A new role for Biofoundries in rapid prototyping, development, and validation of automated clinical diagnostic tests for SARS-CoV-2

The SARS-CoV-2 pandemic has shown how the rapid rise in demand for patient and community sample testing, required for tracing and containing a highly infectious disease, has quickly overwhelmed testing capability globally. With most diagnostic infrastructure dependent on specialised instruments, their exclusive reagent supplies quickly become bottlenecks in times of peak demand, creating an urgent need for novel approaches to boost testing capacity. We address this challenge by refocusing the full synthetic biology stack available at the London Biofoundry onto the development of alternative patient sample testing pipelines. We present a reagent-agnostic automated SARS-CoV-2 testing platform that can be quickly deployed and scaled, and that accepts a diverse range of reagents. Using an in-house-generated, open-source, MS2-virus-like-particle-SARS-CoV-2 standard, we validate RNA extraction and RT-qPCR workflows as well as two novel detection assays based on CRISPR-Cas and Loop-mediated isothermal Amplification (LAMP) approaches. In collaboration with an NHS diagnostic testing lab, we report the performance of the overall workflow and benchmark SARS-CoV-2 detection in patient samples via RT-qPCR, CRISPR-Cas, and LAMP against clinical test sets. The validated RNA extraction and RT-qPCR platform has been installed in NHS diagnostic labs with a testing capacity of 1000 samples per day and now contributes to increased patient sample processing in the UK while we continue to refine and develop novel high-throughput diagnostic methods. Finally, our workflows and protocols can be quickly implemented and adapted by members of the Global Biofoundry Alliance and the wider scientific and medical diagnostics community.

A manual-based vocational rehabilitation program for patients with an acquired brain injury: study protocol of a pragmatic randomized controlled trial (RCT).

BACKGROUND: An acquired brain injury (ABI) is a complex injury often followed by a broad range of cognitive, physical, emotional, and behavioral disabilities. Because of these disabilities, vocational rehabilitation (VR) is a challenging task, however, of great importance, since approximately 75% of the patients with ABI are of working age. Thus, standardized clinically effective and cost-effective methodologies regarding VR for patients with ABI are highly needed. Therefore, the aim of this study is to evaluate the effect of an individually targeted manual-based VR for patient with ABI compared to conventional VR (usual care). METHODS: This study is an interventional, two-arm, six-month follow-up, cluster randomized controlled trial involving four municipalities in the Zealand Region and the Capital Region of Denmark. A total of 84 patients with ABI evenly distributed across four municipalities will be included in the study. The patients will randomly be allocated in a 1:1 ratio to the VR intervention provided by a specialized Brain Injury Centre or the conventional VR provided by the municipalities (usual care). The six- to nine-month intervention will consist of individual and group therapies as well as a work placement program including supported employment. Furthermore, the intervention will include a family intervention program followed up by support to one individual family caregiver. The primary outcomes are increased work or study rate at six-month follow-up. Moreover, a budget impact analysis and possibly a cost-utility analysis of the intervention will be performed. DISCUSSION: This study consists of a comprehensive multidiciplinary VR intervention involving several parties such as the municipalities, a specialized rehabilitation team, and patients' own family caregivers. If this intervention is proven successful when compared to the conventional VR, it will provide evidence for a manual-based individualized holistic approach in returning to work after an ABI. Furthermore, the study will contribute with novel knowledge regarding feasibility and clinical effectiveness of the VR intervention relevant to clinicians, researchers, and policymakers. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03086031 . Registered on 21 March 2017.

Problems with balance and binocular visual dysfunction are associated with post-stroke fatigue.

BACKGROUND: Fatigue after stroke is hard to define and measure and how it is associated with other complications after stroke still needs to be explored. These issues are relevant in stroke rehabilitation and in the patient's daily life. OBJECTIVE: To investigate fatigue after stroke and its relation to balance, gait, and Binocular Visual Dysfunction (BVD). METHODS: Adults with stroke (n = 29, age 18-67 years) were tested with the Modified Fatigue Impact Scale (MFIS), objective and subjective BVD measures, Balance Evaluation Systems Test, Ten Meter Walk Test, and a Health-Related Quality of Life questionnaire, before and after a four-month intervention program and at three- and six-month follow-ups. We used principle component analysis to extract underlying factors of MFIS. Associations between MFIS factors and patient characteristics were analyzed by repeated measures ANOVA. The associations between MFIS factors and physical measures were assessed using pairwise correlations. RESULTS: Three components were extracted from the MFIS, explaining 71% of variance: Cognitive fatigue, Physical fatigue and Arousal. We found that women register higher MFIS scores than men. There was a strong association between the level of Cognitive and Physical Fatigue and BVD, between Arousal and balance and dizziness, and between Cognitive Fatigue and gait. CONCLUSION: The three extracted components of MFIS proved clinically informative. The arousal component revealed particularly interesting results in studying fatigue. The correlation analysis shown at this component differs from cognitive and physical fatigue and describes another aspect of PSF, important in future treatment and research.