A practical approach to communicating benefit-risk decisions of medicines to stakeholders.

© 2015 Leong, Walker and Salek. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Purpose: The importance of a framework for a systematic structured assessment of the benefits and risks has been established, but in addition, it is necessary that the benefit-risk decisions and the processes to derive those decisions are documented and communicated to various stakeholders for accountability. Hence there is now a need to find appropriate tools to enhance communication between regulators and other stakeholders, in a manner that would uphold transparency, consistency and standards. Methods: A retrospective, non-comparative study was conducted to determine the applicability and practicality of a summary template in documenting benefit-risk assessment and communicating benefit-risk balance and conclusions for reviewers to other stakeholders. The benefit-risk (BR) Summary Template and its User Manual was evaluated by 12 reviewers within a regulatory agency in Singapore, the Health Sciences Authority (HSA). Results: The BR Summary Template was found to be adequate in documenting benefits, risks, relevant summaries and conclusions, while the User Manual was useful in guiding the reviewer in completing the template. The BR Summary Template was also considered a useful tool for communicating benefit-risk decisions to a variety of stakeholders. Conclusions: The use of a template may be of value for the communicating benefit-risk assessment of medicines to stakeholders.Peer reviewedFinal Published versio

Optimised access to user analysis data using the gLite DPM

The ScotGrid distributed Tier-2 now provides more that 4MSI2K and 500TB for LHC computing, which is spread across three sites at Durham, Edinburgh and Glasgow. Tier-2 sites have a dual role to play in the computing models of the LHC VOs. Firstly, their CPU resources are used for the generation of Monte Carlo event data. Secondly, the end user analysis data is distributed across the grid to the site's storage system and held on disk ready for processing by physicists' analysis jobs. In this paper we show how we have designed the ScotGrid storage and data management resources in order to optimise access by physicists to LHC data. Within ScotGrid, all sites use the gLite DPM storage manager middleware. Using the EGEE grid to submit real ATLAS analysis code to process VO data stored on the ScotGrid sites, we present an analysis of the performance of the architecture at one site, and procedures that may be undertaken to improve such. The results will be presented from the point of view of the end user (in terms of number of events processed/second) and from the point of view of the site, which wishes to minimise load and the impact that analysis activity has on other users of the system

A protocol to examine vision and gait in Parkinson’s disease: impact of cognition and response to visual cues

Background Cognitive and visual impairments are common in Parkinson's disease (PD) and contribute to gait deficit and falls. To date, cognition and vision in gait in PD have been assessed separately. Impact of both functions (which we term 'visuo-cognition') on gait however is likely interactive and can be tested using visual sampling (specifically saccadic eye movements) to provide an online behavioural measure of performance. Although experiments using static paradigms show saccadic impairment in PD, few studies have quantified visual sampling during dynamic motor tasks such as gait. This article describes a protocol developed for testing visuo-cognition during gait in order to examine the: 1) independent roles of cognition and vision in gait in PD, 2) interaction between both functions, and 3) role of visuo-cognition in gait in PD. Methods Two groups of older adults (≥50 years old) were recruited; non-demented people with PD (n=60) and age-matched controls (n=40). Participants attended one session and a sub-group (n=25) attended two further sessions in order to establish mobile eye-tracker reliability. Participants walked in a gait laboratory under different attentional (single and dual task), environmental (walk straight, through a door and turning), and cueing (no visual cues and visual cues) conditions. Visual sampling was recorded using synchronised mobile eye-tracker and electrooculography systems, and gait was measured using 3D motion analysis. Discussion This exploratory study examined visuo-cognitive processes and their impact on gait in PD. Improved understanding of the influence of cognitive and visual functions on visual sampling during gait and gait in PD will assist in development of interventions to improve gait and reduce falls risk. This study will also help establish robust mobile eye-tracking methods in older adults and people with PD

Saccade frequency response to visual cues during gait in Parkinson's disease: the selective role of attention

Gait impairment is a core feature of Parkinson's disease (PD) with implications for falls risk. Visual cues improve gait in PD, but the underlying mechanisms are unclear. Evidence suggests that attention and vision play an important role; however, the relative contribution from each is unclear. Measurement of visual exploration (specifically saccade frequency) during gait allows for real-time measurement of attention and vision. Understanding how visual cues influence visual exploration may allow inferences of the underlying mechanisms to response which could help to develop effective therapeutics. This study aimed to examine saccade frequency during gait in response to a visual cue in PD and older adults and investigate the roles of attention and vision in visual cue response in PD. A mobile eye-tracker measured saccade frequency during gait in 55 people with PD and 32 age-matched controls. Participants walked in a straight line with and without a visual cue (50 cm transverse lines) presented under single task and dual-task (concurrent digit span recall). Saccade frequency was reduced when walking in PD compared to controls; however, visual cues ameliorated saccadic deficit. Visual cues significantly increased saccade frequency in both PD and controls under both single task and dual-task. Attention rather than visual function was central to saccade frequency and gait response to visual cues in PD. In conclusion, this study highlights the impact of visual cues on visual exploration when walking and the important role of attention in PD. Understanding these complex features will help inform intervention development

The Measurement of Eye Movements in Mild Traumatic Brain Injury: A Structured Review of an Emerging Area

Mild traumatic brain injury (mTBI), or concussion, occurs following a direct or indirect force to the head that causes a change in brain function. Many neurological signs and symptoms of mTBI can be subtle and transient, and some can persist beyond the usual recovery timeframe, such as balance, cognitive or sensory disturbance that may pre-dispose to further injury in the future. There is currently no accepted definition or diagnostic criteria for mTBI and therefore no single assessment has been developed or accepted as being able to identify those with an mTBI. Eye-movement assessment may be useful, as specific eye-movements and their metrics can be attributed to specific brain regions or functions, and eye-movement involves a multitude of brain regions. Recently, research has focused on quantitative eye-movement assessments using eye-tracking technology for diagnosis and monitoring symptoms of an mTBI. However, the approaches taken to objectively measure eye-movements varies with respect to instrumentation, protocols and recognition of factors that may influence results, such as cognitive function or basic visual function. This review aimed to examine previous work that has measured eye-movements within those with mTBI to inform the development of robust or standardized testing protocols. Medline/PubMed, CINAHL, PsychInfo and Scopus databases were searched. Twenty-two articles met inclusion/exclusion criteria and were reviewed, which examined saccades, smooth pursuits, fixations and nystagmus in mTBI compared to controls. Current methodologies for data collection, analysis and interpretation from eye-tracking technology in individuals following an mTBI are discussed. In brief, a wide range of eye-movement instruments and outcome measures were reported, but validity and reliability of devices and metrics were insufficiently reported across studies. Interpretation of outcomes was complicated by poor study reporting of demographics, mTBI-related features (e.g., time since injury), and few studies considered the influence that cognitive or visual functions may have on eye-movements. The reviewed evidence suggests that eye-movements are impaired in mTBI, but future research is required to accurately and robustly establish findings. Standardization and reporting of eye-movement instruments, data collection procedures, processing algorithms and analysis methods are required. Recommendations also include comprehensive reporting of demographics, mTBI-related features, and confounding variables

Gait in Parkinson’s disease: a visuo-cognitive challenge

Vision and cognition have both been related to gait impairment in Parkinson’s disease (PD) through separate strands of research. The cumulative and interactive effect of both (which we term visuo-cognition) has not been previously investigated and little is known about the influence of cognition on vision with respect to gait. Understanding the role of vision, cognition and visuo-cognition in gait in PD is critical for data interpretation and to infer and test underlying mechanisms. The purpose of this comprehensive narrative review was to examine the interdependent and interactive role of cognition and vision in gait in PD and older adults. Evidence from a broad range of research disciplines was reviewed and summarised. A key finding was that attention appears to play a pivotal role in mediating gait, cognition and vision, and should be considered emphatically in future research in this field

fNIRS response during walking — Artefact or cortical activity? A systematic review

This systematic review aims to (i) evaluate functional near infrared spectroscopy (fNIRS) walking study design in young adults, older adults and people with Parkinson’s disease (PD); (ii) examine signal processing techniques to reduce artefacts and physiological noise in fNIRS data; and (iii) provide evidence-based recommendations for fNIRS walking study design and signal analysis techniques. An electronic search was undertaken. The search request detailed the measurement technique, cohort and walking task. Thirty-one of an initial yield of 73 studies satisfied the criteria. Protocols and methods for removing artefacts and noise varied. Differences in fNIRS signals between studies were found in rest vs. walking, speed of walking, usual vs. complex walking and easy vs. difficult tasks. In conclusion, there are considerable technical and methodological challenges in conducting fNIRS studies during walking which can introduce inconsistencies in study findings. We provide recommendations for the construction of robust methodologies and suggest signal processing techniques implementing a theoretical framework accounting for the physiology of haemodynamic responses

On the Indeterministic Nature of Star Formation on the Cloud Scale

Molecular clouds are turbulent structures whose star formation efficiency (SFE) is strongly affected by internal stellar feedback processes. In this paper we determine how sensitive the SFE of molecular clouds is to randomised inputs in the star formation feedback loop, and to what extent relationships between emergent cloud properties and the SFE can be recovered. We introduce the yule suite of 26 radiative magnetohydrodynamic (RMHD) simulations of a 10,000 solar mass cloud similar to those in the solar neighbourhood. We use the same initial global properties in every simulation but vary the initial mass function (IMF) sampling and initial cloud velocity structure. The final SFE lies between 6 and 23 percent when either of these parameters are changed. We use Bayesian mixed-effects models to uncover trends in the SFE. The number of photons emitted early in the cluster's life and the length of the cloud provide are the strongest predictors of the SFE. The HII regions evolve following an analytic model of expansion into a roughly isothermal density field. The more efficient feedback is at evaporating the cloud, the less the star cluster is dispersed. We argue that this is because if the gas is evaporated slowly, the stars are dragged outwards towards surviving gas clumps due to the gravitational attraction between the stars and gas. While star formation and feedback efficiencies are dependent on nonlinear processes, statistical models describing cloud-scale processes can be constructed.Comment: 24 pages, 16 figures, 6 tables. Accepted to MNRAS, version updated with published titl