Fifty years of spellchecking

A short history of spellchecking from the late 1950s to the present day, describing its development through dictionary lookup, affix stripping, correction, confusion sets, and edit distance to the use of gigantic databases

Who should be prioritized for renal transplantation?: Analysis of key stakeholder preferences using discrete choice experiments

Background Policies for allocating deceased donor kidneys have recently shifted from allocation based on Human Leucocyte Antigen (HLA) tissue matching in the UK and USA. Newer allocation algorithms incorporate waiting time as a primary factor, and in the UK, young adults are also favoured. However, there is little contemporary UK research on the views of stakeholders in the transplant process to inform future allocation policy. This research project aimed to address this issue. Methods Discrete Choice Experiment (DCE) questionnaires were used to establish priorities for kidney transplantation among different stakeholder groups in the UK. Questionnaires were targeted at patients, carers, donors / relatives of deceased donors, and healthcare professionals. Attributes considered included: waiting time; donor-recipient HLA match; whether a recipient had dependents; diseases affecting life expectancy; and diseases affecting quality of life. Results Responses were obtained from 908 patients (including 98 ethnic minorities); 41 carers; 48 donors / relatives of deceased donors; and 113 healthcare professionals. The patient group demonstrated statistically different preferences for every attribute (i.e. significantly different from zero) so implying that changes in given attributes affected preferences, except when prioritizing those with no rather than moderate diseases affecting quality of life. The attributes valued highly related to waiting time, tissue match, prioritizing those with dependents, and prioritizing those with moderate rather than severe diseases affecting life expectancy. Some preferences differed between healthcare professionals and patients, and ethnic minority and non-ethnic minority patients. Only non-ethnic minority patients and healthcare professionals clearly prioritized those with better tissue matches. Conclusions Our econometric results are broadly supportive of the 2006 shift in UK transplant policy which emphasized prioritizing the young and long waiters. However, our findings suggest the need for a further review in the light of observed differences in preferences amongst ethnic minorities, and also because those with dependents may be a further priority.</p

Use of mixed methods designs in substance research: a methodological necessity in Nigeria

The utility of mixed methods (qualitative and quantitative) is becoming increasingly accepted in health sciences, but substance studies are yet to substantially benefit from such utilities. While there is a growing number of mixed methods alcohol articles concerning developed countries, developing nations are yet to embrace this method. In the Nigerian context, the importance of mixed methods research is yet to be acknowledged. This article therefore, draws on alcohol studies to argue that mixed methods designs will better equip scholars to understand, explore, describe and explain why alcohol consumption and its related problems are increasing in Nigeria. It argues that as motives for consuming alcohol in contemporary Nigeria are multiple, complex and evolving, mixed method approaches that provide multiple pathways for proffering solutions to problems should be embraced

Extracting Relevance and Affect Information from Physiological Text Annotation

We present physiological text annotation, which refers to the practice of associating physiological responses to text content in order to infer characteristics of the user information needs and affective responses. Text annotation is a laborious task, and implicit feedback has been studied as a way to collect annotations without requiring any explicit action from the user. Previous work has explored behavioral signals, such as clicks or dwell time to automatically infer annotations, and physiological signals have mostly been explored for image or video content. We report on two experiments in which physiological text annotation is studied first to 1) indicate perceived relevance and then to 2) indicate affective responses of the users. The first experiment tackles the user’s perception of relevance of an information item, which is fundamental towards revealing the user’s information needs. The second experiment is then aimed at revealing the user’s affective responses towards a -relevant- text document. Results show that physiological user signals are associated with relevance and affect. In particular, electrodermal activity (EDA) was found to be different when users read relevant content than when they read irrelevant content and was found to be lower when reading texts with negative emotional content than when reading texts with neutral content. Together, the experiments show that physiological text annotation can provide valuable implicit inputs for personalized systems. We discuss how our findings help design personalized systems that can annotate digital content using human physiology without the need for any explicit user interaction

Starreveld scoring method in diagnosing childhood constipation

Four scoring methods exist to assess severity of fecal loading on plain abdominal radiographs in constipated patients (Barr-, Starreveld-, Blethyn- and Leech). So far, the Starreveld score was used only in adult patients. To determine accuracy and intra- and inter-observer agreement of the Starreveld scoring method in the diagnosis of functional constipation among pediatric patients. In addition, we compared the Starreveld with the Barr scoring method. Thirty-four constipated and 34 non-constipated children were included. Abdominal radiographs, obtained before treatment, were rated (Starreveld- and Barr) by 4 observers. A second observation after 4 weeks was done by 3 observers. Cut-off level for the Starreveld score, accuracy as measured by the area under the receiver operator characteristics curve, and inter- and intra-observer agreement were calculated. Cut-off value for the Starreveld score was 10. AUC for Starreveld score was 0.54 and for Barr score 0.38, indicating poor discriminating power. Inter-observer agreement was 0.49-0.52 4 (Starreveld) and 0.44 (Barr), which is considered moderate. Intra-observer agreement was 0.52-0.71 (Starreveld) and 0.62- 0.76 (Barr). The Starreveld scoring method to assess fecal loading on a plain abdominal radiograph is of limited value in the diagnosis of childhood constipatio

FimL Regulates cAMP Synthesis in Pseudomonas aeruginosa

Pseudomonas aeruginosa, a ubiquitous bacteria found in diverse ecological niches, is an important cause of acute infections in immunocompromised individuals and chronic infections in patients with Cystic Fibrosis. One signaling molecule required for the coordinate regulation of virulence factors associated with acute infections is 3′, 5′-cyclic adenosine monophosphate, (cAMP), which binds to and activates a catabolite repressor homolog, Vfr. Vfr controls the transcription of many virulence factors, including those associated with Type IV pili (TFP), the Type III secretion system (T3SS), the Type II secretion system, flagellar-mediated motility, and quorum sensing systems. We previously identified FimL, a protein with histidine phosphotransfer-like domains, as a regulator of Vfr-dependent processes, including TFP-dependent motility and T3SS function. In this study, we carried out genetic and physiologic studies to further define the mechanism of action of FimL. Through a genetic screen designed to identify suppressors of FimL, we found a putative cAMP-specific phosphodiesterase (CpdA), suggesting that FimL regulates cAMP levels. Inactivation of CpdA increases cAMP levels and restores TFP-dependent motility and T3SS function to fimL mutants, consistent with in vivo phosphodiesterase activity. By constructing combinations of double and triple mutants in the two adenylate cyclase genes (cyaA and cyaB), fimL, and cpdA, we show that ΔfimL mutants resemble ΔcyaB mutants in TM defects, decreased T3SS transcription, and decreased cAMP levels. Similar to some of the virulence factors that they regulate, we demonstrate that CyaB and FimL are polarly localized. These results reveal new complexities in the regulation of diverse virulence pathways associated with acute P. aeruginosa infections

Mind-modelling with corpus stylistics in David Copperfield

We suggest an innovative approach to literary discourse by using corpus linguistic methods to address research questions from cognitive poetics. In this article, we focus on the way that readers engage in mind-modelling in the process of characterisation. The article sets out our cognitive poetic model of characterisation that emphasises the continuity between literary characterisation and real-life human relationships. The model also aims to deal with the modelling of the author’s mind in line with the modelling of the minds of fictional characters. Crucially, our approach to mind-modelling is text-driven. Therefore we are able to employ corpus linguistic techniques systematically to identify textual patterns that function as cues triggering character information. In this article, we explore our understanding of mind-modelling through the characterisation of Mr. Dick from David Copperfield by Charles Dickens. Using the CLiC tool (Corpus Linguistics in Cheshire) developed for the exploration of 19th-century fiction, we investigate the textual traces in non-quotations around this character, in order to draw out the techniques of characterisation other than speech presentation. We show that Mr. Dick is a thematically and authorially significant character in the novel, and we move towards a rigorous account of the reader’s modelling of authorial intention

ADAM15 mediates upregulation of Claudin-1 expression in breast cancer cells

A Disintegrin and Metalloproteinase-15 (ADAM15) is a transmembrane protein involved in protein ectodomain shedding, cell adhesion and signalling. We previously cloned and characterised alternatively spliced variants of ADAM15 that differ in their intracellular domains and demonstrated correlation of the expression of specific variants with breast cancer prognosis. In this study we have created isogenic cell panels (MDA-MB-231 and MCF-7) expressing five ADAM15 variants including wildtype and catalytically inactive forms. The expression of ADAM15 isoforms in MDA-MB-231 cells led to cell clustering to varying degree, without changes in EMT markers vimentin, slug and E-cadherin. Analysis of tight junction molecules revealed ADAM15 isoform specific, catalytic function dependent upregulation of Claudin-1. The expression of ADAM15A, and to a lesser degree of C and E isoforms led to an increase in Claudin-1 expression in MDA-MB-231 cells, while ADAM15B had no effect. In MCF-7 cells, ADAM15E was the principal variant inducing Claudin-1 expression. Sh-RNA mediated down-regulation of ADAM15 in ADAM15 over-expressing cells reduced Claudin-1 levels. Additionally, downregulation of endogenous ADAM15 expression in T47D cells by shRNA reduced endogenous Claudin-1 expression confirming a role for ADAM15 in regulating Claudin-1 expression. The PI3K/Akt/mTOR pathway was involved in regulating Claudin-1 expression downstream of ADAM15. Immunofluorescence analysis of MDA-MB-231 ADAM15A expressing cells showed Claudin-1 at cell-cell junctions, in the cytoplasm and nuclei. ADAM15 co-localised with Claudin-1 and ZO1 at cell-cell junctions. Immunoprecipitation analysis demonstrated complex formation between ADAM15 and ZO1/ZO2. These findings highlight the importance of ADAM15 Intra Cellular Domain-mediated interactions in regulating substrate selection and breast cancer cell phenotype

Antigenic Variation in Plasmodium falciparum Malaria Involves a Highly Structured Switching Pattern

Many pathogenic bacteria, fungi, and protozoa achieve chronic infection through an immune evasion strategy known as antigenic variation. In the human malaria parasite Plasmodium falciparum, this involves transcriptional switching among members of the var gene family, causing parasites with different antigenic and phenotypic characteristics to appear at different times within a population. Here we use a genome-wide approach to explore this process in vitro within a set of cloned parasite populations. Our analyses reveal a non-random, highly structured switch pathway where an initially dominant transcript switches via a set of switch-intermediates either to a new dominant transcript, or back to the original. We show that this specific pathway can arise through an evolutionary conflict in which the pathogen has to optimise between safeguarding its limited antigenic repertoire and remaining capable of establishing infections in non-naïve individuals. Our results thus demonstrate a crucial role for structured switching during the early phases of infections and provide a unifying theory of antigenic variation in P. falciparum malaria as a balanced process of parasite-intrinsic switching and immune-mediated selection