The implausibility of ‘usual care’ in an open system: sedation and weaning practices in Paediatric Intensive Care Units (PICUs) in the United Kingdom (UK)

Background: The power of the randomised controlled trial depends upon its capacity to operate in a closed system whereby the intervention is the only causal force acting upon the experimental group and absent in the control group, permitting a valid assessment of intervention efficacy. Conversely, clinical arenas are open systems where factors relating to context, resources, interpretation and actions of individuals will affect implementation and effectiveness of interventions. Consequently, the comparator (usual care) can be difficult to define and variable in multi-centre trials. Hence outcomes cannot be understood without considering usual care and factors that may affect implementation and impact on the intervention. Methods: Using a fieldwork approach, we describe PICU context, ‘usual’ practice in sedation and weaning from mechanical ventilation, and factors affecting implementation prior to designing a trial involving a sedation and ventilation weaning intervention. We collected data from 23 UK PICUs between June and November 2014 using observation, individual and multi-disciplinary group interviews with staff. Results: Pain and sedation practices were broadly similar in terms of drug usage and assessment tools. Sedation protocols linking assessment to appropriate titration of sedatives and sedation holds were rarely used (9 % and 4 % of PICUs respectively). Ventilator weaning was primarily a medical-led process with 39 % of PICUs engaging senior nurses in the process: weaning protocols were rarely used (9 % of PICUs). Weaning methods were variably based on clinician preference. No formal criteria or use of spontaneous breathing trials were used to test weaning readiness. Seventeen PICUs (74 %) had prior engagement in multi-centre trials, but limited research nurse availability. Barriers to previous trial implementation were intervention complexity, lack of belief in the evidence and inadequate training. Facilitating factors were senior staff buy-in and dedicated research nurse provision. Conclusions: We examined and identified contextual and organisational factors that may impact on the implementation of our intervention. We found usual practice relating to sedation, analgesia and ventilator weaning broadly similar, yet distinctively different from our proposed intervention, providing assurance in our ability to evaluate intervention effects. The data will enable us to develop an implementation plan; considering these factors we can more fully understand their impact on study outcomes

The Kalman-Bucy Filter for Integrable Levy Processes with Infinite Second Moment

We extend the Kalman-Bucy filter to the case where both the system and observation processes are driven by finite dimensional L´evy processes, but whereas the process driving the system dynamics is square-integrable, that driving the observations is not; however it remains integrable. The main result is that the components of the observation nose that have infinite variance make no contribution to the filtering equations. The key technique used is approximation by processes having bounded jumps

Recurrent deletions of ULK4 in schizophrenia : a gene crucial for neuritogenesis and neuronal motility

Peer reviewedPublisher PD

Spin flip from dark to bright states in InP quantum dots

We report measurements of the time for spin flip from dark (non-light emitting) exciton states in quantum dots to bright (light emitting) exciton states in InP quantum dots. Dark excitons are created by two-photon excitation by an ultrafast laser. The time for spin flip between dark and bright states is found to be approximately 200 ps, independent of density and temperature below 70 K. This is much shorter than observed in other quantum dot systems. The rate of decay of the luminescence intensity, approximately 300 ps, is not simply equal to the radiative decay rate from the bright states, because the rate of decay is limited by the rate of conversion from dark excitons into bright excitons. The dependence of the luminescence decay time on the spin flip time is a general effect that applies to many experiments.Comment: 3 figure

Genome-wide linkage analysis of 972 bipolar pedigrees using single-nucleotide polymorphisms.

Because of the high costs associated with ascertainment of families, most linkage studies of Bipolar I disorder (BPI) have used relatively small samples. Moreover, the genetic information content reported in most studies has been less than 0.6. Although microsatellite markers spaced every 10 cM typically extract most of the genetic information content for larger multiplex families, they can be less informative for smaller pedigrees especially for affected sib pair kindreds. For these reasons we collaborated to pool family resources and carried out higher density genotyping. Approximately 1100 pedigrees of European ancestry were initially selected for study and were genotyped by the Center for Inherited Disease Research using the Illumina Linkage Panel 12 set of 6090 single-nucleotide polymorphisms. Of the ~1100 families, 972 were informative for further analyses, and mean information content was 0.86 after pruning for linkage disequilibrium. The 972 kindreds include 2284 cases of BPI disorder, 498 individuals with bipolar II disorder (BPII) and 702 subjects with recurrent major depression. Three affection status models (ASMs) were considered: ASM1 (BPI and schizoaffective disorder, BP cases (SABP) only), ASM2 (ASM1 cases plus BPII) and ASM3 (ASM2 cases plus recurrent major depression). Both parametric and non-parametric linkage methods were carried out. The strongest findings occurred at 6q21 (non-parametric pairs LOD 3.4 for rs1046943 at 119 cM) and 9q21 (non-parametric pairs logarithm of odds (LOD) 3.4 for rs722642 at 78 cM) using only BPI and schizoaffective (SA), BP cases. Both results met genome-wide significant criteria, although neither was significant after correction for multiple analyses. We also inspected parametric scores for the larger multiplex families to identify possible rare susceptibility loci. In this analysis, we observed 59 parametric LODs of 2 or greater, many of which are likely to be close to maximum possible scores. Although some linkage findings may be false positives, the results could help prioritize the search for rare variants using whole exome or genome sequencing

Streaming and 3D mapping of agri-data on mobile devices

Farm monitoring and operations generate heterogeneous AGRI-data from a variety of different sources that have the potential to be delivered to users ‘on the go’ and in the field to inform farm decision making. A software framework capable of interfacing with existing web mapping services to deliver in-field farm data on commodity mobile hardware was developed and tested. This raised key research challenges related to: robustness of data steaming methods under typical farm connectivity scenarios, and mapping and 3D rendering of AGRI-data in an engaging and intuitive way. The presentation of AGRI-data in a 3D and interactive context was explored using different visualisation techniques; currently the 2D presentation of AGRI- data is the dominant practice, despite the fact that mobile devices can now support sophisticated 3D graphics via programmable pipelines. The testing found that WebSockets were the most reliable streaming method for high resolution image/texture data. From our focus groups there was no single visualisation technique that was preferred demonstrating that a range of methods is a good way to satisfy a large user base. Improved 3D experience on mobile phones is set to revolutionize the multimedia market and a key challenge is identifying useful 3D visualisation methods and navigation tools that support the exploration of data driven 3D interactive visualisation frameworks for AGRI-data