FAST: Towards safe and effective subcutaneous immunotherapy of persistent life-threatening food allergies.

To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.ABSTRACT: The FAST project (Food Allergy Specific Immunotherapy) aims at the development of safe and effective treatment of food allergies, targeting prevalent, persistent and severe allergy to fish and peach. Classical allergen-specific immunotherapy (SIT), using subcutaneous injections with aqueous food extracts may be effective but has proven to be accompanied by too many anaphylactic side-effects. FAST aims to develop a safe alternative by replacing food extracts with hypoallergenic recombinant major allergens as the active ingredients of SIT. Both severe fish and peach allergy are caused by a single major allergen, parvalbumin (Cyp c 1) and lipid transfer protein (Pru p 3), respectively. Two approaches are being evaluated for achieving hypoallergenicity, i.e. site-directed mutagenesis and chemical modification. The most promising hypoallergens will be produced under GMP conditions. After pre-clinical testing (toxicology testing and efficacy in mouse models), SCIT with alum-absorbed hypoallergens will be evaluated in phase I/IIa and IIb randomized double-blind placebo-controlled (DBPC) clinical trials, with the DBPC food challenge as primary read-out. To understand the underlying immune mechanisms in depth serological and cellular immune analyses will be performed, allowing identification of novel biomarkers for monitoring treatment efficacy. FAST aims at improving the quality of life of food allergic patients by providing a safe and effective treatment that will significantly lower their threshold for fish or peach intake, thereby decreasing their anxiety and dependence on rescue medication

On Consistent Theories of Massive Spin-2 Fields Coupled to Gravity

We consider the issues that arise out of interpreting the ghost-free bimetric theory as a theory of a spin-2 field coupled to gravity. This requires identifying a gravitational metric and parameterizing deviations of the resulting theory from general relativity. To this end, we first consider the most general bimetric backgrounds for which a massless and a massive spin-2 fluctuation with Fierz-Pauli mass exist. These backgrounds coincide with solutions in general relativity. Based on this, we obtain nonlinear extensions of the massive and massless spin-2 fields. The background value of the nonlinear massive field parameterizes generic deviations of the bimetric theory from GR. It is also shown that the nonlinear massless field does not have standard ghost-free matter couplings, and hence cannot represent the gravitational metric. However, an appropriate gravitational metric can still be identified in the weak gravity limit. Hence in the presence of other neutral spin-2 fields, the weak gravity limit is crucial for compatibility with general relativity. We also write down the action in terms of the nonlinear massive spin-2 field and obtain its ghost-free couplings to matter. The discussion is then generalized to multimetric theories.Comment: Latex, 31 page

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion