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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.

The choice of second person singular pronouns in authentic and constructed dialogue in late sixteenth century English.

Though the relation between religion and morality is mentioned in almost every major work Hume wrote, he never dedicated a work to examining this relation. Moreover, his treatment of the subject, where it does appear, is unsystematic. Unfortunately, looking to the secondary literature for help in understanding Hume's thought on the relation between religion and morality is of little help, since past writers have largely neglected this area of Hume's thought. The purpose of this thesis, therefore, is to systematize Hume's thought on the relation between religion and morality. In my introduction I begin with a brief presentation of the historical context in which Hume's comments on this subject were made. This aids in understanding Hume by illustrating the types of views that he was responding to. I also examine the secondary literature that has been written on Hume and his views concerning religion and morality in order to show what has been written and what sort of work still needs to be done. The core of this thesis is dedicated to systematizing Hume's thought on religion and morality. I argue that all of Hume's main claims about religion and its relation to morality support at least one of three major conclusions: (1) that morality is secular, (2) that religion cannot be the foundation for morality and (3) that religion is pernicious to morality. A chapter is dedicated to each of these topics. Lastly, I address the issue of whether or not Hume believed in a true religion. The answer to this question is essential in evaluating just how injurious Hume's comments about religion are. I argue that Hume did not believe that there can be a true religion.Dept. of Philosophy. Paper copy at Leddy Library: Theses & Major Papers - Basement, West Bldg. / Call Number: Thesis1996 .M93. Source: Masters Abstracts International, Volume: 37-01, page: 0077. Adviser: John P. Wright. Thesis (M.A.)--University of Windsor (Canada), 1996.

An uncertain global economy, offset by strong commodity prices, provided the backdrop to a subdued yet solid level of exploration activity in 2010. The major loci of activity in the Australian oil and gas industry were the Exmouth Plateau, where exploration for conventional gas in support of LNG projects was the primary driver, and the Bowen/Surat Basin, where coal seam gas (CSG) for LNG was the main target. Onshore permit awards dominated new licensing in 2010, with 31 exploration permits awarded over an area of 190,000 km2. The majority of these permits are focused on unconventional gas exploration. Conversely only 14 exploration permits (30,000 km) were awarded offshore, all in northwest Australia. This historically low level can be related to an already extensive coverage of existing permits in the offshore petroleum provinces and delays in the announcement of acreage awards from the 2009(II) acreage release. Twenty-nine 2D seismic surveys were started in 2010, with three still active at the end of the year. Once completed, the 2010 surveys will total nearly 37,000 km of data, with 76% offshore. Twenty-one 3D seismic surveys commenced in 2010, with six still active at year end. The 2010 surveys will ultimately comprise approximately 29,000 km2 of data, with 95% offshore. Northwest Australia dominated seismic activities. Exploration drilling for conventional hydrocarbon resources was relatively subdued in 2010, with 63 wells spudded, compared to 92 wells in 2008 and 74 in 2009. Of the 49 wildcat wells where results are known, 51% reported hydrocarbon discoveries. This was a little less than the 57% in 2009 and up on the 39% in 2008. The discoveries were distributed across most of the traditional petroleum provinces. High levels of CSG drilling continued in 2010, exceeding 2008 activity but less than that of 2009. At least 648 CSG wells were spudded in 2010, mostly in the new heartland plays of the Bowen/Surat, Gunnedah and Clarence-Moreton basins. This compares with more than 600 CSG wells drilled in 2008 and more than 900 in 2009. The first dedicated Australian shale gas exploration drilling took place in 2010. Emerging shale plays in the Cooper and Perth basins were tested.

Dynamic ultrasonic imaging of superficial body organs adds a new dimension to clinical sonographic examinations in that it enables the real-time evaluation of tissue motion and vascular pulsations. A high-frequency (7.2 MHz) linear-array system has been newly developed that generates simultaneous A- and B-mode displays at 60 frames/sec. The instrument produces real-time scan-converted images in standard television format for direct viewing on television (TV) monitors or clinical recording through videotape equipment. Clinical application of this dynamic imaging system has increased the diagnostic capabilities of ultrasound in ophthalmology, radiology, and pediatrics.

Abstract Laboratory investigations and test-well oscilloscope pictures were made to determine the application of acoustic signals for evaluating the effectiveness of casing cementing. This work indicated the possibilities of measuring the amplitude of acoustic signals from the pipe and from the formation, both in open and cased hole, to indicate the bonding to pipe and to formation. Field tests have shown the applicability of the system, but experience and further model tests have shown that a number of variables affect the interpretation. Some of these variables such as type of cement, quantity of admixes, sheath thickness and time of logging after cementing-are being investigated, and the results to date are included. These results indicate that it will be possible to evaluate the effectiveness of cementing under most conditions. Introduction When production tests do not agree with log, core-analysis or other formation evaluation data, the effectiveness of casing cementing is usually questioned. Even in wells which have been produced for some time and then begin to produce water or excess gas, the isolation by cement behind the casing has been found to be incomplete by a squeeze and reperforation. The answers to these questions in the past have been quite expensive and often damaging to formation productivity during the process of repair. Considerable research effort recently has been expended by service and producing companies on the cement bond log, which offers the possibility of evaluating the effectiveness of cementing. The process involves measuring the amplitude of an acoustic signal, with the quality of the cement bond (plus some other variables) affecting the signal amplitude. At this point a definition of the term "bond" should be established. For the purpose of this paper, a "bond" is defined as a coupling which joins either the pipe and cement or the cement and formation in such a manner that no intervening space is present and no density discontinuity exists except from steel to cement or from cement to formation. Acoustic Cement Bond Logging Experimental Investigation To completely evaluate the possibilities of determining the effectiveness of cement isolation with acoustic signals, a series of test holes was set up with various cement conditions using ideal Portland 15-lb/gal cement. Using an acoustic logging tool, oscilloscope pictures were taken of various spaced-receiver signals under a number of conditions. As expected, it was found that the signal through the pipe depended upon the cement bond to the pipe. Also, the amplitude of the formation signal depended upon the cement bond to the formation. The pipe signal can be considered as a vibration of the pipe which has an arrival time of 57 microseconds/ft, the bonded pipe having a very low-amplitude signal because of the damping effect of the cement sheath. The amplitude of the formation signal depends upon the presence of a bonded path through which the acoustic energy can travel. If the cement is not bonded to the formation, the signal must cross four additional solid-liquid interfaces, with the resulting loss of energy at each. Of course, some energy will be lost because of the density variation existing at the cement bond-to-formation interface, but this loss will be much less for the unbonded condition. Some of the scope pictures from this study (3 ft between the transmitter and the receiver) are presented in Figs. 1 and 2. Fig. 1(A) shows the high-amplitude pipe signal from uncemented pipe, with a very low amplitude formation signal super-imposed on the ringout of the pipe vibration. Views B and C of Fig. 1 show the same low amplitude in bonded pipe, although the section of pipe in View C was sandblasted to remove mill scale, etc. In both B and C, the high-amplitude formation signal indicates the good bond to the formation. Views D, E and F of Fig. 1 show different widths of channels and the thicknesses of cement sheaths. This and other data indicate that the thickness of the cement sheath affects the amplitude up to about a 2-in. sheath (for Portland cement); but after that point, essentially no change in amplitude can be distinguished. The channels in these three pictures were rectangular, which probably is not too common in the field; the more common situation is decentralized pipe, with insufficient cement between the pipe and formation on one side (a condition which will be shown later). JPT P. 1093^