Methods for prediction of peptide binding to MHC molecules: A comparative study

Background: A variety of methods for prediction of peptide binding to major histocompatibility complex (MHC) have been proposed. These methods are based on binding motifs, binding matrices, hidden Markov models (HMM), or artificial neural networks (ANN). There has been little prior work on the comparative analysis of these methods. Materials and Methods: We performed a comparison of the performance of six methods applied to the prediction of two human MHC class I molecules, including binding matrices and motifs, ANNs, and HMMs. Results: The selection of the optimal prediction method depends on the amount of available data (the number of peptides of known binding affinity to the MHC molecule of interest), the biases in the data set and the intended purpose of the prediction (screening of a single protein versus mass screening). When little or no peptide data are available, binding motifs are the most useful alternative to random guessing or use of a complete overlapping set of peptides for selection of candidate binders. As the number of known peptide binders increases, binding matrices and HMM become more useful predictors. ANN and HMM are the predictive methods of choice for MHC alleles with more than 100 known binding peptides. Conclusion: The ability of bioinformatic methods to reliably predict MHC binding peptides, and thereby potential T-cell epitopes, has major implications for clinical immunology, particularly in the area of vaccine design.

Strategic research partnerships: Empirical evidence from Asia

This paper evaluates the role Strategic Research Partnerships (SRPs) play in Asia. Specific Asian institutional settings influence the roles of SRPs. Japan is regarded as a forerunner in the practice of SRPs. In Japan, lack of spillover channels, limited opportunities for mergers and acquisitions, weak university research and pressure for internal diversification motivate firms to form SRPs. In Korea, SRPs are regarded as a means to promote large-scale research projects. In Taiwan, SRPs are formed to facilitate technological diffusion. Empirical findings on SRPs, focusing on government-sponsored R&D consortia in Japan, are summarized. Issues regarding SRP formation, their effect on R&D spending of participating firms, and productivity, are examined. Reference is made to alternative forms of measurement of SRPs and their potential application to Asian countries is assessed. Enhancing the capacity of policy-makers to assess the extent and contribution of SRPs is considered to be a priority.

Predicting energy requirements in the clinical setting: Are current methods evidence based?

Estimating energy requirements is necessary in clinical practice when indirect calorimetry is impractical. This paper systematically reviews current methods for estimating energy requirements. Conclusions include: there is discrepancy between the characteristics of populations upon which predictive equations are based and current populations; tools are not well understood, and patient care can be compromised by inappropriate application of the tools. Data comparing tools and methods are presented and issues for practitioners are discussed. (C) 2003 International Life Sciences Institute.

Does the tendency to act impulsively underlie binge eating and alcohol use problems? An empirical investigation

The co-occurrence of problem drinking and binge eating and purging has been well documented. However, there has been relatively little investigation of etiological models that may influence the development of this co-occurrence. This study tests the hypotheses that impulsivity is heightened in eating disordered women compared with controls, and that women with comorbid bulimia and alcohol use disorders show higher impulsivity than bulimic-only women. The Impulsivity scale, BIS/BAS scales, State Anxiety Inventory, and a behavioural measure of reward responsiveness (CARROT) were administered to 22 women with bulimia, 23 women with comorbid bulimia and alcohol abuse/dependence, and 21 control women. As hypothesised, eating disordered women scored higher than controls on several self-report measures of impulsivity and sorted cards faster during a financially rewarded trial on the behavioural task. Also, as predicted, comorbid women scored higher than bulimic women on the Impulsivity scale. These findings suggest that individual differences in impulsiveness and a tendency to approach rewarding stimuli may contribute to developing these disorders. (C) 2003 Elsevier Ltd. All rights reserved.

Formal methods within a totally functional approach to programming

Taking functional programming to its extremities in search of simplicity still requires integration with other development (e.g. formal) methods. Induction is the key to deriving and verifying functional programs, but can be simplified through packaging proofs with functions, particularly folds, on data (structures). Totally Functional Programming avoids the complexities of interpretation by directly representing data (structures) as platonic combinators - the functions characteristic to the data. The link between the two simplifications is that platonic combinators are a kind of partially-applied fold, which means that platonic combinators inherit fold-theoretic properties, but with some apparent simplifications due to the platonic combinator representation. However, despite observable behaviour within functional programming that suggests that TFP is widely-applicable, significant work remains before TFP as such could be widely adopted.

Assessing cost-effectiveness - Mental health: introduction to the study and methods

Objective: The Assessing Cost-Effectiveness - Mental Health (ACE-MH) study aims to assess from a health sector perspective, whether there are options for change that could improve the effectiveness and efficiency of Australia's current mental health services by directing available resources toward 'best practice' cost-effective services. Method: The use of standardized evaluation methods addresses the reservations expressed by many economists about the simplistic use of League Tables based on economic studies confounded by differences in methods, context and setting. The cost-effectiveness ratio for each intervention is calculated using economic and epidemiological data. This includes systematic reviews and randomised controlled trials for efficacy, the Australian Surveys of Mental Health and Wellbeing for current practice and a combination of trials and longitudinal studies for adherence. The cost-effectiveness ratios are presented as cost (A$) per disability-adjusted life year (DALY) saved with a 95% uncertainty interval based on Monte Carlo simulation modelling. An assessment of interventions on 'second filter' criteria ('equity', 'strength of evidence', 'feasibility' and 'acceptability to stakeholders') allows broader concepts of 'benefit' to be taken into account, as well as factors that might influence policy judgements in addition to cost-effectiveness ratios. Conclusions: The main limitation of the study is in the translation of the effect size from trials into a change in the DALY disability weight, which required the use of newly developed methods. While comparisons within disorders are valid, comparisons across disorders should be made with caution. A series of articles is planned to present the results.

Computational methods for prediction of T-cell epitopes - a framework for modelling, testing, and applications

Computational models complement laboratory experimentation for efficient identification of MHC-binding peptides and T-cell epitopes. Methods for prediction of MHC-binding peptides include binding motifs, quantitative matrices, artificial neural networks, hidden Markov models, and molecular modelling. Models derived by these methods have been successfully used for prediction of T-cell epitopes in cancer, autoimmunity, infectious disease, and allergy. For maximum benefit, the use of computer models must be treated as experiments analogous to standard laboratory procedures and performed according to strict standards. This requires careful selection of data for model building, and adequate testing and validation. A range of web-based databases and MHC-binding prediction programs are available. Although some available prediction programs for particular MHC alleles have reasonable accuracy, there is no guarantee that all models produce good quality predictions. In this article, we present and discuss a framework for modelling, testing, and applications of computational methods used in predictions of T-cell epitopes. (C) 2004 Elsevier Inc. All rights reserved.

The effects of adolescent cannabis use: How should the empirical evidence inform drug policy for young people? : Meeting abstract

Ethics as a subject is now consistently taught in medical schools within Australia. The theoretical Ethical models used, and the associated clinical discussions, vary between schools. Registrars have further theoretical Ethics teaching within Psychiatry Fellowship Training, and ongoing clinical work that is likely to provide exposure to complex and frequent Ethical dilemmas. As Psychiatry Trainees approach subspecialty training in Child and Adolescent Psychiatry they therefore have a rich experience of both theoretical Ethics teaching and clinical exposure to Ethical issues. In this symposium, the difficulties Child and Adolescent Psychiatry Trainees may have in the integration of multiple theoretical Ethical models are discussed. It is suggested that these difficulties make Ethics Teaching for Child and Adolescent Psychiatry Trainees particularly challenging. This is important given the complex Ethical issues often present when working with Children and their Families. The three main Ethical models of Deontology, Virtue Ethics and Consequentialism are described and their usefulness for the Child and Adolescent Psychiatrist examined. Limitations of these models, and “Four Principles” approaches (such as that of Beauchamp and Childress), for Child and Adolescent Psychiatry, are also considered. Clinical cases are included for discussion. Finally, the ways in which these models may be used to enhance Child and Adolescent Psychiatry Training, and subsequent clinical practice as a Child and Adolescent Psychiatrist, are discussed. The integration of different theoretical Ethical models is considered, with implications identified for clinical practice.

A family of perfect hashing methods

Minimal perfect hash functions are used for memory efficient storage and fast retrieval of items from static sets. We present an infinite family of efficient and practical algorithms for generating order preserving minimal perfect hash functions. We show that almost all members of the family construct space and time optimal order preserving minimal perfect hash functions, and we identify the one with minimum constants. Members of the family generate a hash function in two steps. First a special kind of function into an r-graph is computed probabilistically. Then this function is refined deterministically to a minimal perfect hash function. We give strong theoretical evidence that the first step uses linear random time. The second step runs in linear deterministic time. The family not only has theoretical importance, but also offers the fastest known method for generating perfect hash functions.

A comparison of computer-based methods for the determination of onset of muscle contraction using electromyography

Little consensus exists in the literature regarding methods for determination of the onset of electromyographic (EMG) activity. The aim of this study was to compare the relative accuracy of a range of computer-based techniques with respect to EMG onset determined visually by an experienced examiner. Twenty-seven methods were compared which varied in terms of EMG processing (low pass filtering at 10, 50 and 500 Hz), threshold value (1, 2 and 3 SD beyond mean of baseline activity) and the number of samples for which the mean must exceed the defined threshold (20, 50 and 100 ms). Three hundred randomly selected trials of a postural task were evaluated using each technique. The visual determination of EMG onset was found to be highly repeatable between days. Linear regression equations were calculated for the values selected by each computer method which indicated that the onset values selected by the majority of the parameter combinations deviated significantly from the visually derived onset values. Several methods accurately selected the time of onset of EMG activity and are recommended for future use. Copyright (C) 1996 Elsevier Science Ireland Ltd.

An investigation of the anti-pronation effect of two taping methods after application and exercise

This study investigated the effect of two anti-pronation taping techniques on vertical navicular height, an indicator of foot pronation, after its application and 20 min of exercise. The taping techniques were: the low dye (LD) and low dye with the addition of calcaneal slings and reverse sixes (LDCR). A repeated measures study was used. It found that LDCR was superior to LD and control immediately after application and exercise. LD was better than control immediately after application but not after exercise. These findings provide practical directions to clinicians regularly using anti-pronation taping techniques.