement of these strategies into the clinic, it can be reasonably anticipated that the landscape of treatment options for SBMA and other neuromuscular conditions will change rapidly in the near future

‘Why am I having to do this?’ The nature and purpose of concurrent courses in Scottish primary teacher education

In his Report of a Review of Teacher Education in Scotland (2010), Donaldson presents the idea of the ‘twenty-first century teacher’. Central to this is the requirement for an ‘extended professionalism’ in which emphasis is placed on the development of the student teacher’s academic and intellectual qualities. This article aims to analyse the role of concurrent courses (i.e. university courses taken by education students outside of core education subjects) in the development of this extended professionalism. It does so by comparing it with the ‘graduate attributes’ agenda adopted by many universities, and by outlining two dimensions and three possible models of the relationship between concurrent courses and the purposes of teacher education. It is argued that one of these models best fits the word and spirit of the Donaldson Report, but that further research is required to establish how different models of concurrency have been, or might be, received by students and staff on Scottish primary education degrees

Applying university strategic objectives at the school level

University Teachers at the School of Interdisciplinary Studies are working together on the Teaching, Learning and Participation Project. This project encompasses three strands: widening participation, student experience, and innovative learning and teaching; all key aspects of the University’s strategic objectives. The widening participation strand has focused primarily on partnership with local schools. This includes Campus Days whereby pupils who have the ability, but perhaps not the confidence, to enter higher education come to the University's two campuses and experience a day as a student. Additionally this strand is seeking to conduct a comparative study of assessment and feedback processes in secondary and higher education. The student experience strand has concentrated on employability and internationalisation. Examples include working with the local education authority to extend student learning and provide staff CPD opportunities via the establishment of an annual education lecture, and developing opportunities for internships overseas. Finally, the innovative learning and teaching strand has sought to review current teaching practices within the School, and to identify and trial innovative methodologies in an effort to engage learners more fully and thereby to enhance both the student and staff learning experiences

Beyond motor neurons: expanding the clinical spectrum in Kennedy's disease

Kennedy's disease, or spinal and bulbar muscular atrophy (SBMA), is an X-linked neuromuscular condition clinically characterised by weakness, atrophy and fasciculations of the limb and bulbar muscles, as a result of lower motor neuron degeneration. The disease is caused by an abnormally expanded triplet repeat expansions in the ubiquitously expressed androgen receptor gene, through mechanisms which are not entirely elucidated. Over the years studies from both humans and animal models have highlighted the involvement of cell populations other than motor neurons in SBMA, widening the disease phenotype. The most compelling aspect of these findings is their potential for therapeutic impact: muscle, for example, which is primarily affected in the disease, has been recently shown to represent a valid alternative target for therapy to motor neurons. In this review, we discuss the emerging study of the extra-motor neuron involvement in SBMA, which, besides increasingly pointing towards a multidisciplinary approach for affected patients, deepens our understanding of the pathogenic mechanisms and holds potential for providing new therapeutic targets for this disease

Collapse displacements for a mechanism of spreading-induced supports in a masonry arch

Masonry arch systems and vaulted structures constitute a structural typology widely spread in the historical building heritage. Small displacements of the supports, due to different causes, among which subsidence of foundation systems or movements of underlying structures can lead the masonry arch to a condition of collapse because of gradual change in its geometry. This paper presents a tool, based on a kinematic approach, for the computation of the magnitude of the displacements that cause the collapse of circular arches subject to dead loads, and allows the evaluation of the related thrust value. A parametric study has been carried out in order to develop a deeper understanding of the influence of the involved parameters. In addition, analytic formulations of the maximum allowed displacement and the associated thrust are proposed. Finally, a case study related to the behavior of a masonry arch on spreading-induced abutments is undertaken and discussed

Outdoor learning: Scottish primary teachers’ perceptions of training and professional development

Outdoor learning has long been an important feature of Scottish education, but the non-prescriptive nature of the curriculum has contributed to wide variations in schools’ provision of outdoor educational experiences (Ross et al., 2007). Curriculum for Excellence (CfE) further encourages the use of the outdoors as a context for learning, but still does not make this mandatory (Beames et al., 2009). However, changes to the Standards for Teacher Registration require all teachers to demonstrate use of the outdoors in their teaching (GTCS, 2012).<p></p> As part of research exploring educational farm visits for primary school children, a survey of teachers in May 2013 included questions on teachers’ perceptions of knowledge and training on outdoor learning. The survey results informed a series of teacher interviews, during which these topics were also discussed.<p></p> The survey results indicate that primary teachers’ perceptions of their own training vary widely, while they tend to feel that probationer teachers are not well informed on outdoor learning. The need for further training and CPD was a clear theme in the qualitative elements of the survey, and early interview findings suggest that learning informally, from colleagues sharing their own experiences, is an important feature of teachers’ professional development.<p></p> Although “prospects for learning outdoors have rarely been better” than under CfE (Thorburn & Allison, 2013), survey findings indicate that previously identified issues around training and CPD (e.g. Nicol et al., 2007) seem to persist. Whether the views of teachers taking part in interviews support these early indications will be known by summer 2014

Study of 222−220Rn Measurement Systems Based on Electrostatic Collection by Using Geant4+COMSOL Simulation

Using Monte Carlo (with Geant4) and COMSOL simulations, the authors have defined a useful tool to reproduce the alpha spectroscopy of 222Rn, 220Rn and their ionized daughters by measurement systems based on electrostatic collection on a silicon detector, inside a metallic chamber. Several applications have been performed: (i) simulating commercial devices worldwide used, and comparing them with experimental theoretical results; (ii) studying of realization of new measurement systems through investigation of the detection efficiency versus different chamber geometries. New considerations and steps forward have been drawn. The present work is a novelty in the literature concerning this research framework

Dataset on gait patterns in degenerative neurological diseases

We collected the gait parameters and lower limb joint kinematics of patients with three different types of primary degenerative neurological diseases: (i) cerebellar ataxia (19 patients), (ii) hereditary spastic paraparesis (26 patients), and (iii) Parkinson's disease (32 patients). Sixty-five gender-age matched healthy subjects were enrolled as control group. An optoelectronic motion analysis system was used to measure time-distance parameters and lower limb joint kinematics during gait in both patients and healthy controls

Atorvastatin combined to interferon to verify the efficacy (ACTIVE) in relapsing-remitting active multiple sclerosis patients: a longitudinal controlled trial of combination therapy.

A large body of evidence suggests that, besides their cholesterol-lowering effect, statins exert anti-inflammatory action. Consequently, statins may have therapeutic potential in immune-mediated disorders such as multiple sclerosis. Our objectives were to determine safety, tolerability and efficacy of low-dose atorvastatin plus high-dose interferon beta-1a in multiple sclerosis patients responding poorly to interferon beta-1a alone. Relapsing–remitting multiple sclerosis patients, aged 18–50 years, with contrast-enhanced lesions or relapses while on therapy with interferon beta-1a 44 mg (three times weekly) for 12 months, were randomized to combination therapy (interferon+atorvastatin 20mg per day; group A) or interferon alone (group B) for 24 months. Patients underwent blood analysis and clinical assessment with the Expanded Disability Status Scale every 3 months, and brain gadolinium-enhanced magnetic resonance imaging at screening, and 12 and 24 months thereafter. Primary outcome measure was contrast-enhanced lesion number. Secondary outcome measures were number of relapses, EDSS variation and safety laboratory data. Forty-five patients were randomized to group A (n 1⁄4 21) or B (n 1⁄4 24). At 24 months, group A had significantly fewer contrast-enhanced lesions versus baseline (p 1⁄4 0.007) and significantly fewer relapses versus the two pre-randomization years (p < 0.001). At survival analysis, the risk for a 1-point EDSS increase was slightly higher in group B than in group A (p 1⁄4 0.053). Low-dose atorvastatin may be beneficial, as add-on therapy, in poor responders to high-dose interferon beta-1a alone