The application of metrics to industrial prototyping processes: An empirical study

A key problem in the development of information systems is understanding features of the development process. To this end, in recent years, considerable interest has been focused on modelling processes. In this paper, the results of an empirical investigation into the use of prototyping in information systems development is described. Nine prototyping processes across eight different sites of varying size were analysed and data relating to each process collected. The notation of Role Activity Diagrams (RADs) was used to capture each of the nine processes. Analysis of the interactions in each process revealed that the project manager interacted with the prototyper far more often in large developments than in small or medium-sized developments. However, significantly more interactions between the project manager and end-user were found in small-sized developments than for any other sized site. The study demonstrates how measures of business models can aid analysis of the process rather than the product and highlights the need for more empirical investigation into this and other facets of the development process. A number of lessons have been learnt from our analysis; these we also explain

An empirical study of evolution of inheritance in Java OSS

Previous studies of Object-Oriented (OO) software have reported avoidance of the inheritance mechanism and cast doubt on the wisdom of ‘deep’ inheritance levels. From an evolutionary perspective, the picture is unclear - we still know relatively little about how, over time, changes tend to be applied by developers. Our conjecture is that an inheritance hierarchy will tend to grow ‘breadth-wise’ rather than ‘depth-wise’. This claim is made on the basis that developers will avoid extending depth in favour of breadth because of the inherent complexity of having to understand the functionality of superclasses. Thus the goal of our study is to investigate this empirically. We conduct an empirical study of seven Java Open-Source Systems (OSSs) over a series of releases to observe the nature and location of changes within the inheritance hierarchies. Results show a strong tendency for classes to be added at levels one and two of the hierarchy (rather than anywhere else). Over 96% of classes added over the course of the versions of all systems were at level 1 or level 2. The results suggest that changes cluster in the shallow levels of a hierarchy; this is relevant for developers since it indicates where remedial activities such as refactoring should be focused

Anticoagulants for acute ischaemic stroke

Peer reviewedPublisher PD

Using Counts as Heuristics for the Analysis of Static Models

The upstream activities of software development are often viewed as both the most important, in terms of cost, and the yet the least understood, and most problematic, particularly in terms of satisfying customer requirements. Business process modelling is one solution that is being increasingly used in conjunction with traditional software development, often feeding in to requirements and analysis activities. In addition, research in Systems Engineering for Business Process Change, highlights the importance of modelling business processes in evolving and maintaining the legacy systems that support those processes. However, the major use of business process modelling, is to attempt to restructure the business process, in order to improve some given aspect, e.g., cost or time. This restructuring may be seen either as separate activity or as a pre-cursor to the development of systems to support the new or improved process. Hence, the analysis of these business models is vital to the improvement of the process, and as a consequence to the development of supporting software systems. Supporting this analysis is the focus of this paper. Business processes are typically described with static (diagrammatic) models. This paper proposes the use of measures (counts) to aid analysis and comparison of these static process descriptions. The proposition is illustrated by showing how measures can be applied to a commonly used process-modelling notation, Role Activity Diagrams (RADs). Heuristics for RADs are described and measures suggested which support those heuristics. An example process is used to show how a coupling measure can be used to highlight features in RADs useful to the process modeller. To fully illustrate the proposition the paper describes and applies a framework for the theoretical validation of the coupling measure. An empirical evaluation follows. This is illustrated by two case studies; the first based on the bidding process of a large telecommunications systems supplier, and the second a study of ten prototyping processes across a number of organisations. These studies found that roles of the same type exhibited similar levels of coupling across processes. Where roles did not adhere to tentative threshold values, further investigation revealed unusual circumstances or hidden behaviour. Notably, study of the prototyping roles, which exhibited the greatest variation in coupling, found that coupling was highly correlated with the size of the development team. This suggests that prototyping in large projects had a different process to that for small projects, using more mechanisms for communication. Hence, the empirical studies support the view that counts (measures) may be useful in the analysis of static process models

Effects of Mini-Dystrophin on Dystrophin-Deficient, Human Skeletal Muscle-Derived Cells

BACKGROUND: We are developing a novel therapy for Duchenne muscular dystrophy (DMD), involving the transplantation of autologous, skeletal muscle-derived stem cells that have been genetically corrected to express dystrophin. Dystrophin is normally expressed in activated satellite cells and in differentiated muscle fibres. However, in past preclinical validation studies, dystrophin transgenes have generally been driven by constitutive promoters that would be active at every stage of the myogenic differentiation process, including in proliferating muscle stem cells. It is not known whether artificial dystrophin expression would affect the properties of these cells. AIMS: Our aims are to determine if mini-dystrophin expression affects the proliferation or myogenic differentiation of DMD skeletal muscle-derived cells. METHODS: Skeletal muscle-derived cells from a DMD patient were transduced with lentivirus coding for mini-dystrophins (R3-R13 spectrin-like repeats (ΔR3R13) or hinge2 to spectrin-like repeats R23 (ΔH2R23)) with EGFP (enhanced green fluorescence protein) fused to the C-terminus, driven by a constitutive promoter, spleen focus-forming virus (SFFV). Transduced cells were purified on the basis of GFP expression. Their proliferation and myogenic differentiation were quantified by ethynyl deoxyuridine (EdU) incorporation and fusion index. Furthermore, dystrophin small interfering ribonucleic acids (siRNAs) were transfected to the cells to reverse the effects of the mini-dystrophin. Finally, a phospho-mitogen-activated protein kinase (MAPK) array assay was performed to investigate signalling pathway changes caused by dystrophin expression. RESULTS: Cell proliferation was not affected in cells transduced with ΔR3R13, but was significantly increased in cells transduced with ΔH2R23. The fusion index of myotubes derived from both ΔR3R13- and ΔH2R23 -expressing cells was significantly compromised in comparison to myotubes derived from non-transduced cells. Dystrophin siRNA transfection restored the differentiation of ΔH2R23-expressing cells. The Erk1/2- signalling pathway is altered in cells transduced with mini-dystrophin constructs. CONCLUSIONS: Ectopic expression of dystrophin in cultured human skeletal muscle-derived cells may affect their proliferation and differentiation capacity. Caution should be taken when considering genetic correction of autologous stem cells to express dystrophin driven by a constitutive promoter

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

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

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