The New Labour government’s (1997-2010) policy of personalised learning was announced as an idea ‘exciting’ the profession and promising ‘radical implications’ for the shape of education in England. The policy attracted much debate and criticism and its enactment is a site worthy of research. This study makes a contribution to knowledge through researching the rarely heard stories of young people in this policy enactment. It makes a further contribution to policy scholarship through the interplay of the data from school practices and moral philosophy drawn from Alasdair MacIntyre.Qualitative interviews and focus group activities were conducted with young people in three different secondary schools in order to understand their stories of personalised learning some two years into New Labour’s third term of government. To understand more of the context for the stories of the young people, some strategic actors in policy dissemination were interviewed, as were the headteachers of the three schools.Personalised learning promised to engage the voice of the learner in learning practices. The research finds a young peoples’ story that is consistently one of a mute and invisible identity within the schools. An argument is presented that the purposes of schools ought to be judged on standards of excellence definitive of, and extended by, a concept of virtues. A distinction is made between effectiveness in producing exam results and a richer sense of excellence in education practice. It is argued that virtues that define standards of excellence at the institutional level of practice can enrich and prefigure wider concepts of justice than are contained in policy. Young peoples’ stories in this research indicate that, contrary to policy ideals, they often perceived unfairness and arbitrariness in their school experiences. Personalised learning needs to be set within the narrative of the personalisation of public services: a reforming rubric, employing the motif of the citizen-consumer as a proposition about social justice and modernisation. New Labour’s ideology and models of governance are explored and related to the testimony of headteachers to understand more about the young peoples’ perceptions. Literatures are drawn upon to place personalisation in a historical context, linking it to moral orders of contemporary social imaginaries. New Labour made a case for personalised learning as furthering the cause of social justice and is thus a policy in need of ethical examination. Following MacIntyre, it is argued that modernity has left few moral resources by which to evaluate the personal, but the experiences of young people suggested that a richer moral agency is glimpsed within their stories of schooling. The social practice at the level of schools is thus critical but requires policy to enable ethical spaces for schools to re-invigorate their purposes. I argue that in the light of some critical fault lines, such as neoliberalism and a reconfiguration of tiers of local governance, personalisation as a ‘modernising’ policy proposition could do little to extend the goods of schooling beyond some narrow conceptions of effectiveness.

A comprehensive molecular and phenotypic analysis of congenital and childhood cataractRachel L. Gillespie; The University of Manchester, Doctor of Philosophy, 2015Congenital and childhood cataract (CCC) is estimated to affect 3.5-6 per 10,000 children under 16 years in developed countries - a major cause of lifelong visual impairment. It is estimated that 25-50% of CCC cases are caused by genetic mutations. CCC demonstrates extreme heterogeneity with more than 100 associated genes, and may occur as an isolated anomaly of the eye (non-syndromic) or as a manifestation of a multisystem condition (syndromic). Limitations of conventional sequencing technologies have precluded precise genetic diagnosis and limited understanding of the epidemiological basis of the condition. Next generation sequencing (NGS) technologies have revolutionised the approach to the study of human disease. The aim of this research was to conduct a comprehensive molecular and phenotypic analysis of CCC using NGS.A disease-targeted NGS assay was designed to screen, in parallel, 115 genes associated with all forms of CCC. DNA from 36 patients, randomly selected from the study cohort, underwent cataract-targeted NGS. Putative cataract-causing variants were identified in 75% of individuals; 85% of non-syndromic patients and 63% of syndromic CCC patients. Cataract-targeted NGS was able to efficiently delineate disease sub-type and in some cases identified rare syndromic forms of the condition. These findings were envisaged to alter care and management of CCC patients demonstrating the potential clinical utility of the test. In a subset of cases, NGS identified CCC was a manifestation of an inborn error of metabolism. A number of these conditions were eligible for preventative treatment emphasizing the importance of early diagnosis. A strategic approach to the identification of novel recessive causes of CCC was also undertaken. Affected children from seven consanguineous families underwent pre-screening by cataract-targeted NGS to delineate those with mutations in known genes. Mutation negative patients underwent autozygosity-guided whole exome sequencing (WES) analysis. This strategic approach to disease gene discovery led to the identification three novel cataract-causing candidate genes, TRIM8, CCDC13 and GRWD1. It also led to the association of EIF2B2, known to cause adult-onset leukoencephalopathy with vanishing white matter (VWM) disease featuring pre-senile onset cataract, with childhood-onset cataract. This work demonstrated that cataract-targeted NGS offers an efficient and unbiased means of pre-screening, however, causation is difficult to assign to novel disease genes in the absence of experimental evidence. Correspondingly, in vitro analysis of a missense variant in HMX1 demonstrated the deleterious effect of the mutation on protein function. This work confirmed HMX1 as the cause of a rare oculoauricular phenotype and expanded the class of disease-causing mutations in this gene. In conclusion, this study has demonstrated that NGS is effective in the study of CCC and has provided a platform for future studies in to the genetic aetiology of the condition, as well as the molecular mechanisms underlying lens transparency and human development. The work adds to the increasing body of evidence that augurs an era of personalised genomic medicine in ophthalmology that will foresee improved patient outcomes attributable to the implementation of a stratified approach to medicine.

Cancer is a global health issue and is estimated to be the second leading cause of death worldwide. Within cancer treatment, it has become attractive to introduce precision medicine to harness the body’s own immune system to fight cancer. Personalised peptide cancer vaccine can activate the immune system and elicit an immune response by using the patient’s own blood and tumour cells.   The aim of this study was to gather information to better understand the production of individual-specific peptides and the challenges when producing these peptides with focus from a GMP perspective. The methodology for conducting this study and retrieve information for the result was gathered by three different data bases; EMA, European Commission and FDA, and by qualitative semi-structured interviews.   The findings show that these personalised peptides should be manufactured by using solid-phase peptide synthesis, cleavage from the resin, HPLC purification, and final salt exchange. The traditional GMP requirements must be used as a basis to build a pragmatic program. In terms of delivery time, the peptides can be delivered within a few weeks. The main challenges will be to manufacture successful peptides since the peptide sequences vary from patient to patient and due to that fact have different production efficacy, deliver within the set timeframe, and have flexibility in the manufacture process.   Multiple guidelines need to be followed in order to set up a process that consistently delivers the intended product. When producing oncology drugs on-demand it is essential to keep the timeline since the patients are severely ill. However, further studies are needed to determine how the manufacture of personalised peptides could be performed to harmonise with regulatory guidelines.

Abstract The majority of sports injuries involve the lower body, particularly the knees. Roughly 2,5 million people suffer a knee injury each year. Through sudden harsh movements the knee can get damaged. Often, these injuries never truly heal. Once the knee is weakened the risk of injury increases and in many cases the function of the knee will never fully return. The goal of this project was to empower patients who suffer from damage to the Anterior Cruciate Ligament (ACL) to recover faster by providing a personalized and humanized rehabilitation plan. Inspiration and Method Interviews, shadowing sessions and workshops were done with patients, athletes, surgeons and therapists to truly gain an in depth understanding of the rehabilitation process and how to prevent the injury from happening. This showed that there is a clear problem with the rehabilitation between the therapist and the patients. The outcome of the treatment is too much determined by the capabilities of the therapist, who often do not have enough expertise or get too little information to generate a personalized treatment for each individual. Another big problem is the fact that patients lose their motivation since they feel that they are not improving, and alone in the overall process. It became clear that patients need to be empowered and to let them know that the outcome of the rehabilitation is completely in their hands. Result The result of this collaboration is Ara, the smart rehabilitation bracelet. Ara continuously monitors the injured knee to provide an increased amount of insights, which enables practitioners to take humanized, and data driven decisions to personalize the rehabilitation plan for each individual. It empowers patients to take an active part in their own rehabilitation by providing live and precise feedback on their activities throughout the day.

No description available.

Background and Objectives: Economic evaluation and decision analysis provide a framework to evaluate incremental costs and effects associated with alternative health interventions. These methods can also be used as a tool to evaluate alternative clinical behaviours or practice patterns. The objective of this thesis was to investigate the impact of current Canadian practices in human epidermal growth factor receptor-2 (HER2) testing to target trastuzumab in early-stage breast cancer (BC). Methods: Project 1: A systematic review of previous trastuzumab and HER2 testing economic analyses was conducted to identify methodological gaps and key lessons. Project 2: A population-level, retrospective cohort was studied to determine HER2 testing and trastuzumab treatment patterns in Ontario early-stage BC patients. Project 3: A cost-utility analysis of alternative test-treat strategies was conducted using a Markov model of BC calibrated to the Canadian setting, and incorporating Project 2 findings. Results: Project 1: Previous economic evaluations demonstrated that HER2 test accuracy and sequencing were key considerations when modelling the cost-effectiveness of trastuzumab treatment. Consideration of local testing and treatment practices was lacking. Project 2: HER2 testing and treatment practice differed from guidelines, where documentation was available. Only 88% of equivocal results were confirmed, while 57% of HER2 positive patients received trastuzumab. Project 3: Calibration of the BC model minimised gaps between trial-based survival and expected Canadian survival patterns. Deviations from guidelines in practice suggest that primary testing with fluorescence in situ hybridization (FISH) would produce greater health gains at a reduced cost vs. primary immunohistochemistry with FISH confirmation. This finding was more apparent as the prevalence of HER2 positive disease increased. Introduction of newer in situ hybridisation tests may be cost-effective as well. Conclusions: Practice deviations from guidelines are an important consideration when modelling the cost-effectiveness of trastuzumab therapy. Underlying local disease progression and prevalence can also significantly impact outcomes. / Dissertation / Doctor of Philosophy (PhD)

No / This work aims to develop a personalised avatar based virtual environment for motivating weight loss and weight management. Obesity is a worldwide epidemic which has not only enormous resource impact for the healthcare systems but also has substantial health as well as a psychological effect among the individuals who are affected. We propose to tackle this issue via the development of a personalised avatar, the form of which can be adjusted to show the present and the future self of the individual. For the avatar design and development phase, we utilise a parametric based mathematical formulation derived from the solutions of a chosen elliptic partial differential equation. This method not only enables us to generate a parameterised avatar model, but it also allows us to quickly and efficiently create various avatar shapes corresponding to different body weights and even to different body postures. / This research was funded by the NIHR Research for Patient Benefit Programme (project reference PB-PG-1215-20016).

Yes / Despite the abundant use of polyethylene oxides (PEOs) and their integration as an excipient in numerous pharmaceutical products, there have been no previous reports of applying this important thermoplastic polymer species alone to fused deposition modelling (FDM) 3D printing. In this work, we have investigated the manufacture of oral doses via FDM 3D printing by employing PEOs as a backbone polymer in combination with polyethylene glycol (PEG). Blends of PEO (molecular weight 100 K, 200 K, 300 K, 600 K or 900 K) with PEG 6 K (plasticiser) and a model drug (theophylline) were hot-melt extruded. The resultant filaments were used as a feed for FDM 3D printer to fabricate oral dosage forms (ODFs) with innovative designs. ODFs were designed in a radiator-like geometry with connected paralleled plates and inter-plate spacing of either 0.5, 1, 1.5 or 2 mm. X-ray diffraction patterns of the filaments revealed the presence of two distinctive peaks at 2θ = 7° and 12°, which can be correlated to the diffraction pattern of theophylline crystals. Blends of PEO and PEG yielded filaments of variable mechanically resistance (maximum load at break of 357, 608, 649, 882, 781 N for filament produced with PEO 100 K, 200 K, 300 K, 600 K or 900 K, respectively). Filaments of PEO at a molecular weight of 200–600 K were compatible with FDM 3D printing process. Further increase in PEO molecular weight resulted in elevated shear viscosity (>104 Pa.S) at the printing temperature and hindered material flow during FDM 3D printing process. A minimal spacing (1 mm) between parallel plates of the radiator-like design deemed essential to boost drug release from the structure. This is the first report of utilising this widely used biodegradable polymer species (PEOs and PEG) in FDM 3D printing.

Yes / Appeals have been made for eye care professionals to start prescribing anti-myopia therapies as part of their routine management of myopic children. 1–3 These calls are fuelled by two key considerations. Firstly, that interventions to slow myopia progression have shown success in randomized controlled trials (RCTs) 4–7, and secondly, appreciation that the risk of sight-threatening complications rises dose-dependently with the level of myopia. 8,9 Notwithstanding existing gaps in knowledge regarding the efficacy of current treatments (see below), these considerations argue that myopia control interventions should be widely adopted, and that they should be instigated at an early age – especially in children most at risk – in order to reduce the final level of myopia. Therefore in managing a child with myopia, an eye care professional would have to decide not only which therapy to recommend, but at what age to start treatment. In this review we discuss the future role of genetic prediction in helping clinicians treat myopia. / NIHR Senior Research Fellowship. Grant Number: SRF‐2015‐08‐005

Yes / The notion of educating the public through generic healthy eating messages has pervaded dietary health promotion efforts over the years and continues to do so through various media, despite little evidence for any enduring impact upon eating behaviour. There is growing evidence, however, that tailored interventions such as those that could be delivered online can be effective in bringing about healthy dietary behaviour change. The present paper brings together evidence from qualitative and quantitative studies that have considered the public perspective of genomics, nutrigenomics and personalised nutrition, including those conducted as part of the EU-funded Food4Me project. Such studies have consistently indicated that although the public hold positive views about nutrigenomics and personalised nutrition, they have reservations about the service providers’ ability to ensure the secure handling of health data. Technological innovation has driven the concept of personalised nutrition forward and now a further technological leap is required to ensure the privacy of online service delivery systems and to protect data gathered in the process of designing personalised nutrition therapies.