In South Africa, where access to mental health services is poor, the risk of developing mental health issues among children and adolescents is high. Accordingly, there is an urgent need to implement cost-, and time-effective interventions to address these issues in child-friendly, and child-accessible settings. Evidence suggests that CBT-based interventions have potential to mitigate the onset of mental illness by addressing symptoms of anxiety and depression in younger children, and thus may be considered primary preventative interventions. We aim to determine the acceptability and feasibility of a culturally-specific and context-sensitive CBT-based psychoeducational programme to support psychological well-being amongst children and adolescents (11-14 years) in an impoverished area of the Western Cape. As such, our study seeks to develop (using core CBT principles of existing evidence-based programmes) a school-based universal intervention to reduce symptoms of anxiety and depression amongst adolescents and to determine if this intervention is acceptable and can feasibly be delivered by NGO school-based counsellors. We will: - Develop a CBT-based intervention programme for anxiety and depression. - Train NGO counsellors to deliver and pilot the intervention to primarily establish feasibility and acceptability, and, as a secondary outcome, preliminary effectiveness at reducing symptoms of anxiety and depression. Mental health problems like anxiety and depression often begin in childhood. In developing countries, like South Africa, there is a lack of help available to young people who develop these problems. We know that treatments like Cognitive Behaviour Therapy (CBT) can be really helpful. We want to use the core principles of CBT to develop a mental health problem prevention programme that is appropriate and acceptable for young people in schools in South Africa. Counsellors would deliver the programme to young people (grades 5-7, age approximately 11-14 years). We will test whether our programme is possible to do in practice in two schools, and will get feedback from the young people, teachers, parents and counsellors. We will also measure anxiety and depression symptoms to see if they are less after treatment.

With this funding, we intend to fully automate radiotherapy for the treatment of acute oncological conditions such as severe pain, bleeding and neurological symptoms in patients with a diverse range of advanced cancers. These treatments, which are currently prepared manually, make up around 80% of the indications for radiotherapy in patients presenting for treatment in low- and middle-income countries. Our tools, which include artificial intelligence, will use automated quality assurance to ensure safe, effective, and timely treatments – minimizing reliance on manual checks which are time-consuming and can be inefficient. It is expected that patients can be treated very quickly after receiving a CT scan (minutes), rather than waiting days or weeks. Overall, this project is synergistic with ongoing work in our group focused on automating other radiotherapy planning tasks. Our goal is to make these services available as a cloud-based service for minimal cost for clinics in low- and middle-income countries to rapidly scale up and help deliver affordable and equitable cancer treatment. This supports the overall long term goal of making radiotherapy available to all patients who could benefit (both treating urgent and emergency presentations, as in this proposal, and curative treatments), irrespective of financial status. Radiotherapy is both inaccessible and unaffordable for the majority of patients diagnosed with cancer in low and middle income countries due to shortfalls in basic infrastructure, equipment and specialist manpower. Eighty-percent of patients in these settings are diagnosed with locally advanced or widely disseminated cancers. We will use artificial intelligence to automate radiotherapy plan preparation for acute oncological conditions in patients with a diverse range of advanced cancers that are endemic in these country settings such as cervical, breast and head and neck cancers. This will mean that patients can be treated very quickly after receiving a CT scan (10 minutes), rather than waiting days or weeks as is the current norm. This will directly benefit patients in LMICs by increasing the likelihood of palliating symptoms of disseminated malignancy (pain, bleeding, shortness of breath, spinal cord compression), improving long term control of cancer, and reducing the cost of treatment.

The mechanisms underlying drug resistance in M. tuberculosis are more complex than was initially proposed. Recent evidence has suggested that mechanisms in addition to gene mutations are involved in regulating the level (MIC) of drug resistance. However the molecular basis of such mechanisms in clinical isolates, where the selective pressure is quite different (and largely unknown) than in vitro generated mutants, remains to be determined. Rifampicin (RIF) is the cornerstone to first-line therap y and resistance to RIF is the gateway to MDR-TB and XDR-TB. This study aims to test the hypothesis that the MIC of RIF in RIF resistant clinical isolates of Mycobacterium tuberculosis is defined by mutations in addition to those in the rpoB gene and that these additional mutations control the intracellular concentration of RIF. Complimentary experimental strategies, namely whole genome sequencing, a candidate gene Q-RT PCR approach will be used in order to maximize the identification of genomi c targets and point mutagenesis to confirm the targets that regulate the intracellular concentration of rifampicin in clinical isolates of M. tuberculosis.