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Rationale The Environmental Exposure Unit (EEU), a controlled allergen exposure model of allergic rhinitis (AR), has traditionally utilized seasonal allergens. We sought to clinically validate the use of house dust mite (HDM), a perennial allergen, in the HDM-EEU, a specially designed facility within the larger EEU. Methods Forty-four HDM-allergic and eleven non-allergic participants were screened and deemed eligible for one of two 3-h exposure sessions in the HDM-EEU. Participants were exposed to a modest or higher HDM target, with blood and nasal brushing samples collected before and after allergen exposure. Symptomatic data, including Total Nasal Symptom Score (TNSS), Total Ocular Symptom Score (TOSS), Total Rhinoconjunctivitis Symptom Score (TRSS), and Peak Nasal Inspiratory Flow (PNIF) were collected at baseline, every 30 min until 3 h, on an hourly basis for up to 12 h, and at 24 h following the onset of HDM exposure. Results The modest and higher HDM target sessions respectively featured cumulative total particle counts of 156,784 and 266,694 particles (2.5–25 µm), Der f 1 concentrations of 2.67 ng/m3 and 3.80 ng/m3, and Der p 1 concentrations of 2.07 ng/m3 and 6.66 ng/m3. Allergic participants experienced an increase in symptoms, with modest target participants plateauing at 1.5 to 2 h and achieving a mean peak TNSS of 5.74 ± 0.65, mean peak TOSS of 2.47 ± 0.56, and mean peak TRSS of 9.16 ± 1.32. High HDM-target allergics reached a mean peak TNSS of 8.17 ± 0.71, mean peak TOSS of 4.46 ± 0.62, and mean peak TRSS of 14.08 ± 1.30 at 3 h. All allergic participants’ symptoms decreased but remained higher than baseline after exiting the HDM-EEU. Sixteen participants (37.2%) were classified as Early Phase Responders (EPR), eleven (25.6%) as protracted EPR (pEPR), seven (16.3%) as Dual Phase Responders (DPR), and nine (20.9%) as Poor Responders (PR). Allergic participants experienced significant percent PNIF reductions at hours 2 and 3 compared to healthy controls. Non-allergics were asymptomatic during the study period. Conclusions The HDM-EEU is an appropriate model to study HDM-induced AR as it can generate clinically relevant AR symptoms amongst HDM-allergic individuals.

Cet article decrit une ressource electronique contenant des textes qui representent le discours oral du passe de l’anglais moderne naissant. La ressource en question est A Corpus of English Dialogues 1560–1760, un corpus de 1.2 million de mots comprenant cinq genres : les rapports de proces, depositions de temoins, pieces de theâtre, œuvres didactiques et la prose fictionnelle. Les proces et les depositions representent des dialogues authentiques avec l’intervention minimale d’un scripteur et les autres genres constituent des dialogues construits par des auteurs connus ou anonymes. Nous decrivons les proprietes des genres inclus dans ce corpus et les illustrons en commentant des extraits tires du corpus. Apres avoir presente les recherches effectuees jusqu’a present sur la base de ce materiel, nous concluons en decrivant les differentes versions du corpus disponibles pour les utilisateurs.

Introduction: Allergic rhinitis (AR) is an inflammatory disease of the nasal mucosa that can be modeled using Controlled Allergen Exposure Facilities (CACF). Recently, we clinically validated the house dust mite (HDM) Environmental Exposure Unit (EEU) facility. In the current study, we aimed to assess biological responses in the blood following HDM exposure in the HDM-EEU.Methods: Fifty-five participants passed a screening visit, where they provided consent and completed a skin prick test (SPT), then attended a modest or higher HDM exposure session. Baseline and post-exposure blood samples were collected. Complete blood counts with differentials were measured, and isolated serum was used to determine Dermatophagoides farinae- and Dermatophagoides pteronyssinus-specific IgE (sIgE) and cytokine concentrations (IL-4, IL-5, IL-6, IL-10, IL-13, TNF-α).Results: HDM-allergic participants had significantly greater SPT wheal sizes than healthy controls. sIgE concentrations were significantly greater in allergic participants, with a strong correlation between Dermatophagoides farinae and Dermatophagoides pteronyssinus. Serum eosinophil counts were significantly decreased post-exposure for allergic participants. White blood cell, neutrophil, and lymphocyte counts were significantly increased for both allergic and non-allergic participants post-exposure. Serum IL-13 concentrations were significantly reduced post-exposure in allergics while TNF-α was significantly reduced in non-allergics.Conclusion: The HDM-EEU is a useful model for investigating biologic mechanisms of HDM-induced AR. Allergic participants produced measurable biological changes compared to healthy controls following allergen exposure, specifically with serum expression of eosinophils and related markers, namely IL-5, which promotes the proliferation and differentiation of eosinophils, and IL-13, a cytokine released by eosinophils. The exact mechanisms at play require further investigation.

This chapter introduces the field of speech representation research. It gives a brief overview of scholarship on speech representation and some crucial concepts in this research field. It identifies three broad core areas that have received substantial attention in previous research—mechanics of speech representation, modes of speech representation, and the sociopragmatics of speech representation—and reviews some of the studies on present-day as well as historical materials within those areas. The authors outline the chapters of this volume, highlighting their contributions to current research. Finally, the chapter suggests a possible program for future research, identifying key topics and general contexts that deserve further attention.

This chapter explores speech representation structures in Early Modern English that exhibit a mixture of direct speech and indirect speech. Drawing data from an Electronic Text Edition of Depositions 1560–1760 (ETED), we chart the frequency and characteristics of different types of speech representation that overlap between direct and indirect speech (such as the mixture of third-person and first-person reference, and the use of reporting expression + that + direct speech representation). We show that accounting for such uses as “slipping,” free indirect speech, and/or signs of a system under development is less convincing. Instead, we argue that the mixture should be seen as exploitation of speech representation resources for various sociopragmatic and communicative purposes, such as disambiguating voices and shifting responsibilities for the speech report. The chapter thus contributes to the broader goal of enhancing our understanding of the sociopragmatics of speech representation in the history of English.

This paper explores how the Environmental Exposure Unit (EEU) experimental model can be used to further our understanding of pharmacotherapies and immunotherapies for the treatment of allergic rhinitis (AR). EEUs are used increasingly for the study of combination therapies, immunotherapies, and novel AR treatments. A combined antihistamine/corticosteroid nasal spray formulation was seen to have a faster onset of action relative to the therapies individually in the Environmental Exposure Chamber. House dust mite sublingual immunotherapy tablets are both safe and efficacious as evaluated by the Vienna Challenge Chamber. The Kingston EEU found that a novel peptide-based immunotherapy approach to be effective in reducing grass pollen-induced AR. Lastly, nasal filters were determined to reduce seasonal AR symptoms, given out-of-season in the Denmark Environmental Exposure Unit. EEUs are controlled, replicable models that provide valuable insight into the efficacy, onset and duration of action, and dose-related impacts of AR therapeutics, with direct clinical relevance.

This paper explores the representation of speech in Early Modern English witness depositions. We demonstrate that Semino and Short’s (2004) framework of description, which has for the most part been used in explorations of present-day texts, is generally applicable to our historical data. Our study shows that factors such as the importance of the evidence cited and the clarity of the deposition narrative were crucial considerations in representing speech in different contexts.

This study concerns the development of the determiners mine/my and thine/thy in the Early Modern English period. The -n forms had essentially been ousted before words starting with consonants over the Middle English period, and over the subsequent centuries, these forms also fell into disuse before words starting with initial vowels and h. While the rise of the n-less variants has been the object of several previous studies, the present investigation aims at accounting for the fate of the declining n-variants in the Corpus of English Dialogues 1560–1760, a data source comprising speech-related texts. We look into the chronological stages of development for the declining mine and thine forms, the genres that maintained these forms longest, and the speaker groups that were the last to use the forms. Comparisons are made with the results obtained in previous studies on mine/my and thine/thy variation.

“he saith yt he thinkes yt” : Linguistic Factors Influencing Third Person Singular Present Tense Verb Inflection in Early Modern English Depositions

We used mitochondrial DNA (mtDNA) control region (CR) sequences and genotypes from eight microsatellite DNA (msatDNA) loci to determine the genetic structure of the school shark ( Galeorhinus galeus ) in New Zealand, Australia and Chile. The estimates of mtDNA haplotype and nucleotide diversity were very similar in New Zealand ( h = 0.735 ± 0.032, π = 0.001 ± 0.001) and Australia ( h = 0.729 ± 0.027, π = 0.001 ± 0.001), but in Chile they were higher ( h = 0.800 ± 0.089, π = 0.002 ± 0.001). The haplotype genealogy showed evidence of two distinct clades, New Zealand and Australia combined (clade 1), and Chile (clade 2). A power analysis suggested that sample sizes were large enough to detect any significant differences within clade 1. Neutrality test, mismatch distribution, and demographic reconstructions based on a coalescence approach, suggested that the Oceania population (clade 1) went through a period of population expansion, whereas the population size of the Chile population (clade 2) has been relatively stable over the last 20,000 years. Data from microsatellite loci also supported the separation of the Oceania and Chile populations. Principal component analysis suggested that there might also be a separation of groups within clade 1, which was not statistically significant ( P = 0.434). The genetic data reported in this study supported the model of a single G. galeus stock in New Zealand and Australia. Our findings were consistent with previous tagging data that showed individual G. galeus migrate across the Tasman Sea between Australia and New Zealand, and at least some of these migration events result in successful reproduction.

Bridging the gap between university and upper secondary school English studies : The ULE project

Third-person present singular verb inflection in Early Modern English : New evidence from speech-related texts

The aim of this paper is to consider the nature and reliability of the three contemporaneous accounts relating to the 1645 Assize at Bury St. Edmunds in Suffolk, with the primary focus on the manus...

The aim of this study is to review advances in basic and clinical allergic rhinitis (AR) research over the past decade that have been conducted using controlled allergen challenge facility (CACF) models of allergen challenge. Databases, including PubMed, Medline, and Web of Science were searched for articles employing an ambient pollen exposure in a controlled facility to study AR, published between 2004 and the present date, using the terms as follows: CACF, Environmental Exposure Unit (EEU), Vienna Challenge Chamber (VCC), Fraunhofer Institute Environmental Challenge Chamber, Atlanta Allergen Exposure Unit, Biogenics Research Chamber, Allergen BioCube, Chiba and Osaka Environmental Challenge Chamber, exposure unit, challenge chamber, or environmental exposure chamber. Articles were then selected for relevance to the goals of the present review, including important contributions toward clinical and/or basic science allergy research. CACFs offer sensitive, specific, and reproducible methodology for allergen challenge. They have been employed since the 1980s and offer distinct advantages over traditional in-season multicentre trials when evaluating new treatments for AR. They have provided clinically applicable efficacy and pharmacologic information about important allergy medications, including antihistamines, decongestants, antileukotrienes, immunotherapies, and nasal steroids. CACF models have also contributed to basic science and novel/experimental therapy research. To date, no direct studies have been conducted comparing outcomes from one CACF to another. Over the past decade, CACF models have played an essential role in investigating the pathophysiology of AR and evaluating new therapies. The future opportunities for this model continue to expand.

Review of Ulrich Busse. Linguistic Variation in the Shakespeare Corpus : Morphosyntactic Variability of Second Person Pronouns.

The historical linguist has to rely on written records of a speech event for evidence regarding spoken interaction of the past. The authors consider records of trial proceedings and witness depositions, two genres that are included in A Corpus of English Dialogues 1560-1760 (currently under compilation). They present evidence both for and against the reliability of these written records as representations of past speech. The role of the scribe, as well as the printer and editor, is discussed. The authors also offer evidence to suggest that records that are contemporaneous with the speech event are preferable to later printings and editions for linguistic research. They conclude that the study of speech-related texts is of value in its own right, although these texts cannot be equated with present-day audio recordings of spoken interaction.

Testifying to Language and Life in Early Modern England : Including CD-ROM: An Electronic Text Edition of Depositions 1560-1760 (ETED)

Background Clinical predictive models leave gaps in our ability to stratify cardiovascular risk. High-throughput molecular profiling promises to improve risk classification. Methods Horizon 1 of the M easurement to U nderstand the R eclassification of D isease of C abarrus and K annapolis (MURDOCK) Study was conceived to apply emerging molecular techniques to existing data sets to characterize mechanistic diversity underlying complex human diseases, response to therapy, and prognosis. No previous studies have applied multiple, complementary molecular techniques in combination with well-developed clinical risk models to refine cardiovascular risk prediction. The MURDOCK Cardiovascular Disease Study will assess molecular profiles integrated with clinical data in "clinomic" profiles for cardiovascular risk classification. Conclusion Herein, we describe the design of and rationale for the MURDOCK Cardiovascular Disease Study.

A growing number of organizations that have several years' experience with total quality management and other forms of continuous improvement are reporting that their programs are running out of steam or have failed to live up to expectations. Most are concerned with finding better ways to execute cultural change over time. Others believe that they have let the issue of rewards fall through the cracks.

Background: Several studies suggest that inhaled and oral corticosteroids repress systemic inflammation in chronic obstructive pulmonary disease (COPD). However, the cytokines that may respond to these medications are unclear. Method: We used data from 41 patients with a history of stable moderate COPD (average age 64 years) who were randomised to inhaled fluticasone (500 μg twice daily from a Diskus inhaler), oral prednisone (30 mg daily) or placebo for 2 weeks. Using a multiplexed array system, different serum cytokines that have been implicated in COPD pathogenesis were measured. Results: We found that compared with placebo, inhaled fluticasone significantly reduced levels of soluble tumour necrosis factor receptor-2 (sTNF-R2) by 24% (95% CI, 7—38%; p = 0.01), monocyte chemoattractant protein-1 by 20% (95% CI, 5—32%; p = 0.01), interferon gamma inducible CXCL10 (IP-10) by 43% (95% CI, 3—66%; p = 0.04), and soluble L-selectin levels by 15% (95% CI, 1—28%; p = 0.04). Compared with placebo, oral prednisone reduced levels of sTNF-R2 by 26% (95% CI, 15—36%; p < 0.001), L-selectin by 22% (95% CI, 8—34%; p = 0.004), intercellular adhesion molecule-1 by 31% (95% CI, 9—48%; p = 0.01), pulmonary and activation-regulated chemokine (PARC) by 18% (95% CI, 2—32%; p = 0.03) and IP-10 by 40% (95% CI, 0—64%; p = 0.05). sTNF-R2, L-selectin and IP-10 were significantly reduced by both oral and inhaled corticosteroids. The other cytokines were not significantly repressed by either oral or inhaled corticosteroids. Conclusions: In summary, inhaled and oral corticosteroids significantly repressed a selected number of systemic cytokines in patients with stable, moderate COPD; most of the steroid-responsive cytokines appear to be chemoattractants.