Symbolic Shareholder Democracy:Toward a Behavioral Understanding of the Role of Shareholder Voting in CEO Dismissals

We investigate the effect of expressive shareholder dissent voting, in which shareholders use their votes symbolically to express their discontent with management, on subsequent chief executive officer (CEO) dismissals. Using the routine but highly symbolic executive board discharge proposal voted on at the annual shareholder meetings of German firms, we argue that the board of directors understands these votes as a "vote of confidence in management" that challenges the CEO's mandate to lead the firm. Arguing that board chairs are uniquely positioned to take up the stance of a steward of the firm and its leadership, we examine how independent and family board chairs moderate the board's response to expressive voting dissent. Using a sample of German public firms over the period 2008-2015, we find that expressive voting dissent increases the chance of CEO dismissal increasingly with the level of dissent expressed. Contrary to prevailing agency theoretical expectations, we do not find that independent chairs are more responsive to expressive voting dissent, nor that this relationship is strengthened by the degree of minority institutional investor ownership of the firm. Consistent with the symbolic perspective on shareholder voting that we seek to develop, however, we find that family chairs are more likely to lead the board to dismiss the CEO due to the intrinsic disvalue they incur from symbolic leadership legitimacy challenges in their firms, and that the positive effect of having a family chair on the dissent induced chance of CEO dismissal is strengthened by the level of family ownership in the firm

Allergen immunotherapy for allergic airway diseases:Use lessons from the past to design a brighter future

Allergic respiratory diseases, such as allergic dermatitis, food allergy, allergic rhino conjunctivitis and allergic asthma, are chronic inflammatory diseases with increasing prevalence. Symptoms include such as watery or itchy itching of the mouth, skin, or the eyes, swelling of the face or throat, sneezing, congestion or vomiting, wheezing, shortness of breath and coughing. For allergic asthma, additional symptoms include tightness of chest, cough, wheezing, and reversible airflow limitation. These symptoms can be triggered by inhalation of aller -gens such as food allergens or airborne allergens such as those from tree-or grass pollen and house dust mites. Pharmacological intervention in allergic disease includes the use of antihistamines, immune suppressive drugs and in case of asthma, the use of (long acting) beta-agonists for relaxation of the constricted airways. These treat-ment options merely suppress symptoms and do not cure the disease. Allergen immunotherapy (AIT), in con -trast, has the capacity of inducing long-term tolerance, with symptom relief persisting decennia after discontinuation of treatment, despite recurrent re-exposure to the allergen. However, AIT is not effective for all allergic disorders, and treatment for several years is required to obtain long-term protection. Moreover, some forms of AIT have safety concerns, with risk of mild to severe allergic reactions. To improve safety and efficacy of AIT, the underlying mechanisms have been studied extensively in the clinic as well as in experimental models of allergic airway inflammation.Despite more than a century of clinical experience and a vast body of experimental and translational studies into the immunological and cellular mechanisms underpinning its therapeutic potential, AIT is still not implemented in routine clinical care for allergic asthma. This review provides an overview of the substantial developments that contribute to our knowledge of the pathogenesis of allergic airway diseases, the mechanism of action of AIT, its treatment routes and schedules, the standardization of extracts and use of adjuvantia. Moreover, the main con-clusions from experimental models of AIT with regard to the safety and effectiveness of the treatment are summarized, and future directions for further improvements are outlined. AIT urgently requires further improvements in order to increase its efficiency and shorten the treatment duration while remaining safe and costeffective.(c) 2022 Published by Elsevier Inc

Supplementary feeding with either ready-to-use fortified spread or corn-soy blend in wasted adults starting antiretroviral therapy in Malawi: randomised, investigator blinded, controlled trial

Objective To investigate the effect of two different food supplements on body mass index (BMI) in wasted Malawian adults with HIV who were starting antiretroviral therapy

Haptic Shared Control in Tele-Manipulation: Effects of Inaccuracies in Guidance on Task Execution

Haptic shared control is a promising approach to improve tele-manipulated task execution, by making safe and effective control actions tangible through guidance forces. In current research, these guidance forces are most often generated based on pre-generated, errorless models of the remote environment. Hence such guidance forces are exempt from the inaccuracies that can be expected in practical implementations. The goal of this research is to quantify the extent to which task execution is degraded by inaccuracies in the model on which haptic guidance forces are based. In a human-in-the-loop experiment, subjects (n = 14) performed a realistic tele-manipulated assembly task in a virtual environment. Operators were provided with various levels of haptic guidance, namely no haptic guidance (conventional tele-manipulation), haptic guidance without inaccuracies, and haptic guidance with translational inaccuracies (one large inaccuracy, in the order of magnitude of the task, and a second smaller inaccuracy). The quality of natural haptic feedback (i.e., haptic transparency) was varied between high and low to identify the operator\u27s ability to detect and cope with inaccuracies in haptic guidance. The results indicate that haptic guidance is beneficial for task execution when no inaccuracies are present in the guidance. When inaccuracies are present, this may degrade task execution, depending on the magnitude and the direction of the inaccuracy. The effect of inaccuracies on overall task performance is dominated by effects found for the Constrained Translational Movement, due to its potential for jamming. No evidence was found that a higher quality of haptic transparency helps operators to detect and cope with inaccuracies in the haptic guidance.</p

1,25(OH)2VitD3 supplementation enhances suppression of grass pollen-induced allergic asthma by subcutaneous and sublingual immunotherapy in a mouse model

Allergen specific immunotherapy (AIT) can provide long-term alleviation of symptoms for allergic disease but is hampered by suboptimal efficiency. We and others have previously shown that 1,25(OH)2-VitaminD3 (VitD3) can improve therapeutic efficacy of AIT. However, it is unknown whether VitD3 supplementation has similar effects in sublingual and subcutaneous immunotherapy. Therefore, we aimed to test VitD3 supplementation in both grass pollen (GP) subcutaneous-IT (SCIT) and sublingual-IT (SLIT) in a mouse model for allergic airway inflammation. To this end, GP-sensitized BALB/c mice received GP-SCIT or GP-SLIT with or without 10 ng VitD3, followed by intranasal GP challenges and measurement of airway hyperresponsiveness (AHR) and inflammation. VitD3 supplementation of GP-SCIT resulted in enhanced induction of GP-specific (sp)-IgG2a and suppression of spIgE after challenge. In addition, eosinophil numbers were reduced and levels of IL10 and Amphiregulin were increased in lung tissue. In GP-SLIT, VitD3 supplementation resulted in enhanced sp-IgG2a levels in serum, enhanced suppression of eosinophils and increased IL10 levels in lung tissue, as well as suppression of AHR to methacholine. These data show that VitD3 increases efficacy of both SCIT and SLIT, by enhancing induction of blocking antibodies and suppression of airway inflammation, underscoring the relevance of proficient VitD3 levels for successful AIT

High dose vitamin D3 empowers effects of subcutaneous immunotherapy in a grass pollen-driven mouse model of asthma

Allergen-specific immunotherapy (AIT) has the potential to provide long-term protection against allergic diseases. However, efficacy of AIT is suboptimal, while application of high doses allergen has safety concerns. The use of adjuvants, like 1,25(OH)2VitD3 (VitD3), can improve efficacy of AIT. We have previously shown that low dose VitD3 can enhance suppression of airway inflammation, but not airway hyperresponsiveness in a grass pollen (GP)-subcutaneous immunotherapy (SCIT) mouse model of allergic asthma. We here aim to determine the optimal dose and formulation of VitD3 for the GP SCIT. GP-sensitized BALBc/ByJ mice received three SCIT injections of VitD3-GP (30, 100, and 300 ng or placebo). Separately, synthetic lipids, SAINT, was added to the VitD3-GP-SCIT formulation (300 nmol) and control groups. Subsequently, mice were challenged with intranasal GP, and airway hyperresponsiveness, GP-specific IgE, -IgG1, and -IgG2a, ear-swelling responses (ESR), eosinophils in broncho-alveolar lavage fluid and lung were measured. VitD3 supplementation of GP-SCIT dose-dependently induced significantly enhanced suppression of spIgE, inflammation and hyperresponsiveness, while neutralizing capacity was improved and ESR were reduced. Addition of VitD3 further decreased Th2 cytokine responses and innate cytokines to allergens in lung tissue by GP-SCIT. However, addition of synthetic lipids to the allergen/VitD3 mixes had no additional effect on VitD3-GP-SCIT. We find a clear, dose dependent effect of VitD3 on GP-SCIT-mediated suppression of allergic inflammation and airway hyperresponsiveness. In contrast, addition of synthetic lipids to the allergen/VitD3 mix had no therapeutic effect. These studies underscore the relevance of VitD3 as an adjuvant to improve clinical efficacy of SCIT treatment regimens

Bridging the gap between public health and primary care in prevention of cardiometabolic diseases; background of and experiences with the Prevention Consultation in The Netherlands

Background. There is an increasing need for programmatic prevention of cardiometabolic diseases (cardiovascular disease, type 2 diabetes and chronic kidney disease). Therefore, in the Netherlands, a prevention programme linked to primary care has been developed. This initiative was supported by the national professional organizations of GPs and occupational physicians as well as three large health foundations

Viral mimic poly-(I:C) attenuates airway epithelial T cell suppressive capacity; implications for asthma

In allergen-sensitised asthmatic individuals, allergen-specific type-2 T-helper cells proliferate and secrete type-2 cytokines (e.g. interleukin (IL)-4, -5 and -13), driving the airway inflammatory response that gives rise to the clinical symptoms of asthma. Both early-life sensitisation to aeroallergens and lower respiratory viral infections are important environmental risk factors for developing asthma. Additionally, respiratory viral infections are the most common trigger for asthma exacerbations. Of interest, many asthma susceptibility genes are expressed in the airway epithelium [1], which forms the first continuous line of defence against inhaled environmental insults, including viruses and aeroallergens. Impaired immune regulation and failure to maintain tolerance to allergens is thought to contribute to allergic sensitisation. Asthma epithelium may be deficient in its innate immune defence against viral infections, resulting in increased viral replication upon rhinovirus infection compared to nonasthma-derived epithelial cultures [2]. Furthermore, there is evidence for loss of the mucosal immune barrier in asthma, with disruption of epithelial integrity [1, 3]. This may lead not only to increased permeability, but also to the release of pro-inflammatory mediators, specifically of cytokines that drive type-2 responses [3, 4]. We recently observed that the ability of allergens to disrupt epithelial barrier function is related to the development of type-2-mediated inflammation in asthma [5, 6]. Furthermore, we demonstrated that healthy murine lung epithelium is a potent inhibitor of T-cell proliferation and that this inhibition is lost upon viral infection [7]. It is unknown if this immune regulatory effect is displayed by human epithelium and is dysregulated in asthma. We hypothesise that changes in this regulatory effect translate into aberrant regulation of T-cell responses in asthma. We studied the epithelial regulation of T-cell proliferation and cytokine responses upon epithelial stimulation with a viral mimic, using co-culture of human T-cells and primary bronchial epithelial cells (PBECs) from healthy controls and asthma patients

Case study on the efficacy of a lanthanum-enriched clay (Phoslock®) in controlling eutrophication in Lake Het Groene Eiland (The Netherlands)

Lake Het Groene Eiland was created in the beginning of 2008 by construction of dikes for isolating it from the surrounding 220-ha water body. This so-called claustrum of 5 ha was treated using lanthanum-modified clay (Phoslock®) to control eutrophication and mitigate cyanobacterial nuisance. Cyanobacteria chlorophyll-a were significantly lower in the claustrum than those in the reference water body, where a massive bloom developed in summer, 2008. However, PO4-P and TP did not statistically differ in these two waters. TN and NO3-N were significantly lower in the claustrum, where dense submerged macrophytes beds developed. Lanthanum concentrations were elevated after the applications of the modified clay in the claustrum, but filterable lanthanum dropped rapidly below the Dutch standard of 10.1 μg l−1. During winter, dozens of Canada geese resided at the claustrum. Geese droppings contained an average of 2 mg PO4-P g−1 dry weight and 12 mg NH3-N g−1 dry weight and might present a growing source of nutrients to the water. Constructing the claustrum enabled unrestricted bathing in subsequent three summers, as no swimming bans had to be issued due to cyanobacteria blooms. However, the role of the modified clay in this positive outcome remains unclear, and longevity of the measures questionable.