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Underachievement at GCSE level has significant effects on an individual's life chances. Each year, around half of 16-year-olds leave school without having achieved a full level-2 qualification (five GCSEs at A*-C including English and maths). Many of these students enrol on a programme of study at local further education (FE) colleges. Recent Coalition government reforms, including raising the participation age and compulsory English and Maths study up to aged 19, have reaffirmed FE as an agent to improve students' life chances and act as a catalyst to reduce youth unemployment. Further education colleges provide a "second chance" for learners who have failed at school. This research shows that students who have previously attended low-performing schools, arrive with low motivation, low levels of self-efficacy and a negative perception of education. Focus-group discussions with GCSE re-sit students studying at an FE college, followed by individual interviews, revealed that school experience of unprofessional teacher-pupil relationships, a lack of discipline, inconsistently applied sanctions, a lack of academic support and prevalent low-level disruption all contributed to demotivating the students. The data revealed that students' experience at college was significantly different when compared to secondary school. Professional and supportive relationships with teachers, classroom management strategies leading to learner ownership and autonomy, consistently applied behaviour management practices and visible senior leadership enabled learners to re-engage in education at FE and successfully re-sit their GCSE examinations.

In pediatric acute lymphoblastic leukemia (ALL), mutations/deletions affecting the TP53 gene are rare at diagnosis. However, at relapse about 12% of patients show TP53 aberrations, which are predictive of a very poor outcome. Since p53-mediated apoptosis is an endpoint for many cytotoxic drugs, loss of p53 function frequently leads to therapy failure. In this study we show that CRISPR/Cas9-induced loss of TP53 drives resistance to a large majority of drugs used to treat relapsed ALL, including novel agents such as inotuzumab ozogamicin. Using a high-throughput drug screen, we identified the histone deacetylase inhibitor romidepsin as a potent sensitizer of drug responsiveness, improving sensitivity to all chemotherapies tested. In addition, romidepsin improved the response to cytarabine in TP53-deleted ALL cells in vivo. Together, these results indicate that the histone deacetylase inhibitor romidepsin can improve the efficacy of salvage therapies for relapsed TP53-mutated leukemia. Since romidepsin has been approved for clinical use in some adult malignancies, these findings may be rapidly translated to clinical practice.