OPTIMIST: A new conflict resolution algorithm for ACT-R.

Several studies have suggested recently that a more dynamic conflict resolution mechanism in the ACT-R cognitive architecture (Anderson & Lebiere, 1998) could improve the decision-making behaviour of cognitive models. This part of ACT-R theory is revisited and a new solution is proposed. The new algorithm (OPTIMIST) has been implemented as an overlay to the ACT-R architecture, and can be used as an alternative mechanism. The operation of the new algorithm is tested in a model of the classical Yerkes and Dodson experiement of animals' learning. When OPTIMIST is used, the resulting model fits the data better than the previous model (e.g. R2 (R squared) increases from .85 to .93 in one example)

Testate amoebae in pollen slides

Among the non-pollen micro-fossils commonly encountered in Quaternary sediment samples prepared for pollen analysis are many shells of testate amoebae. Testate amoebae are eukaryotic micro-organisms which are increasingly used in ecological and palaeoecological studies, particularly as indicators of hydrological change in Sphagnum-dominated peatlands. In this study we address the extent to which testate amoebae are used in palynological research, the key challenges to more widespread use, and the extent to which ecological information is retained in the testate amoeba assemblages of standard palynological slides. To achieve this we review the literature on the use of testate amoebae in palynology, compare testate amoeba records produced by palynological and water-based preparation methods and carry out simulations using previously-derived datasets. Our results show that testate amoebae are widely encountered in Quaternary palynological studies, primarily in peatlands, but the information which they can provide is undermined by limited taxonomic knowledge. Many taxa are destroyed in pollen preparations, but for taxa that are retained patterns of abundance parallel those determined using water-based preparation methods. Although the loss of sensitive taxa limits the ecological information contained in testate amoeba assemblages the information preserved is likely to be useful in a multiproxy approach to palaeoenvironmental reconstruction. To help improve taxonomic awareness and encourage the use of testate amoebae in palynology we present a basic introduction to testate amoeba taxonomy and a guide to the taxonomic literature

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes

Hundreds of thousands of genetic variants have been reported to cause severe monogenic diseases, but the probability that a variant carrier develops the disease (termed penetrance) is unknown for virtually all of them. Additionally, the clinical utility of common polygenetic variation remains uncertain. Using exome sequencing from 77,184 adult individuals (38,618 multi-ancestral individuals from a type 2 diabetes case-control study and 38,566 participants from the UK Biobank, for whom genotype array data were also available), we apply clinical standard-of-care gene variant curation for eight monogenic metabolic conditions. Rare variants causing monogenic diabetes and dyslipidemias display effect sizes significantly larger than the top 1% of the corresponding polygenic scores. Nevertheless, penetrance estimates for monogenic variant carriers average 60% or lower for most conditions. We assess epidemiologic and genetic factors contributing to risk prediction in monogenic variant carriers, demonstrating that inclusion of polygenic variation significantly improves biomarker estimation for two monogenic dyslipidemias

Genetic insights into resting heart rate and its role in cardiovascular disease.

Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development

A note on LeCam’s bound for the distance between the Poisson binomial and the Poisson distribution

Poisson binomial distribution, Poisson approximation, total variation distance,

Regulating more effectively : the relationship between procedural justice, legitimacy and tax non-compliance.

In recent years, a significant number of middle-income taxpayers have been making use of aggressive tax planning strategies to reduce tax. In many cases, it is unclear whether these are designed and used by tax- payers to minimize tax legally or to avoid tax illegally. Those that are designed to exploit loopholes in tax law need to be dealt with in a way that restores faith and equity to the system. But how can tax authorities best manage taxpayers who may have inadvertently become involved in such illegal tax planning practices? Using longitudinal survey data, it will be shown that attempts to coerce and threaten taxpayers into compliance can undermine the legitimacy of the Tax Office\u27s authority, which in turn can affect taxpayers\u27 subsequent compliance behaviour. Responsive regulation, which is based on principles of procedural justice, will be discussed as an alternative enforcement strategy.<br /

Variability in transport of fish eggs and larvae. III. Effects of hydrodynamics and larval behaviour on recruitment in plaice

Transport of plaice eggs and larvae in the southern North Sea was modelled using a finite-volume advection-dispersion model with high spatial and temporal resolution. Hydrodynamic forcing was based on actual river discharge and meteorological data for a 7 mo period in the winter and spring of 1989 and 1996 to 2003. Egg and larval development was linked to temperature and each developmental stage had its own physical and behavioural properties. Two hypotheses on transport mechanisms in the late larval stages were compared: passive drift versus selective tidal stream transport (triggered by environmental cues). Modelled larval stage durations closely corresponded to empirical estimates based on otolith daily ring counts. Close correspondence was also observed between model results and survey data on settlement in the western Wadden Sea, especially for the abundance of the strong 1996 year-class and the early settlement of the 2002 year-class. Transport patterns and the proportion of larvae reaching inshore nurseries varied substantially between years. Recruitment was negatively correlated with the distance over which eggs and larvae were transported, probably because of a breakdown in connectivity between spawning and nursery areas with increased transport rates. In conclusion, meteorologically driven variability in the hydrodynamics of the southern North Sea greatly affects the transport patterns of plaice eggs and larvae and may play an important role in determining recruitment variability and spatial connectivity