Exhaustive search of the SNP-sNP interactome identifies epistatic effects on brain volume in two cohorts

The SNP-SNP interactome has rarely been explored in the context of neuroimaging genetics mainly due to the complexity of conducting approximately 10(11) pairwise statistical tests. However, recent advances in machine learning, specifically the iterative sure independence screening (SIS) method, have enabled the analysis of datasets where the number of predictors is much larger than the number of observations. Using an implementation of the SIS algorithm (called EPISIS), we used exhaustive search of the genome-wide, SNP-SNP interactome to identify and prioritize SNPs for interaction analysis. We identified a significant SNP pair, rs1345203 and rs1213205, associated with temporal lobe volume. We further examined the full-brain, voxelwise effects of the interaction in the ADNI dataset and separately in an independent dataset of healthy twins (QTIM). We found that each additional loading in the epistatic effect was associated with approximately 5% greater brain regional brain volume (a protective effect) in both the ADNI and QTIM samples.

Discovery and replication of dopamine-related gene effects on caudate volume in young and elderly populations (N1198) using genome-wide search

The caudate is a subcortical brain structure implicated in many common neurological and psychiatric disorders. To identify specific genes associated with variations in caudate volume, structural magnetic resonance imaging and genome-wide genotypes were acquired from two large cohorts, the Alzheimer's Disease NeuroImaging Initiative (ADNI; N=734) and the Brisbane Adolescent/Young Adult Longitudinal Twin Study (BLTS; N=464). In a preliminary analysis of heritability, around 90% of the variation in caudate volume was due to genetic factors. We then conducted genome-wide association to find common variants that contribute to this relatively high heritability. Replicated genetic association was found for the right caudate volume at single-nucleotide polymorphism rs163030 in the ADNI discovery sample (P=2.36 × 10 -6) and in the BLTS replication sample (P=0.012). This genetic variation accounted for 2.79 and 1.61% of the trait variance, respectively. The peak of association was found in and around two genes, WDR41 and PDE8B, involved in dopamine signaling and development. In addition, a previously identified mutation in PDE8B causes a rare autosomal-dominant type of striatal degeneration. Searching across both samples offers a rigorous way to screen for genes consistently influencing brain structure at different stages of life. Variants identified here may be relevant to common disorders affecting the caudate.

Identifying candidate gene effects by restricting search space in a multivariate genetic analysis of white matter microstructure

Several genetic variants are thought to influence white matter (WM) integrity, measured with diffusion tensor imaging (DTI). Voxel based methods can test genetic associations, but heavy multiple comparisons corrections are required to adjust for searching the whole brain and for all genetic variants analyzed. Thus, genetic associations are hard to detect even in large studies. Using a recently developed multi-SNP analysis, we examined the joint predictive power of a group of 18 cholesterol-related single nucleotide polymorphisms (SNPs) on WM integrity, measured by fractional anisotropy. To boost power, we limited the analysis to brain voxels that showed significant associations with total serum cholesterol levels. From this space, we identified two genes with effects that replicated in individual voxel-wise analyses of the whole brain. Multivariate analyses of genetic variants on a reduced anatomical search space may help to identify SNPs with strongest effects on the brain from a broad panel of genes.

In search of good probability assessors: An experimental comparison of elicitation rules for confidence judgments

In this paper, we use an experimental design to compare the performance of elicitation rules for subjective beliefs. Contrary to previous works in which elicited beliefs are compared to an objective benchmark, we consider a purely subjective belief framework (confidence in one’s own performance in a cognitive task and a perceptual task). The performance of different elicitation rules is assessed according to the accuracy of stated beliefs in predicting success. We measure this accuracy using two main factors: calibration and discrimination. For each of them, we propose two statistical indexes and we compare the rules’ performances for each measurement. The matching probability method provides more accurate beliefs in terms of discrimination, while the quadratic scoring rule reduces overconfidence and the free rule, a simple rule with no incentives, which succeeds in eliciting accurate beliefs. Nevertheless, the matching probability appears to be the best mechanism for eliciting beliefs due to its performances in terms of calibration and discrimination, but also its ability to elicit consistent beliefs across measures and across tasks, as well as its empirical and theoretical properties.

Balancing exploration and exploitation in particle swarm optimization on search tasking

In this study we present a combinatorial optimization method based on particle swarm optimization and local search algorithm on the multi-robot search system. Under this method, in order to create a balance between exploration and exploitation and guarantee the global convergence, at each iteration step if the distance between target and the robot become less than specific measure then a local search algorithm is performed. The local search encourages the particle to explore the local region beyond to reach the target in lesser search time. Experimental results obtained in a simulated environment show that biological and sociological inspiration could be useful to meet the challenges of robotic applications that can be described as optimization problems.

Document timespan normalisation and understanding temporality for clinical records search

Previous qualitative research has highlighted that temporality plays an important role in relevance for clinical records search. In this study, an investigation is undertaken to determine the effect that the timespan of events within a patient record has on relevance in a retrieval scenario. In addition, based on the standard practise of document length normalisation, a document timespan normalisation model that specifically accounts for timespans is proposed. Initial analysis revealed that in general relevant patient records tended to cover a longer timespan of events than non-relevant patient records. However, an empirical evaluation using the TREC Medical Records track supports the opposite view that shorter documents (in terms of timespan) are better for retrieval. These findings highlight that the role of temporality in relevance is complex and how to effectively deal with temporality within a retrieval scenario remains an open question.

Development and Simulation of a Variable Rate Controller for an Air search and Air Sampling Unmanned Aerial System

This report describes the development and simulation of a variable rate controller for a 6-degree of freedom nonlinear model. The variable rate simulation model represents an off the shelf autopilot. Flight experiment involves risks and can be expensive. Therefore a dynamic model to understand the performance characteristics of the UAS in mission simulation before actual flight test or to obtain parameters needed for the flight is important. The control and guidance is implemented in Simulink. The report tests the use of the model for air search and air sampling path planning. A GUI in which a set of mission scenarios, in which two experts (mission expert, i.e. air sampling or air search and an UAV expert) interact, is presented showing the benefits of the method.

An analysis of theories of search and search behavior

Theories of search and search behavior can be used to glean insights and generate hypotheses about how people interact with retrieval systems. This paper examines three such theories, the long standing Information Foraging Theory, along with the more recently proposed Search Economic Theory and the Interactive Probability Ranking Principle. Our goal is to develop a model for ad-hoc topic retrieval using each approach, all within a common framework, in order to (1) determine what predictions each approach makes about search behavior, and (2) show the relationships, equivalences and differences between the approaches. While each approach takes a different perspective on modeling searcher interactions, we show that under certain assumptions, they lead to similar hypotheses regarding search behavior. Moreover, we show that the models are complementary to each other, but operate at different levels (i.e., sessions, patches and situations). We further show how the differences between the approaches lead to new insights into the theories and new models. This contribution will not only lead to further theoretical developments, but also enables practitioners to employ one of the three equivalent models depending on the data available.

Still in Search of the Good Life

At the 2014 G20 held in Brisbane, Australia took the position that climate change is not an economic issue. Most others thought it was - especially the Turkish Prime Minister who is hosting the 2015 G20. It is certainly an economic issue. But, it is not just an economic issue - either in the source or the solution.

The search for genes contributing to endometriosis risk

BACKGROUND: Genetic variation contributes to the risk of developing endometriosis. This review summarizes gene mapping studies in endometriosis and the prospects of finding gene pathways contributing to disease using the latest genome-wide strategies. METHODS: To identify candidate-gene association studies of endometriosis, a systematic literature search was conducted in PubMed of publications up to 1 April 2008, using the search terms 'endometriosis' plus 'allele' or 'polymorphism' or 'gene'. Papers included were those with information on both case and control selection, showed allelic and/or genotypic results for named germ-line polymorphisms and were published in the English language. RESULTS: Genetic variants in 76 genes have been examined for association, but none shows convincing evidence of replication in multiple studies. There is evidence for genetic linkage to chromosomes 7 and 10, but the genes (or variants) in these regions contributing to disease risk have yet to be identified. Genome-wide association is a powerful method that has been successful in locating genetic variants contributing to a range of common diseases. Several groups are planning these studies in endometriosis. For this to be successful, the endometriosis research community must work together to genotype sufficient cases, using clearly defined disease classifications, and conduct the necessary replication studies in several thousands of cases and controls. CONCLUSIONS: Genes with convincing evidence for association with endometriosis are likely to be identified in large genome-wide studies. This will provide a starting point for functional and biological studies to develop better diagnosis and treatment for this debilitating disease.

Knowledge discovery from tree databases using balanced optimal search

This research is a step forward in discovering knowledge from databases of complex structure like tree or graph. Several data mining algorithms are developed based on a novel representation called Balanced Optimal Search for extracting implicit, unknown and potentially useful information like patterns, similarities and various relationships from tree data, which are also proved to be advantageous in analysing big data. This thesis focuses on analysing unordered tree data, which is robust to data inconsistency, irregularity and swift information changes, hence, in the era of big data it becomes a popular and widely used data model.

Older job seekers' job search intensity: The interplay of proactive personality, age and occupational future time perspective

Long-term unemployment of older people can have severe consequences for individuals, communities and ultimately economies, and is therefore a serious concern in countries with an ageing population. However, the interplay of chronological age and other individual difference characteristics in predicting older job seekers' job search is so far not well understood. This study investigated relationships among age, proactive personality, occupational future time perspective (FTP) and job search intensity of 182 job seekers between 43 and 77 years in Australia. Results were mostly consistent with expectations based on a combination of socio-emotional selectivity theory and the notion of compensatory psychological resources. Proactive personality was positively related to job search intensity and age was negatively related to job search intensity. Age moderated the relationship between proactive personality and job search intensity, such that the relationship was stronger at higher compared to lower ages. One dimension of occupational FTP (perceived remaining time left in the occupational context) mediated this moderating effect, but not the overall relationship between age and job search intensity. Implications for future research, including the interplay of occupational FTP and proactive personality, and some tentative practical implications are discussed.

Standardization efforts: The relationship between knowledge dimensions, search processes and innovation outcomes

We explore how a standardization effort (i.e., when a firm pursues standards to further innovation) involves different search processes for knowledge and innovation outcomes. Using an inductive case study of Vanke, a leading Chinese property developer, we show how varying degrees of knowledge complexity and codification combine to produce a typology of four types of search process: active, integrative, decentralized and passive, resulting in four types of innovation outcome: modular, radical, incremental and architectural. We argue that when the standardization effort in a firm involves highly codified knowledge, incremental and architectural innovation outcomes are fostered, while modular and radical innovations are hindered. We discuss how standardization efforts can result in a second-order innovation capability, and conclude by calling for comparative research in other settings to understand how standardization efforts can be suited to different types of search process in different industry contexts.

Dominating search: Google before the law

For many, particularly in the Anglophone world and Western Europe, it may be obvious that Google has a monopoly over online search and advertising and that this is an undesirable state of affairs, due to Google's ability to mediate information flows online. The baffling question may be why governments and regulators are doing little to nothing about this situation, given the increasingly pivotal importance of the internet and free flowing communications in our lives. However, the law concerning monopolies, namely antitrust or competition law, works in what may be seen as a less intuitive way by the general public. Monopolies themselves are not illegal. Conduct that is unlawful, i.e. abuses of that market power, is defined by a complex set of rules and revolves principally around economic harm suffered due to anticompetitive behavior. However the effect of information monopolies over search, such as Google’s, is more than just economic, yet competition law does not address this. Furthermore, Google’s collection and analysis of user data and its portfolio of related services make it difficult for others to compete. Such a situation may also explain why Google’s established search rivals, Bing and Yahoo, have not managed to provide services that are as effective or popular as Google’s own (on this issue see also the texts by Dirk Lewandowski and Astrid Mager in this reader). Users, however, are not entirely powerless. Google's business model rests, at least partially, on them – especially the data collected about them. If they stop using Google, then Google is nothing.