Development of models for predicting Torsade de Pointes cardiac arrhythmias using perceptron neural networks

Blockage of some ion channels and in particular, the hERG cardiac potassium channel delays cardiac repolarization and can induce arrhythmia. In some cases it leads to a potentially life-threatening arrhythmia known as Torsade de Pointes (TdP). Therefore recognizing drugs with TdP risk is essential. Candidate drugs that are determined not to cause cardiac ion channel blockage are more likely to pass successfully through clinical phases II and III trials (and preclinical work) and not be withdrawn even later from the marketplace due to cardiotoxic effects. The objective of the present study is to develop an SAR model that can be used as an early screen for torsadogenic (causing TdP arrhythmias) potential in drug candidates. The method is performed using descriptors comprised of atomic NMR chemical shifts and corresponding interatomic distances which are combined into a 3D abstract space matrix. The method is called 3D-SDAR (3 dimensional spectral data-activity relationship) and can be interrogated to identify molecular features responsible for the activity, which can in turn yield simplified hERG toxicophores. A dataset of 55 hERG potassium channel inhibitors collected from Kramer et al. consisting of 32 drugs with TdP risk and 23 with no TdP risk was used for training the 3D-SDAR model.An ANN model with multilayer perceptron was used to define collinearities among the independent 3D-SDAR features. A composite model from 200 random iterations with 25% of the molecules in each case yielded the following figures of merit: training, 99.2 %; internal test sets, 66.7%; external (blind validation) test set, 68.4%. In the external test set, 70.3% of positive TdP drugs were correctly predicted. Moreover, toxicophores were generated from TdP drugs. A 3D-SDAR was successfully used to build a predictive model for drug-induced torsadogenic and non-torsadogenic drugs.Comment: Accepted for publication in BMC Bioinformatics (Springer) July 201

The 'Good' Teacher? Constructing Teacher Identities for Lifelong Learning

The symposium will focus on trans-national constructions of the 'good' teacher through popular culture, through professional development orthodoxies and through professional practices such as professional growth plans, inspection and teacher regulation

Internet-of-Things Devices, Intellectual Property, Venture Capital, China Manufacturing, and the Art of a Clean Deal: Who Owns What?

Internet-of-Things Devices, Intellectual Property, Venture Capital, China Manufacturing, and the Art of a Clean Deal: Who Owns What

A national facilitation project to improve primary palliative care : impact of the Gold Standards Framework on process and self-ratings of quality

Background: Improving quality of end-of-life care is a key driver of UK policy. The Gold Standards Framework (GSF) for Palliative Care aims to strengthen primary palliative care through facilitating implementation of systematic clinical and organisational processes. Objectives: To describe the general practices that participated in the GSF programme in 2003–5 and the changes in process and perception of quality that occurred in the year following entry into the programme, and to identify factors associated with the extent of change. Methods: Participating practices completed a questionnaire at baseline and another approximately 12 months later. Data were derived from categorical questions about the implementation of 35 organisational and clinical processes, and self-rated assessments of quality, associated with palliative care provision. Participants: 1305 practices (total registered population almost 10 million). Follow-up questionnaire completed by 955 (73.2%) practices (after mean (SD) 12.8 (2.8) months; median 13 months). Findings: Mean increase in total number of processes implemented (maximum = 35) was 9.6 (95% CI 9.0 to 10.2; p<0.001; baseline: 15.7 (SD 6.4), follow-up: 25.2 (SD 5.2)). Extent of change was largest for practices with low baseline scores. Aspects of process related to coordination and communication showed the greatest change. All dimensions of quality improved following GSF implementation; change was highest for the "quality of palliative care for cancer patients" and "confidence in assessing, recording and addressing the physical and psychosocial areas of patient care". Conclusion: Implementation of the GSF seems to have resulted in substantial improvements in process and quality of palliative care. Further research is required of the extent to which this has enhanced care (physical, practical and psychological outcomes) for patients and carers

Country classifications for a changing world

"The distinction between developing and developed countries has long been central to development studies and to debates on development policy. In earlier decades, it was in many respects accurate, and was for many purposes useful. Although the world is still very much divided between rich and poor countries, relationships among countries have changed so much that the developing-developed country distinction has become an obstacle to understanding current problems and opportunities and, even more, to thinking productively about the future. It is time to stop using it. Many alternative ways of categorising countries have been suggested. In recent years in particular, large numbers of organisations have begun annually to rank countries according to a wide variety of criteria: from economic vulnerability, bribe payers, competitiveness, digital access, ease of doing business, food insecurity, governance, and happiness to water poverty and welfare. These do not adequately capture the structural and relational changes that have occurred in our multi-polar world with substantially altered flows of ideas, resources and influence. Focusing on the needs of European policymakers, this paper suggests two axes for classifying countries. The first is the external capacity of states to influence and work with other states. This is captured in the (measureable) concept of 'anchor countries' developed by the German Development Institute and beginning to be put into practice in the enlargement from the G8 to the G20. The second is internal state capacity, as shaped by the sources of government income, in particular contrasting tax, aid, and oil. Using sources of public revenue as a way of classifying countries requires more work but would help to steer the development debate toward the key issue of improving the quality of governance and thus strengthening the capacity of poor countries to help themselves." (author's abstract

Incentives Toward Conservation of Argaii Ovis Ammon: A Case Study of Trophy Hunting in Western China

We investigated management of wildlife, habitat and the hunting programme in Aksai County, Gansu Province, People\u27s Republic of China, during 1997-2000. Argali Ovis amnion is the focal species both for conservation and hunting. The hunting programme is intended to produce incentives to conserve wildlife and habitat. Poaching, a serious concern throughout western China, has been reduced in recent years in Aksai. Wildlife population trends are unknown because standardized surveys were begun only in 2000. Threats to argali in Aksai include livestock grazing, placer gold mining, and development of a dam, reservoir and aqueduct. The number of hunters participating in the programme (c. 3 per year) could provide considerable funding (c. $60,000 per year), but the allocation of these funds within China has provided too little for conservation at the local level, thus undermining the intended incentive system. Because local wildlife protection officials have been denied both funding and authority to deal with threats to the wildlife, the programme\u27s contribution to conservation has been minor. We recommend that hunters pay fees directly to county-level staff, thus increasing the proportion of funds retained at county-level, and that this added income is used to obtain wildlife grazing rights on important seasonal habitats for argali. These changes would promote local wildlife conservation without the need for additional external funding

Parental Co‐Construction of 5‐ to 13‐Year‐Olds\u27 Global Self‐Esteem Through Reminiscing About Past Events

The current study explored parental processes associated with children\u27s global self‐esteem development. Eighty 5‐ to 13‐year‐olds and one of their parents provided qualitative and quantitative data through questionnaires, open‐ended questions, and a laboratory‐based reminiscing task. Parents who included more explanations of emotions when writing about the lowest points in their lives were more likely to discuss explanations of emotions experienced in negative past events with their child, which was associated with child attachment security. Attachment was associated with concurrent self‐esteem, which predicted relative increases in self‐esteem 16 months later, on average. Finally, parent support also predicted residual increases in self‐esteem. Findings extend prior research by including younger ages and uncovering a process by which two theoretically relevant parenting behaviors impact self‐esteem development

Alternative Development Practice: The Role of Personal Conceptions of Development and Self-Understanding

It seems to be a favourite past time of development studies lecturers to begin their courses with the question: “What is development?” This old chestnut invariably serves its purpose of challenging and complicating our understandings of development and stimulating a good deal of debate. It is rare however, if this question is ever followed by any real guidance on how to answer it or consideration of what the answer might mean for one’s practice. For those seeking an alternative development practice in the context of a ‘development’ that grows ever more theoretically complex and morally ambiguous, I argue that engaging with and answering this question at a personal level is of vital importance. Within development studies, debate continues to grow over the definition of development’s ends and means, and over who controls it, defines it and benefits from it. In particular, alternative development approaches originating from Another Development thinkers of the 1970s are concerned with challenging the conceptualisation of development by opening its interpretation to multiple value systems and realities. At the same time there is an increasing awareness of the ‘primacy of the personal’ (Chambers, 1994 p3) through the implication of personal ethics and awareness in development practice. I argue that the combination of these factors gives rise to a personal challenge for alternative development practitioners to engage with and understand their own conceptions of development. A challenge that practitioners are not equipped to meet as they lack the conceptual and methodological tools required to move from abstract development theory to concrete practice. In response to these challenges my research draws on my personal experience as an intern in Latin America and employs an innovative auto-ethnographic methodology to examine the potential of development ‘theorias’ for orientating alternative development practice. Theorias are personal conceptions of development that allow practitioners to work with their own understandings of good change and structure these in relation to development and development practice. Employing reflective practice methods, I draw on my own experience as a novice development practitioner to investigate the elaboration of development theorias and their consequences for alternative development practice. The results suggest that theorias could provide practitioners with appropriate ‘tools’ with which to reflect upon, work through and explore personal conceptions of development as the basis for alternative development practice. My research indicates that theorias could also form the basis of an ‘alignment based approach’ to alternative development that facilitates cooperative processes aimed at co-creating and working towards new conceptualisations of development. The overall result is a unique contribution to the field of development studies which provides an example of reflective processes and conceptual tools for practitioners to constructively engage with the central questions of development’s ends and means from within the context of their own practice. The lack of literature regarding reflective engagement with practitioner conceptions of development highlights the importance of this research and its potential to contribute to alternative development practice and theory

Long-term Follow up of Van Nes Rotationplasty for Congenital Proximal Focal Femoral Deficiency

Van Nes rotationplasty may be used for patients with congenital proximal focal femoral deficiency (PFFD). The lower limb is rotated to use the ankle and foot as a functional knee joint within a prosthesis. A small series of cases was investigated to determine the long-term outcome. At a mean of 21.5 years (11 to 45) after their rotationplasty, a total of 12 prosthetic patients completed the Short-Form (SF)-36, Faces Pain Scale-Revised, Harris hip score, Oswestry back pain score and Prosthetic Evaluation Questionnaires, as did 12 age- and gender-matched normal control participants. A physical examination and gait analysis, computerised dynamic posturography (CDP), and timed ‘Up & Go’ testing was also completed. Wilcoxon Signed rank test was used to compare each PFFD patient with a matched control participant with false discovery rate of 5%. There were no differences between the groups in overall health and well-being on the SF-36. Significant differences were seen in gait parameters in the PFFD group. Using CDP, the PFFD group had reduced symmetry in stance, and reduced end point and maximum excursions. Patients who had undergone Van Nes rotationplasty had a high level of function and quality of life at long-term follow-up, but presented with significant differences in gait and posture compared with the control group