Standardized evaluation of algorithms for computer-aided diagnosis of dementia based on structural MRI: The CADDementia challenge

Algorithms for computer-aided diagnosis of dementia based on structural MRI have demonstrated high performance in the literature, but are difficult to compare as different data sets and methodology were used for evaluation. In addition, it is unclear how the algorithms would perform on previously unseen data, and thus, how they would perform in clinical practice when there is no real opportunity to adapt the algorithm to the data at hand. To address these comparability, generalizability and clinical applicability issues, we organized a grand challenge that aimed to objectively compare algorithms based on a clinically representative multi-center data set. Using clinical practice as the starting point, the goal was to reproduce the clinical diagnosis. Therefore, we evaluated algorithms for multi-class classification of three diagnostic groups: patients with probable Alzheimer's disease, patients with mild cognitive impairment and healthy controls. The diagnosis based on clinical criteria was used as reference standard, as it was the best available reference despite its known limitations. For evaluation, a previously unseen test set was used consisting of 354 T1-weighted MRI scans with the diagnoses blinded. Fifteen research teams participated with a total of 29 algorithms. The algorithms were trained on a small training set (n = 30) and optionally on data from other sources (e.g., the Alzheimer's Disease Neuroimaging Initiative, the Australian Imaging Biomarkers and Lifestyle flagship study of aging). The best performing algorithm yielded an accuracy of 63.0% and an area under the receiver-operating-characteristic curve (AUC) of 78.8%. In general, the best performances were achieved using feature extraction based on voxel-based morphometry or a combination of features that included volume, cortical thickness, shape and intensity. The challenge is open for new submissions via the web-based framework: http://caddementia.grand-challenge.org.

Observing wind, aerosol particles, clouds and precipitation: Finland's new ground-based remote-sensing network

The Finnish Meteorological Institute, in collaboration with the University of Helsinki, has established a new ground-based remote-sensing network in Finland. The network consists of five topographically, ecologically and climatically different sites distributed from southern to northern Finland. The main goal of the network is to monitor air pollution and boundary layer properties in near real time, with a Doppler lidar and ceilometer at each site. In addition to these operational tasks, two sites are members of the Aerosols, Clouds and Trace gases Research InfraStructure Network (ACTRIS); a Ka band cloud radar at Sodankylä will provide cloud retrievals within CloudNet, and a multi-wavelength Raman lidar, PollyXT (POrtabLe Lidar sYstem eXTended), in Kuopio provides optical and microphysical aerosol properties through EARLINET (the European Aerosol Research Lidar Network). Three C-band weather radars are located in the Helsinki metropolitan area and are deployed for operational and research applications. We performed two inter-comparison campaigns to investigate the Doppler lidar performance, compare the backscatter signal and wind profiles, and to optimize the lidar sensitivity through adjusting the telescope focus length and data-integration time to ensure sufficient signal-to-noise ratio (SNR) in low-aerosol-content environments. In terms of statistical characterization, the wind-profile comparison showed good agreement between different lidars. Initially, there was a discrepancy in the SNR and attenuated backscatter coefficient profiles which arose from an incorrectly reported telescope focus setting from one instrument, together with the need to calibrate. After diagnosing the true telescope focus length, calculating a new attenuated backscatter coefficient profile with the new telescope function and taking into account calibration, the resulting attenuated backscatter profiles all showed good agreement with each other. It was thought that harsh Finnish winters could pose problems, but, due to the built-in heating systems, low ambient temperatures had no, or only a minor, impact on the lidar operation – including scanning-head motion. However, accumulation of snow and ice on the lens has been observed, which can lead to the formation of a water/ice layer thus attenuating the signal inconsistently. Thus, care must be taken to ensure continuous snow removal.

Making internalization theory good for practice: the essence of Alan Rugman’s contributions to international business

This perspectives paper and its associated commentaries examine Alan Rugman's conceptual contribution to international business scholarship. Most significantly, we highlight Rugman's version of internalization theory as an approach that integrates transaction cost economics and ‘classical’ internalization theory with elements from the resource-based view, such that it is especially relevant to strategic management. In reviewing his oeuvre, we also offer observations on his ideas for ‘new internalization theory’. We classify his other novel insights into four categories: Network Multinationals; National competitiveness; Development and public policy; and Emerging Economy MNEs. This special section offers multiple views on how his work informed the larger academic debate and considers how these ideas might evolve in the longer term.

The transaction cost economics theory of the family firm: family-based human asset specificity and the bifurcation bias

We develop a transaction cost economics theory of the family firm, building upon the concepts of family-based asset specificity, bounded rationality, and bounded reliability. We argue that the prosperity and survival of family firms depend on the absence of a dysfunctional bifurcation bias. The bifurcation bias is an expression of bounded reliability, reflected in the de facto asymmetric treatment of family vs. nonfamily assets (especially human assets). We propose that absence of bifurcation bias is critical to fostering reliability in family business functioning. Our study ends the unproductive divide between the agency and stewardship perspectives of the family firm, which offer conflicting accounts of this firm type's functioning. We show that the predictions of the agency and stewardship perspectives can be usefully reconciled when focusing on how family firms address the bifurcation bias or fail to do so.

Phosphorothioate backbone modifications of nucleotide-based drugs are potent platelet activators

Nucleotide-based drug candidates such as antisense oligonucleotides, aptamers, immunoreceptor-activating nucleotides, or (anti)microRNAs hold great therapeutic promise for many human diseases. Phosphorothioate (PS) backbone modification of nucleotide-based drugs is common practice to protect these promising drug candidates from rapid degradation by plasma and intracellular nucleases. Effects of the changes in physicochemical properties associated with PS modification on platelets have not been elucidated so far. Here we report the unexpected binding of PS-modified oligonucleotides to platelets eliciting strong platelet activation, signaling, reactive oxygen species generation, adhesion, spreading, aggregation, and thrombus formation in vitro and in vivo. Mechanistically, the platelet-specific receptor glycoprotein VI (GPVI) mediates these platelet-activating effects. Notably, platelets from GPVI function-deficient patients do not exhibit binding of PS-modified oligonucleotides, and platelet activation is fully abolished. Our data demonstrate a novel, unexpected, PS backbone-dependent, platelet-activating effect of nucleotide-based drug candidates mediated by GPVI. This unforeseen effect should be considered in the ongoing development programs for the broad range of upcoming and promising DNA/RNA therapeutics.

Interviewing children and young people with learning disabilities: guidelines for researchers and multi-professional practice

We argue that it is important for researchers and service providers to not only recognize the rights of children and young people with learning disabilities to have a ‘voice’, but also to work actively towards eliciting views from all. A set of guidelines for critical self-evaluation by those engaged in systematically collecting the views of children and young people with learning disabilities is proposed. The guidelines are based on a series of questions concerning: research aims and ethics (encompassing access/gatekeepers; consent/assent; confidentiality/anonymity/secrecy, recognition, feedback and ownership; and social responsibility) sampling, design and communication

Small wars and insurgencies in theory and practice, 1500-1850

In early modern times, warfare in Europe took on many diverse and overlapping forms. Our modern notions of ‘regular’ and ‘irregular’ warfare, of ‘major war’ and ‘small war’, have their roots in much greater diversity than such binary notions allow for. While insurgencies go back to time immemorial, they have become conceptually fused with ‘small wars’. This is a term first used to denote special operations, often carried out by military companies formed from special ethnic groups and then recruited into larger armies. In its Spanish form, guerrilla, the term ‘small war’ came to stand for an ideologically-motivated insurgency against the state authorities or occupying forces of another power. There is much overlap between the phenomena of irregular warfare in the sense of special operations alongside regular operations, and irregular warfare of insurgents against the regular forces of a state. This book demonstrates how long the two phenomena were in flux and fed on each other, from the raiding operations of the 16th century to the ‘small wars’ or special operations conducted by special units in the 19th century, which existed alongside and could merge with a popular insurgency. This book is based on a special issue of the journal Small Wars & Insurgencies.

Designing in caves: using immersive visualisations in design practice

This paper describes a study of the use of immersive Virtual reality technologies in the design of a new hospital. It uses Schön’s concept of reflective practice and video-based methods to analyse the ways design teams approach and employ a full scale 3D immersive environment – a CAVE – in collaborative design work. The analysis describes four themes relating to reflective practice occurring in the setting: orienting to the CAVE technology itself, orienting to the representation of the specific design within the CAVE, activities accounting for, or exploring alternatives within the design for the use and users of the space, and more strategic interactions around how to best represent the design and model to the client within the CAVE setting. The analysis also reveals some unique aspects of design work in this environment. Perhaps most significantly, rather than enhancing or adding to an existing understanding of design through paper based or non-immersive digital representations, it is often acting to challenge or surprise the participants as they experience the immersive, full scale version of their own design.

The Masters in Teaching and Learning (MTL): a retrospective, intrinsic case study of the process of policy into practice and its impact on teacher participants

The research reported here is a retrospective case study of the recent (2010) introduction of the Masters in Teaching and Learning (MTL) as a post-graduate level programme of professional development for teachers. It contributes to the debate and research over the past two decades about the impact of post-graduate professional development and appropriate ways of delivering it. The study is located within an extensive body of literature dealing with the importance of the teaching profession with regard to the success of schools and pupils and the impact of professional development on teaching quality and of teaching quality on attainment. A further relevant context is the ongoing tension between the teaching profession and academics on the one hand and government and political actors on the other, in respect of the approaches to professional development and to the control of educational processes. The research questions which inform the study deal with the perspectives of various participants – policy makers, programme directors, coaches and teachers studying for the MTL – on the extent to which the MTL is likely to have an ameliorative effect on teaching and pupil attainment, their experiences of the process of policy development and their experiences as course participants. The study adopts a case study approach which involves elite interviews with those responsible for the development and implementation of the MTL, questionnaires completed by MTL course participants and a comparison group taking a conventional MA and in depth interviews with participants and coaches. The results revealed tensions and difficulties associated with the development of the MTL including uneasy relationships between HE institutions and government agencies, ideas about ‘producer capture’, the relevance of the MBA model and concern over the role of coaches. However, while acknowledging various difficulties and some misconceived expectations they viewed its potential to meet its expressed aims positively, given time. Course participants were positive about their experience of the MTL and felt that it had contributed to many aspects of their professional development. Most saw it as a positive experience despite the variable quality of support from their schools, particularly in the form of the school-based coach the concept of which had been heralded as the bellwether of the MTL. It was striking that the responses of the MTL participants were very similar to those of teachers taking a conventional MA. A finding which would repay further investigation is that while the great majority of course participants felt that the MTL (and the MA) had contributed to their becoming more effective teachers they were much less confident that it had contributed to increased pupil attainment.