Assessing behavioural manifestations prior to clinical diagnosis of Huntington disease: "anger and irritability" and "obsessions and compulsions"

The Functional Rating Scale Taskforce for pre-Huntington Disease (FuRST-pHD) is a multinational, multidisciplinary initiative with the goal of developing a data-driven, comprehensive, psychometrically sound, rating scale for assessing symptoms and functional ability in prodromal and early Huntington disease (HD) gene expansion carriers. The process involves input from numerous sources to identify relevant symptom domains, including HD individuals, caregivers, and experts from a variety of fields, as well as knowledge gained from the analysis of data from ongoing large-scale studies in HD using existing clinical scales. This is an iterative process in which an ongoing series of field tests in prodromal (prHD) and early HD individuals provides the team with data on which to make decisions regarding which questions should undergo further development or testing and which should be excluded. We report here the development and assessment of the first iteration of interview questions aimed to assess "Anger and Irritability" and "Obsessions and Compulsions" in prHD individuals.

Sox1-deficient mice suffer from epilepsy associated with abnormal ventral forebrain development and olfactory cortex hyperexcitability

Mutations in several classes of embryonically-expressed transcription factor genes are associated with behavioral disorders and epilepsies. However, there is little known about how such genetic and neurodevelopmental defects lead to brain dysfunction. Here we present the characterization of an epilepsy syndrome caused by the absence of the transcription factor SOX1 in mice. In vivo electroencephalographic recordings from SOX1 mutants established a correlation between behavioral changes and cortical output that was consistent with a seizure origin in the limbic forebrain. In vitro intracellular recordings from three major forebrain regions, neocortex, hippocampus and olfactory (piriform) cortex (OC) showed that only the OC exhibits abnormal enhanced synaptic excitability and spontaneous epileptiform discharges. Furthermore, the hyperexcitability of the OC neurons was present in mutants prior to the onset of seizures but was completely absent from both the hippocampus and neocortex of the same animals. The local inhibitory GABAergic neurotransmission remained normal in the OC of SOX1-deficient brains, but there was a severe developmental deficit of OC postsynaptic target neurons, mainly GABAergic projection neurons within the olfactory tubercle and the nucleus accumbens shell. Our data show that SOX1 is essential for ventral telencephalic development and suggest that the neurodevelopmental defect disrupts local neuronal circuits leading to epilepsy in the SOX1-deficient mice

Oswald Mosley and the New Party

The book is a study of the New Party formed by Sir Oswald Mosley in 1931 following his leaving the Labour Party and prior to his forming the British Union of Fascists. It examines Mosley's transition from socialism to fascism within the wider context of British politics between the wars.

Very short delays prior to escape from potential predators may function efficiently as adaptive risk-assessment periods

Periods between predator detection and an escape response (escape delays) by prey upon attack by a predator often arise because animals trade-off the benefits such a delay gives for assessing risk accurately with the costs of not escaping as quickly as possible. We tested whether freezing behaviour (complete immobility in a previously foraging bird) observed in chaffinches before escaping from an approaching potential threat functions as a period of risk-assessment, and whether information on predator identity is gained even when time available is very short. We flew either a model of a sparrowhawk (predator) or a woodpigeon (no threat) at single chaffinches. Escape delays were significantly shorter with the hawk, except when a model first appeared close to the chaffinch. Chaffinches were significantly more vigilant when they resumed feeding after exposure to the sparrowhawk compared to the woodpigeon showing that they were able to distinguish between threats, and this applied even when time available for assessment was short (an average of 0.29 s). Our results show freezing in chaffinches functions as an effective economic risk assessment period, and that threat information is gained even when very short periods of time are available during an attack.

Intercontinental dispersal prior to human translocation revealed in a cryptogenic invasive tree

In this study, complementary species-level and intraspecific phylogenies were used to better circumscribe the original native range and history of translocation of the invasive tree Parkinsonia aculeata. Species-level phylogenies were reconstructed using three chloroplast gene regions, and amplified fragment length polymorphism (AFLP) markers were used to reconstruct the intraspecific phylogeny. Together, these phylogenies revealed the timescale of transcontinental lineage divergence and the likely source of recent introductions of the invasive. The sequence data showed that divergence between North American and Argentinean P. aculeata occurred at least 5.7 million years ago, refuting previous hypotheses of recent dispersal between North and South America. AFLP phylogenies revealed the most likely sources of naturalized populations. The AFLP data also identified putatively introgressed plants, underlining the importance of wide sampling of AFLPs and of comparison with uniparentally inherited marker data when investigating hybridizing groups. Although P. aculeata has generally been considered North American, these data show that the original native range of P. aculeata included South America; recent introductions to Africa and Australia are most likely to have occurred from South American populations.

Three-level main-effects designs exploiting prior information about model uncertainty

To explore the projection efficiency of a design, Tsai, et al [2000. Projective three-level main effects designs robust to model uncertainty. Biometrika 87, 467-475] introduced the Q criterion to compare three-level main-effects designs for quantitative factors that allow the consideration of interactions in addition to main effects. In this paper, we extend their method and focus on the case in which experimenters have some prior knowledge, in advance of running the experiment, about the probabilities of effects being non-negligible. A criterion which incorporates experimenters' prior beliefs about the importance of each effect is introduced to compare orthogonal, or nearly orthogonal, main effects designs with robustness to interactions as a secondary consideration. We show that this criterion, exploiting prior information about model uncertainty, can lead to more appropriate designs reflecting experimenters' prior beliefs. (c) 2006 Elsevier B.V. All rights reserved.

Interceptive timing: prior knowledge matters

Fast interceptive actions, such as catching a ball, rely upon accurate and precise information from vision. Recent models rely on flexible combinations of visual angle and its rate of expansion of which the tau parameter is a specific case. When an object approaches an observer, however, its trajectory may introduce bias into tau-like parameters that render these computations unacceptable as the sole source of information for actions. Here we show that observer knowledge of object size influences their action timing, and known size combined with image expansion simplifies the computations required to make interceptive actions and provides a route for experience to influence interceptive action.

Grey-box radial basis function modelling: the art of incorporating prior knowledge

A basic principle in data modelling is to incorporate available a priori information regarding the underlying data generating mechanism into the modelling process. We adopt this principle and consider grey-box radial basis function (RBF) modelling capable of incorporating prior knowledge. Specifically, we show how to explicitly incorporate the two types of prior knowledge: the underlying data generating mechanism exhibits known symmetric property and the underlying process obeys a set of given boundary value constraints. The class of orthogonal least squares regression algorithms can readily be applied to construct parsimonious grey-box RBF models with enhanced generalisation capability.

First-dimension separation with the MicroRotoforTM cell prior to SDS-PAGE and LC-MS/MS analysis

Free-flow isoelectric focusing (IEF) is a gel-free method for separating proteins based on their isoelectric point (pl) in a liquid environment and in the presence of carrier ampholytes. this method has been used with the RotoforTM cell at the preparative scale to fractionate proteins from samples containing several hundred milligrams of protein; see the refeences listed in Bio-Rad bulletin 3152. the MicroRotofor cell applies the same method to much sl=maller protein samples without dilution, separating and recoverng milligram quantities of protein in a total volume of about 2 ml.

Local versus organic: a turn in consumer preferences and willingness-to-pay

Demand for local food in the United States has significantly increased over the last decade. In an attempt to understand the drivers of this demand and how they have changed over time, we investigate the literature on organic and local foods over the last few decades. We focus our review on studies that allow comparison of characteristics now associated with both local and organic food. We summarize the major findings of these studies and their implications for understanding drivers of local food demand. Prior to the late 1990s, most studies failed to consider factors now associated with local food, and the few that included these factors found very little support for them. In many cases, the lines between local and organic were blurred. Coincident with the development of federal organic food standards, studies began to find comparatively more support for local food as distinct and separate from organic food. Our review uncovers a distinct turn in the demand for local and organic food. Before the federal organic standards, organic food was linked to small farms, animal welfare, deep sustainability, community support, and many other factors that are not associated with most organic foods today. Based on our review, we argue that demand for local food arose largely in response to corporate cooptation of the organic food market and the arrival of “organic lite.” This important shift in consumer preferences away from organic and toward local food has broad implications for the environment and society. If these patterns of consumer preferences prove to be sustainable, producers, activists, and others should be aware of the implications that these trends have for the food system at large.