The spatial patterns of beta/A4 deposit subtypes in Alzheimer's disease

The spatial patterns of diffuse, primitive, classic (cored) and compact (burnt-out) subtypes of beta/A4 deposits were studied in coronal sections of the frontal lobe and hippocampus, including the adjacent gyri, in nine cases of Alzheimer's disease (AD). If the more mature deposits were derived from the diffuse deposits then there should be a close association between their spatial patterns in a brain region. In the majority of tissues examined, all deposit subtypes occurred in clusters which varied in dimension from 200 to 6400 microns. In many tissues, the clusters appeared to be regularly spaced parallel to the pia or alveus. The mean dimension of the primitive deposit clusters was greater than those of the diffuse, classic and compact types. In about 60% of cortical tissues examined, the clusters of primitive and diffuse deposits were not in phase, i.e. they alternated along the cortical strip. Clusters of classic deposits appeared to be distributed independently of the diffuse deposit clusters. Cluster size of the primitive deposits was positively correlated with the density of the primitive deposits in a tissue but no such relationship could be detected for the diffuse deposits. This study suggested that there was a complex relationship between the clusters of the different subtypes of beta/A4 deposits. If the diffuse deposits do give rise to the primitive and classic varieties then factors unrelated to the initial deposition of beta/A4 in the form of diffuse plaques were important in the formation of the mature deposits.

Different molecular pathologies result in similar spatial patterns of cellular inclusions in neurodegenerative disease:a comparative study of eight disorders

Recent research suggests cell-to-cell transfer of pathogenic proteins such as tau and α-synuclein may play a role in neurodegeneration. Pathogenic spread along neural pathways may give rise to specific spatial patterns of the neuronal cytoplasmic inclusions (NCI) characteristic of these disorders. Hence, the spatial patterns of NCI were compared in four tauopathies, viz., Alzheimer's disease, Pick's disease, corticobasal degeneration, and progressive supranuclear palsy, two synucleinopathies, viz., dementia with Lewy bodies and multiple system atrophy, the 'fused in sarcoma' (FUS)-immunoreactive inclusions in neuronal intermediate filament inclusion disease, and the transactive response DNA-binding protein (TDP-43)-immunoreactive inclusions in frontotemporal lobar degeneration, a TDP-43 proteinopathy (FTLD-TDP). Regardless of molecular group or morphology, NCI were most frequently aggregated into clusters, the clusters being regularly distributed parallel to the pia mater. In a significant proportion of regions, the regularly distributed clusters were in the size range 400-800 μm, approximating to the dimension of cell columns associated with the cortico-cortical pathways. The data suggest that cortical NCI in different disorders exhibit a similar spatial pattern in the cortex consistent with pathogenic spread along anatomical pathways. Hence, treatments designed to protect the cortex from neurodegeneration may be applicable across several different disorders. © 2012 Springer-Verlag.

High performance numerical modeling of ultra-short laser pulse propagation based on multithreaded parallel hardware

The focus of this study is development of parallelised version of severely sequential and iterative numerical algorithms based on multi-threaded parallel platform such as a graphics processing unit. This requires design and development of a platform-specific numerical solution that can benefit from the parallel capabilities of the chosen platform. Graphics processing unit was chosen as a parallel platform for design and development of a numerical solution for a specific physical model in non-linear optics. This problem appears in describing ultra-short pulse propagation in bulk transparent media that has recently been subject to several theoretical and numerical studies. The mathematical model describing this phenomenon is a challenging and complex problem and its numerical modeling limited on current modern workstations. Numerical modeling of this problem requires a parallelisation of an essentially serial algorithms and elimination of numerical bottlenecks. The main challenge to overcome is parallelisation of the globally non-local mathematical model. This thesis presents a numerical solution for elimination of numerical bottleneck associated with the non-local nature of the mathematical model. The accuracy and performance of the parallel code is identified by back-to-back testing with a similar serial version.

Dissociable patterns of neural activity during response inhibition in depressed adolescents with and without suicidal behavior

Objectives - Impaired attentional control and behavioral control are implicated in adult suicidal behavior. Little is known about the functional integrity of neural circuitry supporting these processes in suicidal behavior in adolescence. Method - Functional magnetic resonance imaging was used in 15 adolescent suicide attempters with a history of major depressive disorder (ATTs), 15 adolescents with a history of depressive disorder but no suicide attempt (NATs), and 14 healthy controls (HCs) during the performance of a well-validated go-no-go response inhibition and motor control task that measures attentional and behavioral control and has been shown to activate prefrontal, anterior cingulate, and parietal cortical circuitries. Questionnaires assessed symptoms and standardized interviews characterized suicide attempts. Results - A 3 group by 2 condition (go-no-go response inhibition versus go motor control blocks) block-design whole-brain analysis (p < .05, corrected) showed that NATs showed greater activity than ATTs in the right anterior cingulate gyrus (p = .008), and that NATs, but not ATTs, showed significantly greater activity than HCs in the left insula (p = .004) to go-no-go response inhibition blocks. Conclusions - Although ATTs did not show differential patterns of neural activity from HCs during the go-no-go response inhibition blocks, ATTs and NATs showed differential activation of the right anterior cingulate gyrus during response inhibition. These findings indicate that suicide attempts during adolescence are not associated with abnormal activity in response inhibition neural circuitry. The differential patterns of activity in response inhibition neural circuitry in ATTs and NATs, however, suggest different neural mechanisms for suicide attempt versus major depressive disorder in general in adolescence that should be a focus of further study.

Was it good for them? Reflections on the use of MENTOR and changes in course design using general performance measures

This paper considers the use of general performance measures in evaluating specific planning and design decisions in higher education and reflects on the students' learning process. Specifically, it concerns the use of the MENTOR multimedia computer aided learning package for helping students learn about OR as part of a general business degree. It includes the transfer of responsibility for a learning module to a new staff member and a change from a single tutor to a system involving multiple tutors. Student satisfaction measures, learning outcome measures and MENTOR usage patterns are examined in monitoring the effects of the changes in course delivery. The results raise some questions about the effectiveness of general performance measures in supporting specific decisions relating to course design and planning.

Spatial patterns of phosphorylation-dependent TDP-43-immunoreactive neuronal cytoplasmic inclusions (NCI) in frontotemporal lobar degeneration with TDP-43 proteinopathy (FTLD-TDP)

The transactive response (TAR) DNA-binding protein of 43kDa (TDP-43) is an RNA binding protein encoded by the TARDPB gene. Abnormal aggregations of TDP-43 in neurons in the form of neuronal cytoplasmic inclusions (NCI) are the pathological hallmark of frontotemporal lobar degeneration with TDP-43 proteinopathy (FTLD-TDP). To investigate the role of TDP-43 in FTLD-TDP, the spatial patterns of the NCI were studied in frontal and temporal cortex of FTLD-TDP cases using a phosphorylation dependent anti-TDP-43 antibody (pTDP-43). In many regions, the NCI formed clusters and the clusters were distributed regularly parallel to the tissue boundary. In about 35% of cortical regions, cluster size of the NCI was within the size range of the modular columns of the cortex. The spatial patterns of the pTDP-immunoreactive inclusions were similar to those revealed by a phosphorylation-independent anti-TDP-43 antibody and also similar to inclusions characterized by other molecular pathologies such as tau, ?-synuclein and ‘fused in sarcoma’ (FUS). In conclusion, the data suggest degeneration of cortical and hippocampal anatomical pathways associated with accumulation of cellular pTDP-43 is characteristic of FTLD-TDP. In addition, the data are consistent with the hypothesis of cell to cell transfer of pTDP-43 within the brain.

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.

Guidelines for the design of online-questionnaires

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 (Bandilla et al., 2003; Dillman, 2000; Kwak and Radler, 2002). 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. Despite this, and the introduction of numerous tools to support online-questionnaire creation, current electronic survey design typically replicates that of paper-based questionnaires, failing to harness the full power of the electronic delivery medium. Worse, a recent environmental scan of online-questionnaire design tools found that little, if any, support is incorporated within these tools to guide questionnaire designers according to best-practice (Lumsden and Morgan, 2005). This article introduces a comprehensive set of guidelines - a practical reference guide - for the design of online-questionnaires.

Outsourcing decisions:the case of parallel production

Purpose – The purpose of this paper is to investigate an underexplored aspect of outsourcing involving a mixed strategy in which parallel production is continued in-house at the same time as outsourcing occurs. Design/methodology/approach – The study applied a multiple case study approach and drew on qualitative data collected through in-depth interviews with wood product manufacturing companies. Findings – The paper posits that there should be a variety of mixed strategies between the two governance forms of “make” or “buy.” In order to address how companies should consider the extent to which they outsource, the analysis was structured around two ends of a continuum: in-house dominance or outsourcing dominance. With an in-house-dominant strategy, outsourcing complements an organization's own production to optimize capacity utilization and outsource less cost-efficient production, or is used as a tool to learn how to outsource. With an outsourcing-dominant strategy, in-house production helps maintain complementary competencies and avoids lock-in risk. Research limitations/implications – This paper takes initial steps toward an exploration of different mixed strategies. Additional research is required to understand the costs of different mixed strategies compared with insourcing and outsourcing, and to study parallel production from a supplier viewpoint. Practical implications – This paper suggests that managers should think twice before rushing to a “me too” outsourcing strategy in which in-house capacities are completely closed. It is important to take a dynamic view of outsourcing that maintains a mixed strategy as an option, particularly in situations that involve an underdeveloped supplier market and/or as a way to develop resources over the long term. Originality/value – The concept of combining both “make” and “buy” is not new. However, little if any research has focussed explicitly on exploring the variety of different types of mixed strategies that exist on the continuum between insourcing and outsourcing.

Design, synthesis and thermal behaviour of a series of well-defined clickable and triggerable sulfonate polymers

In the printing industry, the exploitation of triggerable materials that can have their surface properties altered on application of a post-deposition external stimulus has been crucial for the production of robust layers and patterns. To this end, herein, a series of clickable poly(R-alkyl p-styrene sulfonate) homopolymers, with systematically varied thermally-labile protecting groups, has been synthesised via reversible addition-fragmentation chain transfer (RAFT) polymerisation. The polymer range has been designed to offer varied post-deposition thermal treatment to switch them from hydrophobic to hydrophilic. Suitable RAFT conditions have been identified to produce well-defined homopolymers (Đ, Mw/Mn < 1.11 in all cases) at high monomer conversions (>80% for all but one monomer) with controllable molar mass. Poly(p-styrene sulfonate) with an isobutyl protecting group has been shown to be the most readily thermolysed polymer that remains stable at room temperature, and was thus investigated further by incorporation into a diblock copolymer, P3HT-b-PiBSS, by click chemistry. The strategy for preparation of thermal modifiable block copolymers exploiting R-protected p-styrene sulfonates and azide-alkyne click chemistry presented herein allows the design of new, roll-to-roll processable materials for potential application in the printing industry, particularly organic electronics.

A comparison of spatial patterns of TDP-43 cellular inclusions in familial and sporadic frontotemporal lobar degeneration with TDP-43 proteinopathy

Abnormal protein aggregates of transactive response (TAR) DNA-binding protein (TDP-43) in the form of neuronal cytoplasmic inclusions (NCI), oligodendroglial inclusions (GI), neuronal internuclear inclusions (NII), and dystrophic neurites (DN) are the pathological hallmark of frontotemporal lobar degeneration with TDP-43 proteinopathy (FTLD-TDP). To investigate the role of phosphorylated TDP-43 (pTDP-43) in neurodegeneration in FTLD-TDP, the spatial patterns of the pTDP-43-immunoreactive NCI, GI, NII, and DN were studied in frontal and temporal cortex in three groups of cases: (1) familial FTLD-TDP caused by progranulin (GRN) mutation, (2) a miscellaneous group of familial cases containing cases caused by valosin-containing protein (VCP) mutation, ubiquitin associated protein 1 (UBAP1) mutation, and cases not associated with currently known genes, and (3) sporadic FTLD-TDP. In a significant number of brain regions, the pTDP-43-immunoreactive inclusions developed in clusters and the clusters were distributed regularly parallel to the tissue boundary. The spatial patterns of the inclusions were similar to those revealed by a phosphorylation-independent anti-TDP-43 antibody. The spatial patterns and cluster sizes of the pTDP-43-immunoreactive inclusions were similar in GRN mutation cases, remaining familial cases, and in sporadic FTLD-TDP. Hence, pathological changes initiated by different genetic factors in familial cases and by unknown causes in sporadic FTLD-TDP appear to follow a parallel course resulting in very similar patterns of degeneration of frontal and temporal lobes.

Enabling long journeys in electric vehicles:design and demonstration of an infrastructure location model

This research develops a methodology and model formulation which suggests locations for rapid chargers to help assist infrastructure development and enable greater battery electric vehicle (BEV) usage. The model considers the likely travel patterns of BEVs and their subsequent charging demands across a large road network, where no prior candidate site information is required. Using a GIS-based methodology, polygons are constructed which represent the charging demand zones for particular routes across a real-world road network. The use of polygons allows the maximum number of charging combinations to be considered whilst limiting the input intensity needed for the model. Further polygons are added to represent deviation possibilities, meaning that placement of charge points away from the shortest path is possible, given a penalty function. A validation of the model is carried out by assessing the expected demand at current rapid charging locations and comparing to recorded empirical usage data. Results suggest that the developed model provides a good approximation to real world observations, and that for the provision of charging, location matters. The model is also implemented where no prior candidate site information is required. As such, locations are chosen based on the weighted overlay between several different routes where BEV journeys may be expected. In doing so many locations, or types of locations, could be compared against one another and then analysed in relation to siting practicalities, such as cost, land permission and infrastructure availability. Results show that efficient facility location, given numerous siting possibilities across a large road network can be achieved. Slight improvements to the standard greedy adding technique are made by adding combination weightings which aim to reward important long distance routes that require more than one charge to complete.

The spatial patterns of β-amyloid (Aβ) deposits and neurofibrillary tangles (NFT) in late-onset sporadic Alzheimer's disease

The spatial patterns of β-amyloid (Aβ) deposits and neurofibrillary tangles (NFT) were studied in areas of the cerebral cortex in 16 patients with the late-onset, sporadic form of Alzheimer's disease (AD). Diffuse, primitive, and classic Aβ deposits and NFT were aggregated into clusters; the clusters being regularly distributed parallel to the pia mater in many areas. In a significant proportion of regions, the sizes of the regularly distributed clusters approximated to those of the cells of origin of the cortico-cortical projections. The diffuse and primitive Aβ deposits exhibited a similar range of spatial patterns but the classic Aβ deposits occurred less frequently in large clusters >6400m. In addition, the NFT often occurred in larger regularly distributed clusters than the Aβ deposits. The location, size, and distribution of the clusters of Aβ deposits and NFT supports the hypothesis that AD is a 'disconnection syndrome' in which degeneration of specific cortico-cortical and cortico-hippocampal pathways results in synaptic disconnection and the formation of clusters of NFT and Aβ deposits. © 2011 Nova Science Publishers, Inc.

Spatial patterns of neuronal cytoplasmic inclusions in the tauopathies: A comparative study of five disorders

The tauopathies are a major molecular group of neurodegenerative disorders characterised by the deposition of abnormal cellular aggregates of the microtubule associated protein (MAP) tau in the form of neuronal cytoplasmic inclusions (NCI). Recent research suggests that cell to cell propagation of pathogenic tau may be involved in the neurodegeneration of these disorders. If pathogenic tau spreads along anatomical pathways it may give rise to specific spatial patterns of the NCI in brain tissue. To test this hypothesis, the spatial patterns of NCI in cerebral cortical regions were compared in tissue sections taken from five major tauopathies: (1) argyrophilic grain disease (AGD), (2) Alzheimer's disease (AD), (3) corticobasal degeneration (CBD), (4) Pick's disease (PiD), and (5) progressive supranuclear palsy (PSP). In the cerebral cortex of these disorders, NCI were frequently aggregated into clusters and the clusters were regularly distributed parallel to the pia mater. In a significant proportion of regions, the mean size of the regularly distributed clusters of NCI was in the range 400 – 800 m, measured parallel to the pia mater, approximating to the dimension of cell columns associated with the cortico-cortical anatomical pathways. Hence, the data suggest that cortical NCI in the tauopathies exhibit a spatial pattern in the cortex which could result from the spread of pathogenic tau along anatomical pathways. Treatments designed to protect the cortex from tau propagation may therefore be applicable across several different disorders within this molecular group.

The effect of personality on the design team:lessons from industry for design education

This study examines the effect of individual character types in design teams through case studies at ARUP associates and five United Kingdom university design degree programmes. By observing an individual's approach and contribution within a team, patterns of design behaviour are highlighted and compared within the industrial and academic examples. Initial findings have identified discreet differences in design approach and ways of working. By identifying these initial character clusters, design behaviour can be predicted to help teams and individuals to strengthen their design process. This research brings together: 1. The design process and how engineering and design teams work to solve problems. 2. The natural characteristics of individuals and how they approach problems. This difference of approach can be viewed in relation to the design process where engineers and designers will recognise their preference for certain stages of the design process. This study suggests that these individual preferences are suited to different stages of the design process, and that industry uses teams to ensure a broad range of views, an approach design education would do well to apply by establishing collaborative input in the design process.