On Optimal Multiple Changepoint Algorithms for Large Data

There is an increasing need for algorithms that can accurately detect changepoints in long time-series, or equivalent, data. Many common approaches to detecting changepoints, for example based on penalised likelihood or minimum description length, can be formulated in terms of minimising a cost over segmentations. Dynamic programming methods exist to solve this minimisation problem exactly, but these tend to scale at least quadratically in the length of the time-series. Algorithms, such as Binary Segmentation, exist that have a computational cost that is close to linear in the length of the time-series, but these are not guaranteed to find the optimal segmentation. Recently pruning ideas have been suggested that can speed up the dynamic programming algorithms, whilst still being guaranteed to find true minimum of the cost function. Here we extend these pruning methods, and introduce two new algorithms for segmenting data, FPOP and SNIP. Empirical results show that FPOP is substantially faster than existing dynamic programming methods, and unlike the existing methods its computational efficiency is robust to the number of changepoints in the data. We evaluate the method at detecting Copy Number Variations and observe that FPOP has a computational cost that is competitive with that of Binary Segmentation.Comment: 20 page

Organisational development in general practice: lessons from practice and professional development plans (PPDPs)

BACKGROUND: Improving the quality and effectiveness of clinical practice is becoming a key task within all health services. Primary medical care, as organised in the UK is composed of clinicians who work in independent partnerships (general practices) that collaborate with other health care professionals. Although many practices have successfully introduced innovations, there are no organisational development structures in place that support the evolution of primary medical care towards integrated care processes. Providing incentives for attendance at passive educational events and promoting 'teamwork' without first identifying organisational priorities are interventions that have proved to be ineffective at changing clinical processes. A practice and professional development plan feasibility study was evaluated in Wales and provided the experiential basis for a summary of the lessons learnt on how best to guide organisational development systems for primary medical care. RESULTS: Practice and professional development plans are hybrids produced by the combination of ideas from management (the applied behavioural science of organisational development) and education (self-directed adult learning theories) and, in conceptual terms, address the lack of effectiveness of passive educational strategies by making interventions relevant to identified system wide needs. In the intervention, each practice participated in a series of multidisciplinary workshops (minimum 4) where the process outcome was the production of a practice development plan and a set of personal portfolios, and the final outcome was a realised organisational change. It was apparent during the project that organisational admission to a process of developmental planning needed to be a stepwise process, where initial interest can lead to a fuller understanding, which subsequently develops into motivation and ownership, sufficient to complete the exercise. The advantages of introducing expert external facilitation were clear: evaluations of internal group processes were possible, strategic issues could be raised and explored and financial probity ensured. These areas are much more difficult to examine when only internal stakeholders are engaged in a planning process. CONCLUSIONS: It is not possible to introduce practice and professional development plans (organisational development and organisational learning projects) in a publicly funded health care system without first addressing existing educational and management structures. Existing systems are based on educational credits for attendance and emerging accountability frameworks (criteria checklists) for clinical governance. Moving to systems that are less summative and more formative, and based on the philosophies of continual quality improvement, require changes to be made in the relevant support systems in order achieve policy proposals

The chick as an animal model of eye disease

A diverse range of chicken lines harbouring highly-penetrant, spontaneously-occurring mutations with an ocular phenotype have been identified over the past 40 years. These lines serve as models for human monogenic disorders including ocular albinism, retinal dystrophies such as Leber's congenital amaurosis, and coloboma, as well as the common complex traits glaucoma and myopia. Recent technical advances in gene targeting, mapping quantitative trait loci, and phenotypic characterisation of eye phenotypes offer exciting prospects for exploiting chicken genomic resources in fundamental and translational eye research

Mutation in the guanine nucleotide-binding protein beta-3 causes retinal degeneration and embryonic mortality in chickens

PURPOSE. To identify the gene defect that causes blindness and the predisposition to embryonic death in the retinopathy globe enlarged (rge) chicken. METHODS. Linkage analysis, with previously uncharacterized microsatellite markers from chicken chromosome 1, was performed on 138 progeny of an rge/+ and an rge/rge cross, and candidate genes were sequenced. RESULTS. The rge locus was refined and the gene for guanine nucleotide-binding protein β-3 (GNB3), which encodes a cone transducin β subunit, was found to have a 3-bp deletion (D153del) that segregated with the rge phenotype. This mutation deleted a highly conserved aspartic acid residue in the third of seven WD domains in GNB3. In silico modeling suggested that this mutation destabilized the protein. Furthermore, a 70% reduction was found in immunoreactivity to anti-GNB3 in the rge-affected retina. CONCLUSIONS. These findings implicate the β-subunit of cone transducin as the defective protein underlying the rge phenotype. Furthermore, GNB3 is ubiquitously expressed, and the c.825C→T GNB3 splicing variant (MIM 139130) has been associated with hypertension, obesity, diabetes, low birth weight, coronary heart disease, and stroke in the human population. It therefore seems likely that the defect underlying these human diseases also causes reduced embryonic viability in the rge chicken, making it a powerful model for studying the pathology involved in these associations

Practice and professional development plans (PPDPs): results of a feasibility study

BACKGROUND: Dissatisfaction with uniprofessional education structures as a means of improving the quality of healthcare has led to proposals to develop ways of integrating professional learning and organisational development. AIMS: Test the feasibility of introducing practice and professional development plans using a centrally sponsored project in Wales. DESIGN: Qualitative observational study. STUDY SAMPLE: All 541 practices in Wales were alerted to the project and invited to apply. A selection process was suggested to Health Authorities but not always efficiently conducted: 23 practices were selected and 18 participated in the process. METHOD: Central funding was made available to health authorities. The project framework was designed by an educational department and conceptualised as the development of personal portfolios linked to one key organisation change in each practice, facilitated by external consultants who would typically hold workshops or other events. An independent researcher using non-participant observation techniques at workshops and practices undertook documentary analysis and fieldwork in four health authorities. RESULTS: Difficulties were encountered with the process of implementing the project: marketing and practice selection inconsistencies delayed the work and it was difficult to recruit practices into the project. The lack of experienced individuals to do the work and practitioner suspicion about perceived 'management' agendas were significant problems. After initial hesitancies most practices appreciated the value of developing wider ownership and commitment to proposed practice changes. Organisations found it difficult to support individual completion of the personal portfolio component of the plans. The ability to develop systems for clinical services was dependent on having already established a culture of effective teamwork in the organisation. CONCLUSIONS: This work supports the view that organisational development has considerable potential for bringing about effective change, and individual contributions could form a valuable component of personal portfolios. We believe that the existing structures in education and management in the health service are not yet able to support these processes. Evidence from the fields of risk management and quality improvement all point to the need to develop effective organisational systems and the results of this feasibility study indicate that alternative models of sustaining organisational development need careful evaluation