On the 'classification' of neurodegenerative disorders:discrete entities, overlap or continuum?

The traditional method of classifying neurodegenerative diseases is based on the original clinico-pathological concept supported by 'consensus' criteria and data from molecular pathological studies. This review discusses first, current problems in classification resulting from the coexistence of different classificatory schemes, the presence of disease heterogeneity and multiple pathologies, the use of 'signature' brain lesions in diagnosis, and the existence of pathological processes common to different diseases. Second, three models of neurodegenerative disease are proposed: (1) that distinct diseases exist ('discrete' model), (2) that relatively distinct diseases exist but exhibit overlapping features ('overlap' model), and (3) that distinct diseases do not exist and neurodegenerative disease is a 'continuum' in which there is continuous variation in clinical/pathological features from one case to another ('continuum' model). Third, to distinguish between models, the distribution of the most important molecular 'signature' lesions across the different diseases is reviewed. Such lesions often have poor 'fidelity', i.e., they are not unique to individual disorders but are distributed across many diseases consistent with the overlap or continuum models. Fourth, the question of whether the current classificatory system should be rejected is considered and three alternatives are proposed, viz., objective classification, classification for convenience (a 'dissection'), or analysis as a continuum.

Eye movement problems and differential diagnosis of the parkinsonian syndromes

Differential clinical diagnosis of the parkinsonian syndromes, viz., Parkinson’s disease (PD), progressive supranuclear palsy (PSP), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA) can be difficult. Eye movement problems, however, are a chronic complication of many of these disorders and may be a useful aid to diagnosis. Hence, the presence in PSP of vertical supranuclear gaze palsy, fixation instability, lid retraction, blepharospasm, and apraxia of eyelid opening and closing is useful in separating PD from PSP. Moreover, atypical features of PSP include slowing of upward saccades, moderate slowing of downward saccades, the presence of a full range of voluntary vertical eye movements, a curved trajectory of oblique saccades, and absence of square-wave jerks. Downgaze palsy is probably the most useful diagnostic clinical symptom of PSP. By contrast, DLB patients are specifically impaired in both reflexive and saccadic execution and in the performance of more complex saccadic eye movement tasks. Problems in convergence in DLB are also followed by akinesia and rigidity. Abnormal ocular fixation may occur in a significant proportion of MSA patients along with excessive square-wave jerks, a mild supranuclear gaze palsy, a gaze-evoked nystagmus, a positioning down-beat nystagmus, mild-moderate saccadic hypometria, impaired smooth pursuit movements, and reduced vestibulo-ocular reflex (VOR) suppression. There may be considerable overlap between the eye movement problems characteristic of the various parkinsonian disorders, but taken together with other signs and symptoms, can be a useful aid in differential diagnosis, especially in the separation of PD and PSP.

Evaluation of hemifield sector analysis protocol in multifocal visual evoked potential (MFVEP) objective perimetry for the diagnosis and early detection of glaucomatous field defects

Visual field assessment is a core component of glaucoma diagnosis and monitoring, and the Standard Automated Perimetry (SAP) test is considered up until this moment, the gold standard of visual field assessment. Although SAP is a subjective assessment and has many pitfalls, it is being constantly used in the diagnosis of visual field loss in glaucoma. Multifocal visual evoked potential (mfVEP) is a newly introduced method used for visual field assessment objectively. Several analysis protocols have been tested to identify early visual field losses in glaucoma patients using the mfVEP technique, some were successful in detection of field defects, which were comparable to the standard SAP visual field assessment, and others were not very informative and needed more adjustment and research work. In this study, we implemented a novel analysis approach and evaluated its validity and whether it could be used effectively for early detection of visual field defects in glaucoma. OBJECTIVES: The purpose of this study is to examine the effectiveness of a new analysis method in the Multi-Focal Visual Evoked Potential (mfVEP) when it is used for the objective assessment of the visual field in glaucoma patients, compared to the gold standard technique. METHODS: 3 groups were tested in this study; normal controls (38 eyes), glaucoma patients (36 eyes) and glaucoma suspect patients (38 eyes). All subjects had a two standard Humphrey visual field HFA test 24-2 and a single mfVEP test undertaken in one session. Analysis of the mfVEP results was done using the new analysis protocol; the Hemifield Sector Analysis HSA protocol. Analysis of the HFA was done using the standard grading system. RESULTS: Analysis of mfVEP results showed that there was a statistically significant difference between the 3 groups in the mean signal to noise ratio SNR (ANOVA p<0.001 with a 95% CI). The difference between superior and inferior hemispheres in all subjects were all statistically significant in the glaucoma patient group 11/11 sectors (t-test p<0.001), partially significant 5/11 (t-test p<0.01) and no statistical difference between most sectors in normal group (only 1/11 was significant) (t-test p<0.9). sensitivity and specificity of the HAS protocol in detecting glaucoma was 97% and 86% respectively, while for glaucoma suspect were 89% and 79%. DISCUSSION: The results showed that the new analysis protocol was able to confirm already existing field defects detected by standard HFA, was able to differentiate between the 3 study groups with a clear distinction between normal and patients with suspected glaucoma; however the distinction between normal and glaucoma patients was especially clear and significant. CONCLUSION: The new HSA protocol used in the mfVEP testing can be used to detect glaucomatous visual field defects in both glaucoma and glaucoma suspect patient. Using this protocol can provide information about focal visual field differences across the horizontal midline, which can be utilized to differentiate between glaucoma and normal subjects. Sensitivity and specificity of the mfVEP test showed very promising results and correlated with other anatomical changes in glaucoma field loss.

A new three phase method (SDP method) for the multi-objective vehicle routing problem with simultaneous delvery and pickup (VRPSDP)

Transportation service operators are witnessing a growing demand for bi-directional movement of goods. Given this, the following thesis considers an extension to the vehicle routing problem (VRP) known as the delivery and pickup transportation problem (DPP), where delivery and pickup demands may occupy the same route. The problem is formulated here as the vehicle routing problem with simultaneous delivery and pickup (VRPSDP), which requires the concurrent service of the demands at the customer location. This formulation provides the greatest opportunity for cost savings for both the service provider and recipient. The aims of this research are to propose a new theoretical design to solve the multi-objective VRPSDP, provide software support for the suggested design and validate the method through a set of experiments. A new real-life based multi-objective VRPSDP is studied here, which requires the minimisation of the often conflicting objectives: operated vehicle fleet size, total routing distance and the maximum variation between route distances (workload variation). The former two objectives are commonly encountered in the domain and the latter is introduced here because it is essential for real-life routing problems. The VRPSDP is defined as a hard combinatorial optimisation problem, therefore an approximation method, Simultaneous Delivery and Pickup method (SDPmethod) is proposed to solve it. The SDPmethod consists of three phases. The first phase constructs a set of diverse partial solutions, where one is expected to form part of the near-optimal solution. The second phase determines assignment possibilities for each sub-problem. The third phase solves the sub-problems using a parallel genetic algorithm. The suggested genetic algorithm is improved by the introduction of a set of tools: genetic operator switching mechanism via diversity thresholds, accuracy analysis tool and a new fitness evaluation mechanism. This three phase method is proposed to address the shortcoming that exists in the domain, where an initial solution is built only then to be completely dismantled and redesigned in the optimisation phase. In addition, a new routing heuristic, RouteAlg, is proposed to solve the VRPSDP sub-problem, the travelling salesman problem with simultaneous delivery and pickup (TSPSDP). The experimental studies are conducted using the well known benchmark Salhi and Nagy (1999) test problems, where the SDPmethod and RouteAlg solutions are compared with the prominent works in the VRPSDP domain. The SDPmethod has demonstrated to be an effective method for solving the multi-objective VRPSDP and the RouteAlg for the TSPSDP.

A bi-objective weighted model for improving the discrimination power in MCDEA

Lack of discrimination power and poor weight dispersion remain major issues in Data Envelopment Analysis (DEA). Since the initial multiple criteria DEA (MCDEA) model developed in the late 1990s, only goal programming approaches; that is, the GPDEA-CCR and GPDEA-BCC were introduced for solving the said problems in a multi-objective framework. We found GPDEA models to be invalid and demonstrate that our proposed bi-objective multiple criteria DEA (BiO-MCDEA) outperforms the GPDEA models in the aspects of discrimination power and weight dispersion, as well as requiring less computational codes. An application of energy dependency among 25 European Union member countries is further used to describe the efficacy of our approach. © 2013 Elsevier B.V. All rights reserved.

Maternal cognitions, psychopathologic symptoms, and infant temperament as predictors of early infant feeding problems:a longitudinal study

Objective: The current study examined the contribution of prenatal and postnatal maternal core beliefs, self-esteem, psychopathologic symptoms, and postnatal infant temperament to the prediction of infant feeding difficulties. Method: Ninety-nine women completed questionnaires assessing their core beliefs, psychopathology, and self-esteem during pregnancy and at 6 months postpartum. At 6 months, mothers also rated their infant's temperament and feeding, and were observed feeding their infants. Results: Maternal reports of child feeding difficulties were predicted by higher levels of emotional deprivation and entitlement core beliefs and lower levels of self-sacrifice and enmeshment core beliefs during pregnancy. Postnatal social isolation core beliefs, lower maternal self-esteem, and more difficult infant temperament added significantly to the variance explained by prenatal factors. Maternal core beliefs, self-esteem, psychopathology, and infant temperament failed to significantly predict independent observations of child food refusal. Conclusion: Maternal cognitions are implicated in the development of maternal reports of feeding difficulty.

Using the max-sum algorithm for supply chain emergence in dynamic multiunit environments

Supply chain formation (SCF) is the process of determining the set of participants and exchange relationships within a network with the goal of setting up a supply chain that meets some predefined social objective. Many proposed solutions for the SCF problem rely on centralized computation, which presents a single point of failure and can also lead to problems with scalability. Decentralized techniques that aid supply chain emergence offer a more robust and scalable approach by allowing participants to deliberate between themselves about the structure of the optimal supply chain. Current decentralized supply chain emergence mechanisms are only able to deal with simplistic scenarios in which goods are produced and traded in single units only and without taking into account production capacities or input-output ratios other than 1:1. In this paper, we demonstrate the performance of a graphical inference technique, max-sum loopy belief propagation (LBP), in a complex multiunit unit supply chain emergence scenario which models additional constraints such as production capacities and input-to-output ratios. We also provide results demonstrating the performance of LBP in dynamic environments, where the properties and composition of participants are altered as the algorithm is running. Our results suggest that max-sum LBP produces consistently strong solutions on a variety of network structures in a multiunit problem scenario, and that performance tends not to be affected by on-the-fly changes to the properties or composition of participants.

Multiple criteria optimization of contemporary logistics distribution network problems

In the contemporary customer-driven supply chain, maximization of customer service plays an equally important role as minimization of costs for a company to retain and increase its competitiveness. This article develops a multiple-criteria optimization approach, combining the analytic hierarchy process (AHP) and an integer linear programming (ILP) model, to aid the design of an optimal logistics distribution network. The proposed approach outperforms traditional cost-based optimization techniques because it considers both quantitative and qualitative factors and also aims at maximizing the benefits of deliverer and customers. In the approach, the AHP is used to determine the relative importance weightings or priorities of alternative warehouses with respect to some critical customer-oriented criteria. The results of AHP prioritization are utilized as the input of the ILP model, the objective of which is to select the best warehouses at the lowest possible cost. In this article, two commercial packages are used: including Expert Choice and LINDO.

Forecasting Problems for Economic Macroparameters

The article deals with problems of forecasting of economic macroparameters on the basis of the principle of «subjective multideterminism», i.e. an expert account of maximal amount of interrelated «objective» and «subjective» causes. A description is given of the system of support of decision-making in forecasting the level of inflation and gross domestic product on the basis of the tree solution method.

Two Fundamental Problems Connected with AI

This paper is about two fundamental problems in the field of computer science. Solving these two problems is important because it has to do with the creation of Artificial Intelligence. In fact, these two problems are not very famous because they have not many applications outside the field of Artificial Intelligence. In this paper we will give a solution neither of the first nor of the second problem. Our goal will be to formulate these two problems and to give some ideas for their solution.

The Greater London Authority:problems of strategy integration

The Act that established the Greater London Authority (GLA) incorporated many of New Labour's aspirations for modern governance. Among those aspirations was the notion of policy integration, or 'joining up'. The Mayor of Greater London was required to develop a number of strategies, broadly in the planning and environmental policy domains, and to ensure that those strategies meshed into a coherent overall strategy for promoting London's economic, social and environmental well-being. How would this work in practice, given the need for coordination between the GLA and a number of related functional bodies, and given the political imperative for the GLA to make an impact quickly? Through our analysis of the strategy development and integration efforts of the GLA in its first nine months, we have gleaned new insights into the highly complex and difficult process of policy integration. We argue that the high aspirations of the Act for policy integration have not been met, policy integration instead being narrowly interpreted as the coordination of strategies to the Mayor's political agenda. Finally,we reflect on the likelihood of the GLA, as currently constituted, evolving to meet the functional requirement of policy integration.

Generalized Scalarizing Problems GENS and GENSLex of Multicriteria Optimization

* This paper is partially supported by the National Science Fund of Bulgarian Ministry of Education and Science under contract № I–1401\2004 "Interactive Algorithms and Software Systems Supporting Multicriteria Decision Making".

Multiscale modelling:approaches and challenges

Multiscale systems that are characterized by a great range of spatial–temporal scales arise widely in many scientific domains. These range from the study of protein conformational dynamics to multiphase processes in, for example, granular media or haemodynamics, and from nuclear reactor physics to astrophysics. Despite the diversity in subject areas and terminology, there are many common challenges in multiscale modelling, including validation and design of tools for programming and executing multiscale simulations. This Theme Issue seeks to establish common frameworks for theoretical modelling, computing and validation, and to help practical applications to benefit from the modelling results. This Theme Issue has been inspired by discussions held during two recent workshops in 2013: ‘Multiscale modelling and simulation’ at the Lorentz Center, Leiden (http://www.lorentzcenter.nl/lc/web/2013/569/info.php3?wsid=569&venue=Snellius), and ‘Multiscale systems: linking quantum chemistry, molecular dynamics and microfluidic hydrodynamics’ at the Royal Society Kavli Centre. The objective of both meetings was to identify common approaches for dealing with multiscale problems across different applications in fluid and soft matter systems. This was achieved by bringing together experts from several diverse communities.

Recent research trend of economic-lot scheduling problems

Purpose - This research note aims to present a summary of research concerning economic-lot scheduling problem (ELSP). Design/methodology/approach - The paper's approach is to review over 100 selected studies published in the last 15 years (1997-2012), which are then grouped under different research themes. Findings - Five research themes are identified and insights for future studies are reported at the end of this paper. Research limitations/implications - The motivation of preparing this research note is to summarize key research studies in this field since 1997, when the ELSP problems have been verified as NP-hard. Originality/value - ELSP is an important scheduling problem that has been studied since the 1950s. Because of its complexity in delivering a feasible analytical closed form solution, many studies in the last two decades employed heuristic algorithms in order to come up with good and acceptable solutions. As a consequence, the solution approaches are quite diversified. The major contribution of this paper is to provide researchers who are interested in this area with a quick reference guide on the reviewed studies. © Emerald Group Publishing Limited.

Monte Carlo Algorithms for Linear Problems

MSC Subject Classification: 65C05, 65U05.