The Economics of Reducing Package Size: Consumer response and returns to manufacturers.

Marketing, Production Economics,

Using historical lesion volume data in the design of a new phase II clinical trial in acute stroke

<p><b>Background and Purpose:</b> Clinical research into the treatment of acute stroke is complicated, is costly, and has often been unsuccessful. Developments in imaging technology based on computed tomography and magnetic resonance imaging scans offer opportunities for screening experimental therapies during phase II testing so as to deliver only the most promising interventions to phase III. We discuss the design and the appropriate sample size for phase II studies in stroke based on lesion volume.</p> <p><b>Methods:</b> Determination of the relation between analyses of lesion volumes and of neurologic outcomes is illustrated using data from placebo trial patients from the Virtual International Stroke Trials Archive. The size of an effect on lesion volume that would lead to a clinically relevant treatment effect in terms of a measure, such as modified Rankin score (mRS), is found. The sample size to detect that magnitude of effect on lesion volume is then calculated. Simulation is used to evaluate different criteria for proceeding from phase II to phase III.</p> <p><b>Results:</b> The odds ratios for mRS correspond roughly to the square root of odds ratios for lesion volume, implying that for equivalent power specifications, sample sizes based on lesion volumes should be about one fourth of those based on mRS. Relaxation of power requirements, appropriate for phase II, lead to further sample size reductions. For example, a phase III trial comparing a novel treatment with placebo with a total sample size of 1518 patients might be motivated from a phase II trial of 126 patients comparing the same 2 treatment arms.</p> <p><b>Discussion:</b> Definitive phase III trials in stroke should aim to demonstrate significant effects of treatment on clinical outcomes. However, more direct outcomes such as lesion volume can be useful in phase II for determining whether such phase III trials should be undertaken in the first place.</p&gt

Guttate leukoderma and acrokeratosis verruciformis of Hopf: a rare combination in Darier disease

A distinct Darier phenotype presenting with confetti-like hypopigmented macules was first described in 1965. Designated as "guttate leukoderma," this skin finding is a rarely-reported presentation of Darier disease. It has been theorized that the mutation in ATP2A2 causes defective E-cadherin, which in turn disrupts the adhesion of melanocytes to keratinocytes, thus leading to impaired dendrite formation, hindered melanin transfer, and ultimately to melanocyte apoptosis. Herein, we contribute a case of a 56-year old woman who presented with the rarely-described guttate leukoderma of Darier disease and acrokeratosis verruciformis of Hopf

Excitotoxicity Induces Changes in Rat Brain Gangliosides

開始ページ、終了ページ: 冊子体のページ付

Shapes and Shears, Stars and Smears: Optimal Measurements for Weak Lensing

We present the theoretical and analytical bases of optimal techniques to measure weak gravitational shear from images of galaxies. We first characterize the geometric space of shears and ellipticity, then use this geometric interpretation to analyse images. The steps of this analysis include: measurement of object shapes on images, combining measurements of a given galaxy on different images, estimating the underlying shear from an ensemble of galaxy shapes, and compensating for the systematic effects of image distortion, bias from PSF asymmetries, and `"dilution" of the signal by the seeing. These methods minimize the ellipticity measurement noise, provide calculable shear uncertainty estimates, and allow removal of systematic contamination by PSF effects to arbitrary precision. Galaxy images and PSFs are decomposed into a family of orthogonal 2d Gaussian-based functions, making the PSF correction and shape measurement relatively straightforward and computationally efficient. We also discuss sources of noise-induced bias in weak lensing measurements and provide a solution for these and previously identified biases.Comment: Version accepted to AJ. Minor fixes, plus a simpler method of shape weighting. Version with full vector figures available via http://www.astro.lsa.umich.edu/users/garyb/PUBLICATIONS

In Silico Analysis of Putative Paralytic Shellfish Poisoning Toxins Export Proteins in Cyanobacteria

Lopez-Cortes, XA (Lopez-Cortes, Xaviera A.) Univ Talca, Nanobiotechnol Div, Fraunhofer Chile Res Fdn, Ctr Syst Biotechnol, Talca, Chile.Paralytic shellfish poisoning toxins (PSTs) are a family of more than 30 natural alkaloids synthesized by dinoflagellates and cyanobacteria whose toxicity in animals is mediated by voltage-gated Na+ channel blocking. The export of PST analogues may be through SxtF and SxtM, two putative MATE (multidrug and toxic compound extrusion) family transporters encoded in PSTs biosynthetic gene cluster (sxt). sxtM is present in every sxt cluster analyzed; however, sxtF is only present in the Cylindrospermopsis-Raphidiopsis clade. These transporters are energetically coupled with an electrochemical gradient of proton (H+) or sodium (Na+) ions across membranes. Because the functional role of PSTs remains unknown and methods for genetic manipulation in PST-producing organisms have not yet been developed, protein structure analyses will allow us to understand their function. By analyzing the sxt cluster of eight PST-producing cyanobacteria, we found no correlation between the presence of sxtF or sxtM and a specific PSTs profile. Phylogenetic analyses of SxtF/M showed a high conservation of SxtF in the Cylindrospermopsis-Raphidiopsis clade, suggesting conserved substrate affinity. Two domains involved in Na+ and drug recognition from NorM proteins (MATE family) of Vibrio parahaemolyticus and V. cholerae are present in SxtF/M. The Na+ recognition domain was conserved in both SxtF/M, indicating that Na+ can maintain the role as a cation anti-transporter. Consensus motifs for toxin binding differed between SxtF and SxtM implying differential substrate binding. Through protein modeling and docking analysis, we found that there is no marked affinity between the recognition domain and a specific PST analogue. This agrees with our previous results of PST export in R. brookii D9, where we observed that the response to Na+ incubation was similar to different analogues. These results reassert the hypothesis regarding the involvement of Na+ in toxin export, as well as the motifs L(398)XGLQD(403) (SxtM) and L(390)VGLRD(395) (SxtF) in toxin recognition

A Deep Multicolor Survey. VI. Near-Infrared Observations, Selection Effects, and Number Counts

I present near-infrared J (1.25um), H (1.65um), and K (2.2um) imaging observations of 185 square arcminutes in 21 high galactic latitude fields. These observations reach limiting magnitudes of J ~ 21 mag, H ~ 20 mag and K ~ 18.5 mag. The detection efficiency, photometric accuracy and selection biases as a function of integrated object brightness, size, and profile shape are quantified in detail. I evaluate several popular methods for measuring the integrated light of faint galaxies and show that only aperture magnitudes provide an unbiased measure of the integrated light that is independent of apparent magnitude. These J, H, and K counts and near-infrared colors are in best agreement with passive galaxy formation models with at most a small amount of merging (for Omega_M = 0.3, Omega_Lambda = 0.7).Comment: AJ Accepted (Feb 2001). 28 pages, 7 embedded ps figures, AASTEX5. Minor changes to submitted version. Also available at http://www.astronomy.ohio-state.edu/~martini/pubs

Post-merger Signatures of Red-sequence Galaxies in Rich Abell Clusters at z≲0.1z\lesssim 0.1

We have investigated the post-merger signatures of red-sequence galaxies in rich Abell clusters at $z \lesssim$ 0.1: A119, A2670, A3330 and A389. Deep images in u', g', r' and medium-resolution galaxy spectra were taken using MOSAIC 2 CCD and Hydra MOS mounted on a Blanco 4-m telescope at CTIO. Post-merger features are identified by visual inspection based on asymmetric disturbed features, faint structures, discontinuous halo structures, rings and dust lanes. We found that ~ 25% of bright (M_r < -20) cluster red-sequence galaxies show post-merger signatures in four clusters consistently. Most (~ 71%) of the featured galaxies were found to be bulge-dominated, and for the subsample of bulge-dominated red-sequence galaxies, the post-merger fraction rises to ~ 38%. We also found that roughly 4% of bulge-dominated red-sequence galaxies interact (on-going merger). A total of 42% (38% post-merger, 4% on-going merger) of galaxies show merger-related features. Compared to a field galaxy study with a similar limiting magnitude (van Dokkum 2005), our cluster study presents a similar post-merger fraction but a markedly lower on-going merger fraction. The merger fraction derived is surprisingly high for the high density of our clusters, where the fast internal motions of galaxies are thought to play a negative role in galaxy mergers. The fraction of post-merger and on-going merger galaxies can be explained as follows. Most of the post-merger galaxies may have carried over their merger features from their previous halo environment, whereas interacting galaxies interact in the current cluster in situ. According to our semi-analytic calculation, massive cluster haloes may very well have experienced tens of halo mergers over the last 4-5 Gyr; post-merger features last that long, allowing these features to be detected in our clusters today. (Abridged)Comment: 16 pages, 15 figures, 7 tables, accepted for publication in ApJ