Identifying cell class specific losses from serially generated electroretinogram components

Purpose. Processing of information through the cellular layers of the retina occurs in a serial manner. In the electroretinogram (ERG), this complicates interpretation of inner retinal changes as dysfunction may arise from "upstream" neurons or may indicate a direct loss to that neural generator. We propose an approach that addresses this issue by defining ERG gain relationships.

Methods. Regression analyses between two serial ERG parameters in a control cohort of rats are used to define gain relationships. These gains are then applied to two models of retinal disease.

Results. The PIIIamp to PIIamp gain is unity whereas the PIIamp to pSTRamp and PIIamp to nSTRamp gains are greater than unity, indicating "amplification" (P <0.05). Timing relationships show amplification between PIIIit to PIIit and compression for PIIit to pSTRit and PIIit to nSTRit, (P <0.05). Application of these gains to ?-3-deficiency indicates that all timing changes are downstream of photoreceptor changes, but a direct pSTR amplitude loss occurs (P <0.05). Application to diabetes indicates widespread inner retinal dysfunction which cannot be attributed to outer retinal changes (P <0.05).

Conclusions. This simple approach aids in the interpretation of inner retinal ERG changes by taking into account gain characteristics found between successive ERG components of normal animals.

The Relationship between Components of the Behavioural Phenotype in Prader-Willi Syndrome

Background

Repetitive questions and temper outbursts form part of the behavioural phenotype of Prader-Willi syndrome (PWS). We investigated the phenomenology of temper outbursts in PWS and their relationship with other PWS behavioural characteristics.

Method

Four individuals with PWS were observed (5-10 h), during a number of experimental and natural environment challenges, some of which were expected to trigger temper outbursts. Individual behaviours including crying, ignoring, arguing, questioning, stereotypy, frowning and posture changes were recorded and subjected to lag sequential analysis.

Results

All participants were significantly more likely to show repetitive questioning before more challenging behaviours such as crying, arguing or ignoring requests. Precursor behaviours such as frowning and stereotypical behaviour were identified in three participants.

Conclusions

Temper outbursts in PWS may be associated with other PWS behavioural phenotypic characteristics such as repetitive questions and 'stubbornness'. A progression of behaviours may lead up to the most challenging temper outburst behaviours. This may have important implications for effective coping strategies.

Auditory observation of stepping actions can cue both spatial and temporal components of gait in Parkinson's disease patients

Objectives: A common behavioural symptom of Parkinson’s disease (PD) is reduced step length (SL). Whilst sensory cueing strategies can be effective in increasing SL and reducing gait variability, current cueing strategies conveying spatial or temporal information are generally confined to the use of either visual or auditory cue modalities, respectively. We describe a novel cueing strategy using ecologically-valid ‘action-related’ sounds (footsteps on gravel) that convey both spatial and temporal parameters of a specific action within a single cue.
Methods: The current study used a real-time imitation task to examine whether PD affects the ability to re-enact changes in spatial characteristics of stepping actions, based solely on auditory information. In a second experimental session, these procedures were repeated using synthesized sounds derived from recordings of the kinetic interactions between the foot and walking surface. A third experimental session examined whether adaptations observed when participants walked to action-sounds were preserved when participants imagined either real recorded or synthesized sounds.
Results: Whilst healthy control participants were able to re-enact significant changes in SL in all cue conditions, these adaptations, in conjunction with reduced variability of SL were only observed in the PD group when walking to, or imagining the recorded sounds.
Conclusions: The findings show that while recordings of stepping sounds convey action information to allow PD patients to re-enact and imagine spatial characteristics of gait, synthesis of sounds purely from gait kinetics is insufficient to evoke similar changes in behaviour, perhaps indicating that PD patients have a higher threshold to cue sensorimotor resonant responses.

Modelling lay-up automation and production rate interaction on the cost of large stiffened panel components

This paper presents an integrated design and costing method for large stiffened panels for the purpose of investigating the influence and interaction of lay-up technology and production rate on manufacturing cost. A series of wing cover panels (≈586kg, 19·9m2) have been sized with realistic requirements considering manual and automated lay-up routes. The integrated method has enabled the quantification of component unit cost sensitivity to changes in annual production rate and employed equipment maximum deposition rate. Moreover the results demonstrate the interconnected relationship between lay-up process and panel design, and unit cost. The optimum unit cost solution when using automated lay-up is a combination of the minimum deposition rate and minimum number of lay-up machines to meet the required production rate. However, the location of the optimum unit cost, at the boundaries between the number of lay-up machines required, can make unit cost very sensitive to small changes in component design, production rate, and equipment maximum deposition rate. - See more at: http://aerosociety.com/News/Publications/Aero-Journal/Online/1941/Modelling-layup-automation-and-production-rate-interaction-on-the-cost-of-large-stiffened-panel-components#sthash.0fLuu9iG.dpuf

Rapid design of discrete orthonormal wavelet transforms using silicon IP components

A rapid design methodology for orthonormal wavelet transform cores has been developed. This methodology is based on a generic, scaleable architecture utilising time-interleaved coefficients for the wavelet transform filters. The architecture has been captured in VHDL and parameterised in terms of wavelet family, wavelet type, data word length and coefficient word length. The control circuit is embedded within the cores and allows them to be cascaded without any interface glue logic for any desired level of decomposition. Case studies for stand alone and cascaded silicon cores for single and multi-stage wavelet analysis respectively are reported. The design time to produce silicon layout of a wavelet based system has been reduced to typically less than a day. The cores are comparable in area and performance to handcrafted designs. The designs are portable across a range of foundries and are also applicable to FPGA and PLD implementations.

Tiotropium and olodaterol fixed-dose combination versus mono-components in COPD (GOLD 2-4)

Efficacy and safety of tiotropium+olodaterol fixed-dose combination (FDC) compared with the mono-components was evaluated in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) in two replicate, randomised, double-blind, parallel-group, multicentre, phase III trials. Patients received tiotropium+olodaterol FDC 2.5/5 μg or 5/5 μg, tiotropium 2.5 μg or 5 μg, or olodaterol 5 μg delivered once-daily via Respimat inhaler over 52 weeks. Primary end points were forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h (AUC0-3) response, trough FEV1 response and St George's Respiratory Questionnaire (SGRQ) total score at 24 weeks. In total, 5162 patients (2624 in Study 1237.5 and 2538 in Study 1237.6) received treatment. Both FDCs significantly improved FEV1 AUC0-3 and trough FEV1 response versus the mono-components in both studies. Statistically significant improvements in SGRQ total score versus the mono-components were only seen for tiotropium+olodaterol FDC 5/5 μg. Incidence of adverse events was comparable between the FDCs and the mono-components. These studies demonstrated significant improvements in lung function and health-related quality of life with once-daily tiotropium+olodaterol FDC versus mono-components over 1 year in patients with moderate to very severe COPD.