Multi-system neurological disease is common in patients with OPA1 mutations

Additional neurological features have recently been described in seven families transmitting pathogenic mutations in OPA1, the most common cause of autosomal dominant optic atrophy. However, the frequency of these syndromal ‘dominant optic atrophy plus’ variants and the extent of neurological involvement have not been established. In this large multi-centre study of 104 patients from 45 independent families, including 60 new cases, we show that extra-ocular neurological complications are common in OPA1 disease, and affect up to 20% of all mutational carriers. Bilateral sensorineural deafness beginning in late childhood and early adulthood was a prominent manifestation, followed by a combination of ataxia, myopathy, peripheral neuropathy and progressive external ophthalmoplegia from the third decade of life onwards. We also identified novel clinical presentations with spastic paraparesis mimicking hereditary spastic paraplegia, and a multiple sclerosis-like illness. In contrast to initial reports, multi-system neurological disease was associated with all mutational subtypes, although there was an increased risk with missense mutations [odds ratio = 3.06, 95% confidence interval = 1.44–6.49; P = 0.0027], and mutations located within the guanosine triphosphate-ase region (odds ratio = 2.29, 95% confidence interval = 1.08–4.82; P = 0.0271). Histochemical and molecular characterization of skeletal muscle biopsies revealed the presence of cytochrome c oxidase-deficient fibres and multiple mitochondrial DNA deletions in the majority of patients harbouring OPA1 mutations, even in those with isolated optic nerve involvement. However, the cytochrome c oxidase-deficient load was over four times higher in the dominant optic atrophy + group compared to the pure optic neuropathy group, implicating a causal role for these secondary mitochondrial DNA defects in disease pathophysiology. Individuals with dominant optic atrophy plus phenotypes also had significantly worse visual outcomes, and careful surveillance is therefore mandatory to optimize the detection and management of neurological disability in a group of patients who already have significant visual impairment

Finite cavity expansion method for near-surface effects and layering during earth penetration

A finite spherical cavity expansion technique is developed to simulate the loading on projectiles penetrating geologic media. Damaged Mohr-Coulomb plasticity models and general pressure-dependent damaged plasticity models are used with incompressible kinematics to approximate a wide range of targets. The finite cavity expansion approximation together with directional sampling reasonably captures near surface and layering effects without resort to ad hoc or empirical correction factors. The Mohr-Coulomb models are integrated exactly to provide a very efficient loading algorithm for use with conventional implicit or explicit finite element structural analysis. The more general constitutive model requires numerical integration and leads to a more computationally intensive procedure. However, subcycling is easily implemented with the numerical integration and thus an efficient loading method is readily achieved even for large complex simulations using explicit finite element analysis. The utility of the finite cavity expansion approach is demonstrated by comparison of simulations to measured test data from projectiles penetrating rock and soil targets

Neutron induced gamma spectrometry for on-line compositional analysis in coal conversion and fluidized-bed combustion plants

Nuclear techniques involving relatively penetrating radiation may offer the possibility of non-invasive, continuous on-line instrumental monitoring which is representative of the full process stream. Prompt gamma rays following neutron capture are particularly attractive because the penetrating power of the neutrons and the, typically several MeV, capture gammas makes possible interrogation of material within a pipe. We are evaluating neutron capture gamma techniques for this application, both for elemental composition monitoring and for mass-flow measurement purposes, and this paper will present some recent work on composition analysis by neutron induced gamma spectrometry

Application of a new economic analysis tool to a two-stage-to-orbit RBCC launch vehicle design

6th AIAA/USAF/NASA/ISSMO Symposium on Multidisciplinary Analysis and Optimization, Bellevue, WA, September 1996.As aerospace industries are forced to compete in an environment of declining federal budgets and increased competition, 'design for performance' is quickly giving way to 'design for cost.' Many modern launch vehicle programs are initiated with the goal of lowering the cost of delivering payloads to orbit while limiting investment costs and yielding a reasonable rate of return. Designers of new vehicles will need tools to quickly evaluate not only the costs, but also the revenue potential of various design options. To provide information that can be used to drive design decisions or an optimization process, these economic analysis tools must be fully integrated into the design environment. This paper reports the status of research to create a design-oriented economic analysis tool for conceptual launch vehicle design (called CAM). An overview of each CAM component is presented -- program definition, non-recurring costs, recurring costs, market evaluation, and revenue. As a demonstration, CAM is used to optimize the end-customer launch prices to four individual launch markets for a multi-market capable two-stage-to-orbit launch system. The vehicle utilizes rocket-based combined-cycle engines on the booster state and has two interchangeable rocket upper stages (one for GTO missions and one for LEO missions). Business-oriented results such as rate of return, and sensitivities to government investment, airframe life, and operations costs are presented

Lithium as a Differential Neuroprotector During Brain Irradiation

info:eu-repo/semantics/publishe

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical science. © The Author(s) 2019. Published by Oxford University Press