Co-morbidity burden in Parkinson’s disease : Comparison with controls and its influence on prognosis

Financial support This study was funded by Parkinson’s UK, the Scottish Chief Scientist Office, NHS Grampian endowments, the BMA Doris Hillier award, RS Macdonald Trust, the BUPA Foundation, and SPRING. The funders had no involvement in the study. Acknowledgements We acknowledge funding for the PINE study from Parkinson’s UK (G-0502, G-0914, G-1302), the Scottish Chief Scientist Office(CAF/12/05), the BMA Doris Hillier award, RS Macdonald Trust, the BUPA Foundation, NHS Grampian endowments and SPRING. We thank the patients and controls for their participation and the research staff who collected data and supported the study database.Peer reviewedPostprintPostprintPublisher PD

Medium-term prognosis of an incident cohort of parkinsonian patients compared to controls

Funding This work was supported by Parkinson's UK (grant numbers G0502, G0914), BMA Doris Hillier Award, the BUPA Foundation, NHS Grampian Endowments, RS MacDonald Trust.Peer reviewedPublisher PD

A review of Leptospermum scoparium (Myrtaceae) in New Zealand

Information about Leptospermum scoparium (Myrtaceae), the most widespread and important New Zealand indigenous shrub species, is reviewed. L. scoparium is a variable species, requiring more study of the genetically based differences between New Zealand populations and the affinity of these populations to Australian populations and other closely allied Australian species. Improved understanding of the species’ variation will assist both its conservation roles and economic uses, and the need to sustain genetically distinct varieties is emphasised. Ecologically, the species has a dominant role in infertile and poorly drained environments, and a wider occurrence as a seral shrub species in successions to forest where it may be regarded as a woody weed of pasture or a useful species for erosion control, carbon sesquestration, and vegetation restoration. The main economic products derived from the species are ornamental shrubs, essential oils, and honey. The species’ development as an ornamental plant and further definition of the pharmacologically active components are recommended as priority areas for research

Software fault characteristics: A synthesis of the literature

Faults continue to be a significant problem in software. Understanding the nature of these faults is important for practitioners and researchers. There are many published fault characteristics schemes but no one scheme dominates. Consequently it is difficult for practitioners to effectively evaluate the nature of faults in their software systems, and it is difficult for researchers to compare the types of faults found by different fault detection techniques. In this paper we synthesise previous fault characteristics schemes into one comprehensive scheme. Our scheme provides a richer view of faults than the previous schemes published and presents a comprehensive, unified approach which accommodates the many previous schemes. A characteristics-based view of faults should be considered by future researchers in the analysis of software faults and in the design and evaluation of new fault detection tools. We recommend that our fault characteristics scheme be used as a benchmark scheme

Publishing interim results of randomised clinical trials in peer-reviewed journals

Background: Interim analyses of randomised controlled trials are sometimes published before the final results are available. In several cases, the treatment effects were noticeably different after patient recruitment and follow-up completed. We therefore conducted a literature review of peer-reviewed journals to compare the reported treatment effects between interim and final publications and to examine the magnitude of the difference. Methods: We performed an electronic search of MEDLINE from 1990 to 2014 (keywords: ‘clinical trial’ OR ‘clinical study’ AND ‘random*’ AND ‘interim’ OR ‘preliminary’), and we manually identified the corresponding final publication. Where the electronic search produced a final report in which the abstract cited interim results, we found the interim publication. We also manually searched every randomised controlled trial in eight journals, covering a range of impact factors and general medical and specialist publications (1996–2014). All paired articles were checked to ensure that the same comparison between interventions was available in both. Results: In all, 63 studies are included in our review, and the same quantitative comparison was available in 58 of these. The final treatment effects were smaller than the interim ones in 39 (67%) trials and the same size or larger in 19 (33%). There was a marked reduction, defined as a ≥20% decrease in the size of the treatment effect from interim to final analysis, in 11 (19%) trials compared to a marked increase in 3 (5%), p = 0.057. The magnitude of percentage change was larger in trials where commercial support was reported, and increased as the proportion of final events at the interim report decreased in trials where commercial support was reported (interaction p = 0.023). There was no evidence of a difference between trials that stopped recruitment at the interim analysis where this was reported as being pre-specified versus those that were not pre-specified (interaction p = 0.87). Conclusion: Published interim trial results were more likely to be associated with larger treatment effects than those based on the final report. Publishing interim results should be discouraged, in order to have reliable estimates of treatment effects for clinical decision-making, regulatory authority reviews and health economic analyses. Our work should be expanded to include conference publications and manual searches of additional journal publications

Gene therapy for inherited metabolic diseases

Over the last two decades, gene therapy has been successfully translated to many rare diseases. The number of clinical trials is rapidly expanding and some gene therapy products have now received market authorisation in the western world. Inherited metabolic diseases (IMD) are orphan diseases frequently associated with a severe debilitating phenotype with limited therapeutic perspective. Gene therapy is progressively becoming a diseasechanging therapeutic option for these patients. In this review, we aim to summarise the development of this emerging field detailing the main gene therapy strategies, routes of administration, viral and non-viral vectors and gene editing tools. We discuss the respective advantages and pitfalls of these gene therapy strategies and review their application in IMD, providing examples of clinical trials with lentiviral or adeno-associated viral gene therapy vectors in rare diseases. The rapid development of the field and implementation of gene therapy as a realistic therapeutic option for various IMD in a short term also require a good knowledge and understanding of these technologies from physicians to counsel the patients at best

A framework for the simulation of structural software evolution

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2008 ACM.As functionality is added to an aging piece of software, its original design and structure will tend to erode. This can lead to high coupling, low cohesion and other undesirable effects associated with spaghetti architectures. The underlying forces that cause such degradation have been the subject of much research. However, progress in this field is slow, as its complexity makes it difficult to isolate the causal flows leading to these effects. This is further complicated by the difficulty of generating enough empirical data, in sufficient quantity, and attributing such data to specific points in the causal chain. This article describes a framework for simulating the structural evolution of software. A complete simulation model is built by incrementally adding modules to the framework, each of which contributes an individual evolutionary effect. These effects are then combined to form a multifaceted simulation that evolves a fictitious code base in a manner approximating real-world behavior. We describe the underlying principles and structures of our framework from a theoretical and user perspective; a validation of a simple set of evolutionary parameters is then provided and three empirical software studies generated from open-source software (OSS) are used to support claims and generated results. The research illustrates how simulation can be used to investigate a complex and under-researched area of the development cycle. It also shows the value of incorporating certain human traits into a simulation—factors that, in real-world system development, can significantly influence evolutionary structures

Incidence and risk factors of institutionalisation in Parkinson's disease and atypical parkinsonism

Open Access via the Elsevier Agreement We would like to thank the patients for their participation and the research staff who collected data and supported the study database. The PINE study was funded by Parkinson's UK (grant numbers G0502, G0914, and G1302), the Scottish Chief Scientist Office (CAF/12/05, PCL/17/10), NHS Grampian endowments, the BMA Doris Hillier award, RS Macdonald Trust, the BUPA Foundation and SPRING. Yan Li is funded by a studentship from the Meikle Foundation.Peer reviewedPublisher PD