Statistical design considerations for pilot studies transitioning therapies from the bench to the bedside

Pilot studies are often used to transition therapies developed using animal models to a clinical setting. Frequently, the focus of such trials is on estimating the safety in terms of the occurrence of certain adverse events. With relatively small sample sizes, the probability of observing even relatively common events is low; however, inference on the true underlying event rate is still necessary even when no events of interest are observed. The exact upper limit to the event rate is derived and illustrated graphically. In addition, the simple algebraic expression for the confidence bound is seen to be useful in the context of planning studies

Experimental evaluation of corner turning vanes

Two types of turning vane airfoils (a controlled-diffusion shape and a circular arc shape) have been evaluated in the high-speed and fan-drive corners of a 0.1-scale model of NASA Lewis Research Center's proposed Altitude Wind Tunnel. The high-speed corner was evaluated with and without a simulated engine exhaust removal scoop. The fan-drive corner was evaluated with and without the high-speed corner. Flow surveys of pressure and flow angle were taken for both the corners and the vanes to determine their respective losses. The two-dimensional vane losses were low; however, the overall corner losses were higher because three-dimensional flow was generated by the complex geometry resulting from the turning vanes intersecting the end wall. The three-dimensional effects were especially pronounced in the outer region of the circular corner

Detailed flow surveys of turning vanes designed for a 0.1-scale model of NASA Lewis Research Center's proposed altitude wind tunnel

Detailed flow surveys downstream of the corner turning vanes and downstream of the fan inlet guide vanes have been obtained in a 0.1-scale model of the NASA Lewis Research Center's proposed Altitude Wind Tunnel. Two turning vane designs were evaluated in both corners 1 and 2 (the corners between the test section and the drive fan). Vane A was a controlled-diffusion airfoil and vane B was a circular-arc airfoil. At given flows the turning vane wakes were surveyed to determine the vane pressure losses. For both corners the vane A turning vane configuration gave lower losses than the vane B configuration in the regions where the flow regime should be representative of two-dimensional flow. For both vane sets the vane loss coefficient increased rapidly near the walls

Experimental Evaluation of Turning Vane Designs for High-speed and Coupled Fan-drive Corners of 0.1-scale Model of NASA Lewis Research Center's Proposed Altitude Wind Tunnel

Two turning vane designs were experimentally evaluated for the fan-drive corner (corner 2) coupled to an upstream diffuser and the high-speed corner (corner 1) of the 0.1 scale model of NASA Lewis Research Center's proposed Altitude Wind Tunnel. For corner 2 both a controlled-diffusion vane design (vane A4) and a circular-arc vane design (vane B) were studied. The corner 2 total pressure loss coefficient was about 0.12 with either vane design. This was about 25 percent less loss than when corner 2 was tested alone. Although the vane A4 design has the advantage of 20 percent fewer vanes than the vane B design, its vane shape is more complex. The effects of simulated inlet flow distortion on the overall losses for corner 1 or 2 were small

Temperature-tuning of near-infrared monodisperse quantum dot solids at 1.5 um for controllable Forster energy transfer

We present the first time-resolved cryogenic observations of Forster energy transfer in large, monodisperse lead sulphide quantum dots with ground state transitions near 1.5 um (0.83 eV), in environments from 160 K to room temperature. The observed temperature-dependent dipole-dipole transfer rate occurs in the range of (30-50 ns)^(-1), measured with our confocal single-photon counting setup at 1.5 um wavelengths. By temperature-tuning the dots, 94% efficiency of resonant energy transfer can be achieved for donor dots. The resonant transfer rates match well with proposed theoretical models

Matching Grants and Public Goods: A Closed-Ended Contingent Valuation Experiment

Matching grants are commonly used to influence the bundle of public goods provided by governments. We design a contingent valuation experiment to determine the value individuals place on improved recreational facilities under a matching grant proposal. The experiment provides an opportunity to examine preferences given the public good exists in an active and well-defined market, and the valuation experiment is perceived as meaningful to public policy. We estimate a mean willingness-to-pay for park improvements of $8.30, far less than the implied tax increase of$21 provided by local politicians opposed to the project, but nearly doubled the actual tax increase for the average property owner

Breast vibro-acoustography: initial results show promise

INTRODUCTION: Vibro-acoustography (VA) is a recently developed imaging modality that is sensitive to the dynamic characteristics of tissue. It detects low-frequency harmonic vibrations in tissue that are induced by the radiation force of ultrasound. Here, we have investigated applications of VA for in vivo breast imaging. METHODS: A recently developed combined mammography-VA system for in vivo breast imaging was tested on female volunteers, aged 25 years or older, with suspected breast lesions on their clinical examination. After mammography, a set of VA scans was acquired by the experimental device. In a masked assessment, VA images were evaluated independently by 3 reviewers who identified mass lesions and calcifications. The diagnostic accuracy of this imaging method was determined by comparing the reviewers' responses with clinical data. RESULTS: We collected images from 57 participants: 7 were used for training and 48 for evaluation of diagnostic accuracy (images from 2 participants were excluded because of unexpected imaging artifacts). In total, 16 malignant and 32 benign lesions were examined. Specificity for diagnostic accuracy was 94% or higher for all 3 reviewers, but sensitivity varied (69% to 100%). All reviewers were able to detect 97% of masses, but sensitivity for detection of calcification was lower (≤ 72% for all reviewers). CONCLUSIONS: VA can be used to detect various breast abnormalities, including calcifications and benign and malignant masses, with relatively high specificity. VA technology may lead to a new clinical tool for breast imaging applications

Book Reviews

Book reviews of: William F. Winter and the New Mississippi: A Biography. By Charles C. Bolton Jackson: University Press of Mississippi, 2013. Pp. vii, 368. Illustrations, map, acknowledgements, notes, index. $35.00 cloth. ISBN: 9781617037870. Born of Conviction: White Methodists and Mississippi’s Closed Society. By Joseph T. Reiff. (New York: Oxford University Press, 2016. Acknowledgements, illustrations, map, notes, index. Pp. xxi, 384.$35 Hardcover. ISBN: 9780190246815). In Katrina’s Wake: The U.S. Coast Guard and the Gulf Coast Hurricanes of 2005. By Donald L. Canney. (Gainesville: University Press of Florida, 2010. Foreword, notes, index. Pp. xv, 228. $27.50 cloth.) Slavery, Race and Conquest in the Tropic: Lincoln, Douglas and the Future of America. By Robert E. May. (New York: Cambridge University Press, 2013. Acknowledgements, illustrations, maps, notes, index. Pp. xi, 296.$80 cloth, $26.99 paper,$22 e-book. ISBN: 9780521132527.) Rivers of Sand: Creek Indian Emigration, Relocation, and Ethnic Cleansing in the American South. By Christopher D. Haveman. (Nebraska: University of Nebraska Press, 2016. Illustrations, preface, acknowledgments, notes on terminology, index. Pp. ix, 414. Trouble in Goshen: Plain Folk, Roosevelt, Jesus, and Marx in the Great Depression. By Fred C. Smith (Jackson: University Press of Mississippi, 2014. Acknowledgements, illustrations, map notes, index. Pp. xi, 214. $60.00 cloth. ISBN: 9781617039560.) Builders of a New South: Merchants, Capital, and the Remaking of Natchez, 1865-1914. By Aaron D. Anderson (Jackson: University Press of Mississippi, 2013. Acknowledgments, illustrations, photographs, notes, graphics, index. Pp. 279.$40 cloth. ISBN: 978-1- 61703-667-5.) Adventurism and Empire: The Struggle for Mastery in the Louisiana- Florida Borderlands 1762-1803. By David Narrett. (Chapel Hill: The University of North Carolina Press, 2015. Acknowledgements, illustrations, notes, index. Pp. xi, 365. $45 cloth,$44.99 e-book. ISBN: 978-1-4696-1833-3.) Empty Sleeves: Amputation in the Civil War South. By Brian Craig Miller. (Athens: University of Georgia Press, 2015. Illustrations, acknowledgments, appendix, notes, index. Pp. xvi, 257. $79.95 cloth,$29.95 paper. ISBN: 0820343327.) Signposts: New Directions in Southern Legal History. By Sally E. Hadden and Patricia Hagler Minter, eds. (Athens and London: The University of Georgia Press, 2013. Acknowledgements, illustrations, index. Pp. xi, 480. $69.95 cloth,$26.95 paper, $26.95 ebook. ISBN: 978-0-8203-4499-7.) The Color of Christ: The Son of God and the Saga of Race in America. By Edward J. Blum and Paul Harvey. (Chapel Hill: University of North Carolina Press, 2012. Pp. 325.$32.50 Cloth. ISBN: 9780807835722.

Combining genomics and epidemiology to track mumps virus transmission in the United States.

Unusually large outbreaks of mumps across the United States in 2016 and 2017 raised questions about the extent of mumps circulation and the relationship between these and prior outbreaks. We paired epidemiological data from public health investigations with analysis of mumps virus whole genome sequences from 201 infected individuals, focusing on Massachusetts university communities. Our analysis suggests continuous, undetected circulation of mumps locally and nationally, including multiple independent introductions into Massachusetts and into individual communities. Despite the presence of these multiple mumps virus lineages, the genomic data show that one lineage has dominated in the US since at least 2006. Widespread transmission was surprising given high vaccination rates, but we found no genetic evidence that variants arising during this outbreak contributed to vaccine escape. Viral genomic data allowed us to reconstruct mumps transmission links not evident from epidemiological data or standard single-gene surveillance efforts and also revealed connections between apparently unrelated mumps outbreaks

The Suppressor of AAC2 Lethality SAL1 Modulates Sensitivity of Heterologously Expressed Artemia ADP/ATP Carrier to Bongkrekate in Yeast

The ADP/ATP carrier protein (AAC) expressed in Artemia franciscana is refractory to bongkrekate. We generated two strains of Saccharomyces cerevisiae where AAC1 and AAC3 were inactivated and the AAC2 isoform was replaced with Artemia AAC containing a hemagglutinin tag (ArAAC-HA). In one of the strains the suppressor of ΔAAC2 lethality, SAL1, was also inactivated but a plasmid coding for yeast AAC2 was included, because the ArAACΔsal1Δ strain was lethal. In both strains ArAAC-HA was expressed and correctly localized to the mitochondria. Peptide sequencing of ArAAC expressed in Artemia and that expressed in the modified yeasts revealed identical amino acid sequences. The isolated mitochondria from both modified strains developed 85% of the membrane potential attained by mitochondria of control strains, and addition of ADP yielded bongkrekate-sensitive depolarizations implying acquired sensitivity of ArAAC-mediated adenine nucleotide exchange to this poison, independent from SAL1. However, growth of ArAAC-expressing yeasts in glycerol-containing media was arrested by bongkrekate only in the presence of SAL1. We conclude that the mitochondrial environment of yeasts relying on respiratory growth conferred sensitivity of ArAAC to bongkrekate in a SAL1-dependent manner. © 2013 Wysocka-Kapcinska et al