Nonnormal amplification in random balanced neuronal networks

In dynamical models of cortical networks, the recurrent connectivity can amplify the input given to the network in two distinct ways. One is induced by the presence of near-critical eigenvalues in the connectivity matrix W, producing large but slow activity fluctuations along the corresponding eigenvectors (dynamical slowing). The other relies on W being nonnormal, which allows the network activity to make large but fast excursions along specific directions. Here we investigate the tradeoff between nonnormal amplification and dynamical slowing in the spontaneous activity of large random neuronal networks composed of excitatory and inhibitory neurons. We use a Schur decomposition of W to separate the two amplification mechanisms. Assuming linear stochastic dynamics, we derive an exact expression for the expected amount of purely nonnormal amplification. We find that amplification is very limited if dynamical slowing must be kept weak. We conclude that, to achieve strong transient amplification with little slowing, the connectivity must be structured. We show that unidirectional connections between neurons of the same type together with reciprocal connections between neurons of different types, allow for amplification already in the fast dynamical regime. Finally, our results also shed light on the differences between balanced networks in which inhibition exactly cancels excitation, and those where inhibition dominates.Comment: 13 pages, 7 figure

Phase 1 Safety and Tolerability Study of BMP-7 in Symptomatic Knee Osteoarthritis

BACKGROUND: There are no proven therapies that modify the structural changes associated with osteoarthritis (OA). Preclinical data suggests that intra-articular recombinant human BMP-7 (bone morphogenetic protein-7) has reparative effects on cartilage, as well as on symptoms of joint pain. The objective of this study was to determine the safety and tolerability as well as dose-limiting toxicity and maximal tolerated dose of intra-articular BMP-7. The secondary objectives were to determine the effect on symptomatic responses through 24 weeks. METHODS: This was a Phase 1, double-blind, randomized, multi-center, placebo-controlled, single-dose escalation safety study consisting of 4 dosing cohorts in participants with knee OA. Each cohort was to consist of 8 treated participants, with treatment allocation in a 3:1 active (intra-articular BMP-7) to placebo ratio. Eligible participants were persons with symptomatic radiographic knee OA over the age of 40. The primary objective of this study was to determine the safety and tolerability of BMP-7 including laboratory assessments, immunogenicity data and radiographic assessments. Secondary objectives were to determine the proportion of participants with a 20%, 50%, and 70% improvement in the WOMAC pain and function subscales at 4, 8, 12, and 24 weeks. Other secondary outcomes included the change from baseline to 4, 8, 12, and 24 weeks for the OARSI responder criteria. RESULTS: The mean age of participants was 60 years and 73% were female. All 33 participants who were enrolled completed the study and most adverse events were mild or moderate and were similar in placebo and BMP-7 groups. The 1 mg BMP-7 group showed a higher frequency of injection site pain and there was no ectopic bone formation seen on plain x-rays. By week 12, most participants in both the BMP-7 and placebo groups experienced a 20% improvement in pain and overall the BMP-7 group was similar to placebo with regard to this measurement. In the participants who received 0.1 mg and 0.3 mg BMP-7, there was a trend toward greater symptomatic improvement than placebo. The other secondary endpoints showed similar trends including the OARSI responder criteria for which the BMP-7 groups had more responders than placebo. CONCLUSIONS: There was no dose limiting toxicity identified in this study. The suggestion of a symptom response, together with the lack of dose limiting toxicity provide further support for the continued development of this product for the treatment of osteoarthritis.ARC Future Fellowship; Stryker Biotec

Supporting the automated generation of modular product line safety cases

Abstract The effective reuse of design assets in safety-critical Software Product Lines (SPL) would require the reuse of safety analyses of those assets in the variant contexts of certification of products derived from the SPL. This in turn requires the traceability of SPL variation across design, including variation in safety analysis and safety cases. In this paper, we propose a method and tool to support the automatic generation of modular SPL safety case architectures from the information provided by SPL feature modeling and model-based safety analysis. The Goal Structuring Notation (GSN) safety case modeling notation and its modular extensions supported by the D-Case Editor were used to implement the method in an automated tool support. The tool was used to generate a modular safety case for an automotive Hybrid Braking System SPL

Spaceboard II Panels: Preliminary Evaluation of Mechanical Properties

This preliminary evaluation of the properties of Spaceboard II (SBII) was undertaken to establish the potential of a pulp-molded product in structural-use applications and to develop a basis upon which to optimize the Spaceboard pulp molding process. Various tests were implemented to characterize significant engineering properties, including static concentrated load, panel bending, panel shear, bearing strength, and coupon tension and compression strength. Although these tests were preliminary in nature, they were nonetheless adequate to show that SBII panels perform quite satisfactorily under "dry" conditions, relative to the current performance requirements established for structural-use panels. Our tests on SBII demonstrated that with proper formation and densification, a three-dimensional pulp molding process such as Spaceboard provides the opportunity to create structural products from fiber and to obtain the performance required of conventional products

Pilot of ‘Families for Health’ : community-based family intervention for obesity

Objective - To develop and evaluate ‘Families for Health’ - a new community based family intervention for childhood obesity. Design – Programme development, pilot study and evaluation using intention-to-treat analysis. Setting – Coventry, England Participants – 27 overweight or obese children aged 7-13 years (18 girls, 9 boys) and their parents, from 21 families. Intervention – ‘Families for Health’ is a 12 week programme with parallel groups for parents and children, addressing parenting, lifestyle change and social & emotional development. Main Outcome Measures – Primary: change in baseline BMI z-score at end of programme (3 months) and 9 month follow-up. Attendance, drop-out, parents’ perception of programme, child’s quality of life and self esteem, parental mental health, parent-child relationships and lifestyle changes were also measured. Results: Attendance rate was 62%, with 18 of the 27 (67%) children completing the programme. For the 22 children with follow-up data (including 4 drop-outs), BMI z-score was reduced by -0.18 (95%CI -0.30 to -0.05) at end of programme and by -0.21 (-0.35 to -0.07) at 9 months. Statistically significant improvements were observed in children’s quality of life and lifestyle (reduced sedentary behaviour, increased steps and reduced exposure to unhealthy foods), child-parent relationships and parents’ mental health. Fruit and vegetable consumption, participation in moderate/vigorous exercise and children’s self-esteem did not change significantly. Topics on parenting skills, activity and food were rated as helpful and were used with confidence by the majority of parents. Conclusions Families for Health is a promising new childhood obesity intervention. Definitive evaluation of its clinical effectiveness by randomised controlled trial is now required

Effect of partially-screened nuclei on fast-electron dynamics

We analyze the dynamics of fast electrons in plasmas containing partially ionized impurity atoms, where the screening effect of bound electrons must be included. We derive analytical expressions for the deflection and slowing-down frequencies, and show that they are increased significantly compared to the results obtained with complete screening, already at sub-relativistic electron energies. Furthermore, we show that the modifications to the deflection and slowing down frequencies are of equal importance in describing the runaway current evolution. Our results greatly affect fast-electron dynamics and have important implications, e.g. for the efficacy of mitigation strategies for runaway electrons in tokamak devices, and energy loss during relativistic breakdown in atmospheric discharges.Comment: 6 pages, 3 figures, fixed minor typo

Late metal-silicate separation on the IAB parent asteroid: Constraints from combined W and Pt isotopes and thermal modelling

The short-lived $^{182}$Hf-$^{182}$W decay system is a powerful chronometer for constraining the timing of metal-silicate separation and core formation in planetesimals and planets. Neutron capture effects on W isotopes, however, significantly hamper the application of this tool. In order to correct for neutron capture effects, Pt isotopes have emerged as a reliable in-situ neutron dosimeter. This study applies this method to IAB iron meteorites, in order to constrain the timing of metal segregation on the IAB parent body. The $\epsilon^{182}$W values obtained for the IAB iron meteorites range from -3.61 $\pm$ 0.10 to -2.73 $\pm$ 0.09. Correlating $\epsilon^{\mathrm{i}}$Pt with $^{182}$W data yields a pre-neutron capture $^{182}$W of -2.90 $\pm$ 0.06. This corresponds to a metal-silicate separation age of 6.0 $\pm$ 0.8 Ma after CAI for the IAB parent body, and is interpreted to represent a body-wide melting event. Later, between 10 and 14 Ma after CAI, an impact led to a catastrophic break-up and subsequent reassembly of the parent body. Thermal models of the interior evolution that are consistent with these estimates suggest that the IAB parent body underwent metal-silicate separation as a result of internal heating by short-lived radionuclides and accreted at around 1.4 $\pm$ 0.1 Ma after CAIs with a radius of greater than 60 km.Comment: 11 pages, 8 figures, 2 tables; open access article under the CC BY-NC-ND license (see http://creativecommons.org/licenses/by-nc-nd/4.0/

A unified framework for Schelling's model of segregation

Schelling's model of segregation is one of the first and most influential models in the field of social simulation. There are many variations of the model which have been proposed and simulated over the last forty years, though the present state of the literature on the subject is somewhat fragmented and lacking comprehensive analytical treatments. In this article a unified mathematical framework for Schelling's model and its many variants is developed. This methodology is useful in two regards: firstly, it provides a tool with which to understand the differences observed between models; secondly, phenomena which appear in several model variations may be understood in more depth through analytic studies of simpler versions.Comment: 21 pages, 3 figure