The behavioural assessment of unilateral visual neglect

Unilateral spatial neglect is one of the most striking consequences of right-sided brain damage and is characterised by the patient's failure to respond to stimuli on the side contralateral to the cerebral lesion. Visual neglect disrupts many aspects of daily living such as mobility, dressing and reading, yet the underlying mechanisms remain poorly understood. Previous attempts to explain the condition have resulted in a wide variety of terms and test procedures. An adequate theoretical account of neglect requires a data-base that represents the basic patterns of impaired and preserved performance within and between individuals. Despite considerable interest in neglect, no such large scale data-base currently exists. A consideration of the factors and difficulties that contribute to this situation are reviewed in Chapter 2. The present thesis describes the development, standardisation and validation of a test battery designed to identify a wide variety of neglect behaviours observed in clinical practice. The Behavioural Inattention Test (BIT) which was standardised using a large stroke population (80) is described. Unlike existing studies of visual neglect the BIT relates test results to functional assessment and the rehabilitation of the patient. Using the test battery and normative data from 50 age matched controls, 30 patients were classified as demonstrating neglect. Neglect is more frequent and severe following right rather than left sided lesions. Inter-rater, test-retest, and parallel forms of the test show the neglect battery to be a reliable measure of patient performance. Evidence from factor analysis and correlations with "conventional" and clinical judgments demonstrate the underlying validity of the battery. Detailed group and single case studies are used to show how results from the test battery contribute and redefine current conceptions of visual neglect. These studies address aspects of visual neglect, such as the effects of line length and hemispatial position in the case of line bisection performance. They also consider vertical dimensions of visual neglect and present evidence to suggest that what is "neglected in visual neglect may still influence patient's judgments and behaviour". It is concluded that recent developments within clinical assessment and cognitive neuropsychology provide a conceptual framework within which to investigate and characterise the condition in a manner that underpins rehabilitation programmes

Giving up on consciousness as the ghost in the machine

Consciousness as used here, refers to the private, subjective experience of being aware of our perceptions, thoughts, feelings, actions, memories (psychological contents) including the intimate experience of a unified self with the capacity to generate and control actions and psychological contents. This compelling, intuitive consciousnesscentric account has, and continues to shape folk and scientific accounts of psychology and human behavior. Over the last 30 years, research from the cognitive neurosciences has challenged this intuitive social construct account when providing a neurocognitive architecture for a human psychology. Growing evidence suggests that the executive functions typically attributed to the experience of consciousness are carried out competently, backstage and outside subjective awareness by a myriad of fast, efficient non-conscious brain systems. While it remains unclear how and where the experience of consciousness is generated in the brain, we suggested that the traditional intuitive explanation that consciousness is causally efficacious is wrong-headed when providing a cognitive neuroscientific account of human psychology. Notwithstanding the compelling 1st-person experience (inside view) that convinces us that subjective awareness is the mental curator of our actions and thoughts, we argue that the best framework for building a scientific account is to be consistent with the biophysical causal dependency of prior neural processes. From a 3rd person perspective, (outside view), we propose that subjective awareness lacking causal influence, is (no more) than our experience of being aware, our awareness of our psychological content, knowing that we are aware, and the belief that that such experiences are evidence of an agentive capacity shared by others. While the human mind can be described as comprising both conscious and nonconscious aspects, both ultimately depend on neural process in the brain. In arguing for the counter-intuitive epiphenomenal perspective, we suggest that a scientific approach considers all mental aspects of mind including consciousness in terms of their underlying, preceding (causal) biological changes, in the realization that most brain processes are not accompanied by any discernible change in subjective awareness

Are lay people good at recognising the symptoms of schizophrenia?

©2013 Erritty, Wydell. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.This article has been made available through the Brunel Open Access Publishing Fund.Aim: The aim of this study was to explore the general public’s perception of schizophrenia symptoms and the need to seekhelp for symptoms. The recognition (or ‘labelling’) of schizophrenia symptoms, help-seeking behaviours and public awareness of schizophrenia have been suggested as potentially important factors relating to untreated psychosis. Method: Participants were asked to rate to what extent they believe vignettes describing classic symptoms (positive and negative) of schizophrenia indicate mental illness. They were also asked if the individuals depicted in the vignettes required help or treatment and asked to suggest what kind of help or treatment. Results: Only three positive symptoms (i.e., Hallucinatory behaviour, Unusual thought content and Suspiciousness) of schizophrenia were reasonably well perceived (above 70%) as indicating mental illness more than the other positive or negative symptoms. Even when the participants recognised that the symptoms indicated mental illness, not everyone recommended professional help. Conclusion: There may be a need to improve public awareness of schizophrenia and psychosis symptoms, particularly regarding an awareness of the importance of early intervention for psychosis

Assessing Recent Selection and Functionality at Long Non-Coding RNA Loci in the Mouse Genome

This work was supported by the Biotechnology and Biological Sciences Research Council and The Wellcome Trust. A.N. was supported by the Swiss National Science Foundation (Grant: PZ00P3_142636). H.K. was supported by the European Research Council Starting (Grant: 242597, SexGenTransEvolution) and the Swiss National Science Foundation (Grants: 130287 and 146474).Long noncoding RNAs (lncRNAs) are one of the most intensively studied groups of noncoding elements. Debate continues over what proportion of lncRNAs are functional or merely represent transcriptional noise. Although characterization of individual lncRNAs has identified approximately 200 functional loci across the Eukarya, general surveys have found only modest or no evidence of long-term evolutionary conservation. Although this lack of conservation suggests that most lncRNAs are nonfunctional, the possibility remains that some represent recent evolutionary innovations. We examine recent selection pressures acting on lncRNAs in mouse populations. We compare patterns of within-species nucleotide variation at approximately 10,000 lncRNA loci in a cohort of the wild house mouse, Mus musculus castaneus, with between-species nucleotide divergence from the rat (Rattus norvegicus). Loci under selective constraint are expected to show reduced nucleotide diversity and divergence. We find limited evidence of sequence conservation compared with putatively neutrally evolving ancestral repeats (ARs). Comparisons of sequence diversity and divergence between ARs, protein-coding (PC) exons and lncRNAs, and the associated flanking regions, show weak, but significantly lower levels of sequence diversity and divergence at lncRNAs compared with ARs. lncRNAs conserved deep in the vertebrate phylogeny show lower within-species sequence diversity than lncRNAs in general. A set of 74 functionally characterized lncRNAs show levels of diversity and divergence comparable to PC exons, suggesting that these lncRNAs are under substantial selective constraints. Our results suggest that, in mouse populations, most lncRNA loci evolve at rates similar to ARs, whereas older lncRNAs tend to show signals of selection similar to PC genes.PostprintPeer reviewe

Cost-effectiveness analysis of 3-D computerized tomography colonography versus optical colonoscopy for imaging symptomatic gastroenterology patients.

BACKGROUND: When symptomatic gastroenterology patients have an indication for colonic imaging, clinicians have a choice between optical colonoscopy (OC) and computerized tomography colonography with three-dimensional reconstruction (3-D CTC). 3-D CTC provides a minimally invasive and rapid evaluation of the entire colon, and it can be an efficient modality for diagnosing symptoms. It allows for a more targeted use of OC, which is associated with a higher risk of major adverse events and higher procedural costs. A case can be made for 3-D CTC as a primary test for colonic imaging followed if necessary by targeted therapeutic OC; however, the relative long-term costs and benefits of introducing 3-D CTC as a first-line investigation are unknown. AIM: The aim of this study was to assess the cost effectiveness of 3-D CTC versus OC for colonic imaging of symptomatic gastroenterology patients in the UK NHS. METHODS: We used a Markov model to follow a cohort of 100,000 symptomatic gastroenterology patients, aged 50 years or older, and estimate the expected lifetime outcomes, life years (LYs) and quality-adjusted life years (QALYs), and costs (£, 2010-2011) associated with 3-D CTC and OC. Sensitivity analyses were performed to assess the robustness of the base-case cost-effectiveness results to variation in input parameters and methodological assumptions. RESULTS: 3D-CTC provided a similar number of LYs (7.737 vs 7.739) and QALYs (7.013 vs 7.018) per individual compared with OC, and it was associated with substantially lower mean costs per patient (£467 vs £583), leading to a positive incremental net benefit. After accounting for the overall uncertainty, the probability of 3-D CTC being cost effective was around 60 %, at typical willingness-to-pay values of £20,000-£30,000 per QALY gained. CONCLUSION: 3-D CTC is a cost-saving and cost-effective option for colonic imaging of symptomatic gastroenterology patients compared with OC

Recent evolution in Rattus norvegicus is shaped by declining effective population size

The brown rat, Rattus norvegicus, is both a notorious pest and a frequently used model in biomedical research. By analyzing genome sequences of 12 wild-caught brown rats from their presumed ancestral range in NE China, along with the sequence of a black rat, Rattus rattus, we investigate the selective and demographic forces shaping variation in the genome. We estimate that the recent effective population size (N(e)) of this species = [Formula: see text] , based on silent site diversity. We compare patterns of diversity in these genomes with patterns in multiple genome sequences of the house mouse (Mus musculus castaneus), which has a much larger N(e). This reveals an important role for variation in the strength of genetic drift in mammalian genome evolution. By a Pairwise Sequentially Markovian Coalescent analysis of demographic history, we infer that there has been a recent population size bottleneck in wild rats, which we date to approximately 20,000 years ago. Consistent with this, wild rat populations have experienced an increased flux of mildly deleterious mutations, which segregate at higher frequencies in protein-coding genes and conserved noncoding elements. This leads to negative estimates of the rate of adaptive evolution (α) in proteins and conserved noncoding elements, a result which we discuss in relation to the strongly positive estimates observed in wild house mice. As a consequence of the population bottleneck, wild rats also show a markedly slower decay of linkage disequilibrium with physical distance than wild house mice

Evidence for Pervasive Adaptive Protein Evolution in Wild Mice

The relative contributions of neutral and adaptive substitutions to molecular evolution has been one of the most controversial issues in evolutionary biology for more than 40 years. The analysis of within-species nucleotide polymorphism and between-species divergence data supports a widespread role for adaptive protein evolution in certain taxa. For example, estimates of the proportion of adaptive amino acid substitutions (alpha) are 50% or more in enteric bacteria and Drosophila. In contrast, recent estimates of alpha for hominids have been at most 13%. Here, we estimate alpha for protein sequences of murid rodents based on nucleotide polymorphism data from multiple genes in a population of the house mouse subspecies Mus musculus castaneus, which inhabits the ancestral range of the Mus species complex and nucleotide divergence between M. m. castaneus and M. famulus or the rat. We estimate that 57% of amino acid substitutions in murids have been driven by positive selection. Hominids, therefore, are exceptional in having low apparent levels of adaptive protein evolution. The high frequency of adaptive amino acid substitutions in wild mice is consistent with their large effective population size, leading to effective natural selection at the molecular level. Effective natural selection also manifests itself as a paucity of effectively neutral nonsynonymous mutations in M. m. castaneus compared to humans

Contributions of protein-coding and regulatory change to adaptive molecular evolution in murid rodents

The contribution of regulatory versus protein change to adaptive evolution has long been controversial. In principle, the rate and strength of adaptation within functional genetic elements can be quantified on the basis of an excess of nucleotide substitutions between species compared to the neutral expectation or from effects of recent substitutions on nucleotide diversity at linked sites. Here, we infer the nature of selective forces acting in proteins, their UTRs and conserved noncoding elements (CNEs) using genome-wide patterns of diversity in wild house mice and divergence to related species. By applying an extension of the McDonald-Kreitman test, we infer that adaptive substitutions are widespread in protein-coding genes, UTRs and CNEs, and we estimate that there are at least four times as many adaptive substitutions in CNEs and UTRs as in proteins. We observe pronounced reductions in mean diversity around nonsynonymous sites (whether or not they have experienced a recent substitution). This can be explained by selection on multiple, linked CNEs and exons. We also observe substantial dips in mean diversity (after controlling for divergence) around protein-coding exons and CNEs, which can also be explained by the combined effects of many linked exons and CNEs. A model of background selection (BGS) can adequately explain the reduction in mean diversity observed around CNEs. However, BGS fails to explain the wide reductions in mean diversity surrounding exons (encompassing ~100 Kb, on average), implying that there is a substantial role for adaptation within exons or closely linked sites. The wide dips in diversity around exons, which are hard to explain by BGS, suggest that the fitness effects of adaptive amino acid substitutions could be substantially larger than substitutions in CNEs. We conclude that although there appear to be many more adaptive noncoding changes, substitutions in proteins may dominate phenotypic evolution

Re-visiting Meltsner: Policy Advice Systems and the Multi-Dimensional Nature of Professional Policy Analysis

10.2139/ssrn.15462511-2