Assessment of day-to-day functioning in prodromal and early Huntington disease

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 functional impact in day-to-day activities in prHD and early HD individuals.

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.

Assessment of depression, anxiety and apathy in prodromal and early Huntington disease

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 Depression, Anxiety and Apathy in prHD and early HD individuals.

Assessment of motor symptoms and functional impact in prodromal and early Huntington disease.

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 functional impact of motor manifestations in prHD and early HD individuals.

An item response analysis of the motor and behavioral subscales of the unified Huntington's disease rating scale in huntington disease gene expansion carriers

Although the Unified Huntington's Disease Rating Scale (UHDRS) is widely used in the assessment of Huntington disease (HD), the ability of individual items to discriminate individual differences in motor or behavioral manifestations has not been extensively studied in HD gene expansion carriers without a motor-defined clinical diagnosis (ie, prodromal-HD or prHD). To elucidate the relationship between scores on individual motor and behavioral UHDRS items and total score for each subscale, a nonparametric item response analysis was performed on retrospective data from 2 multicenter longitudinal studies. Motor and behavioral assessments were supplied for 737 prHD individuals with data from 2114 visits (PREDICT-HD) and 686 HD individuals with data from 1482 visits (REGISTRY). Option characteristic curves were generated for UHDRS subscale items in relation to their subscale score. In prHD, overall severity of motor signs was low, and participants had scores of 2 or above on very few items. In HD, motor items that assessed ocular pursuit, saccade initiation, finger tapping, tandem walking, and to a lesser extent, saccade velocity, dysarthria, tongue protrusion, pronation/supination, Luria, bradykinesia, choreas, gait, and balance on the retropulsion test were found to discriminate individual differences across a broad range of motor severity. In prHD, depressed mood, anxiety, and irritable behavior demonstrated good discriminative properties. In HD, depressed mood demonstrated a good relationship with the overall behavioral score. These data suggest that at least some UHDRS items appear to have utility across a broad range of severity, although many items demonstrate problematic features.

Health-related quality of life in Huntington’s Disease patients: a comparison of proxy assessment and patient self-rating using the disease-specific Huntington’s Disease health-related quality of life questionnaire (HDQoL)

Huntington’s disease (HD) is a fatal, neurodegenerative disease for which there is no known cure. Proxy evaluation is relevant for HD as its manifestation might limit the ability of persons to report their health-related quality of life (HrQoL). This study explored patient–proxy ratings of HrQoL of persons at different stages of HD, and examined factors that may affect proxy ratings. A total of 105 patient–proxy pairs completed the Huntington’s disease health-related quality of life questionnaire (HDQoL) and other established HrQoL measures (EQ-5D and SF-12v2). Proxy–patient agreement was assessed in terms of absolute level (mean ratings) and intraclass correlation. Proxies’ ratings were at a similar level to patients’ self-ratings on an overall Summary Score and on most of the six Specific Scales of the HDQoL. On the Specific Hopes and Worries Scale, proxies on average rated HrQoL as better than patients’ self-ratings, while on both the Specific Cognitive Scale and Specific Physical and Functional Scale proxies tended to rate HrQoL more poorly than patients themselves. The patient’s disease stage and mental wellbeing (SF-12 Mental Component scale) were the two factors that primarily affected proxy assessment. Proxy scores were strongly correlated with patients’ self-ratings of HrQoL, on the Summary Scale and all Specific Scales. The patient–proxy correlation was lower for patients at moderate stages of HD compared to patients at early and advanced stages. The proxy report version of the HDQoL is a useful complementary tool to self-assessment, and a promising alternative when individual patients with advanced HD are unable to self-report.

A reappraisal of blood clotting response tests for anticoagulant resistance and a proposal for a standardised BCR test methodology

Blood clotting response (BCR) resistance tests are available for a number of anticoagulant rodenticides. However, during the development of these tests many of the test parameters have been changed, making meaningful comparisons between results difficult. It was recognised that a standard methodology was urgently required for future BCR resistance tests and, accordingly, this document presents a reappraisal of published tests, and proposes a standard protocol for future use (see Appendix). The protocol can be used to provide information on the incidence and degree of resistance in a particular rodent population; to provide a simple comparison of resistance factors between active ingredients, thus giving clear information about cross-resistance for any given strain; and to provide comparisons of susceptibility or resistance between different populations. The methodology has a sound statistical basis in being based on the ED50 response, and requires many fewer animals than the resistance tests in current use. Most importantly, tests can be used to give a clear indication of the likely practical impact of the resistance on field efficacy. The present study was commissioned and funded by the Rodenticide Resistance Action Committee (RRAC) of CropLife International.

The information content of REIT credit rating actions and transparency

We examine the short-run and long-run price reaction of equity REIT shares following credit rating actions, testing the transparency of the REIT structure. Generally, the economic effect on the stock price is subdued for both upgrades and downgrades compared to prior literature examining the broader U.S. equity market. An examination of trading volume revealed a significant increase in trading in reaction to downgrade credit rating changes, with a more subdued response to upgrades. The findings support the notion that REITs are more publicly forthcoming about the expectation of positive news in comparison to negative news.

Thinking for speaking and linguistic relativity among bilinguals: towards a new research agenda

This article evaluates how the different papers in this special issue fill a gap in our understanding of cognitive processes that are being activated when second language learners or bilinguals prepare to speak. All papers are framed in Slobin’s (1987) Thinking for Speaking theory, and aim to test whether the conceptualisation patterns that were learned in early childhood can be relearned or restructured in L2 acquisition. In many papers the focus is on identifying constraints on this restructuring process. Among these constraints, the role of typological differences between languages is investigated in great depth. The studies involve different types of learners, language combinations and tasks. As all informants were given verbal rather than non-verbal tasks, the focus is here on the effects of conceptual transfer from one language on another, and not on the effects of language on non-linguistic cognition. The paper also sketches different avenues for further research in this field and proposes that researchers working in this field might want to take up the challenge of investigating whether speakers of different languages perceive motion outside explicitly verbal contexts differently, as this will enable us to gain an understanding of linguistic relativity effects in this domain. Studying which teaching methods can help learners to restructure their conceptualisation patterns may also shed new light on the aspects of discourse organization and motion event construal that are most difficult for learners.

Reviewing the sustainability/stationarity of current account imbalances with tests for bounded integration

We investigate for 26 OECD economies whether their current account imbalances to GDP are driven by stochastic trends. Regarding bounded stationarity as the more natural counterpart of sustainability, results from Phillips–Perron tests for unit root and bounded unit root processes are contrasted. While the former hint at stationarity of current account imbalances for 12 economies, the latter indicate bounded stationarity for only six economies. Through panel-based test statistics, current account imbalances are diagnosed as bounded non-stationary. Thus, (spurious) rejections of the unit root hypothesis might be due to the existence of bounds reflecting hidden policy controls or financial crises.

Some implications of a sample of practical Turing tests

A series of imitation games involving 3-participant (simultaneous comparison of two hidden entities) and 2-participant (direct interrogation of a hidden entity) were conducted at Bletchley Park on the 100th anniversary of Alan Turing’s birth: 23 June 2012. From the ongoing analysis of over 150 games involving (expert and non-expert, males and females, adults and child) judges, machines and hidden humans (foils for the machines), we present six particular conversations that took place between human judges and a hidden entity that produced unexpected results. From this sample we focus on features of Turing’s machine intelligence test that the mathematician/code breaker did not consider in his examination for machine thinking: the subjective nature of attributing intelligence to another mind.

Can environmental performance rating programmes succeed in Africa?: an evaluation of Ghana’s AKOBEN project

The purpose of the article is to describe and analyse Ghana’s AKOBEN programme which is the first environmental performance rating and public disclosure programme in Africa. Furthermore, by means of a SWOT analysis, the article assesses the suitability of AKOBEN as a veritable tool for promoting good environmental governance in Ghana specifically and Africa in general.

The ‘thinking’ in thinking-for-speaking: where is it?

According to the thinking-for-speaking (TFS) hypothesis, speakers of different languages think differently while in the process of mentally preparing content for speech. The aim of the present paper is to critically discuss the research carried out within the TFS paradigm, against the background of the basic tenets laid out by the proponents of this framework. We will show that despite substantial progress in the investigation of crosslinguistic differences in the organisation of information in discourse, the studies that actually examine the cognitive aspects of speech production are, to date, vanishingly few. This state of affairs creates a gap in our knowledge about the thought processes that co-occur with speech production during language use and acquisition. We will argue that in order to reach a more comprehensive picture of the cognitive processes and outcomes of speech production, methodologies additional to the analysis of information organisation must be used.

Broadly speaking: vocabulary in semantic dementia shifts towards general, semantically diverse words

One of the cardinal features of semantic dementia (SD) is a steady reduction in expressive vocabulary. We investigated the nature of this breakdown by assessing the psycholinguistic characteristics of words produced spontaneously by SD patients during an autobiographical memory interview. Speech was analysed with respect to frequency and imageability, and a recently-developed measure called semantic diversity. This measure quantifies the degree to which a word can be used in a broad range of different linguistic contexts. We used this measure in a formal exploration of the tendency for SD patients to replace specific terms with more vague and general words, on the assumption that more specific words are used in a more constrained set of contexts. Relative to healthy controls, patients were less likely to produce low-frequency, high-imageability words, and more likely to produce highly frequent, abstract words. These changes in the lexical-semantic landscape were related to semantic diversity: the highly frequent and abstract words most prevalent in the patients' speech were also the most semantically diverse. In fact, when the speech samples of healthy controls were artificially engineered such that low semantic diversity words (e.g., garage, spanner) were replaced with broader terms (e.g., place, thing), the characteristics of their speech production came to closely resemble that of SD patients. A similar simulation in which low-frequency words were replaced was less successful in replicating the patient data. These findings indicate systematic biases in the deterioration of lexical-semantic space in SD. As conceptual knowledge degrades, speech increasingly consists of general terms that can be applied in a broad range of linguistic contexts and convey less specific information.