A dose-ranging study in older adults to compare the safety and immunogenicity profiles of MF59®-adjuvanted and non-adjuvanted seasonal influenza vaccines following intradermal and intramuscular administration

Strategies to optimize responses to seasonal influenza vaccination in older adults include the use of adjuvants, higher antigen doses, and intradermal delivery. In this study adults aged >= 65 years (n = 450) received a single dose of 1 of 2 non-adjuvanted trivalent influenza vaccine (TIV) formulations administered intradermally (ID), both containing 6 mu g of A/H1N1 and B, differing in A/H3N2 content (6 mu g or 12 mu g), or a single dose of 1 of 8 TIV formulations administered intramuscularly (IM) all containing 15 mu g of A/H1N1 and B, differing in A/H3N2 hemagglutinin (HA) content (15 mu g or 30 mu g) and/or in MF59 (R) adjuvant content (0%, 25%, 50%, or 100% of the standard dose). This paper focuses on the comparisons of low-dose non-adjuvanted ID, full-dose non-adjuvanted IM and full-dose MF59-adjuvanted IM formulations (n = 270). At day 22 post-vaccination, at least one European licensure immunogenicity criterion was met by all groups against all 3 strains; however, all three criteria were met against all 3 vaccine strains by the low-dose non-adjuvanted ID and the full-dose MF59-adjuvanted IM groups only. The full-dose MF59-adjuvanted IM group elicited significantly higher immune response vs. the low-dose non-adjuvanted ID formulations for most comparisons. The full-dose MF59 adjuvanted IM groups were associated with increased pain at the site of injection (P < 0.01) compared to the ID groups, and the low-dose non-adjuvanted ID groups were associated with increased erythema, induration, and swelling at the injection site (P < 0.0001) and unsolicited AEs compared with the IM groups. There were no differences between IM and ID groups in the frequencies of subjects experiencing solicited systemic reactions. Overall, while MF59 adjuvantation increased pain at the site of injection, and intradermal delivery increased unsolicited adverse events, erythema, induration, and swelling at the injection site, both strategies of vaccination strongly enhanced the immunogenicity of seasonal influenza vaccine in older adults compared with conventional non-adjuvanted intramuscular delivery

Immunogenicity and tolerability of an MF59-adjuvanted, egg-derived, A/H1N1 pandemic influenza vaccine in children 6-35 months of age

Background: Vaccines against pandemic A/H1N1 influenza should provide protective immunity in children, because they are at greater risk of disease than adults. This study was conducted to identify the optimal dose of an MF59 (R)-adjuvanted, egg-derived, A/H1N1 influenza vaccine for young children. Methods: Children 6-11 months (N = 144) and 12-35 months (N = 186) of age received vaccine formulations containing either 3.75 mu g antigen with half the standard dose of MF59 or 7.5 mu g antigen with a standard dose of MF59, or a nonadjuvanted formulation containing 15 mu g antigen (children 12-35 months only). Participants were given 2 primary vaccine doses 3 weeks apart, followed by 1 booster dose of MF59-adjuvanted seasonal influenza vaccine 1 year later. Immunogenicity was assessed by hemagglutination inhibition and microneutralization assays. Results: All vaccine formulations were highly immunogenic and met all 3 European licensure criteria after 2 doses. MF59-adjuvanted vaccines met all licensure criteria after 1 dose in both age cohorts, while nonadjuvanted vaccine did not meet all criteria after 1 dose in children 12-35 months. A single booster dose was highly immunogenic, and stable antibody persistence was observed in response to all vaccines. All vaccines were well tolerated. Conclusions: In this study, a single dose of 3.75 mu g antigen with half the standard dose of MF59 was shown to be optimal, providing adequate levels of immediate and long-term antibodies in pediatric subjects 6-35 months of age. These data demonstrated that MF59 adjuvant allowed for reduced antigen content and promoted significant long-term antibody persistence in children, with a satisfactory safety profile

Faster Onset of Bronchodilation with Formoterol than with Salmeterol in Patients with Stable, Moderate-Severe Copd: Results of a Randomized, Double-Blind Clinical Study

OBJECTIVES: To compare the onset and magnitude of bronchodilation after dry powder inhalations of formoterol fumarate (Foradil Aerolizer) versus salmeterol xinofoate (Serevent Diskus) with respect to normalized (*) forced expiratory volume in 1 s area under the curve 0 to 1 h after inhalation (FEV1AUC*0-1 h).DESIGN: A double-blind, double-dummy, multicentre, randomized, placebo controlled, single-dose, five-period crossover study.SETTING: Five centres in four countries -- one centre each in France, Greece and Italy, and two centres in the Netherlands.PATIENTS: Forty-seven patients aged 42 to 80 years (mean age 63.5 years) with chronic obstructive pulmonary disease (COPD) stage II and III, and mean baseline FEV11.17 L (range 0.56 to 1.77 L).INTERVENTIONS: Patients inhaled single doses of formoterol dry powder (12 and 24 μg), single doses of salmeterol (50 and 100 μg) and matching placebo on five separate days.MAIN RESULTS: The estimates of treatment difference in absolute terms (0.086 L) and percentage change from predose baseline (7.8%) for the primary end point, FEV1AUC*0-1 h, showed that formoterol 12 μg was statistically significantly superior to salmeterol 50 μg (P=0.0044 and P=0.0021, respectively). In addition, both doses of formoterol were statistically superior to placebo for both absolute improvement and percentage change (P=0.0001). The analysis of secondary variables also confirmed the superiority of formoterol over salmeterol.CONCLUSIONS: Formoterol is associated with a faster onset of bronchodilation than salmeterol in patients with COPD

Predictors of carotid occlusion intolerance?during proximal protected?carotid artery?stenting.

OBJECTIVES: The aim of this study was to identify predictors of occlusion intolerance (OI) developing during proximal protected carotid artery stenting (CAS). BACKGROUND: The use of proximal embolic protection devices, such as endovascular occlusion, during CAS has been demonstrated to be particularly safe and effective. However, endovascular occlusion can expose the ipsilateral hemisphere to hypoperfusion and produce transient neurological symptoms (OI). METHODS: From March 2010 to March 2012, 605 consecutive patients underwent proximal protected CAS at our institution. To identify independent predictors of OI, a multivariate logistic regression model was developed that included all patients' clinical/angiographic and procedural characteristics. RESULTS: OI developed in a total of 184 patients (30.4%). Compared with patients in whom OI did not develop, those who experienced OI had lower occlusion pressure (OP) (42.3 ± 12.7 mm Hg vs. 61.9 ± 15.4 mm Hg, p < 0.001). Receiver-operating characteristic curve analysis demonstrated that OP was the most consistent predictor of OI with a C-statistic of 0.85 (95% confidence interval [CI]: 0.82 to 0.88) with best cutoff being ≤40 mm Hg (sensitivity, 68.5%; specificity, 93.3%). By logistic regression analysis, the most powerful independent predictor of OI developing was an OP ≤40 mm Hg (odds ratio: 33.2, 95% CI: 19.1 to 57.7) and the most powerful clinical predictor of such OP was the presence of contralateral internal carotid artery occlusion (odds ratio: 3.1, 95% CI: 1.5 to 6.2). CONCLUSIONS: OI may occur in as many as one-third of the patients undergoing proximal protected CAS. This event is more common in those patients with an OP ≤40 mm Hg. Patients presenting with concomitant occlusion of the contralateral internal carotid artery more frequently have an OP ≤40 mm Hg

Challenges in early clinical development of adjuvanted vaccines.

To access publisher's full text version of this article click on the hyperlink at the bottom of the pageA three-step approach to the early development of adjuvanted vaccine candidates is proposed, the goal of which is to allow ample space for exploratory and hypothesis-generating human experiments and to select dose(s) and dosing schedule(s) to bring into full development. Although the proposed approach is more extensive than the traditional early development program, the authors suggest that by addressing key questions upfront the overall time, size and cost of development will be reduced and the probability of public health advancement enhanced. The immunogenicity end-points chosen for early development should be critically selected: an established immunological parameter with a well characterized assay should be selected as primary end-point for dose and schedule finding; exploratory information-rich end-points should be limited in number and based on pre-defined hypothesis generating plans, including system biology and pathway analyses. Building a pharmacodynamic profile is an important aspect of early development: to this end, multiple early (within 24h) and late (up to one year) sampling is necessary, which can be accomplished by sampling subgroups of subjects at different time points. In most cases the final target population, even if vulnerable, should be considered for inclusion in early development. In order to obtain the multiple formulations necessary for the dose and schedule finding, "bed-side mixing" of various components of the vaccine is often necessary: this is a complex and underestimated area that deserves serious research and logistical support.Novartis Vaccines and Diagnostic

An Evolutionary Approach to the Dynamical Reconfiguration of PhotoVoltaic Panels

Received 1 September 2014 Received in revised form 31 March 2015 Accepted 20 April 2015 Available online 3 July 2015 Keywords: Photovoltaic systems Maximum power production Dynamical reconfiguration 1. Introduction The efficiency of a photovoltaic (PV) panel is actually about 15%, but in real applications this figure is even lower because of many reasons. One of the reasons occurring especially in urban context is the mismatched operating conditions at which the panels forming a PV plant work [10]. As some panels are connected in series in order to reach a voltage level that fits with the input specifications of the commercial inverters, the presence of a partial shadowing affecting some cells or other inhomogeneity among the parameters of the cells, e.g., due to aging, failures or manufactur- ing tolerances, might cause a significant drop in the power production [24]. Producers usually install bypass diodes in the panels for mitigating the power loss in case of mismatching, but these diodes greatly change the voltage vs. current ðV IÞ char- acteristic of the PV array. When the diodes enter into conduction for compensating a current mismatching among the cells of the string, the voltage vs. power (V P) characteristic of the array shows more than one Maximum Power Point (MPP). To obtain the MPP, the inverter control system is usually equipped with a Maximum Power Point Tracking (MPPT) algorithm and many methods have been proposed in the literature with the aim to find the MPP, including Fuzzy Logic and Neural Networks n Corresponding author. E-mail addresses: [email protected] (P.L. Carotenuto), [email protected] (A. Della Cioppa), [email protected] (A. Marcelli), [email protected] (G. Spagnuolo). http://dx.doi.org/10.1016/j.neucom.2015.04.094 0925-2312/& 2015 Elsevier B.V. All rights reserved. abstract The dynamical reconfiguration of photovoltaic panels is a useful approach for fighting the detrimental effects of mismatching on their power production. The practical implementation of the method has been recently optimized by means of efficient and reliable relays. However, two problems remain still open. The first is to determine the optimal electrical connection among the panels that ensures the maximum power produced at the actual irradiance conditions, while the latter is to constrain the computation time of such optimal configuration to fit the need of real time applications. We present an evolutionary approach to the first problem. It is designed for allowing a straightforward porting to an embedded system and it is aimed at reconfiguring photovoltaic panels, thus not modules like some other approaches do in literature. Simulation results confirm the reliability and convergence capabilities of the proposed method and encourage further work for the adoption of the algorithm in real time applications. The problem of minimizing the computation time is also addressed

Trivalent and quadrivalent MF59(®)-adjuvanted influenza vaccine in young children : a dose- and schedule-finding study.

Young children are at increased risk for influenza infections and related complications. The protection offered to children by conventional trivalent inactivated influenza vaccines (TIV) is suboptimal, due to poor immunogenicity and a higher exposure to infection and complications in this age group, particularly from influenza B strains. In this dose-ranging, factorial design trial, we report the safety and immunogenicity of different combinations of adjuvanted (ATIV) and non-adjuvanted trivalent (TIV) and quadrivalent (QIV) influenza vaccines in 480 healthy children 6 to <36 months of age. The results show that the second B strain added to TIV was immunogenic and did not affect immunogenicity of the other strains. The addition of the MF59(®) adjuvant promoted robust immune responses with notable elevations in antibodies observed even after one dose. A dose-response relationship was observed between the antibody response and MF59 adjuvant. No patterns in safety and tolerability emerged with different adjuvant and antigen doses nor with the addition of a second B strain. MF59-adjuvanted QIV offers potential advantages to young children

Identification of Ferrite Core Inductors Parameters by Evolutionary Algorithms

This paper discusses the identification of Ferrite Core (FC) power inductors parameters in the real operating conditions relevant to Switch-Mode Power Supplies starting from experimental measurements. A novel method for parameters identification is proposed, based on Evolutionary Algorithms (EAs) and on the analysis of inductors non-linear behavior. Two EAs, the Genetic Algorithm and the Differential Evolution, are investigated and compared. The results of the proposed method are experimentally validated by means of a buck converter evaluation board