Efficacy, safety, tolerability and pharmacokinetics of a novel human immune globulin subcutaneous, 20%: a Phase 2/3 study in Europe in patients with primary immunodeficiencies

A highly concentrated (20%) immunoglobulin (Ig)G preparation for subcutaneous administration (IGSC 20%), would offer a new option for antibody replacement therapy in patients with primary immunodeficiency diseases (PIDD). The efficacy, safety, tolerability and pharmacokinetics of IGSC 20% were evaluated in a prospective trial in Europe in 49 patients with PIDD aged 2-67 years. Over a median of 358 days, patients received 2349 IGSC 20% infusions at monthly doses equivalent to those administered for previous intravenous or subcutaneous IgG treatment. The rate of validated acute bacterial infections (VASBIs) was significantly lower than 1 per year (0.022/patient-year, P /= 8 g/l. There was no serious adverse event (AE) deemed related to IGSC 20% treatment; related non-serious AEs occurred at a rate of 0.101 event/infusion. The incidence of local related AEs was 0.069 event/infusion (0.036 event/infusion, when excluding a 13-year-old patient who reported 79 of 162 total related local AEs). The incidence of related systemic AEs was 0.032 event/infusion. Most related AEs were mild, none were severe. For 64.6% of patients and in 94.8% of IGSC 20% infusions, no local related AE occurred. The median infusion duration was 0.95 (range = 0.3-4.1) h using mainly one to two administration sites [median = 2 sites (range = 1-5)]. Almost all infusions (99.8%) were administered without interruption/stopping or rate reduction. These results demonstrate that IGSC 20% provides an effective and well-tolerated therapy for patients previously on intravenous or subcutaneous treatment, without the need for dose adjustment

Adiabatic perturbation theory: from Landau-Zener problem to quenching through a quantum critical point

We discuss the application of the adiabatic perturbation theory to analyze the dynamics in various systems in the limit of slow parametric changes of the Hamiltonian. We first consider a two-level system and give an elementary derivation of the asymptotics of the transition probability when the tuning parameter slowly changes in the finite range. Then we apply this perturbation theory to many-particle systems with low energy spectrum characterized by quasiparticle excitations. Within this approach we derive the scaling of various quantities such as the density of generated defects, entropy and energy. We discuss the applications of this approach to a specific situation where the system crosses a quantum critical point. We also show the connection between adiabatic and sudden quenches near a quantum phase transitions and discuss the effects of quasiparticle statistics on slow and sudden quenches at finite temperatures.Comment: 20 pages, 3 figures, contribution to "Quantum Quenching, Annealing and Computation", Eds. A. Das, A. Chandra and B. K. Chakrabarti, Lect. Notes in Phys., Springer, Heidelberg (2009, to be published), reference correcte

A BIO-MOLECULAR ARCHITECTURAL CONCEPT FOR ENHANCED SENSING OF BIO-SIGNATURES

Author Institution: University of Virginia; Army Research Laboratory, Army Research OfficeRecent research has demonstrated the potential use of terahertz (THz) frequency transmission spectroscopy as a technique for the detection, identification and characterization of biological agents. However, while adequate levels of sensitivity appear to be demonstrated even for remote detection applications, the viability of THz spectroscopy for biological sensing (i.e., point and remote) will ultimately hinge on the level of reliable discrimination it can provide. Two challenges arise within this context. First, there are a reasonably limited number of spectral signatures (i.e., $\preceq 100$) associated with any bio-agent in its natural state and, second, the strong atmospheric absorption limits the sensitivity of the approach at all but a few THz-band transmission channels. However, it is possible to envision bio-molecular electronic architectures that can be effectively utilized for sensing and processing of bio-signature data. The novelty of this approach lies in the strategic use of integrated biological elements to achieve higher-level function and spectral data processing within a nanoscale and molecular-level architecture. An overview of this new bio-molecular architectural concept will be presented along with a report on the initial theoretical studies that are underway for defining the functional bio-molecular components. Hence, this presentation will define a new and novel approach for enhancing the spectral sensing of bio-signatures at THz frequencies

AN ASSESSMENT OF TERAHERTZ-FREQUENCY REMOTE-SENSING FOR APPLICATION TO A BIOLOGICAL WARFARE ATTACK SCENARIO

Author Institution: Research Laboratory, Army Research Office; Research Laboratory, University of California at Los Angeles; Research Laboratory, Edgewood Chemical and Biological Center; Research Laboratory, University of Virginia; Research Laboratory, Naval Surface Warfare CenterThis presentation gives a detailed assessment of terahertz-frequency spectroscopy as a technique for the remote detection of biological warfare agents. Design studies are presented for a differential-absorption-radar (DAR) approach that utilizes the spectral signatures of Bacillus (B.) subtillus spores within the terahertz (THz) regime as the detection mechanism. The signature data used in these studies is taken from laboratory measurements performed on uniform thin films of B. Subtillus spores and the system performance is assessed for both incoherent and coherent detector modalities. These studies consider DAR remote sensing of biological (bio) clouds at significant ranges (i.e., 1 km) and include the effects of realistic atmospheric conditions. A high-level remote-sensor design is used to estimate the probabilities of detection $(p_{d})$ and false-alarm $(p_{fa})$ associated with this general technique. These studies suggest useful remote-detection performance can be achieved (i.e., $p_{d} > 0.9 \& p_{fa} \ll 10^{-4}$ for bio-cloud densities $< 103 cm^{-3}$) at 1 km ranges if the THz signature information remains predictably stable under varying atmospheric conditions (e.g., changes in humidity, spore activity state, etc). Furthermore, a realistic bio-agent airframe attack scenario is utilized to demonstrate standoff detection of bio-clouds with ${\approx}100$ confidence while outside the threat-level concentrations. All together, these results demonstrate that standoff detection of bio-agents is feasible for threat-level concentrations in practical battlefield environments at sufficient ranges to provide for early warning

Efficacy, safety, tolerability and pharmacokinetics of a novel human immune globulin subcutaneous, 20%: a Phase 2/3 study in Europe in patients with primary immunodeficiencies.

A highly concentrated (20%) immunoglobulin (Ig)G preparation for subcutaneous administration (IGSC 20%), would offer a new option for antibody replacement therapy in patients with primary immunodeficiency diseases (PIDD). The efficacy, safety, tolerability and pharmacokinetics of IGSC 20% were evaluated in a prospective trial in Europe in 49 patients with PIDD aged 2-67 years. Over a median of 358 days, patients received 2349 IGSC 20% infusions at monthly doses equivalent to those administered for previous intravenous or subcutaneous IgG treatment. The rate of validated acute bacterial infections (VASBIs) was significantly lower than 1 per year (0·022/patient-year, P &lt; 0·0001); the rate of all infections was 4·38/patient-year. Median trough IgG concentrations were ≥&nbsp;8&nbsp;g/l. There was no serious adverse event (AE) deemed related to IGSC 20% treatment; related non-serious AEs occurred at a rate of 0·101 event/infusion. The incidence of local related AEs was 0·069 event/infusion (0·036 event/infusion, when excluding a 13-year-old patient who reported 79 of 162 total related local AEs). The incidence of related systemic AEs was 0·032 event/infusion. Most related AEs were mild, none were severe. For 64·6% of patients and in 94·8% of IGSC 20% infusions, no local related AE occurred. The median infusion duration was 0·95 (range&nbsp;=&nbsp;0·3-4·1) h using mainly one to two administration sites [median = 2 sites (range&nbsp;=&nbsp;1-5)]. Almost all infusions (99·8%) were administered without interruption/stopping or rate reduction. These results demonstrate that IGSC 20% provides an effective and well-tolerated therapy for patients previously on intravenous or subcutaneous treatment, without the need for dose adjustment