bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient perceptions of the burden of coeliac disease and its treatment in the UK
Authors: WHITAKER J. K. H. , WEST J. , HOLMES G. K. T. , LOGAN R. F. A. 
Published: February 2009

SummaryBackground  Coeliac disease affects about 1% of the population, with the majority being undetected. As a consequence, there have been calls for the introduction of screening. Before screening is given serious consideration, it is important to assess how acceptable early diagnoses and treatment would be.Aim   To assess patients’ views as to the diagnosis and treatment of disease.Methods  Coeliac disease patients who had taken a gluten‐free diet for at least 12 months (mean 60 months) were mailed a questionnaire. Coeliac patients presenting with typical classical symptoms were compared with those diagnosed without such symptoms.Results  Overall, 83% (147/177) of coeliac patients returned the questionnaires. Two‐thirds (68%, 101/147) reported that their dietary restrictions reduced their enjoyment of food; 46% (68/147) believed their food cost them more and estimated this to be an extra £10 (€16) per week. Of those reporting greater cost, 31 (21%) said this was a problem for them. Half (54%, 80/147) reported doing things they enjoyed less often because of their diet, with the most common activity sacrificed being dining out (n = 65). In spite of these findings, 81% (119/147) reported being pleased that they were diagnosed, with 66% (59/89) of cases with classical symptoms wishing they had been diagnosed earlier compared with 45% (23/51) of those without such symptoms (χ2 = 6.0, P < .05). In contrast, 27% (14/51) of coeliacs diagnosed without classical symptoms regretted being diagnosed with their condition compared with 10% (9/89) of those with classical symptoms (χ2 = 7.1, P < .01).Conclusions  Even after several years of a gluten‐free diet, many patients with coeliac disease regard it as a substantial burden, with a quarter of screen detected patients reporting regret at being diagnosed. Our findings question how acceptable screening for coeliac disease would be in people with minimal or no symptoms.
Relationship between omalizumab pharmacokinetics, IgE pharmacodynamics and symptoms in patients with severe persistent allergic (IgE‐mediated) asthma
Authors: Lowe Philip J. , Tannenbaum Stacey , Gautier Aurelie , Jimenez Pablo 
Published: February 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• It had been hypothesized that there must be a relationship between free IgE concentrations and the signs and symptoms of asthma – after all, this is what drove the development of omalizumab.• However, although many statistical analyses of free IgE and spirometry data for patients equilibrated on omalizumab had shown a difference between placebo and treatment, no consistent time‐ and IgE‐dependent relationship had been shown due to the narrow range of free IgE being studied and the sparse nature of the sampling and clinical measurements in Phase III trials.WHAT THIS STUDY ADDS• The above problem was solved using a pharmacokinetic–pharmacodynamic (PK–PD) model to estimate free IgE concentrations for all time points throughout and after treatment with omalizumab, together with patient daily diary data.• This allowed for the first time the direct correlation between free IgE and signs and symptoms of asthma to be observed.• Doses and regimens for omalizumab could then be derived, through PK–PD model simulation, for suppressing free IgE to a point correlated with an improvement in clinical symptoms.AIMSOmalizumab, a subcutaneously administered anti‐IgE antibody, is effective for moderate‐to‐severe persistent allergic asthma. The aims were to (i) describe the population pharmacodynamics of free IgE with a mechanism‐based, nonlinear, omalizumab–IgE binding model; (ii) deduce a target‐free IgE suppression level by correlation with clinical outcomes; and (iii) check the adequacy of current approved dosing tables and explore potential doses and regimens beyond.METHODSConcentration data (omalizumab, free and total IgE) were obtained from 1781 patients aged 12–79 years, in four sparsely sampled randomized, placebo‐controlled studies and 152 subjects in a richly sampled single‐dose study. NONMEM predictive performance across the range of bodyweights (39–150 kg) and baseline IgE (19–1055 IU ml−1) was checked by simulation. Predicted free IgE levels were correlated with time‐averaged patient diary clinical outcomes.RESULTSThe model accurately predicted observed omalizumab, free and total IgE concentrations. Free IgE concentrations correlated well with clinical signs and symptoms, allowing a target concentration of 14 ng ml−1, at the midpoint of 4‐week clinical observation periods, to be set for determining the dose and regimen for omalizumab.CONCLUSIONSThe omalizumab–IgE binding model is predictive for free IgE and demonstrates a nonlinear time‐dependent relationship between free IgE suppression and clinical outcomes in asthma. Although currently approved dosing tables are close to optimal, it should be possible to treat patients with higher levels of baseline IgE if higher doses can be administered.
Using fractional exhaled nitric oxide to guide asthma therapy: design and methodological issues for ASthma TReatment ALgorithm studies
Authors: Gibson P. G. 
Published: February 2009

SummaryBackground
Current asthma guidelines recommend treatment based on the assessment of asthma control using symptoms and lung function. Noninvasive markers are an attractive way to modify therapy since they offer improvedselection of active treatment(s) based on individual response, and improvedtitration of treatment using markers that are better related to treatment outcomes.Aims: To review the methodological and design features of noninvasive marker studies in asthma.Methods
Systematic assessment of published randomized trials of asthma therapy guided by fraction of exhaled nitric oxide(FENO).Results
FENO has appeal as a marker to adjust asthma therapy since it is readily measured, gives reproducible results, and is responsive to changes in inhaled corticosteroid doses. However, the five randomised trials of FENO guided therapy have had mixed results. This may be because there are specific design and methodological issues that need to be addressed in the conduct of ASthma TReatment ALgorithm(ASTRAL) studies. There needs to be a clear dose response relationship for the active drugs used and the outcomes measured. The algorithm decision points should be based on outcomes in the population of interest rather than the range of values in healthy people, and the algorithm used needs to provide a sufficiently different result to clinical decision making in order for there to be any discernible benefit. A new metric is required to assess the algorithm performance, and the discordance:concordance(DC) ratio can assist with this.Conclusion
Incorporating these design features into future FENO studies should improve the study performance and aid in obtaining a better estimate of the value of FENO guided asthma therapy.
Ecological factors drive differentiation in wolves from British Columbia
Authors: Muñoz‐Fuentes Violeta , Darimont Chris T. , Wayne Robert K. , Paquet Paul C. , Leonard Jennifer A. 
Published: February 2009

AbstractAim Limited population structure is predicted for vagile, generalist species, such as the grey wolf (Canis lupusL.). Our aims were to study how genetic variability of grey wolves was distributed in an area comprising different habitats that lay within the potential dispersal range of an individual and to make inferences about the impact of ecology on population structure.Location British Columbia, Canada – which is characterized by a continuum of biogeoclimatic zones across which grey wolves are distributed – and adjacent areas in both Canada and Alaska, United States.Methods We obtained mitochondrial DNA control region sequences from grey wolves from across the province and integrated our genetic results with data on phenotype, behaviour and ecology (distance, habitat and prey composition). We also compared the genetic diversity and differentiation of British Columbia grey wolves with those of other North American wolf populations.Results We found strong genetic differentiation between adjacent populations of grey wolves from coastal and inland British Columbia. We show that the most likely factor explaining this differentiation is habitat discontinuity between the coastal and interior regions of British Columbia, as opposed to geographic distance or physical barriers to dispersal. We hypothesize that dispersing grey wolves select habitats similar to the one in which they were reared, and that this differentiation is maintained largely through behavioural mechanisms.Main conclusions The identification of strong genetic structure on a scale within the dispersing capabilities of an individual suggests that ecological factors are driving wolf differentiation in British Columbia. Coastal wolves are highly distinct and representative of a unique ecosystem, whereas inland British Columbia grey wolves are more similar to adjacent populations of wolves located in Alaska, Alberta and Northwest Territories. Given their unique ecological, morphological, behavioural and genetic characteristics, grey wolves of coastal British Columbia should be considered an Evolutionary Significant Unit (ESU) and, consequently, warrant special conservation status. If ecology can drive differentiation in a highly mobile generalist such as the grey wolf, ecology probably drives differentiation in many other species as well.
The wild goats Capra aegagrus Erxleben, 1777 of the Mediterranean Sea and the Eastern Atlantic Ocean islands
Authors: MASSETI MARCO 
Published: February 2009

ABSTRACT

Populations of wild goats that can be referred to as phenotypes of the pasang, or Bezoar goat, or wild goat Capra aegagrus Erxleben, 1777, still occur on several of the Mediterranean and Eastern Atlantic islands. Other populations became extinct not many decades ago.
Fossil evidence for the natural spread of the wild goat to any of these islands has not been found. Originating in the Near East, the region of its natural range and its earliest domestication, the species was introduced by humans onto the Mediterranean islands starting as early as the Pre‐Pottery Neolithic.
The islands of the Eastern Atlantic were colonized artificially by animals of ‘pre‐Hispanic’ origin. The principal phenotypes expressed by all these populations of goats can be matched with the characteristics of both C. a. aegagrus Erxleben, 1777 (aegagrus phenotype) and C. a. dorcas Reichenow, 1888 (dorcas phenotype).
Most of these animals currently survive on the islands without being fed by humans, and should be protected.
Effects of α1‐acid Glycoprotein Fucosylation on its Ca2+ Mobilizing Capacity in Neutrophils
Authors: Levander L. , Gunnarsson P. , Grenegård M. , Rydén I. , Påhlsson P. 
Published: February 2009

AbstractWe recently showed that the acute‐phase protein α1‐acid glycoprotein (AGP) induces rises in cytosolic calcium concentration, [Ca2+]i, in neutrophils through sialic acid dependent interactions with the neutrophil receptors siglec‐5 and/or siglec‐14. Whereas both siglec‐5 and siglec‐14 have a relatively broad specificity for sialylated oligosaccharide structures, including both structures with terminal α2–3 or α2–6 linked sialic acid, there is a markedly reduced affinity to the fucosylated epitope sialyl Lewis x (SLex). Increased fucosylation, leading to increased expression of SLex on AGP is commonly associated with inflammatory conditions. In the present study, we investigated whether an increased SLex expression would affect the Ca2+‐mobilizing effect of AGP. AGP with elevated fucose content isolated from patients with untreated chronic joint inflammation showed a decreased [Ca2+]i modulatory effect on neutrophils compared to normally fucosylated AGP. Furthermore a hyperfucosylated AGP form produced by in vitro fucosylation, that consequently had an elevated expression of SLex, could not elicit a [Ca2+]i increase in neutrophils. The role of the carbohydrate portion of AGP in modulating neutrophil responses was further strengthened by showing that synthetic glycoconjugates carrying oligosaccharides with terminal α2–3 or α2–6 linked sialic acid were able to mimic the Ca2+‐mobilizing effect of AGP whereas a synthetic glycoconjugate carrying SLex was not. Based on these data, we conclude that increased fucosylation can alter the ability of AGP to induce neutrophil signalling and further supports an important role of the oligosaccharide chains of AGP in the modulation of leukocyte functions during an inflammatory process.
Herpes Simplex Virus Infection Downmodulates NKG2D Ligand Expression
Authors: Schepis D. , D’Amato M. , Studahl M. , Bergström T. , Kärre K. , Berg L. 
Published: February 2009

AbstractHerpes simplex virus (HSV) type 1 infection may cause orofacial infections in humans. The virus resides in a latent form in neural ganglia and occasionally reactivates and infects epithelial cells. Natural killer (NK) cells have been implicated in immune control of herpes virus infections, possibly by downmodulating major histocompatibility complex (MHC) class I and by other, as yet unidentified, mechanisms. Upon HSV‐1 infection of cell lines, surface levels of NKG2D ligands MHC class I related proteins (MIC) A and UL16 binding protein 2 were downmodulated due to late viral gene product(s). As also MHC class I levels were reduced by HSV‐1, NK cell recognition of HeLa cells was not affected by infection. Total cellular MICA contents remained unchanged, suggesting masking, internalization or intracellular retention of MICA as possible mechanisms of viral downregualtion of MICA surface levels. Furthermore, NK cells from patients with active HSV‐1 infection had a tendency towards increased expression level of the activating receptor NKG2D. These data support a role for NKG2D–MICA interactions in immune responses to HSV‐1 reactivation.
Identification of the Arabidopsis dry2/sqe1‐5 mutant reveals a central role for sterols in drought tolerance and regulation of reactive oxygen species
Authors: Posé David , Castanedo Itziar , Borsani Omar , Nieto Benjamín , Rosado Abel , Taconnat Ludivine , Ferrer Albert , Dolan Liam , Valpuesta Victoriano , Botella Miguel A. 
Published: February 2009

SummarySqualene epoxidase enzymes catalyse the conversion of squalene into 2,3‐oxidosqualene, the precursor of cyclic triterpenoids. Here we report that the Arabidopsis drought hypersensitive/squalene epoxidase 1‐5 (dry2/sqe1‐5) mutant, identified by its extreme hypersensitivity to drought stress, has altered stomatal responses and root defects because of a point mutation in the SQUALENE EPOXIDASE 1 (SQE1) gene. GC‐MS analysis indicated that the dry2/sqe1‐5 mutant has altered sterol composition in roots but wild‐type sterol composition in shoots, indicating an essential role for SQE1 in root sterol biosynthesis. Importantly, the stomatal and root defects of the dry2/sqe1‐5 mutant are associated with altered production of reactive oxygen species. As RHD2 NADPH oxidase is de‐localized in dry2/sqe1‐5 root hairs, we propose that sterols play an essential role in the localization of NADPH oxidases required for regulation of reactive oxygen species, stomatal responses and drought tolerance.
Macroscopic Anatomy of the Great Vessels and Structures Associated with the Heart of the Ringed Seal (Pusa hispida)
Authors: Smodlaka H. , Henry R. W. , Reed R. B. 
Published: February 2009

SummaryThe ringed seal [Pusa (Phoca) hispida], as well as other seals, exhibits unique anatomical properties when compared to its terrestrial counterparts. In the ringed seal, the most conspicuous marine adaptation is the aortic bulb. This large dilatation of the ascending aorta is comparable to that found in other seal species and marine mammals. The branches of the ascending aorta (brachiocephalic trunk, left common carotid artery and left subclavian artery) are similar to those of higher primates and man. The peculiarities of the venous system are: three pulmonary veins, a pericardial venous plexus, a caval sphincter, a hepatic sinus with paired caudal vena cavae and a large extradural venous plexus. Generally, three common pulmonary veins (right, left and caudal) empty into the left atrium. The pericardial venous plexus lies deep to the mediastinal pericardial pleura (pleura pericardica) on the auricular (ventral) surface of the heart. The caval sphincter surrounds the caudal vena cava as it passes through the diaphragm. Caudal to the diaphragm, the vena cava is dilated (the hepatic sinus), and near the cranial extremity of the kidneys, it becomes biphid. The azygos vein is formed from the union of the right and left azygos veins at the level of the 5th thoracic vertebra. Cardiovascular physiological studies show some of these anatomical variations, especially of the venous system and the ascending aorta, to be modifications for diving. This investigation documents the large blood vessels associated with the heart and related structures in the ringed seal.
Delayed Lung Maturation of Foetus of Diabetic Mother Rats Develop with a Diminish, but Without Changes in the Proportion of Type I and II Pneumocytes, and Decreased Expression of Protein D‐Associated Surfactant Factor
Authors: Treviño‐Alanís M. , Ventura‐Juárez J. , Hernández‐Piñero J. , Nevárez‐Garza A. , Quintanar‐Stephano A. , González‐Piña A. 
Published: February 2009

SummaryNewborn children of diabetic mothers have an increased morbidity and mortality because of respiratory distress syndrome. We study lung histogenesis during intrauterine development of offspring of diabetic Sprague‐Dawley rats at 18, 19 and 21 days of gestation (DG). Pregnant rats were grouped into diabetic (streptozotocin‐induced), citrate, and control groups; five female and five male offspring were selected randomly from each group at 18, 19 and 21 DG, and a biopsy of the lung was taken and processed in paraffin for histological examination. The biopsy for the transmission electron microscopy (TEM) analysis was taken at 21 days. A delay in alveolization of the offspring at 18, 19 and 21 days of the diabetic group was observed, which was confirmed at TEM level, and also less quantity of protein D associated to surfactant in diabetic group was detected (P < 0.001). The foetuses of the diabetic group presented a delay in lung histogenesis and in differentiation of the type II pneumocytes cells, but conserved the proportion with a decrease in 50% of pneumocytes, accompanied by a diminish of protein D associated to surfactant factor.
Effectiveness of GF‐120NF Fruit Fly Bait as a suppression tool for Bactrocera latifrons (Diptera: Tephritidae)
Authors: McQuate G. T. 
Published: February 2009

Abstract Bactrocera latifrons (Hendel) is a tephritid fruit fly of primarily Asian distribution that has invaded Hawaii and, more recently, the continent of Africa (Tanzania and Kenya). It primarily infests solanaceous fruits, so has the potential to impact production of crops such as peppers (Capsicum annuum L. and Capsicum frutescens L.), eggplant (Solanum melongena L.), African eggplant (Solanum aethiopicum L.) and tomatoes (Solanum lycopersicum L.). Because little work has been done to develop suppression techniques for this fruit fly species, field cage tests of the effectiveness of a commercially available bait spray, GF‐120NF Fruit Fly Bait, against wild B. latifrons were conducted. Sexually mature B. latifrons adults (75 male and 75 female) were introduced to both a control cage and a treatment cage, each of which held six fruiting Anaheim chili pepper (C. annuum L.) plants. Fruits were harvested, and assessed for infestation, both before and after the application of the bait spray in the treatment cage. There was no difference in infestation rate between control and treatment cages before the application of the bait spray, whereas there was a significantly lower infestation rate in treatment cages following the application of the bait spray. Post‐spray infestation rate in the treatment cages (in two separate, replicated bioassays) was always zero and no live flies were detected in the treatment cages at the end of the trials. The results of this study provide evidence that GF‐120NF Fruit Fly Bait should be effective in suppressing B. latifrons populations in the field.
The modulation of visual orienting reflexes across the lifespan
Authors: Iarocci Grace , Enns James T. , Randolph Beth , Burack Jacob A. 
Published: February 2009

AbstractThe development of reflexive and voluntary shifts of visual attention, as well as relations between the two forms of shifting, were examined in three groups of children (5, 7, and 9 years old), one group of young adults (24 years old), and two groups of senior adults (young seniors with an average age of 69 years, and old seniors with an average age of 81 years). The task entailed response to the detection of a target (black dot) in one of four possible locations in the visual field. Relations between reflexive and voluntary shifts of attention were gauged by the degree to which flash and arrow facilitation and inhibition were observed in response to the presentation of both arrow and flash cues together in one trial. All age groups oriented reflexively in response to a flash cue and utilized the arrow cue to orient attention strategically. When flash and arrow cues were presented in quick succession and thereby competed for attention, the youngest children and oldest seniors were least efficient and flexible in their approach to the orienting task as they had difficulty modulating visual reflexes.
Weighting of vowel cues explains patterns of word–object associative learning
Authors: Curtin Suzanne , Fennell Christopher , Escudero Paola 
Published: February 2009

Abstract Previous research has demonstrated that infants under 17 months have difficulty learning novel words in the laboratory when the words differ by only one consonant sound, irrespective of the magnitude of that difference. The current study explored whether 15‐month‐old infants can learn novel words that differ in only one vowel sound. The rich acoustic/phonetic properties of vowels allow for a detailed analysis of the contribution of acoustic/phonetic cues to infants’ performance with similar‐sounding words. Infants succeeded with the vowel pair /i/–/I/, but failed with vowel pairs /i/–/u/ and /I/–/u/. These results suggest that infants initially use the most salient acoustic cues for vowels and that this staged use of acoustic cues both predicts and explains why infants can learn some words that differ in only a single vowel.
Long Work Hours: Volunteers and Conscripts
Authors: Drago Robert , Wooden Mark , Black David 
Published: February 2009

AbstractUsing panel survey data from Australia, we divide long hours workers (persons reporting usually working 50 or more hours per week) into groups of ‘volunteers’, who prefer long hours, and ‘conscripts’, who do not. We study both the static and dynamic prevalence of the phenomenon. Norms surrounding ideal workers and consumerism play major roles in explaining conscript status, with bargaining power less important. The self‐employed often appear as volunteers or conscripts, while gender, rather than motherhood, is a strong predictor of shorter work hours. Both the demand and supply sides of the labour market play a role in explaining the prevalence of long hours conscripts.