Transcript annotation in FANTOM3: Mouse gene catalog based on physical cDNAs

T he international FANTOM consortium aims to produce a comprehensive picture of the mammalian transcriptome, based upon an extensive cDNA collection and functional annotation of full-length enriched cDNAs. The previous dataset, FANTOM(2), comprised 60,770 full- length enriched cDNAs. Functional annotation revealed that this cDNA dataset contained only about half of the estimated number of mouse protein- coding genes, indicating that a number of cDNAs still remained to be collected and identified. To pursue the complete gene catalog that covers all predicted mouse genes, cloning and sequencing of full- length enriched cDNAs has been continued since FANTOM2. In FANTOM3, 42,031 newly isolated cDNAs were subjected to functional annotation, and the annotation of 4,347 FANTOM2 cDNAs was updated. To accomplish accurate functional annotation, we improved our automated annotation pipeline by introducing new coding sequence prediction programs and developed a Web- based annotation interface for simplifying the annotation procedures to reduce manual annotation errors. Automated coding sequence and function prediction was followed with manual curation and review by expert curators. A total of 102,801 full- length enriched mouse cDNAs were annotated. Out of 102,801 transcripts, 56,722 were functionally annotated as protein coding ( including partial or truncated transcripts), providing to our knowledge the greatest current coverage of the mouse proteome by full- length cDNAs. The total number of distinct non- protein- coding transcripts increased to 34,030. The FANTOM3 annotation system, consisting of automated computational prediction, manual curation, and. nal expert curation, facilitated the comprehensive characterization of the mouse transcriptome, and could be applied to the transcriptomes of other species.

Progressive resistance training and stretching following surgery for breast cancer: study protocol for a randomised controlled trial

Background: Currently 1 in 11 women over the age of 60 in Australia are diagnosed with breast cancer. Following treatment, most breast cancer patients are left with shoulder and arm impairments which can impact significantly on quality of life and interfere substantially with activities of daily living. The primary aim of the proposed study is to determine whether upper limb impairments can be prevented by undertaking an exercise program of prolonged stretching and resistance training, commencing soon after surgery. Methods/design: We will recruit 180 women who have had surgery for early stage breast cancer to a multicenter single-blind randomized controlled trial. At 4 weeks post surgery, women will be randomly assigned to either an exercise group or a usual care ( control) group. Women allocated to the exercise group will perform exercises daily, and will be supervised once a week for 8 weeks. At the end of the 8 weeks, women will be given a home-based training program to continue indefinitely. Women in the usual care group will receive the same care as is now typically provided, i.e. a visit by the physiotherapist and occupational therapist while an inpatient, and receipt of pamphlets. All subjects will be assessed at baseline, 8 weeks, and 6 months later. The primary measure is arm symptoms, derived from a breast cancer specific questionnaire (BR23). In addition, range of motion, strength, swelling, pain and quality of life will be assessed. Discussion: This study will determine whether exercise commencing soon after surgery can prevent secondary problems associated with treatment of breast cancer, and will thus provide the basis for successful rehabilitation and reduction in ongoing problems and health care use. Additionally, it will identify whether strengthening exercises reduce the incidence of arm swelling. Trial Registration: The protocol for this study is registered with the Australian Clinical Trials Registry (ACTRN012606000050550).

Does high intensity resistance training maintain bone mass during moderate weight loss in older overweight adults with type 2 diabetes

The aim was to investigate whether the addition of supervised high intensity progressive resistance training to a moderate weight loss program (RT+WLoss) could maintain bone mineral density (BMD) and lean mass compared to moderate weight loss (WLoss) alone in older overweight adults with type 2 diabetes. We also investigated whether any benefits derived from a supervised RT program could be sustained through an additional home-based program. This was a 12-month trial in which 36 sedentary, overweight adults aged 60 to 80 years with type 2 diabetes were randomized to either a supervised gymnasium-based RT+WLoss or WLoss program for 6 months (phase 1). Thereafter, all participants completed an additional 6-month home-based training without further dietary modification (phase 2). Total body and regional BMD and bone mineral content (BMC), fat mass (FM) and lean mass (LM) were assessed by DXA every 6 months. Diet, muscle strength (1-RM) and serum total testosterone, estradiol, SHBG, insulin and IGF-1 were measured every 3 months. No between group differences were detected for changes in any of the hormonal parameters at any measurement point. In phase 1, after 6 months of gymnasium-based training, weight and FM decreased similarly in both groups (P < 0.01), but LM tended to increase in the RT+WLoss (n=16) relative to the WLoss (n = 13) group [net difference (95% CI), 1.8% (0.2, 3.5), P < 0.05]. Total body BMD and BMC remained unchanged in the RT+WLoss group, but decreased by 0.9 and 1.5%, respectively, in the WLoss group (interaction, P < 0.05). Similar, though non-significant, changes were detected at the femoral neck and lumbar spine (L2-L4). In phase 2, after a further 6 months of home-based training, weight and FM increased significantly in both the RT+WLoss (n = 14) and WLoss (n = 12) group, but there were no significant changes in LM or total body or regional BMD or BMC in either group from 6 to 12 months. These results indicate that in older, overweight adults with type 2 diabetes, dietary modification should be combined with progressive resistance training to optimize the effects on body composition without having a negative effect on bone health.

Approaches to training practitioners in the art and science of plant disease diagnosis

Allowing plant pathology students to tackle fictitious or real crop problems during the course of their formal training not only teaches them the diagnostic process, but also provides for a better understanding of disease etiology. Such a problem-solving approach can also engage, motivate, and enthuse students about plant pathologgy in general. This paper presents examples of three problem-based approaches to diagnostic training utilizing freely available software. The first provides an adventure-game simulation where Students are asked to provide a diagnosis and recommendation after exploring a hypothetical scenario or case. Guidance is given oil how to create these scenarios. The second approach involves students creating their own scenarios. The third uses a diagnostic template combined with reporting software to both guide and capture students' results and reflections during a real diagnostic assignment.

Problem-based learning: a case study in providing e-health education using the Internet

The current trend among many universities is to increase the number of courses available online. However, there are fundamental problems in transferring traditional education courses to virtual formats. Delivering current curricula in an online format does not assist in overcoming the negative effects on student motivation which are inherent in providing information passively. Using problem-based learning (PBL) online is a method by which computers can become a tool to encourage active learning among students. The delivery of curricula via goal-based scenarios allows students to learn at different rates and can successfully shift online learning from memorization to discovery. This paper reports on a Web-based e-health course that has been delivered via PBL for the past 12 months. Thirty distance-learning students undertook postgraduate courses in e-health delivered via the Internet (asynchronous communication). Data collected via online student surveys indicated that the PBL format was both flexible and interesting. PBL has the potential to increase the quality of the educational experience of students in online environments.

Sharing Narratives Online: An international, self-organising curriculum in rural health

The aim of the Rural Medicine Rotation (RMR) at the University of Queensland (UQ) is to give all third year medical students exposure to and an understanding of, clinical practice in Australian rural or remote locations. A difficulty in achieving this is the relatively short period of student clinical placements, in only one or two rural or remote locations. A web-based Clinical Discussion Board (CDB) has been introduced to address this problem by allowing students at various rural sites to discuss their rural experiences and clinical issues with each other. The rationale is to encourage an understanding of the breadth and depth of rural medicine through peer-based learning. Students are required to submit a minimum of four contributions over the course of their six week rural placement. Analysis of student usage patterns shows that the majority of students exceeded the minimum submission criteria indicating motivation rather than compulsion to contribute to the CDB. There is clear evidence that contributing or responding to the CDB develops studentâ??s critical thinking skills by giving and receiving assistance from peers, challenging attitudes and beliefs and stimulating reflective thought. This is particularly evident in regard to issues involving ethics or clinical uncertainty, subject areas that are not in the medical undergraduate curriculum, yet are integral to real-world medical practice. The CDB has proved to be a successful way to understand the concerns and interests of third year medical students immersed in their RMR and also in demonstrating how technology can help address the challenge of supporting students across large geographical areas. We have recently broadened this approach by including students from the Rural Program at The Ohio State University College of Medicine. This important international exchange of ideas and approaches to learning is expected to broaden clinical training content and improve understanding of rural issues.

Building learning communities to support beginning teachers use of technology

This paper reports on the early stages of a three year study that is investigating the impact of a technology-enriched teacher education program on beginning teachers' integration of computers, graphics calculators, and the internet into secondary school mathematics classrooms. Whereas much of the existing research on the role of technology in mathematics learning has been concerned with effects on curriculum content or student learning, less attention has been given to the relationship between technology use and issues of pedagogy, in particular the impact on teachers' professional learning in the context of specific classroom and school environments. Our research applies sociocultural theories of learning to consider how beginning teachers are initiated into a collaborative professional community featuring both web-based and face to face interaction, and how participation in such a community shapes their pedagogical beliefs and practices. The aim of this paper is to analyse processes through which the emerging community was established and sustained during the first year of the study. We examine features of this community in terms of identity formation, shifts in values and beliefs, and interaction patterns revealed in bulletin board discussion between students and lecturers.

Tool support for integrating extended enterprises

A current EPSRC project, product introduction process: a simulation in the extended enterprise (PIPSEE) is discussed. PIPSEE attempts to improve the execution of the product introduction process (PIP) within an extended enterprise in the aerospace sector. The modus operandi for accomplishing this has been to develop process understanding amongst a core team, spanning four different companies, through process modelling, review and improvement recommendation. In parallel, a web-based simulation capability is being used to conduct simulation experiments, and to disseminate findings by training others in the lessons that have been learned. It is intended that the use of the PIPSEE simulator should encourage radical thinking about the ‘fuzzy front end’ of the PIP. This presents a topical, exciting and challenging research problem.

An evaluation of pharmacy education and pre-registration training

This thesis covers two major aspects of pharmacy education; undergraduate education and pre-registration training. A cohort of pharmacy graduates were surveyed over a period of four years, on issues related to undergraduate education, pre-registration training and continuing education. These graduates were the first-ever to sit the pre-registration examination. In addition, the opinions of pre-registration tutors were obtained on pre-registration training, during the year that competence-based assessment was introduced. It was concluded that although the undergraduate course provided a broad base of knowledge suitable for graduates in all branches of pharmacy, several issues were identified which would require attention in future developments of the course. These were: 1. the strong support for the expansion of clinical, social and practice-based teaching. 2. the strong support to retain the scientific content to the same extent as in the three-year course. 3. a greater use of problem-based learning methods. The graduates supported the provision of a pre-registration continuing education course to help prepare for the examination and in areas inadequately covered in the undergraduate course. There was also support for the introduction of some form of split branch training. There was no strong evidence to suggest that the training had been an application of undergraduate education. In general, competence-based training was well regarded by tutors as an appropriate and effective method of skill assessment. However, community tutors felt it was difficult to carry out effectively due to day-to-day time constraints. The assistant tutors in hospital pharmacy were found to have a very important role in provision of training, and should be adequately trained and supported. The study recommends the introduction of uniform training and a quality assurance mechanism for all tutors and assistants undertaking this role.

A method for automatically eliciting node weights in a hierarchical knowledge-based structure for reasoning with uncertainty

Hierarchical knowledge structures are frequently used within clinical decision support systems as part of the model for generating intelligent advice. The nodes in the hierarchy inevitably have varying influence on the decisionmaking processes, which needs to be reflected by parameters. If the model has been elicited from human experts, it is not feasible to ask them to estimate the parameters because there will be so many in even moderately-sized structures. This paper describes how the parameters could be obtained from data instead, using only a small number of cases. The original method [1] is applied to a particular web-based clinical decision support system called GRiST, which uses its hierarchical knowledge to quantify the risks associated with mental-health problems. The knowledge was elicited from multidisciplinary mental-health practitioners but the tree has several thousand nodes, all requiring an estimation of their relative influence on the assessment process. The method described in the paper shows how they can be obtained from about 200 cases instead. It greatly reduces the experts’ elicitation tasks and has the potential for being generalised to similar knowledge-engineering domains where relative weightings of node siblings are part of the parameter space.

UncertWeb processing service:making models easer to access on the web

Models are central tools for modern scientists and decision makers, and there are many existing frameworks to support their creation, execution and composition. Many frameworks are based on proprietary interfaces, and do not lend themselves to the integration of models from diverse disciplines. Web based systems, or systems based on web services, such as Taverna and Kepler, allow composition of models based on standard web service technologies. At the same time the Open Geospatial Consortium has been developing their own service stack, which includes the Web Processing Service, designed to facilitate the executing of geospatial processing - including complex environmental models. The current Open Geospatial Consortium service stack employs Extensible Markup Language as a default data exchange standard, and widely-used encodings such as JavaScript Object Notation can often only be used when incorporated with Extensible Markup Language. Similarly, no successful engagement of the Web Processing Service standard with the well-supported technologies of Simple Object Access Protocol and Web Services Description Language has been seen. In this paper we propose a pure Simple Object Access Protocol/Web Services Description Language processing service which addresses some of the issues with the Web Processing Service specication and brings us closer to achieving a degree of interoperability between geospatial models, and thus realising the vision of a useful 'model web'.

Uncertainty analysis in the Model Web

This thesis provides a set of tools for managing uncertainty in Web-based models and workflows.To support the use of these tools, this thesis firstly provides a framework for exposing models through Web services. An introduction to uncertainty management, Web service interfaces,and workflow standards and technologies is given, with a particular focus on the geospatial domain.An existing specification for exposing geospatial models and processes, theWeb Processing Service (WPS), is critically reviewed. A processing service framework is presented as a solutionto usability issues with the WPS standard. The framework implements support for Simple ObjectAccess Protocol (SOAP), Web Service Description Language (WSDL) and JavaScript Object Notation (JSON), allowing models to be consumed by a variety of tools and software. Strategies for communicating with models from Web service interfaces are discussed, demonstrating the difficultly of exposing existing models on the Web. This thesis then reviews existing mechanisms for uncertainty management, with an emphasis on emulator methods for building efficient statistical surrogate models. A tool is developed to solve accessibility issues with such methods, by providing a Web-based user interface and backend to ease the process of building and integrating emulators. These tools, plus the processing service framework, are applied to a real case study as part of the UncertWeb project. The usability of the framework is proved with the implementation of aWeb-based workflow for predicting future crop yields in the UK, also demonstrating the abilities of the tools for emulator building and integration. Future directions for the development of the tools are discussed.

Psychological cue use and implications for a clinical decision support system

Effective clinical decision making depends upon identifying possible outcomes for a patient, selecting relevant cues, and processing the cues to arrive at accurate judgements of each outcome's probability of occurrence. These activities can be considered as classification tasks. This paper describes a new model of psychological classification that explains how people use cues to determine class or outcome likelihoods. It proposes that clinicians respond to conditional probabilities of outcomes given cues and that these probabilities compete with each other for influence on classification. The model explains why people appear to respond to base rates inappropriately, thereby overestimating the occurrence of rare categories, and a clinical example is provided for predicting suicide risk. The model makes an effective representation for expert clinical judgements and its psychological validity enables it to generate explanations in a form that is comprehensible to clinicians. It is a strong candidate for incorporation within a decision support system for mental-health risk assessment, where it can link with statistical and pattern recognition tools applied to a database of patients. The symbiotic combination of empirical evidence and clinical expertise can provide an important web-based resource for risk assessment, including multi-disciplinary education and training. © 2002 Informa UK Ltd All rights reserved.

Editorial

The American Academy of Optometry (AAO) had their annual meeting in San Diego in December 2005 and the BCLA and CLAE were well represented there. The BCLA does have a reasonable number of non-UK based members and hopefully in the future will attract more. This will certainly be beneficial to the society as a whole and may draw more delegates to the BCLA annual conference. To increase awareness of the BCLA at the AAO a special evening seminar was arranged where BCLA president Dr. James Wolffsohn gave his presidential address. Dr. Wolffsohn has given the presidential address in the UK, Ireland, Hong Kong and Japan – making it the most travelled presidential address for the BCLA to date. Aside from the BCLA activity at the AAO there were numerous lectures of interest to all, truly a “something for everyone” meeting. All the sessions were multi-track (often up to 10 things occurring at the same time) and the biggest dilemma was often deciding what to attend and more importantly what you will miss! Nearly 200 new AAO Fellows were inducted at the Gala Dinner from many countries including 3 new fellows from the UK (this year they all just happened to be from Aston University!). It is certainly one of the highlights of the AAO to see fellows from different schools of training from around the world fulfilling the same criteria and being duly rewarded for their commitment to the profession. BCLA members will be aware that 2006 sees the introduction of the new fellowship scheme of the BCLA and by the time you read this the first set of fellowship examinations will have taken place. For more details of the FBCLA scheme see the BCLA web site http://www.bcla.org.uk. Since many of CLAE's editorial panel were at the AAO an informal meeting and dinner was arranged for them where ideas were exchanged about the future of the journal. It is envisaged that the panel will meet twice a year – the next meeting will be at the BCLA conference. The biggest excitement by far was the fact that CLAE is now Medline/PubMed indexed. You may ask why is this significant to CLAE? PubMed is the free web-based service from the US National Library of Medicine. It holds over 15 million biomedical citations and abstracts from the Medline database. Medline is the largest component of PubMed and covers over 4800 journals published in more than 70 countries. The impact of this is that CLAE is starting to attract more submissions as researchers and authors are not worried that their work will not be hidden from other colleagues in the field but rather the work is available to view on the World Wide Web. CLAE is one of a very small number of contact lens journals that is indexed this way. Amongst the other CL journals listed you will note that the International Contact Lens Clinic has now merged with CLAE and the journal CLAO has been renamed Eye and Contact Lenses – making the list of indexed CL journals even smaller than it appears. The on-line submission and reviewing system introduced in 2005 has also made it easier for authors to submit their work and easier for reviewers to check the content. This ease of use has lead to quicker times from submission to publication. Looking back at the articles published in CLAE in 2005 reveals some interesting facts. The majority of the material still tends to be from UK groups related to the field of Optometry, although we hope that in the future we will attract more work from non-UK groups and also from non-Optometric areas such as refractive surgery or anterior eye pathology. Interestingly in 2005 the most downloaded article from CLAE was “Wavefront technology: Past, present and future” by Professor W. Neil Charman, who was also the recipient of the Charles F. Prentice award at the AAO – one of the highest awards honours that the AAO can bestow. Professor Charman was also the keynote speaker at the BCLA's first Pioneer's Day meeting in 2004. In 2006, readers of CLAE will notice more changes, firstly we are moving to 5 issues per year. It is hoped that in the future, depending on increased submissions, a move to 6 issues may be feasible. Secondly, CLAE will aim to have one article per issue that carries CL CET points. You will see in this issue there is an article from Professor Mark Wilcox (who was a keynote speaker at the BCLA conference in 2005). In future articles that carry CET points will be either reviews from BCLA conference keynote speakers, members of the editorial panel or material from other invited persons that will be of interest to the readership of CLAE. Finally, in 2006, you will notice a change to the Editorial Panel, some of the distinguished panel felt that it was good time to step down and new members have been invited to join the remaining panel. The panel represent some of the most eminent names in the fields of contact lenses and/or anterior eye and have varying backgrounds and interests from many of the prominent institutions around the world. One of the tasks that the Editorial Panel undertake is to seek out possible submissions to the journal, either from conferences they attend (posters and papers that they will see and hear) and from their own research teams. However, on behalf of CLAE I would like to extend that invitation to seek original articles to all readers – if you hear a talk and think it could make a suitable publication to CLAE please ask the presenters to submit the work via the on-line submission system. If you found the work interesting then the chances are so will others. CLAE invites submissions that are original research, full length articles, short case reports, full review articles, technical reports and letters to the editor. The on-line submission web page is http://www.ees.elsevier.com/clae/.

Online-questionnaire design:establishing guidelines and evaluating existing eupport

As a new medium for questionnaire delivery, the internet has the potential to revolutionise the survey process. Online (web-based) questionnaires provide several advantages over traditional survey methods in terms of cost, speed, appearance, flexibility, functionality, and usability [1, 2]. For instance, delivery is faster, responses are received more quickly, and data collection can be automated or accelerated [1- 3]. Online-questionnaires can also provide many capabilities not found in traditional paper-based questionnaires: they can include pop-up instructions and error messages; they can incorporate links; and it is possible to encode difficult skip patterns making such patterns virtually invisible to respondents. Like many new technologies, however, online-questionnaires face criticism despite their advantages. Typically, such criticisms focus on the vulnerability of online-questionnaires to the four standard survey error types: namely, coverage, non-response, sampling, and measurement errors. Although, like all survey errors, coverage error (“the result of not allowing all members of the survey population to have an equal or nonzero chance of being sampled for participation in a survey” [2, pg. 9]) also affects traditional survey methods, it is currently exacerbated in online-questionnaires as a result of the digital divide. That said, many developed countries have reported substantial increases in computer and internet access and/or are targeting this as part of their immediate infrastructural development [4, 5]. Indicating that familiarity with information technologies is increasing, these trends suggest that coverage error will rapidly diminish to an acceptable level (for the developed world at least) in the near future, and in so doing, positively reinforce the advantages of online-questionnaire delivery. The second error type – the non-response error – occurs when individuals fail to respond to the invitation to participate in a survey or abandon a questionnaire before it is completed. Given today’s societal trend towards self-administration [2] the former is inevitable, irrespective of delivery mechanism. Conversely, non-response as a consequence of questionnaire abandonment can be relatively easily addressed. Unlike traditional questionnaires, the delivery mechanism for online-questionnaires makes estimation of questionnaire length and time required for completion difficult1, thus increasing the likelihood of abandonment. By incorporating a range of features into the design of an online questionnaire, it is possible to facilitate such estimation – and indeed, to provide respondents with context sensitive assistance during the response process – and thereby reduce abandonment while eliciting feelings of accomplishment [6]. For online-questionnaires, sampling error (“the result of attempting to survey only some, and not all, of the units in the survey population” [2, pg. 9]) can arise when all but a small portion of the anticipated respondent set is alienated (and so fails to respond) as a result of, for example, disregard for varying connection speeds, bandwidth limitations, browser configurations, monitors, hardware, and user requirements during the questionnaire design process. Similarly, measurement errors (“the result of poor question wording or questions being presented in such a way that inaccurate or uninterpretable answers are obtained” [2, pg. 11]) will lead to respondents becoming confused and frustrated. Sampling, measurement, and non-response errors are likely to occur when an online-questionnaire is poorly designed. Individuals will answer questions incorrectly, abandon questionnaires, and may ultimately refuse to participate in future surveys; thus, the benefit of online questionnaire delivery will not be fully realized. To prevent errors of this kind2, and their consequences, it is extremely important that practical, comprehensive guidelines exist for the design of online questionnaires. Many design guidelines exist for paper-based questionnaire design (e.g. [7-14]); the same is not true for the design of online questionnaires [2, 15, 16]. The research presented in this paper is a first attempt to address this discrepancy. Section 2 describes the derivation of a comprehensive set of guidelines for the design of online-questionnaires and briefly (given space restrictions) outlines the essence of the guidelines themselves. Although online-questionnaires reduce traditional delivery costs (e.g. paper, mail out, and data entry), set up costs can be high given the need to either adopt and acquire training in questionnaire development software or secure the services of a web developer. Neither approach, however, guarantees a good questionnaire (often because the person designing the questionnaire lacks relevant knowledge in questionnaire design). Drawing on existing software evaluation techniques [17, 18], we assessed the extent to which current questionnaire development applications support our guidelines; Section 3 describes the framework used for the evaluation, and Section 4 discusses our findings. Finally, Section 5 concludes with a discussion of further work.