Developing Novel Prognostic Biomarkers for Multivariate Fracture Risk Prediction Algorithms

Multivariate prediction algorithms such as FRAX® and QFracture Scores provide an opportunity for new prognostic biomarkers to be developed and incorporated, potentially leading to better fracture prediction. As more research is conducted into these novel biomarkers, a number of factors need to be considered for their successful development for inclusion in these algorithms. In this review, we describe two well-known multivariate prediction algorithms for osteoporosis fracture risk applicable to the UK population, FRAX and QFracture Scores, and comment on the current prognostic tools available for fracture risk; dual X-ray assessment, quantitative ultrasonography, and genomic/biochemical markers. We also highlight the factors that need to be considered in the development of new biomarkers. These factors include the requirement for prospective data, collected in new cohort studies or using archived samples; the need for adequate stability data to be provided; and the need for appropriate storage methods to be used when retrospective data are required. Area under the receiver operating characteristic curve measures have been found to have limited utility in assessing the impact of the addition of new risk factors on the predictive performance of multivariate algorithms. New performance evaluation measures, such as net reclassification index and integrated discrimination improvement, are increasingly important in the evaluation of the impact of the addition of new markers to multivariate algorithms, and these are also discussed. © Springer Science+Business Media, LLC 2012

AEGIS: New Evidence Linking Active Galactic Nuclei to the Quenching of Star Formation

Utilizing Chandra X-ray observations in the All-wavelength Extended Groth Strip International Survey (AEGIS) we identify 241 X-ray selected Active Galactic Nuclei (AGNs, L > 10^{42} ergs/s) and study the properties of their host galaxies in the range 0.4 < z < 1.4. By making use of infrared photometry from Palomar Observatory and BRI imaging from the Canada-France-Hawaii Telescope, we estimate AGN host galaxy stellar masses and show that both stellar mass and photometric redshift estimates (where necessary) are robust to the possible contamination from AGNs in our X-ray selected sample. Accounting for the photometric and X-ray sensitivity limits of the survey, we construct the stellar mass function of X-ray selected AGN host galaxies and find that their abundance decreases by a factor of ~2 since z~1, but remains roughly flat as a function of stellar mass. We compare the abundance of AGN hosts to the rate of star formation quenching observed in the total galaxy population. If the timescale for X-ray detectable AGN activity is roughly 0.5-1 Gyr--as suggested by black hole demographics and recent simulations--then we deduce that the inferred AGN "trigger" rate matches the star formation quenching rate, suggesting a link between these phenomena. However, given the large range of nuclear accretion rates we infer for the most massive and red hosts, X-ray selected AGNs may not be directly responsible for quenching star formation.Comment: 12 pages. Submitted to ApJ. Comments welcom

Air Data Boom System Development for the Max Launch Abort System (MLAS) Flight Experiment

In 2007, the NASA Exploration Systems Mission Directorate (ESMD) chartered the NASA Engineering Safety Center (NESC) to demonstrate an alternate launch abort concept as risk mitigation for the Orion project's baseline "tower" design. On July 8, 2009, a full scale and passively, aerodynamically stabilized MLAS launch abort demonstrator was successfully launched from Wallops Flight Facility following nearly two years of development work on the launch abort concept: from a napkin sketch to a flight demonstration of the full-scale flight test vehicle. The MLAS flight test vehicle was instrumented with a suite of aerodynamic sensors. The purpose was to obtain sufficient data to demonstrate that the vehicle demonstrated the behavior predicted by Computational Fluid Dynamics (CFD) analysis and wind tunnel testing. This paper describes development of the Air Data Boom (ADB) component of the aerodynamic sensor suite

The Team Keck Treasury Redshift Survey of the GOODS-North Field

We report the results of an extensive imaging and spectroscopic survey in the GOODS-North field completed using DEIMOS on the Keck II telescope. Observations of 2018 targets in a magnitude-limited sample of 2911 objects to R=24.4 yield secure redshifts for a sample of 1440 galaxies and AGN plus 96 stars. In addition to redshifts and associated quality assessments, our catalog also includes photometric and astrometric measurements for all targets detected in our R-band imaging survey of the GOODS-North region. We investigate various sources of incompleteness and find the redshift catalog to be 53% complete at its limiting magnitude. The median redshift of z=0.65 is lower than in similar deep surveys because we did not select against low-redshift targets. Comparison with other redshift surveys in the same field, including a complementary Hawaii-led DEIMOS survey, establishes that our velocity uncertainties are as low as 40 km/s for red galaxies and that our redshift confidence assessments are accurate. The distributions of rest-frame magnitudes and colors among the sample agree well with model predictions out to and beyond z=1. We will release all survey data, including extracted 1-D and sky-subtracted 2-D spectra, thus providing a sizable and homogeneous database for the GOODS-North field which will enable studies of large scale structure, spectral indices, internal galaxy kinematics, and the predictive capabilities of photometric redshifts.Comment: 17 pages, 18 figures, submitted to AJ; v2 minor changes; see survey database at http://www2.keck.hawaii.edu/realpublic/science/tksurvey

LSST Science Book, Version 2.0

A survey that can cover the sky in optical bands over wide fields to faint magnitudes with a fast cadence will enable many of the exciting science opportunities of the next decade. The Large Synoptic Survey Telescope (LSST) will have an effective aperture of 6.7 meters and an imaging camera with field of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over 20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a total point-source depth of r~27.5. The LSST Science Book describes the basic parameters of the LSST hardware, software, and observing plans. The book discusses educational and outreach opportunities, then goes on to describe a broad range of science that LSST will revolutionize: mapping the inner and outer Solar System, stellar populations in the Milky Way and nearby galaxies, the structure of the Milky Way disk and halo and other objects in the Local Volume, transient and variable objects both at low and high redshift, and the properties of normal and active galaxies at low and high redshift. It then turns to far-field cosmological topics, exploring properties of supernovae to z~1, strong and weak lensing, the large-scale distribution of galaxies and baryon oscillations, and how these different probes may be combined to constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at http://www.lsst.org/lsst/sciboo

Impact of stratospheric air and surface emissions on tropospheric nitrous oxide during ATom

We measured the global distribution of tropospheric N2O mixing ratios during the NASA airborne Atmospheric Tomography (ATom) mission. ATom measured concentrations of ∼ 300 gas species and aerosol properties in 647 vertical profiles spanning the Pacific, Atlantic, Arctic, and much of the Southern Ocean basins, nearly from pole to pole, over four seasons (2016–2018). We measured N2O concentrations at 1 Hz using a quantum cascade laser spectrometer (QCLS). We introduced a new spectral retrieval method to account for the pressure and temperature sensitivity of the instrument when deployed on aircraft. This retrieval strategy improved the precision of our ATom QCLS N2O measurements by a factor of three (based on the standard deviation of calibration measurements). Our measurements show that most of the variance of N2O mixing ratios in the troposphere is driven by the influence of N2O-depleted stratospheric air, especially at mid- and high latitudes. We observe the downward propagation of lower N2O mixing ratios (compared to surface stations) that tracks the influence of stratosphere–troposphere exchange through the tropospheric column down to the surface. The highest N2O mixing ratios occur close to the Equator, extending through the boundary layer and free troposphere. We observed influences from a complex and diverse mixture of N2O sources, with emission source types identified using the rich suite of chemical species measured on ATom and the geographical origin calculated using an atmospheric transport model. Although ATom flights were mostly over the oceans, the most prominent N2O enhancements were associated with anthropogenic emissions, including from industry (e.g., oil and gas), urban sources, and biomass burning, especially in the tropical Atlantic outflow from Africa. Enhanced N2O mixing ratios are mostly associated with pollution-related tracers arriving from the coastal area of Nigeria. Peaks of N2O are often associated with indicators of photochemical processing, suggesting possible unexpected source processes. In most cases, the results show how difficult it is to separate the mixture of different sources in the atmosphere, which may contribute to uncertainties in the N2O global budget. The extensive data set from ATom will help improve the understanding of N2O emission processes and their representation in global models.This research has been supported by the National Aeronautics and Space Administration (grant nos. NNX15AJ23G, NNX17AF54G, NNX15AG58A, NNX15AH33A, and 80NSSC19K0124) and the National Science Foundation (grant nos. 1852977, AGS-1547626, and AGS-1623745)

Prediction of disability-free survival in healthy older people.

Prolonging survival in good health is a fundamental societal goal. However, the leading determinants of disability-free survival in healthy older people have not been well established. Data from ASPREE, a bi-national placebo-controlled trial of aspirin with 4.7 years median follow-up, was analysed. At enrolment, participants were healthy and without prior cardiovascular events, dementia or persistent physical disability. Disability-free survival outcome was defined as absence of dementia, persistent disability or death. Selection of potential predictors from amongst 25 biomedical, psychosocial and lifestyle variables including recognized geriatric risk factors, utilizing a machine-learning approach. Separate models were developed for men and women. The selected predictors were evaluated in a multivariable Cox proportional hazards model and validated internally by bootstrapping. We included 19,114 Australian and US participants aged ≥65 years (median 74 years, IQR 71.6-77.7). Common predictors of a worse prognosis in both sexes included higher age, lower Modified Mini-Mental State Examination score, lower gait speed, lower grip strength and abnormal (low or elevated) body mass index. Additional risk factors for men included current smoking, and abnormal eGFR. In women, diabetes and depression were additional predictors. The biased-corrected areas under the receiver operating characteristic curves for the final prognostic models at 5 years were 0.72 for men and 0.75 for women. Final models showed good calibration between the observed and predicted risks. We developed a prediction model in which age, cognitive function and gait speed were the strongest predictors of disability-free survival in healthy older people.Trial registration Clinicaltrials.gov (NCT01038583)

Crop Updates 2005 - Cereals

This session covers thirty six papers from different authors: WHEAT AGRONOMY 1. Optimum sowing time of new wheat varieties in Western Australia, Darshan Sharma, Brenda Shackley, Mohammad Amjad, Christine M. Zaicou-Kunesch and Wal Anderson, Department of Agriculture 2. Wheat varieties updated in ‘Flowering Calculator’: A model predicting flowering time, B. Shackley, D. Tennant, D. Sharma and C.M. Zaicou-Kunesch, Department of Agriculture 3. Plant populations for wheat varieties, Christine M. Zaicou-Kunesch, Wal Anderson, Darshan Sharma, Brenda Shackley and Mohammad Amjad, Department of Agriculture 4. New wheat cultivars response to fertiliser nitrogen in four major agricultural regions of Western Australia, Mohammad Amjad, Wal Anderson, Brenda Shackley, Darshan Sharma and Christine Zaicou-Kunesch, Department of Agriculture 5. Agronomic package for EGA Eagle Rock, Steve Penny, Department of Agriculture 6. Field evaluation of eastern and western wheats in large-scale farmer’s trials, Mohammad Amjad, Ben Curtis and Veronika Reck, Department of Agriculture 7. New wheat varieties for a changing environment, Richard Richards, CSIRO Plant Industry; Canberra 8. Farmers can profitably minimise exposure to frost! Garren Knell, Steve Curtin and David Sermon, ConsultAg 9. National Variety Trials, Alan Bedggood, Australian Crops Accreditation System; Horsham 10. Preharvest-sprouting tolerance of wheat in the field, T.B. Biddulph1, T.L. Setter2, J.A. Plummer1 and D.J. Mares3; 1Plant Biology; FNAS, University of Western Australia; 2Department of Agriculture, 3School of Agriculture and Wine, University of Adelaide 11. Waterlogging induces high concentration of Mn and Al in wheat genotypes in acidic soils, H. Khabaz-Saberi, T. Setter, I. Waters and G. McDonald, Department of Agriculture 12. Agronomic responses of new wheat varieties in the Northern Agricultural Region, Christine M. Zaicou-Kunesch and Wal Anderson, Department of Agriculture 13. Agronomic responses of new wheat varieties in the Central Agricultural Region of WA, Darshan Sharma, Steve Penny and Wal Anderson, Department of Agriculture 14. EGA Eagle Rock tolerance to metribuzin and its mixtures, Harmohinder Dhammu, David Nicholson and Chris Roberts, Department of Agriculture 15. Herbicide tolerance of new bread wheats, Harmohinder Dhammu1 and David Nicholson2, Department of Agriculture NUTRITION 16. The impact of fertiliser placement, timing and rates on nitrogen-use efficiency, Stephen Loss, CSBP Ltd 17. Cereals deficient in potassium are most susceptible to some leaf diseases, Ross Brennan and Kith Jayasena, Department of Agriculture 18. Responses of cereal yields to potassium fertiliser type, placement and timing, Eddy Pol, CSBP Limited 19. Sulphate of Potash, the potash of choice at seeding, Simon Teakle, United Farmers Co-operative 20. Essential disease management for successful barley production, K. Jayasena, R. Loughman, C. Beard, B. Paynter, K. Tanaka, G. Poulish and A. Smith, Department of Agriculture 21. Genotypic differences in potassium efficiency of wheat, Paul Damon and Zed Rengel, Faculty of Natural and Agricultural Sciences, University of Western Australia 22. Genotypic differences in potassium efficiency of barley, Paul Damon and Zed Rengel, Faculty of Natural and Agricultural Sciences, University of Western Australia 23. Investigating timing of nitrogen application in wheat, Darshan Sharma and Lionel Martin, Department of Agriculture, and Muresk Institute of Agriculture, Curtin University of Technology 24. Nutrient timing requirements for increased crop yields in the high rainfall cropping zone, Narelle Hill, Ron McTaggart, Dr Wal Anderson and Ray Tugwell, Department of Agriculture DISEASES 25. Integrate strategies to manage stripe rust risk, Geoff Thomas, Robert Loughman, Ciara Beard, Kith Jayasena and Manisha Shankar, Department of Agriculture 26. Effect of primary inoculum level of stripe rust on variety response in wheat, Manisha Shankar, John Majewski and Robert Loughman, Department of Agriculture 27. Disease resistance update for wheat varieties in WA, M. Shankar, J.M. Majewski, D. Foster, H. Golzar, J. Piotrowski and R. Loughman, Department of Agriculture 28. Big droplets for wheat fungicides, Rob Grima, Agronomist, Elders 29. On farm research to investigate fungicide applications to minimise leaf disease impacts in wheat, Jeff Russell and Angie Roe, Department of Agriculture, and Farm Focus Consultants PESTS 30. Rotations for nematode management, Vivien A. Vanstone, Sean J. Kelly, Helen F. Hunter and Mena C. Gilchrist, Department of Agriculture 31. Investigation into the adaqyacy of sealed farm silos in Western Australia to control phosphine-resistant Rhyzopertha dominica, C.R. Newman, Department of Agriculture 32.Insect contamination of cereal grain at harvest, Svetlana Micic and Phil Michael, Department of Agriculture 33. Phosure – Extending the life of phosphine, Gabrielle Coupland and Ern Kostas, Co-operative Bulk Handling SOIL 34. Optimum combinations of ripping depth and tine spacing for increasing wheat yield, Mohammed Hamza and Wal Anderson, Department of Agriculture 35. Hardpan penetration ability of wheat roots, Tina Botwright Acuña and Len Wade, School of Plant Biology, University of Western Australia MARKETS 36. Latin America: An emerging agricultural powerhouse, Ingrid Richardson, Food and Agribusiness Research, Rabobank; Sydne

SAD phasing using iodide ions in a high-throughput structural genomics environment

The Seattle Structural Genomics Center for Infectious Disease (SSGCID) focuses on the structure elucidation of potential drug targets from class A, B, and C infectious disease organisms. Many SSGCID targets are selected because they have homologs in other organisms that are validated drug targets with known structures. Thus, many SSGCID targets are expected to be solved by molecular replacement (MR), and reflective of this, all proteins are expressed in native form. However, many community request targets do not have homologs with known structures and not all internally selected targets readily solve by MR, necessitating experimental phase determination. We have adopted the use of iodide ion soaks and single wavelength anomalous dispersion (SAD) experiments as our primary method for de novo phasing. This method uses existing native crystals and in house data collection, resulting in rapid, low cost structure determination. Iodide ions are non-toxic and soluble at molar concentrations, facilitating binding at numerous hydrophobic or positively charged sites. We have used this technique across a wide range of crystallization conditions with successful structure determination in 16 of 17 cases within the first year of use (94% success rate). Here we present a general overview of this method as well as several examples including SAD phasing of proteins with novel folds and the combined use of SAD and MR for targets with weak MR solutions. These cases highlight the straightforward and powerful method of iodide ion SAD phasing in a high-throughput structural genomics environment