EXHANCE-3: a cohort study of the exhalation delivery system with fluticasone for chronic sinusitis with or without nasal polyps.

BACKGROUND: Inhaled nasal corticosteroid sprays (INS) are often inadequate to treat chronic rhinosinusitis (CRS). The exhalation delivery system with fluticasone (EDS-FLU; XHANCE®) may improve outcomes in CRS by increasing medication delivery to target superior/posterior anatomic sites. This study assessed safety and efficacy of EDS-FLU in a large population with moderate-to-severe CRS with or without nasal polyps (CRSwNP, CRSsNP). METHODS: Prospective, multicenter, 12-week, single-arm study of EDS-FLU 372 Â#181;g twice daily (BID) at 38 U.S. sites. Safety was assessed by adverse-event evaluations, nasal endoscopy, and ocular examinations. Efficacy was serially assessed by outcomes including nasal endoscopy (Lund-Kennedy Score, polyp grade), patient- and physician-reported outcomes (22-item Sinonasal Outcome Test [SNOT-22]), study-defined surgical indicator assessment, and Patient Global Impression of Change (PGIC). RESULTS: 705 comparatively refractory subjects were enrolled, 603 CRSsNP and 102 CRSwNP [moderate-to-severely symptomatic; baseline SNOT-22 ~43, high rates of prior INS use (92.3%) and/or prior surgery (27.5%)]. More than 90% reported improvement on treatment by PGIC. SNOT-22 scores improved substantially and similarly in patients with NP (-23.7) and without NP (-24.4). Among patients with baseline Lund-Kennedy edema scores >0, 33.3% (CRSwNP) and 54.8% (CRSsNP) had complete resolution of edema. In CRSwNP patients, 48% had polyp elimination in ?1 nostril, 63% had ?1-point improvement in polyp grade, mean bilateral polyp grade decreased from 2.9 to 1.6, and study-defined surgical eligibility decreased. EDS-FLU was generally well tolerated, with a safety profile similar to conventional INS sprays when used to treat CRS CONCLUSION: EDS-FLU 372 #181;g BID in the treatment of CRS with or without polyps was safe, well-tolerated, and produced substantial improvement across a broad range of both objective and subjective measures.

Faster power estimation of CMOS designs using vector compaction - a fractal approach.

Low power digital complementary metal oxide semiconductor (CMOS) circuit design requires accurate power estimation. In this paper, we present a compaction algorithm for generating compact vector sets to estimate power efficiently. Power can be estimated using dynamic (simulation) or static (statistical/probabilistic) techniques. Dynamic power estimation techniques simulate the design using a large input vector set for accurate estimation. However, the simulation time is prohibitively long for bigger designs with larger vector sets. The statistical methods, on the other hand, use analytical tools that make them faster but less accurate. To achieve the accuracy of dynamic power estimation and the speed of statistical methods, one approach is to generate a compact, representative vector set that has the same switching transition behavior as the original larger vector set. The compaction algorithm presented in this paper uses fractal concepts to generate such a compact vector set. The fractal technique quantifies correlation by a fractal parameter which can be determined faster than calculating correlation explicitly. Experimental results on circuits from the ISCAS85 and ISCAS89 benchmark suites, with correlated input vector sets, resulted in a maximum compaction ratio of 65.57X (average 38.14X) and maximum power estimation error of 2.4% (average 2.06%). Since the size of the compact vector set used for simulation is smaller, the simulation time will be shorter and will significantly speed up the design cycle.

ECSIT is an evolutionarily conserved intermediate in the Toll/IL-1 signal transduction pathway.

Activation of NF-kappaB as a consequence of signaling through the Toll and IL-1 receptors is a major element of innate immune responses. We report the identification and characterization of a novel intermediate in these signaling pathways that bridges TRAF6 to MEKK-1. This adapter protein, which we have named ECSIT (evolutionarily conserved signaling intermediate in Toll pathways), is specific for the Toll/IL-1 pathways and is a regulator of MEKK-1 processing. Expression of wild-type ECSIT accelerates processing of MEKK-1, whereas a dominant-negative fragment of ECSIT blocks MEKK-1 processing and activation of NF-kappaB. These results indicate an important role for ECSIT in signaling to NF-kappaB and suggest that processing of MEKK-1 is required for its function in the Toll/IL-1 pathway.

Digraph visualization using a neural algorithm with a heuristic activation scheme.

This paper presents an activation scheme for use with Hopfield neural network algorithms that guarantees a valid solution for a particular category of problems. The technique monitors the appropriate neurons and heuristically controls their activation function. As a result it has been possible to eliminate several constraint terms from the energy function that normally would have been required to drive the network toward a valid solution. This saves time and eliminates the need for empirically determining a larger number of constants. This technique has been applied to the combinatorial optimization problem called hierarchical digraph visualization that arises in many application areas where it is necessary to visually realize the relationship between entities in complex systems. Results are presented that compare this new approach with a more traditional neural network approach as well as heuristic approaches, performance improvement in terms of the solution quality as well as execution time relative to both alternative techniques was achieved.

Hierarchical graph visualization using neural networks.

An algorithm based on a Hopfield network for solving the hierarchical graph visualization problem is presented. It simultaneously minimizes the number of crossings and total path length to produce two-dimensional drawings easily interpreted by human observers. Traditional heuristics often follow a more local optimization approach where "readability" criteria are sequentially applied, such as applying the barycentric heuristic followed by the priority layout heuristic. As a result of the more global approach, the neural network achieved comparable crossing minimization to the barycentric heuristic while simultaneously reducing total path length up to 50% over the priority layout heuristic for the benchmarks tested.

Error introduced by specimen handling before determination of inorganic phosphate concentrations in plasma and serum.

Values for serum inorganic phosphate (Pi) concentrations in groups of healthy adults vary widely, the coefficient of variation ranging from 10 to 15%. We undertook to determine in 23 healthy adults whether part of this variation could be accounted for by (a) drawing blood in syringes vs. evacuated tubes (b) the time between blood sampling and separation of serum or plasma, and (c) the prevention of clotting. Values were unaffected by a, decreased significantly with time at room temperature between blood sampling and separation of cells in both serum and plasma, and were significantly lower in plasma than in serum. The group coefficient of variation for Pi averaged 13% and was uninfluenced by the blood-processing technique.