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

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

Resource allocation and feedback in wireless multiuser networks

This thesis focuses on the design of algorithms for resource allocation and feedback in wireless multiuser and heterogeneous networks. In particular, three key design challenges expected to have a major impact on future wireless networks are considered: cross-layer scheduling; structured quantization codebook design for MU-MIMO networks with limited feedback; and resource allocation to provide physical layer security. The first design challenge is cross-layer scheduling, where policies are proposed for two network architectures: user scheduling in single-cell multiuser networks aided by a relay; and base station (BS) scheduling in CoMP. These scheduling policies are then analyzed to guarantee satisfaction of three performance metrics: SEP; packet delay; and packet loss probability (PLP) due to buffer overflow. The concept of the τ-achievable PLP region is also introduced to explicitly describe the tradeoff in PLP between different users. The second design challenge is structured quantization codebook design in wireless networks with limited feedback, for both MU-MIMO and CoMP. In the MU-MIMO network, two codebook constructions are proposed, which are based on structured transformations of a base codebook. In the CoMP network, a low-complexity construction is proposed to solve the problem of variable codebook dimensions due to changes in the number of coordinated BSs. The proposed construction is shown to have comparable performance with the standard approach based on a random search, while only requiring linear instead of exponential complexity. The final design challenge is resource allocation for physical layer security in MU-MIMO. To guarantee physical layer security, the achievable secrecy sum-rate is explicitly derived for the regularized channel inversion (RCI) precoder. To improve performance, power allocation and precoder design are jointly optimized using a new algorithm based on convex optimization techniques

An exploration of the challenges facing developers of affordable dwellings following low carbon and ecological principles, in rural locations in Wales

This paper discusses the challenges in developing ecological, low carbon and affordable dwellings in rural areas of Wales; since much of the funding in the UK is often focused on urban development. The Welsh Assembly Government (WAG) is committed to the aim that the construction of new homes moves towards zero carbon as soon as possible. There is a need to ensure that this strategy recognises that one size does not fit all; and understanding and addressing these issues will be fundamental if WAG objectives are too achieved in rural areas. This paper discusses a three year research project, which commenced in autumn 2010 in collaboration with the University of Wales Institute Cardiff (UWIC) and Pembrokeshire Housing Association (PHA), a registered social landlord and developer of affordable dwellings; to create a development model for affordable, low carbon, ecological rural dwellings to achieve WAG targets. This paper will be of use to rural developers, designers and architects

Two approaches to developing low carbon dwellings in west Wales

In October 2010 Pembrokeshire Housing Association (PHA) completed a development of six residential units, in Pembroke Dock, in west Wales, as part of a Welsh Government pilot project to promote the development of low carbon housing in Wales based on the Code for Sustainable Homes (CfSH). In the same year, in the same town, a small scale developer undertook the design and construction of two houses based on ecological principles using strawbale construction. The houses built by this developer were designed and built outside of the requirements of the CfSH and utilised passive design approaches along with local and natural materials to reduce operational and embodied energy. Researchers from the Ecological Built Environment Research and Enterprise group, at Cardiff Metropolitan University, are working in collaboration with PHA to develop a best practice model for low carbon housing in rural areas of Wales and these two projects provide an opportunity for the researchers to investigate and compare two distinct approaches to low carbon design each with the aim to deliver sustainable, affordable dwellings. To evaluate these two schemes structured interviews were held with the design team of the pilot project and the designer/builder of the eco-house to understand their respective approaches; the influences and obstacles that affected the development of the schemes; and how they considered user behaviour. The paper concludes by considering the lessons that registered social landlords might learn from small scale ecological developers for the design and construction of low and zero energy housing in rural areas

Use of a twelve month's self referral reminder to faciliate uptake of bowel scope (flexible sigmoidoscopy screening) in previous non-responders: a London-based feasibility study

Background: In March 2013, NHS England extended its national Bowel Cancer Screening Programme to include ‘one-off’ Flexible Sigmoidoscopy screening (NHS Bowel Scope Screening, BSS) for men and women aged 55. With less than one in two people currently taking up the screening test offer, there is a strong public health mandate to develop system-friendly interventions to increase uptake while the programme is rolling out. This study aimed to assess the feasibility of sending a reminder to previous BSS non-responders, 12 months after the initial invitation, with consideration for its potential impact on uptake. Method: This study was conducted in the ethnically diverse London Boroughs of Brent and Harrow, where uptake is below the national average. Between September and November 2014, 160 previous non-responders were randomly selected to receive a reminder of the opportunity to self-refer 12 months after their initial invitation. The reminder included instructions on how to book an appointment, and provided options for the time and day of the appointment and the gender of the endoscopist performing the test. To address barriers to screening, the reminder was sent with a brief locally tailored information leaflet designed specifically for this study. Participants not responding within 4 weeks were sent a follow-up reminder, after which there was no further intervention. Self-referral rates were measured 8 weeks after the delivery of the follow-up reminder and accepted as final. Results: Of the 155 participants who received the 12 months’ reminder (returned to sender, n=5), 30 (19.4%) self-referred for an appointment, of which 24 (15.5%) attended and were successfully screened. Attendance rates differed by gender, with significantly more women attending an appointment than men (20.7% vs 8.8%, respectively; OR=2.73, 95% CI=1.02–7.35, P=0.05), but not by area (Brent vs Harrow) or area-level deprivation. Of the 30 people who self-referred for an appointment, 27 (90%) indicated a preference for a same-sex practitioner, whereas three (10%) gave no preference. Preference for a same-sex practitioner was higher among women than men (χ2=7.78, P<0.05), with only 67% of men (six of nine) requesting a same-sex practitioner, compared with 100% of women (n=21). Conclusions: Sending previous non-responders a 12 months’ reminder letter with a brief information leaflet is a feasible and efficacious intervention, which merits further investigation in a randomised controlled trial

Irrigation and drainage in the new millennium

Presented at the 2000 USCID international conference, Challenges facing irrigation and drainage in the new millennium on June 20-24 in Fort Collins, Colorado.Includes bibliographical references.Current global population growth rates require an increase in agricultural food production of about 40-50% over the next thirty to forty years, in order to maintain present levels of food intake. To meet the target, irrigated agriculture must play a vital role, in fact the FAO estimates that 60% of future gains will have to come from irrigation. The practice of controlling drainage involves the extension of on-farm water management to include drainage management. With the integration of irrigation and drainage management, the water balance can be managed to reduce excess water losses and increase irrigation efficiencies. Controlled drainage is relatively new and there are many theoretical and practical issues to be addressed. The technique involves maintaining high water table in the soil profile for extended periods of time, requiring careful management to ensure that crop growth is not affected by anaerobic conditions. A fieldwork programme has been investigated to test controlled drainage in the Nile Delta, where water resources are stretched to the limit. Water saving is essential in the next 20 years. Pressures from the fixed Nile water allocation, population growth, industry and other sectors and the horizontal expansion programme mean that this need is urgent. One crop season has been completed at a site in the Western Nile Delta using simple control devices in the subsurface drainage system. This paper discusses the potential benefits of controlled drainage to save water in agricultural areas such as the Nile Delta, and presents findings from the first crop season

Expression of gain-of-function CFTR in cystic fibrosis airway cells restores epithelial function better than wild-type or codon-optimized CFTR

Class Ia/b cystic fibrosis transmembrane regulator (CFTR) variants cause severe lung disease in 10% of cystic fibrosis (CF) patients and are untreatable with small-molecule pharmaceuticals. Genetic replacement of CFTR offers a cure, but its effectiveness is limited in vivo. We hypothesized that enhancing protein levels (using codon optimization) and/or activity (using gain-of-function variants) of CFTR would more effectively restore function to CF bronchial epithelial cells. Three different variants of the CFTR protein were tested: codon optimized (high codon adaptation index [hCAI]), a gain-of-function (GOF) variant (K978C), and a combination of both (hˆK978C). In human embryonic kidney (HEK293T) cells, initial results showed that hCAI and hˆK978C produced greater than 10-fold more CFTR protein and displayed ∼4-fold greater activity than wild-type (WT) CFTR. However, functionality was profoundly different in CF bronchial epithelial cells. Here, K978C CFTR more potently restored essential epithelial functions (anion transport, airway surface liquid height, and pH) than WT CFTR. hCAI and hˆK978C CFTRs had limited impact because of mislocalization in the cell. These data provide a proof of principle showing that GOF variants may be more effective than codon-optimized forms of CFTR for CF gene therapy. Video abstract: [Video presented