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This paper focuses on corporate governance practices related to insider trading. In particular, we explore a unique and comprehensive dataset on the restrictions that companies impose on their insiders in addition to legal requirements, i.e. corporate insider trading policies. We are interested in the stringency of these restrictions and, more specifically, in which firm characteristics provoke differences in the stringency-level. Furthermore, using a unique database on insider trading activity in Belgium, we examine the effectiveness of the restrictions and examine whether abnormal insider trading gains are lower in companies with more strict insider trading policies. We develop a company-specific stringency index and find that restrictions are more stringent in companies with more growth opportunities and in non-financial companies. Furthermore, using hand-collected data on company board structures, we find that a higher representation of independent directors on the board has a positive impact on the stringency of insider trading policies. Analysis of the effectiveness shows no significant impact of policy stringency on insider trading returns. This lack of effectiveness is especially pronounced in smaller companies.

Head and neck cancer is often associated with second primary neoplasms. These cancers most commonly involve other regions of the head and neck, esophagus, and lung. The majority of cases are also squamous cell carcinomas. In view of this rather frequent occurrence of multiple primary cancers and how they adversely affect the patient's survival, it becomes imperative to analyze how the clinician can intervene effectively. One such approach is to detect multiple primaries as early as possible. As such, panendoscopy as a part of the tumor-staging procedure has been advocated by many investigators to search for simultaneous second primary malignant neoplasms in patients presenting with head and neck cancer. In a 24-month period, data were gathered from 127 consecutive patients referred to University Hospital, Gheni with previously untreated, squamous cell carcinomas of the head and neck. One hundred-eighteen patients underwent an endoscopic examination under general anesthesia, during which 4 simultaneous second primary tumors were found in 3 patients. This represents an incidence of 3.4% of simultaneous second primary neoplasms. The results for the different parts of the endoscopy are discussed and compared with literature findings. Guidelines are given for the initial evaluation of the head and neck cancer patient.

The effects of rise-fall and plateau times for the Pa component of the middle-latency response (MLR) were investigated in normally hearing subjects, and an objective MLR threshold was measured in patients with low- and middle-tone hearing losses, using a selected stimulus-envelope time. Our results showed that the stimulus-envelope time (the rise-fall time and plateau time groups) affected the Pa component of the MLR (quality was determined by the (chi 2-test and amplitude by the F-test). The 4-2-4 tone-pips produced good Pa quality by visual inspection. However, our data revealed no statistically significant Na-Pa amplitude differences between the two subgroups studied when comparing the 2- and 4-ms rise-fall times and the 0- and 2-ms plateau times. In contrast, Na-Pa became significantly smaller from the 4-ms to the 6-ms rise-fall time and from the 2-ms to the 4-ms plateau time (paired t-test). This result allowed us to select the 2- or 4-ms rise-fall time and the 0- or 2-ms plateau time without influencing amplitude. Analysis of the stimulus spectral characteristics demonstrated that a rise-fall time of at least 2ms could prevent spectral splatter and indicated that a stimulus with a 5-ms rise-fall time had a greater frequency-specificity than a stimulus of 2-ms rise-fall time. When considering the synchronous discharge and frequency-specificity of MLR, our findings show that a rise-fall time of four periods with a plateau of two periods is an acceptable compromise for estimating the objective MLR threshold.(ABSTRACT TRUNCATED AT 250 WORDS)

Wound healing is a highly coordinated process involving clot formation, inflammatory reaction, immune response, and tissue remodeling. Transforming growth factor beta (TGF-β), epidermal growth factor (EGF), and platelet-derived growth factor (PDGF) are known to be active during different phases of wound repair. Nasal secretions were obtained from eight patients 1, 2, and 3 weeks after functional endoscopic sinus surgery (FESS) and compared to 13 controls. Nasal fluid was collected by sinus packing and was analyzed by enzyme-linked immunosorbent assay (ELISA) for TGF-β1, TGF-β2, EGF, and PDGF. Comparing patients 1 week after surgery with control subjects, a significant increase in the concentrations of TGF-β1, TGF-β2, and PDGF in nasal secretions could be demonstrated (p

Extracellular matrix (ECM) in nasal polyps is characterized by a subepithelial infiltration of eosinophils and pseudocyst formations. The processes leading to the vacuolisation of the ECM remain unclear but the role of matrix metalloproteinases, because of their proteolytic activities against the different components of the ECM, has been evoked. Immunohistochemistry for MMP-7, MMP-9 and TIMP-1 was performed on frozen sections from 10 controls, 10 patients with nasal polyposis (NP) and 10 with chronic sinusitis (CS). ELISA measurements were performed on tissue homogenates. In NP, when compared to CS or control samples, a staining for MMP-9 and MMP-7 appeared in blood vessels. In NP, MMP-9 was also upregulated in epithelium in glands and MMP-9-positive mononuclear inflammatory cells were increased, especially in the centre of pseudocyst formations. Concentrations of MMP-9 protein were found significantly increased in both CS and NP compared to controls, while MMP-7 was significantly increased in NP compared to controls and CS. TIMP-1 protein was significantly increased in CS, but not in polyps, when compared to normal mucosa. CS and NP show different patterns of MMP-7/-9 and TIMP-1 expression. This difference in regulation of enzymatic proteins could form the basis for the different tissue remodelling processes of these sinus diseases.

Extracellular matrix in nasal polyps (NP) is characterized by a subepithelial infiltration of eosinophils and pseudocyst formation. Hyaluronic acid (HA) occupies a large place in extracellular space. Local deposition of glycosaminoglycans (GAGs), such as HA, by impairing the tissue viscosity, could promote this pseudocystic formation. Hyaluronic acid was measured in nasal tissue ( n =15) and NP ( n =16) by radioimmunoassay (RIA). In the group of polyp patients, 11 did not receive any treatment while 5 were treated by oral corticosteroids. On the other hand, immunohistochemistry against biotinylated hyaluronic acid binding protein was performed on polyps and normal tissue sections. Hyaluronic acid levels were not different between polyp patients and controls or between treated and nontreated patients. Immunostaining for hyaluronic acid was homogeneous in normal nasal mucosa, whereas in the core of NP, a network-like organization can be demonstrated. This is the first study on staining the hyaluronic acid in respiratory mucosa and showing the internal reorganization of GAGs inside nasal polyps.

Most countries of the world have developed a wide array of government assistance programs for companies. However, it is only recently that researchers have started to evaluate the benefits of these programs empirically. This paper contributes to this emerging area of research by examining whether PLATO – a networking and training program sponsored by the Flemish government – increased the labor productivity of the participating companies. Our regression analysis of financial reporting number of a panel data set of Flemish SMEs that existed between 1996 and 2008 confirms that PLATO participants indeed experienced increased labor productivity. In addition, from a qualitative analysis of the PLATO program, we infer some of its success factors, which could inform governments in their design of company support programs.

This study presents survey evidence on the magnitude and determinants of tax compliance costs in Flemish small and medium-sized enterprises (SMEs). Data were obtained from an internet questionnaire among members of a professional network of Flemish entrepreneurs, called VOKA. Analyzing a sample of 151 Flemish SMEs, we find that the tax compliance costs – exceeding over seven percent of gross added value – are relatively high. VAT, labor taxes and corporate taxes are the main components of tax compliance costs. In addition, our evidence confirms the regressivity hypothesis, according to which smaller companies face relatively higher compliance costs. Furthermore, industry, age and the proportion of blue-collar workers prove to be determining factors of relative compliance costs. Our study concludes by formulating a number of policy recommendations that might contribute to lower compliance costs.

This paper provides new empirical evidence on the impact of formal business networking on SME growth. More specifically, using a large, unbalanced panel data set of Flemish SMEs over the period 1992-2008, we examine whether participation in a government-supported program aimed at intense guidance for small business managers affects SME growth. We find that this objective measure of formal business networking is significantly positively correlated with net asset and value added growth. These results confirm that formal business networking contributes to company success.

To cite this article: Papadopoulos NG, Christodoulou I, Rohde G, Agache I, Almqvist C, Bruno A, Bonini S, Bont L, Bossios A, Bousquet J, Braido F, Brusselle G, Canonica GW, Carlsen KH, Chanez P, Fokkens WJ, Garcia‐Garcia M, Gjomarkaj M, Haahtela T, Holgate ST, Johnston SL, Konstantinou G, Kowalski M, Lewandowska‐Polak A, Lødrup‐Carlsen K, Mäkelä M, Malkusova I, Mullol J, Nieto A, Eller E, Ozdemir C, Panzner P, Popov T, Psarras S, Roumpedaki E, Rukhadze M, Stipic‐Markovic A, Todo Bom A, Toskala E, van Cauwenberge P, van Drunen C, Watelet JB, Xatzipsalti M, Xepapadaki P, Zuberbier T. Viruses and bacteria in acute asthma exacerbations – A GA2LEN‐DARE systematic review. Allergy 2011; 66: 458–468. Abstract A major part of the burden of asthma is caused by acute exacerbations. Exacerbations have been strongly and consistently associated with respiratory infections. Respiratory viruses and bacteria are therefore possible treatment targets. To have a reasonable estimate of the burden of disease induced by such infectious agents on asthmatic patients, it is necessary to understand their nature and be able to identify them in clinical samples by employing accurate and sensitive methodologies. This systematic review summarizes current knowledge and developments in infection epidemiology of acute asthma in children and adults, describing the known impact for each individual agent and highlighting knowledge gaps. Among infectious agents, human rhinoviruses are the most prevalent in regard to asthma exacerbations. The newly identified type‐C rhinoviruses may prove to be particularly relevant. Respiratory syncytial virus and metapneumovirus are important in infants, while influenza viruses seem to induce severe exacerbations mostly in adults. Other agents are relatively less or not clearly associated. Mycoplasma and Chlamydophila pneumoniae seem to be involved more with asthma persistence rather than with disease exacerbations. Recent data suggest that common bacteria may also be involved, but this should be confirmed. Although current information is considerable, improvements in detection methodologies, as well as the wide variation in respect to location, time and populations, underline the need for additional studies that should also take into account interacting factors.

Three case reports of mastoiditis caused by atypical mycobacteria are discussed and a review of the world literature is given. Our aim is to focus the attention of the ENT specialist and the pediatrician on these pathological agents in unilateral recurrent otitis media. The case reports illustrate the importance of histologic and microbiologic examination. Difficulties in the differential diagnosis are mentioned. The therapy is slightly different from lymphadenitis caused by atypical mycobacteria because for mastoiditis we prefer the combination of surgery with medical treatment.

A series of 12 children (9 girls, 3 boys) with non-tuberculous mycobacterial lymphadenitis was reviewed to define the most frequent presenting features, helpful diagnostic measures and optimal management. The mean age at diagnosis was 42 months and cervical nodes in the submandibular region were most commonly affected. In most of the children the diagnosis was made on the basis of a positive intradermal skin test with specific antigens for atypical myocobacteria. The diagnosis was confirmed in all but one case by histopathologic examination. Total excision of the affected gland was recommended as the therapy of choice in the patients treated.

The tissue changes and symptoms that occur during an allergic reaction in the upper respiratory tract are due to inflammatory reactions. The authors give a survey of the different allergic reactions and discuss the different components of the IgE mediated hypersensitivity which is the most important type of hypersensitivity in the upper airways. The production of IgE, the immunoglobulin of the immediate hypersensitivity reaction, is modulated by T-cells through the activity of cytokines. Antigen presenting cells, including Langerhans cells, play an important role in the sensitisation phase. Mast cells and basophils degranulate as a result of a complex enzymatic pathway, in which phosphatidylinositol plays an important role. The mediators released by these cells include vasoactive substances, chemotactic agents and inflammatory proteases; these mediators and those liberated by secondary recruited cells, such as eosinophils and basophils will be responsible for the early and late symptoms.

Problem: In 2001, the ARIA guidelines were published to assist healthcare practitioners in managing allergic rhinitis (AR) according to the best evidence. Very limited information, however, is available on the impact of these guidelines on clinical practice. Methods: All Belgian Otorhinolaryngologists were invited to complete a questionnaire, covering demographic and professional characteristics, knowledge, use and perception of the ARIA guidelines and 4 clinical case scenarios of AR. Results: Of the 258 (44%) Belgian Otorhinolaryngologists who participated, almost 90% had ever heard about ARIA and 64% had followed a lecture specifically dedicated to the ARIA guidelines. Furthermore, 62% stated to always or mostly follow the ARIA treatment algorithms in the daily management of AR patients. In the clinical case section, adherence to the ARIA guidelines raised with increased self-reported knowledge and use of the ARIA guidelines and among participants that considered the guidelines more userfriendly. Of the respondents, 51% were considered as good compliers. Younger age was a significant predictor for good compliance. Conclusion: More efforts are required to improve the translation of scientific knowledge into clinical practice and to further identify which factors may influence guideline compliance.

Staphylococcus aureus Enterotoxin B (SEB) has immunomodulatory effects in allergic airway disease. The potential contribution of SEB to the sensitization process to allergens remains obscure.In order to study the effects of staphylococcal-derived toxins on the sensitization to ovalbumin (OVA) and induction of allergic airway inflammation, we have combined the nasal application of OVA with different toxins.Nasal applications of OVA and saline, SEA, SEB, toxic shock syndrome toxin (TSST)-1, protein A or lipopolysaccharide (LPS) were performed on alternate days from day 0 till 12. On day 14, mice were killed for the evaluation of OVA-specific IgE, cytokine production by mediastinal lymph node (MLN) cells and bronchial hyperreactivity (BHR) to inhaled metacholine. The effect of SEB on dendritic cell (DC) migration and maturation, and on T cell proliferation was evaluated.Concomitant endonasal application of OVA and SEB resulted in OVA-specific IgE production, whereas this was not found with SEA, TSST-1, protein A, LPS or OVA alone. Increased DC maturation and migration to the draining lymph nodes were observed in OVA/SEB mice, as well as an increased T cell proliferation. Bronchial inflammation with an influx of eosinophils and lymphocytes was demonstrated in OVA/SEB mice, together with hyperresponsiveness and the production of IL-4, IL-5, IL-10 and IL-13 by MLN stimulated with OVA.Our data demonstrate that SEB facilitates sensitization to OVA and consecutive bronchial inflammation with features of allergic asthma. This is likely due to augmentation of DC migration and maturation, as well as the allergen-specific T cell proliferation upon concomitant OVA and SEB application.

The International Public Sector Accounting Standards Board (IPSASB) is the sole international public sector accounting standard setter worldwide. Its standards (IPSASs) are essentially based on the International Financial Reporting Standards (IFRSs) issued for the private sector, with adjustments for specific governmental characteristics. With respect to Whole of Government Accounting (WGA), the IPSASB has recently established accounting standards for the preparation and presentation of consolidated statements (IPSAS 6, 2007) and financial statements for the General Government Sector (GGS) (IPSAS 22, 2006). Although these standards present well-developed guidelines, it is questionable whether the underlying assumptions of the IPSAS WGA framework correspond sufficiently with the specific characteristics of government.

In 2005, the Belgian government introduced a radically new measure into the corporate tax system: the so-called notional interest deduction. This tax invention allows Belgian companies to deduct a fictitious interest cost on equity from their tax base and directly tackles the classical tax discrimination between equity and debt financing, which characterizes the tax system of most countries. This paper investigates whether the capital structure of Belgian small and medium sized enterprises (SMEs) reflects the cross-sectional variation in tax incentives induced by the notional interest deduction, three year after its introduction. To measure the tax incentives of the notional interest deduction we incorporate the notional interest deduction into a simulation procedure of marginal tax rates. For our sample of SMEs, we find that, due to the notional interest deduction, the simulated marginal tax rates declined from 29% to 2.9%. Consistent with the trade-off theory on capital structure, our regression analysis reveals that the explanatory power of the debt rates of Belgian SMEs on marginal tax rates is higher if the marginal tax rates take the notional interest deduction into account. We interpret this as evidence consistent with a debt policy of Belgian SMEs that takes into account the tax incentives of the notional interest deduction

Quality management is increasingly important in clinical practice. The Global Allergy and Asthma European Network (GA(2)LEN) is a network of clinical and scientific excellence with originally 25 allergy centres in 16 European countries, a scientific society (European Academy of Allergology and Clinical Immunology), and a patient organization (European Federation of Allergy and Airways Diseases Patients' Associations). Although some allergy centres adhere to internal quality criteria, the implementation of a standardized quality management system for allergy centres across Europe was lacking.To implement standardized quality criteria among allergy centres organized within GA(2)LEN and thus ensure equal standards of diagnosis and care as well as to establish a culture of continuous quality improvement.Quality criteria covering, e.g., diagnostic and therapeutic procedures, and emergency preparedness to assure patient safety were developed and agreed upon by all 25 participating centres. To assure implementation of quality criteria, centres were audited to check quality indicators and document deviations. A follow-up survey was used to assess the usefulness of the project.Deviations were documented mainly in the areas of emergency care/patient safety (27.3% lacked regular emergency training of doctors and nurses; 22.7% inadequate emergency intervention equipment; 22.7% lacked critical incidence reporting/root cause analyses) and handling of extracts/pharmaceuticals (31.8% lacked temperature logs of fridges; 4.5% inadequate check of expiration dates). Quality improvement was initiated as shown by findings of re-audits. Usefulness of the project was rated high.The establishment of a quality management system with joint standards of care and harmonized procedures can be achieved in an international health network and ensures quality of care.

Nasal polyps represent a severe eosinophilic inflammation of the upper airways which is characterized by poor impact of therapeutic intervention and frequent recurrences. Based on distinct cytokine, mediator and cell profiles, chronic sinonasal disease in Caucasians can be differentiated into several subgroups such as chronic rhinosinusitis without nasal polyps, chronic rhinosinusitis with nasal polyps, and nasal polyps in cystic fibrosis patients,. In Caucasians, nasal polyps showed a Th2 polarisation with high IL-5 concentrations, while chronic rhinosinusitis without polyps was characterized by a Thl polarisation with high levels of IFN-gamma. In the Caucasian nasal polyps we found that significantly more nasal polyp patients are colonized with S. aureus and that colonization increased in patients with concomitant asthma and aspirin sensitivity. Although there was no major difference in the presence of enterotoxin genes in S. aureus strains derived from nasal polyp or control patients, we found an increased immune response to S. aureus enterotoxins in nasal polyps, which resulted in a more pronounced eosinophilic inflammation and higher total IgE production in those polyps affected. We suggest that S. aureus superantigens amplify the inflammation in about 50% of nasal polyps, resulting in a strong Th2 polarisation, eosinophil activation, and an overproduction of IgG4 and IgE. These findings imply new therapeutic approaches apart from the currently used topical and systemic steroid therapy for nasal polyposis. In three double blind placebo controlled studies it was shown that firstly, oral corticosteroids only led to a short term reduction of polyp size. Secondly that a low dose of doxycycline treatment for 20 days had a sustained clinically relevant effect on polyp size for more than 3 months and thirdly we also showed a significant effect on polyp size by selective antagonizing IL-5 with a monoclonal antibody.

Background Bilastine is a new non-sedative H-1 receptor antagonist, indicated for the treatment of allergic rhinitis (AR) (seasonal and perennial). Objective To assess and compare the efficacy and safety of bilastine 20 mg vs. cetirizine 10 mg and placebo in relieving the symptoms of seasonal allergic rhinitis (SAR). Methods Overall, 683 SAR patients, aged 12-70 years, were randomized to a double-blind treatment with bilastine 20 mg, cetirizine 10 mg or placebo, once daily for 14 days, in 61 centres across Europe. Patients recorded reflective (over the past 12 h) and instantaneous nasal (obstruction, rhinorrhoea, itching and sneezing) and non-nasal (ocular tearing, redness and itching) symptom scores (NSS and NNSS, respectively) twice daily, according to a pre-determined severity scale to provide reflective and instantaneous total symptom scores (TSS). The primary efficacy measure was the area under curve (AUC) of reflective TSS over 14 days of treatment (TSS-AUC(0-14 days)). Secondary efficacy measures included mean change from baseline in TSS, NSS and NNSS; discomfort caused by AR; and investigator's clinical global impression of the treatment. Safety was assessed according to adverse events (AEs), laboratory tests and electrocardiograms. Results The mean TSS-AUC(0-14 days) (score x day) was reduced in bilastine- and cetirizine-treated groups to a similar and significantly greater extent, compared with placebo (76.5, 72.3 and 100.6, respectively; P < 0.001). Similarly, bilastine and cetirizine were comparable and significantly superior to placebo for all secondary outcomes. While all treatments were well tolerated and the AE profiles of bilastine and placebo were similar, significantly fewer patients in the bilastine-treated group experienced somnolence (1.8%; P < 0.001) and fatigue (0.4%; P=0.02) than patients in the cetirizine-treated group (7.5% and 4.8%, respectively). Conclusions Bilastine 20 mg once daily was significantly superior to placebo and comparable to cetirizine 10 mg in relieving symptoms of SAR, although it demonstrated a significantly better AE profile than cetirizine.

Given the key role of interleukin-5 (IL-5) in eosinophil function, we investigated the regulated expression of the membrane-anchored (TM-IL-5R alpha) isoform, or a secreted (SOL IL-5R alpha) isoform, on both protein and transcript level in vitro and in vivo. A real-time PCR, FACS and ELISA were established to determine IL-5R alpha isoform expression in peripheral blood and nasal tissue from control subjects and nasal polyp (NP) patients with or without asthma. Human peripheral blood eosinophils were incubated with IL-5 and were analyzed for SOL-IL-5R alpha and TM-IL-5R alpha mRNA and protein levels in comparison with CD-69 expression. SOL-IL-5R alpha and TM-IL-5R alpha mRNA and protein expression was significantly increased in NP vs controls. In polyp tissue, SOL-IL-5R alpha expression correlated to disease severity and eosinophils counts, whereas TM-IL-5R alpha levels were inversely correlated to eosinophils counts and SOL-IL-5R alpha expression. FACS analysis revealed increased CD-69 and decreased TM-IL-5R alpha expression in NP tissue eosinophils vs blood eosinophils. Incubation of blood eosinophils with IL-5 caused up-regulation of CD-69 and down-regulation of TM-IL-5R alpha after 2 and 24 h. The expression of SOL-IL-5R alpha and TM-IL-5R alpha differs according to the eosinophil activation state and localization in the body (blood vs tissue) and may therefore be involved in the fine-tuning of the eosinophil homeostasis. Exposure of eosinophils to IL-5 reduces their responsiveness to IL-5 by regulated expression of the IL-5R alpha isoforms. Since, TM-IL-5R alpha is down-regulated and SOL-IL-5R alpha (antagonistic) is upregulated in NP tissue, our findings are important to understand the clinical trials with anti-IL-5 in humans.

Udgivelsesdato: July BACKGROUND: There is evidence that selenium levels are relatively low in Europe and may be falling. Low levels of selenium or low activity of some of the enzymes dependent on selenium have been associated with asthma. METHODS: The GA(2)LEN network has organized a multicentre case-control study in Europe to assess the relation of plasma selenium to asthma. The network compared 569 cases in 14 European centres with a diagnosis of asthma and reporting asthma symptoms in the last 12 months with 576 controls from the same centres with no diagnosis of asthma and no asthmatic symptoms in the last 12 months. RESULTS: All cases and controls were selected from the same population defined by age and place of residence. Mean plasma selenium concentrations among the controls ranged from 116.3 microg/l in Palermo to 67.7 microg/l in Vienna and 56.1 microg/l among the children in Oslo. Random effects meta-analysis of the results from the centres showed no overall association between asthma and plasma selenium [odds ratio (OR)/10 microg/l increase in plasma selenium: 1.04; 95% confidence interval (CI): 0.89-1.21] though there was a significantly protective effect in Lodz (OR: 0.48; 95% CI: 0.29-0.78) and a marginally significant adverse effect in Amsterdam (OR: 1.68; 95% CI: 0.98-2.90) and Ghent (OR: 1.35; 95% CI: 1.03-1.77). CONCLUSION: This study does not support a role for selenium in protection against asthma, but effect modification and confounding cannot be ruled out.

Aims: To analyze the changes in the prevalence of asthma, bronchial hyperresponsiveness (BHR) and allergies in elite athletes over the past years, to review the specific pathogenetic features of these conditions and to make recommendations for their diagnosis. Methods: The Task Force reviewed present literature by searching Medline up to November 2006 for relevant papers by the search words: asthma, bronchial responsiveness, EIB, athletes and sports. Sign criteria were used to assess level of evidence and grades of recommendation. Results: The problems of sports-related asthma and allergy are outlined. Epidemiological evidence for an increased prevalence of asthma and BHR among competitive athletes, especially in endurance sports, is provided. The mechanisms for development of asthma and bronchial hyperresponsiveness in athletes are outlined. Criteria are given for the diagnosis of asthma and exercise induced asthma in the athlete. Conclusions: The prevalence of asthma and bronchial hyperresponsiveness is markedly increased in athletes, especially within endurance sports. Environmental factors often contribute. Recommendations for the diagnosis of asthma in athletes are outlined.

Aim: The aims of part II is to review the current recommended treatment of exercise-induced asthma (EIA), respiratory and allergic disorders in sports, to review the evidence on possible improvement of performance in sports by asthma drugs and to make recommendations for their treatment. Methods: The literature cited with respect to the treatment of exercise induced asthma in athletes (and in asthma patients) is mainly based upon the systematic review given by Larsson et al. (Larsson K, Carlsen KH, Bonini S. Anti-asthmatic drugs: treatment of athletes and exercise-induced bronchoconstriction. In: Carlsen KH, Delgado L, Del Giacco S, editors. Diagnosis, prevention and treatment of exercise-related asthma, respiratory and allergic disorders in sports. Sheffield, UK: European Respiratory Journals Ltd, 2005:73-88) during the work of the Task Force. To assess the evidence of the literature regarding use of beta(2)-agonists related to athletic performance, the Task Force searched Medline for relevant papers up to November 2006 using the present search words: asthma, bronchial responsiveness, exercise-induced bronchoconstriction, athletes, sports, performance and beta(2)-agonists. Evidence level and grades of recommendation were assessed according to Sign criteria. Results: Treatment recommendations for EIA and bronchial hyper-responsiveness in athletes are set forth with special reference to controller and reliever medications. Evidence for lack of improvement of exercise performance by inhaled beta(2)-agonists in healthy athletes serves as a basis for permitting their use. There is a lack of evidence of treatment effects of asthma drugs on EIA and bronchial hyper-responsiveness in athletes whereas extensive documentation exists in treatment of EIA in patients with asthma. The documentation on lack of improvement on performance by common asthma drugs as inhaled beta(2)-agonists with relationship to sports in healthy individuals is of high evidence, level (1+). Conclusions: Exercise induced asthma should be treated in athletes along same principles as in ordinary asthma patients with relevance to controller and reliever treatment after careful diagnosis. There is very high level of evidence for the lack of improvement in athletic performance by inhaled beta 2-agonists.

Summary Background Chronic rhinosinusitis (CRS) with nasal polyps (NP) represents a persistent inflammation often characterized by local hyper-immunoglobulinaemia and the presence of specific IgE to Staphylococcus aureus enterotoxins (SAEs). We aimed to study the systemic and local production of Igs in relation to plasma cells, B cells and specific IgE to SAEs. Methods Concentrations of IgE, IgG, IgM, IgA, IgG subclasses and specific IgE to SAE were determined on tissue homogenates and serum from 15 CRS patients with NP, 15 CRS without NP and 10 control patients. Tissue cryo-sections were stained for CD19, CD20 and CD138 to demonstrate B and plasma cells. Results IgA, IgG and IgE concentrations were significantly higher in tissue homogenates, but not in serum, of NP compared with CRS and control subjects. NP with specific IgE to SAEs had significantly higher concentrations of IgG and IgE, and also showed a significantly higher fraction of IgG4 (P=0.003) and a lower fraction of IgG2 (P=0.04) than those without specific IgE production. Furthermore, naive CD19+ B cell and plasma cell counts (CD138+) were significantly higher in NP tissue compared with controls or CRS. Conclusions The difference in IgE, IgG and IgA expression between NP tissue and serum, supported by increased numbers of plasma cells, suggests a local production of these Igs in NP in response to a chronic microbial trigger. The local immune response to SAE is associated with a further increased production of IgE and IgG, and a shift in IgG subclasses.

This paper presents a critical analysis of empirical comprehensive income research, the majority of which consists of value relevance studies. The first part of the analysis focuses on the functional form of the value relevance regressions. The paper distinguishes between the informational and the measurement approach to value relevance research and systematically traces the origin of the specifications under both approaches. The informational approach is characterized by diversity in functional form specifications, which can be traced to differences in expectations models for earnings or price/earnings ratios. In the light of this diversity, it is remarkable to observe that most of the authors provide little or no argumentation for the choice of their particular functional specification. While the authors under the measurement approach try to legitimize their regression specifications by referring to the work of Ohlson, in fact, one of the contributions of the residual income model is that it demonstrates the restrictive nature of these specifications. The second part of the paper performs a detailed investigation of the empirical findings. This analysis reveals several peculiarities that defy economic intuition. These peculiarities are nontrivial since they, together with the low explanatory power of the regressions, affect the credibility of the main research findings. The conclusion of the paper is that there is danger in taking the empirical findings of this research domain at face value and that the potential for informing standards setters is limited.

Summary The purpose of this study is to determine the long-term voice outcome (6.1 years after a well-defined voice treatment program) of hyperfunctional voice disorders in 27 subjects. All patients showed a muscle tension pattern type I (MTP I). Perceptual ratings, aerodynamic and acoustical analyses, Voice Handicap Index (VHI) value, and a determination of the Dysphonia Severity Index (DSI) were performed. The laryngovideostroboscopic images indicated that 51% of the subjects still show pathological laryngological findings. The negative evolution of the DSI from −1 to −3.2 is in agreement with this finding. Analysis of the components of the DSI shows that the main responsible variable for this negative change is the lowest intensity (I-low) that increased with 8.1 dB, indicating that subjects generally speak too loud, which is a typical problem for vocal hyperfunction. The VHI-score indicates an unimportant psychosocial impact of the voice disorder. The more objective and laryngostroboscopic findings indicate a chronic situation for a substantial part of the subjects and even a worse situation for some of them. Whether the long-term voice outcome results can be changed with the insertion of several follow-up voice rehabilitation sessions over the years remains unanswered and is a subject for further research.

It is widely accepted that nonspecific tissue reactivity is a distinct pathophysiological hallmark of allergic diseases, influenced by genetic and environmental factors different from those involved in causing sensitization and allergen response of target organs. This consensus document aims at reviewing procedures currently used for nonspecific provocation of the bronchi, nose and eye and for measuring their responsiveness to nonspecific stimuli.

The pharmacologic treatment of allergic rhinitis proposed by ARIA is an evidence-based and step-wise approach based on the classification of the symptoms. The ARIA workshop, held in December 1999, published a report in 2001 and new information has subsequently been published. The initial ARIA document lacked some important information on several issues. This document updates the ARIA sections on the pharmacologic and anti-IgE treatments of allergic rhinitis. Literature published between January 2000 and December 2004 has been included. Only a few studies assessing nasal and non-nasal symptoms are presented as these will be discussed in a separate document.

Nasal obstruction, also referred to as congestion, blockage or stuffiness, is a crucial symptom in allergic rhinitis (AR) and may affect sleep as well as quality of life. Early- and late-phase-allergic reactions both contribute to nasal obstruction, although it primarily represents a major symptom in the chronic allergic reaction. A complex network of inflammatory and neurogenic phenomena relates to chronic nasal obstruction, including the subepithelial accumulation of inflammatory cells, particularly mast cells and eosinophils, and the release of neuropeptides. Nasal obstruction is a difficult-to-treat symptom. Vasoconstrictors (decongestants) and intranasal corticosteroids, due to their anti-inflammatory properties, have mainly been used for relieving the nasal passages from the congested mucosa. However, there is accumulating evidence recently that the latest-generation potent antihistamines have decongestant properties in AR. This paper aims to review the pathophysiologic background of nasal obstruction and the evidence for an antihistamine, levocetirizine, in relieving nasal congestion. A meta-analysis on the early and late effects of levocetirizine on nasal obstruction under artificial and natural allergen exposure conditions is presented, demonstrating convincingly that levocetirizine shows a consistent effect on nasal obstruction as early as over the first 2 h and sustained over 6 weeks.

This paper reports on an experiment that was conducted to investigate the degree of significance that unsophisticated users attach to fair value income (FVI) for valuation-relevant tasks, given that the matrix of comprehensive income applies. The prominent display of FVI therein is at odds with the limited significance of FVI for valuation. Specifically for unsophisticated users, who rely on financial reports to signal the importance and meaning of financial items, a concern exists that FVI might be overemphasised. This paper investigates this issue and formulates and tests two suggestions, intended to keep unsophisticated users from overemphasising FVI: 1) education about the irrelevance of FVI for valuation; and 2) a two-column matrix that does not display a separate column for total comprehensive income. Participants were provided with the financial reports of two fictitious manufacturing companies, and performed valuation-relevant tasks: income prediction, risk assessment, and management evaluation. The financial reports were devised in such a way that they allowed to infer the significance participants attached to FVI. For income prediction and risk assessments, participants did not attach significance to FVI. However, for management evaluation, FVI was taken into account, however this occurred to a lesser extent when total comprehensive income was not displayed.

SummaryAllergic rhinitis (AR) is a major health concern and numerous guidelines have been developed to standardize and to improve the management of this disease. As in many other areas of medicine, the methodology of the AR guidelines has evolved from opinion-based to evidence-based medicine. Although evidence-based medicine has many benefits, it also has limitations and cannot cancel the value of the individual clinical expertize.More important than the methodology of guideline development is the efficacy of guidelines to change patient and physician behaviour and to improve clinical outcomes. At present, however, studies on the effectiveness of guidelines are few. The International Consensus on Rhinitis from 1994 is the only guideline for AR that has been assessed for its effects on health outcomes. Furthermore, there is a lack of valid and reliable instruments to assess physician's and patient's attitude towards and compliance with guideline recommendations.There is no single effective way to ensure the use of guidelines into practice, but a carefully developed and multifaceted dissemination and implementation strategy and targeting and adapting guideline recommendations to the local and individual level are key elements. The final and most important step of putting guidelines into practice occurs at the level of the patient. Patients should be considered as effective partners in health care. Education of the patient and efforts to change patient's behaviour can maximize compliance, increase satisfaction and optimize health outcomes.

Over the last decades, the prevalence of allergic rhinitis has risen to epidemic proportions. Nasal symptoms involve sneezing, nasal itch, rhinorrhea, and nasal congestion. These symptoms result from an immunologically mediated (usually IgE-mediated) inflammation of the nasal mucosa, following allergen exposure in sensitized patients. Although allergic rhinitis is often trivialized, it has become clear that the disease can cause serious morbidity beyond the nasal manifestations, that it has a significant impact on quality of life and substantial socioeconomic consequences, and that it is associated with multiple comorbidities, including asthma, conjunctivitis, sinusitis, and otitis media. Recently, the Allergic Rhinitis and its Impact on Asthma (ARIA) Working Group proposed a new classification for allergic rhinitis, based on the duration of symptoms, rather than on the type of exposure. The severity of the disease is categorized based on the impact of symptoms on quality of life parameters. Early and correct diagnosis is the basis for the management of allergic rhinitis and starts with a thorough clinical history and physical examination. To confirm the allergic origin of rhinitis symptoms, allergy tests are performed. The test of first choice is the skin prick test, which has a good sensitivity and specificity. Environmental control measures (allergen avoidance), pharmacological treatment, immunotherapy, and education are the cornerstones of therapeutic management of allergic rhinitis. Nowadays, many effective pharmacological agents are available and new potential targets for pharmacotherapy, new routes of administration, and alterations in treatment dosages and schedules are continuously being investigated. To facilitate and standardize the management of allergic rhinitis and to improve the patient care, satisfaction, and compliance, several clinical practice guidelines have been developed. Among those, the ARIA guidelines provide stepwise treatment recommendations, based on the best available evidence from research.

Background: Allergic rhinitis (AR) represents a major challenge in primary care. The Allergic Rhinitis and its Impact on Asthma (ARIA) group proposed a new classification for AR and developed evidence-based guidelines for the management of this disease. We conducted this study to further characterize the classes of AR described by ARIA, and to evaluate whether the management of AR in general practice is in accordance with the ARIA guidelines. Methods: During the pollen season of 2003, 95 Belgian general practitioners (GPs) enrolled 804 patients who presented with symptoms of AR. For each patient, a questionnaire comprising the clinical presentation and management was completed. Results: In 64% of the patients, AR was classified as intermittent and in 36% as persistent. Persistent rhinitis caused more discomfort than intermittent rhinitis. Only 50% of the patients had ever undergone allergy testing. Among them, 51% were allergic to both seasonal and perennial allergens. Eighty-two per cent of the persistent rhinitics were allergic to at least one seasonal allergen and 72% of the intermittent rhinitics to at least one perennial allergen. When compared strictly with the ARIA recommendations, 49% of the patients with mild and/or intermittent AR were overtreated, whereas about 30% of those with moderate/severe persistent rhinitis were undertreated. Conclusion: This study confirms that the previous classification of AR into ‘seasonal’ and ‘perennial’ is not satisfactory and that intermittent and persistent AR are not equivalent to seasonal and perennial AR respectively. Furthermore, persistent rhinitis has been shown to be a distinct disease entity. Further efforts are required to disseminate and implement evidence-based diagnostic and treatment guidelines for AR in primary care practice.

The purpose of this article was to systematically review the literature on the effects of biofeedback therapy in the domain of phonatory disorders and phonatory performance, using studies in peer-reviewed journals. An extensive definition of biofeedback is given and its place in voice treatment is defined. Eighteen group or case studies or reports considering the effects of electromyographic, laryngoscopic and acoustic biofeedback in dysphonic patients (hyperfunctional voice disorders, hypofunctional voice disorders, psychogenic voice disorder, laryngeal trauma, total laryngectomy, vocal cord dysfunction) and participants with normal voices are included and an analysis of procedure as well as research design and results is presented. The usefulness of biofeedback in phonatory disorders and performance was to be interpreted based on tendencies, since there is a lack of randomized controlled efficacy studies. In only 3 of 18 studies (16.7%) did biofeedback therapy fail to improve voice quality or not result in better results than other forms of therapy. Recommendations for improved methodologies are made, which include the use of acoustic voice quality parameters.

Due to its high and increasing prevalence, its impact on quality of life, the association with multiple comorbidities and the considerable socio-economic burden, allergic rhinitis is a major respiratory disorder and represents a global health concern. The ARIA working group has proposed a new classification for allergic rhinitis into intermittent or persistent, based on the duration of symptoms. The severity of allergic rhinitis is graded according to the impact of the disease on the quality of life. The diagnosis of allergic rhinitis involves a thorough history and clinical examination. In patients suspected of having persistent AR a complete and systematic nasal examination is an absolute requirement. Anterior rhinoscopy provides limited information. Nasal endoscopy is more useful, not to confirm AR but in particular to exclude other conditions, such as polyps, foreign bodies, tumours and septal deformations. To confirm the allergic origin of rhinitis symptoms, allergy tests must be performed. The first choice test is the skin prick test. Patients with allergic rhinitis should be evaluated for asthma and patients with asthma should be evaluated for rhinitis. A stepwise therapeutic approach is recommended based on the duration and severity of disease. The treatment of allergic rhinitis consists of allergen avoidance, pharmacotherapy and immunotherapy.

Background The dysfunction of the mucosal interface of the upper respiratory tract in cystic fibrosis (CF) patients is clinically visible by the development of nasal polyps (NP) at a young age. Innate defence markers and inflammatory mediators in NP from patients with CF were compared with non-cystic fibrosis nasal polyps (non-CF-NP) to determine a possible different immunological background in macroscopically similar tissue. Methods Surgical samples were obtained from patients with non-CF-NP, cystic fibrosis patients with nasal polyps (CF-NP) and control patients (CO). With real time PCR, the mRNA expression of human beta defensins (HBD) 2 and 3, toll-like receptors (TLR) 2 and 4 and the macrophage mannose receptor (MMR) were measured. On homogenates of the surgical samples eotaxin, myeloperoxidase (MPO), IL-5 and IL-8 protein content was measured using commercial ELISA kits; IgE and eosinophilic cationic protein (ECP) were measured by the Unicap system. Results In CF-NP we found a statistically significant higher mRNA expression of HBD 2 compared with non-CF-NP and CO and of TLR 2 compared with non-CF-NP. In the non-CF-NP group, MMR mRNA expression was significantly elevated compared with CO and CF-NP. For TLR 4 mRNA expression no statistically significant differences were found between groups. IL-5 was below detection level in all CO and CF-NP, but was measurable in 80% of the non-CF-NP. MPO and IL-8 concentrations were significantly higher in CF-NP compared with CO and non-CF-NP, whereas ECP, eotaxin and IgE were significantly higher in the non-CF-NP group. Conclusions We here demonstrate that CF-NP and non-CF-NP not only differ in terms of inflammatory mediator profile, but also in terms of innate markers.

The IASB is presently involved in a project on reporting comprehensive income. Since the IASB accounting system is a mixture of two income determination methods, to wit historical cost accounting and fair value accounting, an interesting question pertains to whether the display of comprehensive income should be neutral with regard to these two competing paradigms. This paper scrutinizes, with a valuation perspective in mind, the typical arguments made by proponents of historical cost net income and comprehensive fair value income and finds that claims for exclusive reliance on a single concept of earnings are untenable. This means that a case could be made for advancing neutral income display as a policy objective. The matrix format of comprehensive income that is proposed under the IASB performance project certainly allows for such a neutral interpretation. However, given the importance of summarization in financial analysis, as is most extremely reflected in the focus on the earnings per share (EPS) number, if neutrality is to prevail, then it should also be reflected at the highest level of summarization of financial performance reporting. In other words, mandatory publication of two EPS numbers, one for net income and one for comprehensive income, should be considered. Possible effects on perception and actual use of financial reports that should enter such a consideration are suggested as topics for experimental research.

In a recent study, we have shown that gelatinase-B (metalloproteinase [MMP]-9) in nasal secretions can have both monitoring and predictive value on the healing outcome after functional endoscopic sinus surgery (FESS) to treat chronic rhinosinusitis (CRS) and nasal polyposis (NP). In this work, we aimed to explore the source of MMP-9 and the influence of inflammation on MMP-9 expression and release in nasal tissue and secretions during airway remodelling after surgery.Biopsies from 23 patients operated by FESS for CRS or NP were collected 1, 3, and 6 months after sinus surgery. MMP-9 expression in the paranasal mucosa was correlated with healing quality, with MMP-9 concentrations in nasal fluid, and with histomorphologic findings (edema, fibrosis, alphasmooth muscle actin, CD-68, myeloperoxidase, EG2, and transforming growth factor [TGF]-beta1 stainings).MMP-9 concentrations in nasal fluid were paralleled by MMP-9 expression inside the extracellular matrix (ECM) after sinus surgery. MMP-9 expression in ECM was significantly correlated with healing quality (r = 0.378, P = .0181), and poor healers presented significantly more edema (P.05). The amounts of MMP-9 in nasal fluid were significantly and independently predicted by the number of neutrophils (P = .0224) and macrophages (P = .0497) in the tissue. In contrast, MMP-9 expression was not related to fibrosis, number of myofibroblasts, or TGF-beta1 expression in ECM.MMP-9 expression is increased in the ECM during wound healing and parallels concentrations of MMP-9 in nasal fluids. Inflammatory cells represent the major source of increased MMP-9 expression, which is linked to poor healing quality.

Skin prick testing (SPT) is the standard method for diagnosing allergic sensitization but is to some extent performed differently in clinical centres across Europe. There would be advantages in harmonizing the standard panels of allergens used in different European countries, both for clinical purposes and for research, especially with increasing mobility within Europe and current trends in botany and agriculture. As well as improving diagnostic accuracy, this would allow better comparison of research findings in European allergy centres. We have compared the different SPT procedures operating in 29 allergy centres within the Global Allergy and Asthma European Network (GA2LEN). Standard SPT is performed similarly in all centres, e.g. using commercial extracts, evaluation after 15–20min exposure with positive results defined as a wheal >3mm diameter. The perennial allergens included in the standard SPT panel of inhalant allergens are largely similar (e.g. cat: pricked in all centres; dog: 26 of 29 centres and Dermatophagoides pteronyssinus: 28 of 29 centres) but the choice of pollen allergens vary considerably, reflecting different exposure and sensitization rates for regional inhalant allergens. This overview may serve as reference for the practising doctor and suggests a GA2LEN Pan-European core SPT panel.

Skin prick testing (SPT) is the standard method for diagnosing allergic sensitization but is to some extent performed differently in clinical centres across Europe. There would be advantages in harmonizing the standard panels of allergens used in different European countries, both for clinical purposes and for research, especially with increasing mobility within Europe and current trends in botany and agriculture. As well as improving diagnostic accuracy, this would allow better comparison of research findings in European allergy centres. We have compared the different SPT procedures operating in 29 allergy centres within the Global Allergy and Asthma European Network (GA(2)LEN). Standard SPT is performed similarly in all centres, e.g. using commercial extracts, evaluation after 15-20 min exposure with positive results defined as a wheal >3 mm diameter. The perennial allergens included in the standard SPT panel of inhalant allergens are largely similar (e.g. cat: pricked in all centres; dog: 26 of 29 centres and Dermatophagoides pteronyssinus: 28 of 29 centres) but the choice of pollen allergens vary considerably, reflecting different exposure and sensitization rates for regional inhalant allergens. This overview may serve as reference for the practising doctor and suggests a GA(2)LEN Pan-European core SPT panel