Multiple sclerosis: natural history, diagnosis and changes in the brain

This article describes the general symptoms, diagnosis and changes in the nervous system in multiple sclerosis. A second article will describe the specific visual symptoms which are believed to be characteristic of the disease.

Probabilistic methods for drug discovery

This thesis introduces a flexible visual data exploration framework which combines advanced projection algorithms from the machine learning domain with visual representation techniques developed in the information visualisation domain to help a user to explore and understand effectively large multi-dimensional datasets. The advantage of such a framework to other techniques currently available to the domain experts is that the user is directly involved in the data mining process and advanced machine learning algorithms are employed for better projection. A hierarchical visualisation model guided by a domain expert allows them to obtain an informed segmentation of the input space. Two other components of this thesis exploit properties of these principled probabilistic projection algorithms to develop a guided mixture of local experts algorithm which provides robust prediction and a model to estimate feature saliency simultaneously with the training of a projection algorithm.Local models are useful since a single global model cannot capture the full variability of a heterogeneous data space such as the chemical space. Probabilistic hierarchical visualisation techniques provide an effective soft segmentation of an input space by a visualisation hierarchy whose leaf nodes represent different regions of the input space. We use this soft segmentation to develop a guided mixture of local experts (GME) algorithm which is appropriate for the heterogeneous datasets found in chemoinformatics problems. Moreover, in this approach the domain experts are more involved in the model development process which is suitable for an intuition and domain knowledge driven task such as drug discovery. We also derive a generative topographic mapping (GTM) based data visualisation approach which estimates feature saliency simultaneously with the training of a visualisation model.

Investigating the effects of antiepileptic drugs on the electrophysiology of vision

The principal aim of this work was to examine the effects of antiepileptic drugs (AEDs) on vision. Vigabatrin acts by increasing GABA at brain inhibitory synapses by irreversibly binding to GABA-transaminase. Remacemide is a novel non-competitive NMDA receptor antagonist and fast sodium channel inhibitor that results in the inhibition of the NMDA receptors located in the neuronal membrane calcium channels increasing glutamate in the brain. Vigabatrin has been shown to cause a specific pattern of visual field loss, as one in three adults taking vigabatrin have shown a bilateral concentric constriction. Remacemide has unknown effects on vision. The majority of studies of the effects of AEDs on vision have not included the paediatric population due to difficulties assessing visual field function using standard perimetry testing. Evidently an alternative test is required to establish and monitor visual field problems associated with AEDs both in children and in adults who cannot comply with perimetry. In order to test paediatric patients exposed to vigabatrin, a field-specific visual evoked potential was developed. Other tests performed on patients taking either vigabatrin or remacemide were electroretinograms, electro-oculograms, multifocal VEPs and perimetry. Comparing these tests to perimetry results from vigabatrin patients the field specific VEP was found to have a high sensitivity and specificity, as did the 30Hz flicker amplitude. The modified VEP was also found to provide useful results in vigabatrin patients. Remacemide did not produce a similar visual field loss to vigabatrin although macular vision was affected. The field specific VEP is a useful method for detecting vigabatrin associated visual field loss that is well tolerated by young children. This technique combined with the ERG under light adapted (30Hz flicker) condition is presently the superior method for detecting vigabatrin-attributed peripheral field defects present in children below the developmental age of 9. The effects of AEDs on vision should be monitored carefully and the use of multifocal stimulation allows for specific areas of the retina and visual pathway to be monitored.

Self-training from labeled features for sentiment analysis

Sentiment analysis concerns about automatically identifying sentiment or opinion expressed in a given piece of text. Most prior work either use prior lexical knowledge defined as sentiment polarity of words or view the task as a text classification problem and rely on labeled corpora to train a sentiment classifier. While lexicon-based approaches do not adapt well to different domains, corpus-based approaches require expensive manual annotation effort. In this paper, we propose a novel framework where an initial classifier is learned by incorporating prior information extracted from an existing sentiment lexicon with preferences on expectations of sentiment labels of those lexicon words being expressed using generalized expectation criteria. Documents classified with high confidence are then used as pseudo-labeled examples for automatical domain-specific feature acquisition. The word-class distributions of such self-learned features are estimated from the pseudo-labeled examples and are used to train another classifier by constraining the model's predictions on unlabeled instances. Experiments on both the movie-review data and the multi-domain sentiment dataset show that our approach attains comparable or better performance than existing weakly-supervised sentiment classification methods despite using no labeled documents.

Learning sentiment classification model from labeled features

We propose a novel framework where an initial classifier is learned by incorporating prior information extracted from an existing sentiment lexicon. Preferences on expectations of sentiment labels of those lexicon words are expressed using generalized expectation criteria. Documents classified with high confidence are then used as pseudo-labeled examples for automatical domain-specific feature acquisition. The word-class distributions of such self-learned features are estimated from the pseudo-labeled examples and are used to train another classifier by constraining the model's predictions on unlabeled instances. Experiments on both the movie review data and the multi-domain sentiment dataset show that our approach attains comparable or better performance than exiting weakly-supervised sentiment classification methods despite using no labeled documents.

Case based design of knitwear

In the developed world we are surrounded by man-made objects, but most people give little thought to the complex processes needed for their design. The design of hand knitting is complex because much of the domain knowledge is tacit. The objective of this thesis is to devise a methodology to help designers to work within design constraints, whilst facilitating creativity. A hybrid solution including computer aided design (CAD) and case based reasoning (CBR) is proposed. The CAD system creates designs using domain-specific rules and these designs are employed for initial seeding of the case base and the management of constraints. CBR reuses the designer's previous experience. The key aspects in the CBR system are measuring the similarity of cases and adapting past solutions to the current problem. Similarity is measured by asking the user to rank the importance of features; the ranks are then used to calculate weights for an algorithm which compares the specifications of designs. A novel adaptation operator called rule difference replay (RDR) is created. When the specifications to a new design is presented, the CAD program uses it to construct a design constituting an approximate solution. The most similar design from the case-base is then retrieved and RDR replays the changes previously made to the retrieved design on the new solution. A measure of solution similarity that can validate subjective success scores is created. Specification similarity can be used as a guide whether to invoke CBR, in a hybrid CAD-CBR system. If the newly resulted design is suffciently similar to a previous design, then CBR is invoked; otherwise CAD is used. The application of RDR to knitwear design has demonstrated the flexibility to overcome deficiencies in rules that try to automate creativity, and has the potential to be applied to other domains such as interior design.

The impact of general intellectual ability and white matter volume on the functional outcome of patients with bipolar disorder and their relatives

Background: There is substantial evidence that cognitive deficits and brain structural abnormalities are present in patients with Bipolar Disorder (BD) and in their first-degree relatives. Previous studies have demonstrated associations between cognition and functional outcome in BD patients but have not examined the role of brain morphological changes. Similarly, the functional impact of either cognition or brain morphology in relatives remains unknown. Therefore we focused on delineating the relationship between psychosocial functioning, cognition and brain structure, in relation to disease expression and genetic risk for BD. Methods: Clinical, cognitive and brain structural measures were obtained from 41 euthymic BD patients and 50 of their unaffected first-degree relatives. Psychosocial function was evaluated using the General Assessment of Functioning (GAF) scale. We examined the relationship between level of functioning and general intellectual ability (IQ), memory, attention, executive functioning, symptomatology, illness course and total gray matter, white matter and cerebrospinal fluid volumes. Limitations: Cross-sectional design. Results: Multiple regression analyses revealed that IQ, total white matter volume and a predominantly depressive illness course were independently associated with functional outcome in BD patients, but not in their relatives, and accounted for a substantial proportion (53%) of the variance in patients' GAF scores. There were no significant domain-specific associations between cognition and outcome after consideration of IQ. Conclusions: Our results emphasise the role of IQ and white matter integrity in relation to outcome in BD and carry significant implications for treatment interventions. © 2010 Elsevier B.V.

SemSearch:a search engine for the semantic web

Existing semantic search tools have been primarily designed to enhance the performance of traditional search technologies but with little support for ordinary end users who are not necessarily familiar with domain specific semantic data, ontologies, or SQL-like query languages. This paper presents SemSearch, a search engine, which pays special attention to this issue by providing several means to hide the complexity of semantic search from end users and thus make it easy to use and effective.

The role of working memory in compulsive checking and OCD:a systematic classification of 58 experimental findings

Despite the large body of research regarding the role of memory in OCD, the results are described as mixed at best (Hermans et al., 2008). For example, inconsistent findings have been reported with respect to basic capacity, intact verbal, and generally affected visuospatial memory. We suggest that this is due to the traditional pursuit of OCD memory impairment as one of the general capacity and/or domain specificity (visuospatial vs. verbal). In contrast, we conclude from our experiments (i.e., Harkin & Kessler, 2009, 2011; Harkin, Rutherford, & Kessler, 2011) and recent literature (e.g., Greisberg & McKay, 2003) that OCD memory impairment is secondary to executive dysfunction, and more specifically we identify three common factors (EBL: Executive-functioning efficiency, Binding complexity, and memory Load) that we generalize to 58 experimental findings from 46 OCD memory studies. As a result we explain otherwise inconsistent research – e.g., intact vs. deficient verbal memory – that are difficult to reconcile within a capacity or domain specific perspective. We conclude by discussing the relationship between our account and others', which in most cases is complementary rather than contradictory.

Translating specialised texts:an overview of key factors involved in translator training for specialized translation

Translators wishing to work on translating specialised texts are traditionally recommended to spend much time and effort acquiring specialist knowledge of the domain involved, and for some areas of specialised activity, this is clearly essential. For other types of translation-based, domain-specific of communication, however, it is possible to develop a systematic approach to the task which will allow for the production of target texts which are adequate for purpose, in a range of specialised domains, without necessarily having formal qualifications in those areas. For Esselink (2000) translation agencies, and individual clients, would tend to prefer a subject expert who also happens to have competence in one or more languages over a trained translator with a high degree of translation competence, including the ability to deal with specialised translation tasks. The problem, for the would-be translator, is persuading prospective clients that he or she is capable of this. This paper will offer an overview of the principles used to design training intended to teach trainee translators how to use a systematic approach to specialised translation, in order to extend the range of areas in which they can tackle translation, without compromising quality or reliability. This approach will be described within the context of the functionalist approach developed in particular by Reiss and Vermeer (1984), Nord (1991, 1997) inter alia.

English-for-teaching:rethinking teacher proficiency in the classroom

The expansion of English teaching in state education systems places increasing demands on English language teachers and how they are trained. A major thrust of these efforts has focused on improving teachers' English language proficiency. This expectation is manifested in policy and pedagogical directives that teachers 'teach English in English'. We argue for a reconceptualization of teacher language proficiency, not as general English proficiency but as a specialized subset of language skills required to prepare and teach lessons. This concept of English-for-Teaching as a bounded form of English for Specific Purposes (ESP) for the classroom builds on what teachers know about teaching, while introducing and confirming specific classroom language. This article describes how the construct was developed and then describes sample classroom tasks and the language needed to enact them in three major areas: managing the classroom, understanding and communicating lesson content, and assessing students and giving feedback.

A simulation conceptual modelling procedure for SCM applications

Purpose – The purpose of this paper is to outline a seven-phase simulation conceptual modelling procedure that incorporates existing practice and embeds a process reference model (i.e. SCOR). Design/methodology/approach – An extensive review of the simulation and SCM literature identifies a set of requirements for a domain-specific conceptual modelling procedure. The associated design issues for each requirement are discussed and the utility of SCOR in the process of conceptual modelling is demonstrated using two development cases. Ten key concepts are synthesised and aligned to a general process for conceptual modelling. Further work is outlined to detail, refine and test the procedure with different process reference models in different industrial contexts. Findings - Simulation conceptual modelling is often regarded as the most important yet least understood aspect of a simulation project (Robinson, 2008a). Even today, there has been little research development into guidelines to aid in the creation of a conceptual model. Design issues are discussed for building an ‘effective’ conceptual model and the domain-specific requirements for modelling supply chains are addressed. The ten key concepts are incorporated to aid in describing the supply chain problem (i.e. components and relationships that need to be included in the model), model content (i.e. rules for determining the simplest model boundary and level of detail to implement the model) and model validation. Originality/value – Paper addresses Robinson (2008a) call for research in defining and developing new approaches for conceptual modelling and Manuj et al., (2009) discussion on improving the rigour of simulation studies in SCM. It is expected that more detailed guidelines will yield benefits to both expert (i.e. avert typical modelling failures) and novice modellers (i.e. guided practice; less reliance on hopeful intuition)

OntoPedigree:modelling pedigrees for traceability in supply chains

The sharing of product and process information plays a central role in coordinating supply chains operations and is a key driver for their success. "Linked pedigrees" - linked datasets, that encapsulate event based traceability information of artifacts as they move along the supply chain, provide a scalable mechanism to record and facilitate the sharing of track and trace knowledge among supply chain partners. In this paper we present "OntoPedigree" a content ontology design pattern for the representation of linked pedigrees, that can be specialised and extended to define domain specific traceability ontologies. Events captured within the pedigrees are specified using EPCIS - a GS1 standard for the specification of traceability information within and across enterprises, while certification information is described using PROV - a vocabulary for modelling provenance of resources. We exemplify the utility of OntoPedigree in linked pedigrees generated for supply chains within the perishable goods and pharmaceuticals sectors.

The role of the English language in the context of national development vision 2025 with specific reference to agriculture in Tanzania

After thirty years of vacillation, the Tanzanian government has made a firm decision to Swahilize its secondary education system. It has also embarked on an ambitious economic and social development programme (Vision 2025) to transform its peasant society into a modern agricultural community. However, there is a faction in Tanzania opposed to Kiswahili as the medium of education. Already many members of the middle and upper class their children to English medium primary schools to avoid the Kiswahili medium public schools and to prepare their children for the English medium secondary system presently in place. Within the education system, particularly at university level, there is a desire to maintain English as the medium of education. English is seen to provide access to the international scientific community, to cutting edge technology and to the global economy. My interest in this conflict of interests stems from several years' experience teaching English to students at Sokoine University of Agriculture. Students specialise in agriculture and are expected to work with the peasant population on graduation. The students experience difficulties studying in English and then find their Kiswahili skills insufficient to explain to farmers the new techniques and technologies that they have studied in English. They are hampered by a complex triglossic situation in which they use their mother tongue with family and friends, Kiswahili, the national language for early education and most public communication within Tanzania, and English for advanced studies. My aim in this thesis was - to study the language policy in Tanzania and see how it is understood and implemented; - to examine the attitudes towards the various languages and their various roles; - to investigate actual language behaviour in Tanzanian higher education. My conclusion is that the dysfunctionality of the present study has to be addressed. Diglossic public life in Tanzania has to be accommodated. The only solution appears to be a compromise, namely a bilingual education system which supports from all cases of society by using Kiswahili, together with an early introduction of English and its promotion as a privileged foreign language, so that Tanzania can continue to develop internally through Kiswahili and at the same time retain access to the globalising world through the medium of English.

Increased prevalence of sex chromosome aneuploidies in specific language impairment and dyslexia

Aim: Sex chromosome aneuploidies increase the risk of spoken or written language disorders but individuals with specific language impairment (SLI) or dyslexia do not routinely undergo cytogenetic analysis. We assess the frequency of sex chromosome aneuploidies in individuals with language impairment or dyslexia. Method: Genome-wide single nucleotide polymorphism genotyping was performed in three sample sets: a clinical cohort of individuals with speech and language deficits (87 probands: 61 males, 26 females; age range 4 to 23 years), a replication cohort of individuals with SLI, from both clinical and epidemiological samples (209 probands: 139 males, 70 females; age range 4 to 17 years), and a set of individuals with dyslexia (314 probands: 224 males, 90 females; age range 7 to 18 years). Results: In the clinical language-impaired cohort, three abnormal karyotypic results were identified in probands (proband yield 3.4%). In the SLI replication cohort, six abnormalities were identified providing a consistent proband yield (2.9%). In the sample of individuals with dyslexia, two sex chromosome aneuploidies were found giving a lower proband yield of 0.6%. In total, two XYY, four XXY (Klinefelter syndrome), three XXX, one XO (Turner syndrome), and one unresolved karyotype were identified. Interpretation: The frequency of sex chromosome aneuploidies within each of the three cohorts was increased over the expected population frequency (approximately 0.25%) suggesting that genetic testing may prove worthwhile for individuals with language and literacy problems and normal non-verbal IQ. Early detection of these aneuploidies can provide information and direct the appropriate management for individuals. © 2013 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.