Potential Market for Novel Tuberculosis Diagnostics: Worth the Investment?

Background. The potential available market (PAM) for new diagnostics for tuberculosis that meet the specifications of the high-priority target product profiles (TPPs) is currently unknown. Methods. We estimated the PAM in 2020 in 4 high-burden countries (South Africa, Brazil, China, and India) for tests that meet the specifications outlined in the TPPs. The yearly PAM was estimated for the most likely application of each TPP. Results. In 2020 the PAM for all 4 countries together was estimated to be (1) 12M tests/year with a value of 48M-71M USD for a sputum smear-replacement test; (2) 16M tests/year with a value of 65M-97M USD for a biomarker test; (3) 18M tests/year with a value of 18M-35M USD for a triage test; (4) 12M tests/year with a value of 59M-2238M USD for a tuberculosis detection plus drug susceptibility test (DST) all-in-one or 1.5M tests/year for a DST that follows a positive tuberculosis detection test with a corresponding value of 75M-121M for both tuberculosis detection and DST. Conclusions. Although there is a considerable potential market for novel tuberculosis diagnostics that fit the specification of the TPPs in the 4 high-burden countries, the actual market for an individual product remains uncertai

Pragmatic cluster randomised controlled trial of contextualised grammar teaching and small group teaching to improve the writing skills of 11 year old children

Introduction: We evaluated two interventions: a contextualised grammar teaching intervention – Grammar for Writing - to assess whether it improved 11 year old children’s writing skills; and a small group literacy intervention to assess whether or not this was effective. Design and method: We used a pragmatic cluster randomised trial with partial split plot design. Independent concealed randomisation was undertaken at the class level, and, within the intervention group, children were also individually randomised to receive the whole class intervention plus a small group intervention or to receive the intervention in a whole class setting only. The main outcomes were writing and reading assessed by the Progress in English 11 (Long Form) test (GL Assessment). Results: In 2013, 55 schools in England, each with two classes, were recruited and randomised. Within each school, the two classes were randomly allocated to receive either the intervention or the control condition. After randomisation, 2 schools withdrew, leaving 53 schools, 106 classes and 2510 pupils. We observed an effect size (ES) of 0.10 favouring the Grammar for Writing classes; however, this was not statistically significant (95% confidence interval (CI) -0.10 to 0.31). Pupils randomised to the small groups had an increased literacy score when compared with the control classes (ES = 0.24, 95% CI 0.00 to 0.49) and when compared with the intervention children taught in the whole class (ES = 0.21, 95% CI 0.04 to 0.38). Conclusion: There is little evidence that this form of contextualised grammar teaching had an effect on 11 year old children’s writing skills. There was some evidence of an effect for small group teaching

Scottish Medical Imaging Service:Technical and Governance controls

Objectives The Scottish Medical Imaging (SMI) service provides linkable, population based, “research-ready” real-world medical images for researchers to develop or validate AI algorithms within the Scottish National Safe Haven. The PICTURES research programme is developing novel methods to enhance the SMI service offering through research in cybersecurity and software/data/infrastructure engineering. Approach Additional technical and governance controls were required to enable safe access to medical images. The researcher is isolated from the rest of the trusted research environment (TRE) using a Project Private Zone (PPZ). This enables researchers to build and install their own software stack, and protects the TRE from malicious code. Guidelines are under development for researchers on the safe development of algorithms and the expected relationship between the size of the model and the training dataset. There is associated work on the statistical disclosure control of models to enable safe release of trained models from the TRE. Results A policy enabling the use of “Non-standard software” based on prior research, domain knowledge and experience gained from two contrasting research studies was developed.  Additional clauses have been added to the legal control – the eDRIS User Agreement – signed by each researcher and their Head of Department.  Penalties for attempting to import or use malware, remove data within models or any attempt to deceive or circumvent such controls are severe, and apply to both the individual and their institution. The process of building and deploying a PPZ has been developed allowing researchers to install their own software. No attempt has yet been made to add additional ethical controls; however, a future service development could be validating the performance of researchers’ algorithms on our training dataset. Conclusion The availability to conduct research using images poses new challenges and risks for those commissioning and operating TREs. The Private Project Zone and our associated governance controls are a huge step towards supporting the needs of researchers in the 21st century

The promoter from SlREO, a highly-expressed, root-specific Solanum lycopersicum gene, directs expression to cortex of mature roots

Root-specific promoters are valuable tools for targeting transgene expression, but many of those already described have limitations to their general applicability. We present the expression characteristics of SlREO, a novel gene isolated from tomato (Solanum lycopersicum L.). This gene was highly expressed in roots but had a very low level of expression in aerial plant organs. A 2.4-kb region representing the SlREO promoter sequence was cloned upstream of the uidA GUS reporter gene and shown to direct expression in the root cortex. In mature, glasshouse-grown plants this strict root specificity was maintained. Furthermore, promoter activity was unaffected by dehydration or wounding stress but was somewhat suppressed by exposure to NaCl, salicylic acid and jasmonic acid. The predicted protein sequence of SlREO contains a domain found in enzymes of the 2-oxoglutarate and Fe(II)-dependent dioxygenase superfamily. The novel SlREO promoter has properties ideal for applications requiring strong and specific gene expression in the bulk of tomato root tissue growing in soil, and is also likely to be useful in other Solanaceous crop

TRE-FX:Delivering a federated network of trusted research environments to enable safe data analytics

Trusted Research Environments (TREs) are secure locations in which data are placed for researchers to analyse. TREs host administrative data, hospital data or any other data that needs to remain securely isolated, but it is hard for a researcher to perform an analysis across multiple TREs, requesting and gathering the outputs from each one. This is a common problem in the UK's devolved healthcare system of geographical and governance boundaries. There are different ways of implementing TREs and the analysis tools that use them. A solution must be straightforward for existing, independent systems to adopt, must cope with the variety of system implementations, and must work within the "Five Safes" framework that enables data services to provide safe research access to data. TRE-FX assembled leading infrastructure researchers, analysis tool makers, TRE providers and public engagement specialists to streamline the exchange of data requests and results. The "Five Safes RO-Crate" standard packages up (Crates) the Objects needed for Research requests and results with the information needed for the tools and TRE providers to ensure that the crates are reviewed and processed according to Five Safes principles. TRE-FX showed how this works using software components and an end-to-end demonstrator implemented by a TRE in Wales. Two other TREs, in Scotland and England, are preparing to follow suit. Two analysis tool providers (Bitfount and DataSHIELD) modified their systems to use the RO-Crates. The next step is practical implementation as part of the HDR UK programme. Two large European projects will develop the approach further. TRE-FX shows that it is possible to streamline how analysis tools access multiple TREs while enabling the TREs to ensure that the access is safe. The approach scales as more TREs are added and can be adopted by established systems. Researchers will then be able to perform an analysis across multiple TREs much more easily, widening the scope of their research and making more effective use of the UK's data. If we had had this for COVID-19 data analysis, it would have super-charged researchers to be able to quickly answer pressing questions across the UK. This work was funded by UK Research & Innovation [Grant Number MC_PC_23007] as part of Phase 1 of the DARE UK (Data and Analytics Research Environments UK) programme, delivered in partnership with Health Data Research UK (HDR UK) and Administrative Data Research UK (ADR UK)

Affordable online maths tuition: evaluation report and executive summary

No description supplie

Online maths tuition: trial protocol

No description supplie