UCL Australia

(1901). LIII. On lines and planes of closest fit to systems of points in space. The London, Edinburgh, and Dublin Philosophical Magazine and Journal of Science: Vol. 2, No. 11, pp. 559-572.

Summary A generalized form of the cross-validation criterion is applied to the choice and assessment of prediction using the data-analytic concept of a prescription. The examples used to illustrate the application are drawn from the problem areas of univariate estimation, linear regression and analysis of variance.

New evidence and consensus has led to further revision of the McDonald Criteria for diagnosis of multiple sclerosis. The use of imaging for demonstration of dissemination of central nervous system lesions in space and time has been simplified, and in some circumstances dissemination in space and time can be established by a single scan. These revisions simplify the Criteria, preserve their diagnostic sensitivity and specificity, address their applicability across populations, and may allow earlier diagnosis and more uniform and widespread use.

This article summarizes an extensive literature review addressing the question, How can we spread and sustain innovations in health service delivery and organization? It considers both content (defining and measuring the diffusion of innovation in organizations) and process (reviewing the literature in a systematic and reproducible way). This article discusses (1) a parsimonious and evidence-based model for considering the diffusion of innovations in health service organizations, (2) clear knowledge gaps where further research should be focused, and (3) a robust and transferable methodology for systematically reviewing health service policy and management. Both the model and the method should be tested more widely in a range of contexts.

The International Panel on MS Diagnosis presents revised diagnostic criteria for multiple sclerosis (MS). The focus remains on the objective demonstration of dissemination of lesions in both time and space. Magnetic resonance imaging is integrated with dinical and other paraclinical diagnostic methods. The revised criteria facilitate the diagnosis of MS in patients with a variety of presentations, including "monosymptomatic" disease suggestive of MS, disease with a typical relapsing-remitting course, and disease with insidious progression, without clear attacks and remissions. Previously used terms such as "clinically definite" and "probable MS" are no longer recommended. The outcome of a diagnostic evaluation is either MS, "possible MS" (for those at risk for MS, but for whom diagnostic evaluation is equivocal), or "not MS."

BACKGROUND: An integrative theoretical framework, developed for cross-disciplinary implementation and other behaviour change research, has been applied across a wide range of clinical situations. This study tests the validity of this framework. METHODS: Validity was investigated by behavioural experts sorting 112 unique theoretical constructs using closed and open sort tasks. The extent of replication was tested by Discriminant Content Validation and Fuzzy Cluster Analysis. RESULTS: There was good support for a refinement of the framework comprising 14 domains of theoretical constructs (average silhouette value 0.29): 'Knowledge', 'Skills', 'Social/Professional Role and Identity', 'Beliefs about Capabilities', 'Optimism', 'Beliefs about Consequences', 'Reinforcement', 'Intentions', 'Goals', 'Memory, Attention and Decision Processes', 'Environmental Context and Resources', 'Social Influences', 'Emotions', and 'Behavioural Regulation'. CONCLUSIONS: The refined Theoretical Domains Framework has a strengthened empirical base and provides a method for theoretically assessing implementation problems, as well as professional and other health-related behaviours as a basis for intervention development.

The field of aging and dementia is focusing on the characterization of the earliest stages of cognitive impairment. Recent research has identified a transitional state between the cognitive changes of normal aging and Alzheimer's disease (AD), known as mild cognitive impairment (MCI). Mild cognitive impairment refers to the clinical condition between normal aging and AD in which persons experience memory loss to a greater extent than one would expect for age, yet they do not meet currently accepted criteria for clinically probable AD. When these persons are observed longitudinally, they progress to clinically probable AD at a considerably accelerated rate compared with healthy age-matched individuals. Consequently, this condition has been recognized as suitable for possible therapeutic intervention, and several multicenter international treatment trials are under way. Because this is a topic of intense interest, a group of experts on aging and MCI from around the world in the fields of neurology, psychiatry, geriatrics, neuropsychology, neuroimaging, neuropathology, clinical trials, and ethics was convened to summarize the current state of the field of MCI. Participants reviewed the world scientific literature on aging and MCI and summarized the various topics with respect to available evidence on MCI. Diagnostic criteria and clinical outcomes of these subjects are available in the literature. Mild cognitive impairment is believed to be a high-risk condition for the development of clinically probable AD. Heterogeneity in the use of the term was recognized, and subclassifications were suggested. While no treatments are recommended for MCI currently, clinical trials regarding potential therapies are under way. Recommendations concerning ethical issues in the diagnosis and the management of subjects with MCI were made.

(1900). X. On the criterion that a given system of deviations from the probable in the case of a correlated system of variables is such that it can be reasonably supposed to have arisen from random sampling. The London, Edinburgh, and Dublin Philosophical Magazine and Journal of Science: Vol. 50, No. 302, pp. 157-175.

In this position statement of the ESC Working Group on Myocardial and Pericardial Diseases an expert consensus group reviews the current knowledge on clinical presentation, diagnosis and treatment of myocarditis, and proposes new diagnostic criteria for clinically suspected myocarditis and its distinct biopsy-proven pathogenetic forms. The aims are to bridge the gap between clinical and tissue-based diagnosis, to improve management and provide a common reference point for future registries and multicentre randomised controlled trials of aetiology-driven treatment in inflammatory heart muscle disease.

Abstract Consider a population in which sexual selection and natural selection may or may not be taking place. Assume only that the deviations from the mean in the case of any organ of any generation follow exactly or closely the normal law of frequency, then the following expressions may be shown to give the law of inheritance of the population.

This paper aims to foster discussion of the means by which bilinguals control their two language systems. It proposes an inhibitory control (IC) model that embodies the principle that there are multiple levels of control. In the model a language task schema (modulated by a higher level of control) “reactively” inhibits potential competitors for production at the lemma level by virtue of their language tags. The IC model is used to expand the explanation of the effect of category blocking in translation proposed by Kroll and Stewart (1994), and predictions of the model are tested against other data. Its relationship to other proposals and models is considered and future directions proposed.

Accents of English is about the way English is pronounced by different people in different places. Volume 1 provides a synthesizing introduction, which shows how accents vary not only geographically, but also with social class, formality, sex and age; and in volumes 2 and 3 the author examines in greater depth the various accents used by people who speak English as their mother tongue: the accents of the regions of England, Wales, Scotland and Ireland (volume 2), and of the USA, Canada, the West Indies, Australia, New Zealand, South Africa, India, Black Africa and the Far East (volume 3). Each volume can be read independently, and together they form a major scholarly survey, of considerable originality, which not only includes descriptions of hitherto neglected accents, but also examines the implications for phonological theory. Readers will find the answers to many questions: Who makes 'good' rhyme with 'mood'? Which accents have no voiced sibilants? How is a Canadian accent different from an American one, a New Zealand one from an Australian one, a Jamaican one from a Barbadian one? What are the historical reasons for British-American pronunciation differences? What sound changes are currently in progress in New York, in London, in Edinburgh? Dr Wells his written principally for students of linguistics, phonetics and English language, but the motivated general reader will also find the study both fascinating and rewarding.

Abstract The problem of testing statistical hypotheses is an old one. Its origin is usually connected with the name of Thomas Bayes, who gave the well-known theorem on the probabilities a posteriori of the possible “causes“ of a given event. Since then it has been discussed by many writers of whom we shall here mention two only, Bertrand and Borel, whose differing views serve well to illustrate the point from which we shall approach the subject. Bertrand put into statistical form a variety of hypotheses, as for example the hypothesis that a given group of stars with relatively small angular distances between them as seen from the earth, form a “system” or group in space. His method of attack, which is that in common use, consisted essentially in calculating the probability, P, that a certain character, x, of the observed facts would arise if the hypothesis tested were true. If P were very small, this would generally be considered as an indication that the hypothesis, H, was probably false, and vice versa. Bertrand expressed the pessimistic view that no test of this kind could give reliable results. Borel, however, in a later discussion, considered that the method described could be applied with success provided that the character, x, of the observed facts were properly chosen—were, in fact, a character which he terms “en quelque sorte remarquable.”

We investigate the choice of the bandwidth for the regression discontinuity estimator. We focus on estimation by local linear regression, which was shown to have attractive properties (<cross-ref type="bib" refid="bib23">Porter, J. 2003</cross-ref>, “Estimation in the Regression Discontinuity Model” (unpublished, Department of Economics, University of Wisconsin, Madison)). We derive the asymptotically optimal bandwidth under squared error loss. This optimal bandwidth depends on unknown functionals of the distribution of the data and we propose simple and consistent estimators for these functionals to obtain a fully data-driven bandwidth algorithm. We show that this bandwidth estimator is optimal according to the criterion of Li (1987, “Asymptotic Optimality for <it>C</it><inf><it>p</it></inf>, <it>C</it><inf><it>L</it></inf>, Cross-validation and Generalized Cross-validation: Discrete Index Set”, <it>Annals of Statistics</it>, <b>15</b>, 958–975), although it is not unique in the sense that alternative consistent estimators for the unknown functionals would lead to bandwidth estimators with the same optimality properties. We illustrate the proposed bandwidth, and the sensitivity to the choices made in our algorithm, by applying the methods to a data set previously analysed by Lee (2008, “Randomized Experiments from Non-random Selection in U.S. House Elections”, <it>Journal of Econometrics</it>, <b>142</b>, 675–697) as well as by conducting a small simulation study.

urban populations. We begin by defining the state of the art, explaining the science of smart cities. We define six scenarios based on new cities badging themselves as smart, older cities regenerating themselves as smart, the development of science parks, tech cities, and technopoles focused on high technologies, the development of urban services using contemporary ICT, the use of ICT to develop new urban intelligence functions, and the development of online and mobile forms of participation. Seven project areas are then proposed: Integrated Databases for the Smart City, Sensing, Networking and the Impact of New Social Media, Modelling Network Performance, Mobility and Travel Behaviour, Modelling Urban Land Use, Transport and Economic Interactions, Modelling Urban Transactional Activities in Labour and Housing Markets, Decision Support as Urban Intelligence, Participatory Governance and Planning Structures for the Smart City. Finally we anticipate the paradigm shifts that will occur in this research and define a series of key demonstrators which we believe are important to progressing a science of smart cities.

Summary The usual linear statistical model is reanalyzed using Bayesian methods and the concept of exchangeability. The general method is illustrated by applications to two-factor experimental designs and multiple regression.

IntAct (freely available at http://www.ebi.ac.uk/intact) is an open-source, open data molecular interaction database populated by data either curated from the literature or from direct data depositions. IntAct has developed a sophisticated web-based curation tool, capable of supporting both IMEx- and MIMIx-level curation. This tool is now utilized by multiple additional curation teams, all of whom annotate data directly into the IntAct database. Members of the IntAct team supply appropriate levels of training, perform quality control on entries and take responsibility for long-term data maintenance. Recently, the MINT and IntAct databases decided to merge their separate efforts to make optimal use of limited developer resources and maximize the curation output. All data manually curated by the MINT curators have been moved into the IntAct database at EMBL-EBI and are merged with the existing IntAct dataset. Both IntAct and MINT are active contributors to the IMEx consortium (http://www.imexconsortium.org).

BACKGROUND: Somatostatin analogues are commonly used to treat symptoms associated with hormone hypersecretion in neuroendocrine tumors; however, data on their antitumor effects are limited. METHODS: We conducted a randomized, double-blind, placebo-controlled, multinational study of the somatostatin analogue lanreotide in patients with advanced, well-differentiated or moderately differentiated, nonfunctioning, somatostatin receptor-positive neuroendocrine tumors of grade 1 or 2 (a tumor proliferation index [on staining for the Ki-67 antigen] of <10%) and documented disease-progression status. The tumors originated in the pancreas, midgut, or hindgut or were of unknown origin. Patients were randomly assigned to receive an extended-release aqueous-gel formulation of lanreotide (Autogel [known in the United States as Depot], Ipsen) at a dose of 120 mg (101 patients) or placebo (103 patients) once every 28 days for 96 weeks. The primary end point was progression-free survival, defined as the time to disease progression (according to the Response Evaluation Criteria in Solid Tumors, version 1.0) or death. Secondary end points included overall survival, quality of life (assessed with the European Organization for Research and Treatment of Cancer questionnaires QLQ-C30 and QLQ-GI.NET21), and safety. RESULTS: Most patients (96%) had no tumor progression in the 3 to 6 months before randomization, and 33% had hepatic tumor volumes greater than 25%. Lanreotide, as compared with placebo, was associated with significantly prolonged progression-free survival (median not reached vs. median of 18.0 months, P<0.001 by the stratified log-rank test; hazard ratio for progression or death, 0.47; 95% confidence interval [CI], 0.30 to 0.73). The estimated rates of progression-free survival at 24 months were 65.1% (95% CI, 54.0 to 74.1) in the lanreotide group and 33.0% (95% CI, 23.0 to 43.3) in the placebo group. The therapeutic effect in predefined subgroups was generally consistent with that in the overall population, with the exception of small subgroups in which confidence intervals were wide. There were no significant between-group differences in quality of life or overall survival. The most common treatment-related adverse event was diarrhea (in 26% of the patients in the lanreotide group and 9% of those in the placebo group). CONCLUSIONS: Lanreotide was associated with significantly prolonged progression-free survival among patients with metastatic enteropancreatic neuroendocrine tumors of grade 1 or 2 (Ki-67 <10%). (Funded by Ipsen; CLARINET ClinicalTrials.gov number, NCT00353496; EudraCT 2005-004904-35.).

This paper presents a model of consumer demand that is consistent with the observed expenditure patterns of individual consumers in a long time series of expenditure surveys and is also able to provide a detailed welfare analysis of shifts in relative prices. A nonparametric analysis of consumer expenditure patterns suggests that Engel curves require quadratic terms in the logarithm of expenditure. While popular models of demand such as the Translog or the Almost Ideal Demand Systems do allow flexible price responses within a theoretically coherent structure, they have expenditure share Engel curves that are linear in the logarithm of total expenditure. We derive the complete class of integrable quadratic logarithmic expenditure share systems. A specification from this class is estimated on a large pooled data set of U.K. households. Models that fail to account for Engel curvature are found to generate important distortions in the patterns of welfare losses associated with a tax increase.

Abstract There are few branches of the Theory of Evolution which appear to the mathematical statistician so much in need of exact treatment as those of Regression, Heredity, and Panmixia. Round the notion of panmixia much obscurity has accumulated, owing to the want of precise definition and quantitative measurement. The problems of regression and heredity have been dealt with by Mr. Francis Galton in his epochmaking work on ‘Natural Inheritance,’ but, although he has shown exact methods of dealing, both experimentally and mathematically, with the problems of inheritance, it does not appear that mathematicians have hitherto developed his treatment, or that biologists and medical men have yet fully appreciated that he has really shown how many of the problems which perplex them may receive at any rate a partial answer. A considerable portion of the present memoir will be devoted to the expansion and fuller development of Mr. Galton’s ideas, particularly their application to the problem of bi-parental inheritance. At the same time I shall endeavour to point out how the results apply to some current biological and medical problems. In the first place, we must definitely free our minds, in the present state of our knowledge of the mechanism of inheritance and reproduction, of any hope of reaching a mathematical relation expressing the degree of correlation between individual parent and individual offspring. The causes in any individual case of inheritance are far too complex to admit of exact treatment; and up to the present the classification of the circumstances under which greater or less degrees of correlation between special groups of parents and offspring may be expected has made but little progress. This is largely owing to a certain prevalence of almost metaphysical speculation as to the causes of heredity, which has usurped the place of that careful collection and elaborate experiment by which alone sufficient data might have been accumulated, with a view to ultimately narrowing and specialising the circumstances under which correlation was measured. We must proceed from inheritance in the mass to inheritance in narrower and narrwoer classes, rather than attempt to build up general rules on the observation of individual instances. Shortly, we must proceed by the method of statistics, rather than by the consideration of typical cases. It may seem discouraging to the medical practitioner, with the problem before him of inheritance in a particular family, to be told that nothing but averages, means, and probabilities with regard to large classes can as yet be scientifically dealt with ; but the very nature of the distribution of variation, whether healthy or morhid, seems to indicate that we are dealing with that sphere of indefinitely numerous small causes, which in so many other instances has shown itself only amenable to the calculus of chance, and not to any analysis of the individual instance. On the other hand, the mathematical theory wall be of assistance to the medical man by answering, inter alia, in its discussion of regression the problem as to the average effect upon the offspring of given degrees of morbid variation in the parents. It may enable the physician, in many cases, to state a belief based on a high degree of probability, if it offers no ground for dogma in individual cases. One of the most noteworthy results of Mr. Francis Galton’s researches is his discovery of the mode in which a population actually reproduces itself by regression and fraternal variation. It is with some expansion and fuller mathematical treatment of these ideas that this memoir commences.