Collective intelligence for translational medicine: Crowdsourcing insights and innovation from an interdisciplinary biomedical research community.

This is the author accepted manuscript. The final version is available from Taylor & Francis via http://dx.doi.org/10.3109/07853890.2015.1091945Translational medicine bridges the gap between discoveries in biomedical science and their safe and effective clinical application. Despite the gross opportunity afforded by modern research for unparalleled advances in this field, the process of translation remains protracted. Efforts to expedite science translation have included the facilitation of interdisciplinary collaboration within both academic and clinical environments in order to generate integrated working platforms fuelling the sharing of knowledge, expertise, and tools to align biomedical research with clinical need. However, barriers to scientific translation remain, and further progress is urgently required. Collective intelligence and crowdsourcing applications offer the potential for global online networks, allowing connection and collaboration between a wide variety of fields. This would drive the alignment of biomedical science with biotechnology, clinical need, and patient experience, in order to deliver evidence-based innovation which can revolutionize medical care worldwide. Here we discuss the critical steps towards implementing collective intelligence in translational medicine using the experience of those in other fields of science and public health

The Risk of West Nile Virus Infection Is Associated with Combined Sewer Overflow Streams in Urban Atlanta, Georgia, USA

BACKGROUND: At present, the factors favoring transmission and amplification of West Nile Virus (WNV) within urban environments are poorly understood. In urban Atlanta, Georgia, the highly polluted waters of streams affected by combined sewer overflow (CSO) represent significant habitats for the WNV mosquito vector Culex quinquefasciatus. However, their contribution to the risk of WNV infection in humans and birds remains unclear.\ud \ud OBJECTIVES: Our goals were to describe and quantify the spatial distribution of WNV infection in mosquitoes, humans, and corvids, such as blue jays and American crows that are particularly susceptible to WNV infection, and to assess the relationship between WNV infection and proximity to CSO-affected streams in the city of Atlanta, Georgia.\ud \ud MATERIALS AND METHODS: We applied spatial statistics to human, corvid, and mosquito WNV surveillance data from 2001 through 2007. Multimodel analysis was used to estimate associations of WNV infection in Cx. quinquefasciatus, humans, and dead corvids with selected risk factors including distance to CSO streams and catch basins, land cover, median household income, and housing characteristics.\ud \ud RESULTS: We found that WNV infection in mosquitoes, corvids, and humans was spatially clustered and statistically associated with CSO-affected streams. WNV infection in Cx. quinquefasciatus was significantly higher in CSO compared with non-CSO streams, and WNV infection rates among humans and corvids were significantly associated with proximity to CSO-affected streams, the extent of tree cover, and median household income.\ud \ud CONCLUSIONS: Our study strongly suggests that CSO-affected streams are significant sources of Cx. quinquefasciatus mosquitoes that may facilitate WNV transmission to humans within urban environments. Our findings may have direct implications for the surveillance and control of WNV in other urban centers that continue to use CSO systems as a waste management practice

Formulation and Bioequivalence Testing of Fixed-Dose Combination Orally Disintegrating Tablets for the Treatment of Tuberculosis in the Paediatric Population

Tuberculosis (TB) is believed to affect around 10 million people worldwide. Treatment for TB includes isoniazid and rifampicin, with fixed-dose combination (FDC) recommended for improved patient compliance. Similarly, orally disintegrating tablets (ODTs) are an increasingly popular dosage form that aid compliance since they do not require swallowing. In this study ODTs of isoniazid and rifampicin, either as discrete or FDC doses, were formulated and bioequivalence between single and combination doses compared using in vitro and in silico approaches. Dissolution profiles were compared using FDA advised difference (f 1) and similarity (f 2) testing in biorelevant media. Rifampicin release from FDCs decreased by approximately 15% in fed-state media (failed f 1 and f 2), which was attributed to enhanced rifampicin degradation in the presence of isoniazid at lower pH. Apparent permeability (P app) values derived from Caco-2 transport studies were included alongside dissolution results into a physiologically based pharmacokinetic (PBPK) model, to simulate in vivo bioavailability in healthy subjects. Models showed no difference in bioavailability between formulations or dosing (fasted or fed) state, despite the failures in dissolution-based bioequivalence testing, highlighting shortcomings in f 1 and f 2 assessment and the strength of PBPK models

Optimising surgical training in primary total hip replacement

Primary total hip replacement (THR) is one of the most performed and successful operations of the 21st Century. However, despite its prevalence and importance, no agreed teaching methods exist for THR overall, or for any of its key steps. Furthermore, little research has been conducted investigating the learning curve of trainees in THR or attempts made to optimise training in this operation using an evidence-based approach. This thesis aims to develop and evaluate novel simulation training methods to improve surgeon performance and patient outcomes in elective primary THR. A retrospective case series of 348 primary THR demonstrated that operative times and postoperative radiographs cannot be solely used in defining the learning curve and technical skills progression of specialty registrars (StRs) across a 6-month placement. Analysis of National Joint Registry data identified a recent trend for increased early and potentially avoidable revision operations following elective primary THR performed by unsupervised surgical trainees. This highlights the importance of appropriate supervision during trainee performed THR, and the need for continued improvements in training. Expert consensus methodology was used to deconstruct, define, and rank the key steps of a primary THR, and the results used to develop an evidence-based training module for surgical trainees. The impact of this module was then assessed in both simulated laboratory and clinical environments in a group of 34 orthopaedic trainees. A trend for improved knowledge acquisition and templating in THR was observed following simulation training, but no significant differences were observed in simulated skin incision marking, or component orientation tasks. Novel motion analysis techniques have been developed and validated for assessing the intra-operative technical skills performance of surgeons during primary THR. Trainees were significantly slower and performed more movements than consultants in most steps of this operation. However, no significant differences were observed in blood loss, transfusion requirements, patient-reported outcome measures, or post-operative radiographic parameters in relation to surgeon experience. These results support the safety and efficacy of supervised training in THR in relation to patient outcomes. No meaningful clinically important differences were observed in surgeon performance or patient outcome metrics following simulation training in trainee performed THR. However, the small number of trainee (n=7) and patient (n=52) participants in this study were notable limitations. This research fills an important gap in knowledge regarding how to best train surgeons in primary THR and has identified areas for targeted future improvement in training, which may ultimately benefit patients, trainers, and trainees. Organisations and individuals responsible for delivering surgical training should use the findings of this research to maximise the operative experience of trainees during clinical placements, ensure adequate intra-operative supervision, and consider the use and integration of both simulation training and objective metrics for training and assessing performance, competence, and progression through a training program

Validating the accuracy of a novel virtual reality platform for determining implant orientation in simulated primary total hip replacement

Introduction Accurate acetabular cup and femoral stem component orientation are critical for optimising patient outcomes, reducing complications and increasing component longevity following total hip replacement (THR). This study aimed to determine the accuracy of a novel virtual reality (VR) platform in assessing component orientation in a simulated THR model. Methods The VR platform (HTC Vive Pro® system hardware) was compared against the validated Vicon® optical motion capture (MoCap) system. An acetabular cup and femoral stem were manually implanted across a range of orientations into pelvic and femur sawbones, respectively. Simultaneous readings of the acetabular cup operative anteversion (OA) and inclination (OI) and femoral stem alignment (FSA) and neck anteversion (FNA) were obtained from the VR and MoCap systems. Statistical analysis was performed using Pearson product-moment correlation coefficient (PPMCC) (Pearson’s r) and linear regression (R 2 ). Results A total of 55 readings were obtained for the acetabular cup and 68 for the femoral stem model. The mean average differences in OA, OI, FSA and FNA between the systems were 3.44°, −0.01°, 0.01° and −0.04°, respectively. Strong positive correlations were demonstrated between both systems in OA, OI, FSA and FNA, with Pearson’s r = 0.92, 0.94, 0.99 and 0.99, and adjusted R 2  = 0.82, 0.9, 0.98 and 0.98, respectively. Conclusion The novel VR platform is highly accurate and reliable in determining both acetabular cup and femoral stem component orientations in simulated THR models. This adaptable and cost-effective digital tracking platform may be modified for use in a range of simulated surgical training and educational purposes, particularly in orthopaedic surgery