Defining risk thresholds for a 10-year probability of hip fracture model that combines clinical risk factors and quantitative ultrasound: results using the EPISEM cohort.

Using a large prospective cohort of over 12,000 women, we determined 2 thresholds (high risk and low risk of hip fracture) to use in a 10-yr hip fracture probability model that we had previously described, a model combining the heel stiffness index measured by quantitative ultrasound (QUS) and a set of easily determined clinical risk factors (CRFs). The model identified a higher percentage of women with fractures as high risk than a previously reported risk score that combined QUS and CRF. In addition, it categorized women in a way that was quite consistent with the categorization that occurred using dual X-ray absorptiometry (DXA) and the World Health Organization (WHO) classification system; the 2 methods identified similar percentages of women with and without fractures in each of their 3 categories, but the 2 identified only in part the same women. Nevertheless, combining our composite probability model with DXA in a case findings strategy will likely further improve the detection of women at high risk of fragility hip fracture. We conclude that the currently proposed model may be of some use as an alternative to the WHO classification criteria for osteoporosis, at least when access to DXA is limited.

How Reliable Is Ki-67 Immunohistochemistry in Grade 2 Breast Carcinomas? A QA Study of the Swiss Working Group of Breast- and Gynecopathologists.

Adjuvant chemotherapy decisions in breast cancer are increasingly based on the pathologist's assessment of tumor proliferation. The Swiss Working Group of Gyneco- and Breast Pathologists has surveyed inter- and intraobserver consistency of Ki-67-based proliferative fraction in breast carcinomas. METHODS: Five pathologists evaluated MIB-1-labeling index (LI) in ten breast carcinomas (G1, G2, G3) by counting and eyeballing. In the same way, 15 pathologists all over Switzerland then assessed MIB-1-LI on three G2 carcinomas, in self-selected or pre-defined areas of the tumors, comparing centrally immunostained slides with slides immunostained in the different laboratoires. To study intra-observer variability, the same tumors were re-examined 4 months later. RESULTS: The Kappa values for the first series of ten carcinomas of various degrees of differentiation showed good to very good agreement for MIB-1-LI (Kappa 0.56-0.72). However, we found very high inter-observer variabilities (Kappa 0.04-0.14) in the read-outs of the G2 carcinomas. It was not possible to explain the inconsistencies exclusively by any of the following factors: (i) pathologists' divergent definitions of what counts as a positive nucleus (ii) the mode of assessment (counting vs. eyeballing), (iii) immunostaining technique, and (iv) the selection of the tumor area in which to count. Despite intensive confrontation of all participating pathologists with the problem, inter-observer agreement did not improve when the same slides were re-examined 4 months later (Kappa 0.01-0.04) and intra-observer agreement was likewise poor (Kappa 0.00-0.35). CONCLUSION: Assessment of mid-range Ki-67-LI suffers from high inter- and intra-observer variability. Oncologists should be aware of this caveat when using Ki-67-LI as a basis for treatment decisions in moderately differentiated breast carcinomas.

Duration of untreated psychosis: Impact of the definition of treatment onset on its predictive value over three years of treatment.

BACKGROUND: While reduction of DUP (Duration of Untreated Psychosis) is a key goal in early intervention strategies, the predictive value of DUP on outcome has been questioned. We planned this study in order to explore the impact of three different definition of "treatment initiation" on the predictive value of DUP on outcome in an early psychosis sample. METHODS: 221 early psychosis patients aged 18-35 were followed-up prospectively over 36 months. DUP was measured using three definitions for treatment onset: Initiation of antipsychotic medication (DUP1); engagement in a specialized programme (DUP2) and combination of engagement in a specialized programme and adherence to medication (DUP3). RESULTS: 10% of patients never reached criteria for DUP3 and therefore were never adequately treated over the 36-month period of care. While DUP1 and DUP2 had a limited predictive value on outcome, DUP3, based on a more restrictive definition for treatment onset, was a better predictor of positive and negative symptoms, as well as functional outcome at 12, 24 and 36 months. Globally, DUP3 explained 2 to 5 times more of the variance than DUP1 and DUP2, with effect sizes falling in the medium range according to Cohen. CONCLUSIONS: The limited predictive value of DUP on outcome in previous studies may be linked to problems of definitions that do not take adherence to treatment into account. While they need replication, our results suggest effort to reduce DUP should continue and aim both at early detection and development of engagement strategies.

The genome of Rhizobium leguminosarum has recognizable core and accessory components

Background: Rhizobium leguminosarum is an alpha-proteobacterial N-2-fixing symbiont of legumes that has been the subject of more than a thousand publications. Genes for the symbiotic interaction with plants are well studied, but the adaptations that allow survival and growth in the soil environment are poorly understood. We have sequenced the genome of R. leguminosarum biovar viciae strain 3841. Results: The 7.75 Mb genome comprises a circular chromosome and six circular plasmids, with 61% G+C overall. All three rRNA operons and 52 tRNA genes are on the chromosome; essential protein-encoding genes are largely chromosomal, but most functional classes occur on plasmids as well. Of the 7,263 protein-encoding genes, 2,056 had orthologs in each of three related genomes ( Agrobacterium tumefaciens, Sinorhizobium meliloti, and Mesorhizobium loti), and these genes were overrepresented in the chromosome and had above average G+C. Most supported the rRNA-based phylogeny, confirming A. tumefaciens to be the closest among these relatives, but 347 genes were incompatible with this phylogeny; these were scattered throughout the genome but were over-represented on the plasmids. An unexpectedly large number of genes were shared by all three rhizobia but were missing from A. tumefaciens. Conclusion: Overall, the genome can be considered to have two main components: a 'core', which is higher in G+C, is mostly chromosomal, is shared with related organisms, and has a consistent phylogeny; and an 'accessory' component, which is sporadic in distribution, lower in G+C, and located on the plasmids and chromosomal islands. The accessory genome has a different nucleotide composition from the core despite a long history of coexistence.

Predictions of some product parameters based on the processing conditions of ultra-high-temperature milk plants

The temperature-time profiles of 22 Australian industrial ultra-high-temperature (UHT) plants and 3 pilot plants, using both indirect and direct heating, were surveyed. From these data, the operating parameters of each plant, the chemical index C*, the bacteriological index B* and the predicted changes in the levels of beta-lactoglobulin, alpha-lactalbumin, lactulose, furosine and browning were determined using a simulation program based on published formulae and reaction kinetics data. There was a wide spread of heating conditions used, some of which resulted in a large margin of bacteriological safety and high chemical indices. However, no conditions were severe enough to cause browning during processing. The data showed a clear distinction between the indirect and direct heating plants. They also indicated that degree of denaturation of alpha-lactalbumin varied over a wide range and may be a useful discriminatory index of heat treatment. Application of the program to pilot plants illustrated its value in determining processing conditions in these plants to simulate the conditions in industrial UHT plants. (C) 2008 Elsevier Ltd. All rights reserved.

Exploring the role of reanalysis data in simulating regional wind generation variability over Northern Ireland

As wind generation increases, system impact studies rely on predictions of future generation and effective representation of wind variability. A well-established approach to investigate the impact of wind variability is to simulate generation using observations from 10 m meteorological mast-data. However, there are problems with relying purely on historical wind-speed records or generation histories: mast-data is often incomplete, not sited at a relevant wind generation sites, and recorded at the wrong altitude above ground (usually 10 m), each of which may distort the generation profile. A possible complimentary approach is to use reanalysis data, where data assimilation techniques are combined with state-of-the-art weather forecast models to produce complete gridded wind time-series over an area. Previous investigations of reanalysis datasets have placed an emphasis on comparing reanalysis to meteorological site records whereas this paper compares wind generation simulated using reanalysis data directly against historic wind generation records. Importantly, this comparison is conducted using raw reanalysis data (typical resolution ∼50 km), without relying on a computationally expensive “dynamical downscaling” for a particular target region. Although the raw reanalysis data cannot, by nature of its construction, represent the site-specific effects of sub-gridscale topography, it is nevertheless shown to be comparable to or better than the mast-based simulation in the region considered and it is therefore argued that raw reanalysis data may offer a number of significant advantages as a data source.

Comparison of D-region Doppler drift winds measured by the SuperDARN Finland HF radar over an annual cycle using the Kiruna VHF meteor radar

The SuperDARN chain of oblique HF radars has provided an opportunity to generate a unique climatology of horizontal winds near the mesopause at a number of high latitude locations, via the Doppler shifted echoes from sources of ionisation in the D-region. Ablating meteor trails form the bulk of these targets, but other phenomena also contribute to the observations. Due to the poor vertical resolution of the radars, care must be taken to reduce possible biases from sporadic-E layers and Polar Mesospheric Summer echoes that can affect the effective altitude of the geophysical parameters being observed. Second, there is strong theoretical and observational evidence to suggest that the radars are picking up echoes from the backward looking direction that will tend to reduce the measured wind strengths. The effect is strongly frequency dependent, resulting in a 20% reduction at 12 MHz and a 50% reduction at 10 MHz. A comparison of the climatologies observed by the Super-DARN Finland radar between September 1999 and September 2000 and that obtained from the adjacent VHF meteor radar located at Kiruna is also presented. The agreement between the two instruments was very good. Extending the analysis to the SuperDARN Iceland East radar indicated that the principles outlined above could be applied successfully to the rest of the SuperDARN network.

Variability of marine aerosol fine-mode fraction and estimates of anthropogenic aerosol component over cloud-free oceans from the Moderate Resolution Imaging Spectroradiometer (MODIS)

In this study, we examine seasonal and geographical variability of marine aerosol fine-mode fraction ( fm) and its impacts on deriving the anthropogenic component of aerosol optical depth (ta) and direct radiative forcing from multispectral satellite measurements. A proxy of fm, empirically derived from the Moderate Resolution Imaging Spectroradiometer (MODIS) Collection 5 data, shows large seasonal and geographical variations that are consistent with the Goddard Chemistry Aerosol Radiation Transport (GOCART) and Global Modeling Initiative (GMI) model simulations. The so-derived seasonally and spatially varying fm is then implemented into a method of estimating ta and direct radiative forcing from the MODIS measurements. It is found that the use of a constant value for fm as in previous studies would have overestimated ta by about 20% over global ocean, with the overestimation up to �45% in some regions and seasons. The 7-year (2001–2007) global ocean average ta is 0.035, with yearly average ranging from 0.031 to 0.039. Future improvement in measurements is needed to better separate anthropogenic aerosol from natural ones and to narrow down the wide range of aerosol direct radiative forcing.

Horizontal and vertical structure of the Eyjafjallajökull ash cloud over the UK: a comparison of airborne lidar observations and simulations

During April and May 2010 the ash cloud from the eruption of the Icelandic volcano Eyjafjallajökull caused widespread disruption to aviation over northern Europe. The location and impact of the eruption led to a wealth of observations of the ash cloud were being obtained which can be used to assess modelling of the long range transport of ash in the troposphere. The UK FAAM (Facility for Airborne Atmospheric Measurements) BAe-146-301 research aircraft overflew the ash cloud on a number of days during May. The aircraft carries a downward looking lidar which detected the ash layer through the backscatter of the laser light. In this study ash concentrations derived from the lidar are compared with simulations of the ash cloud made with NAME (Numerical Atmospheric-dispersion Modelling Environment), a general purpose atmospheric transport and dispersion model. The simulated ash clouds are compared to the lidar data to determine how well NAME simulates the horizontal and vertical structure of the ash clouds. Comparison between the ash concentrations derived from the lidar and those from NAME is used to define the fraction of ash emitted in the eruption that is transported over long distances compared to the total emission of tephra. In making these comparisons possible position errors in the simulated ash clouds are identified and accounted for. The ash layers seen by the lidar considered in this study were thin, with typical depths of 550–750 m. The vertical structure of the ash cloud simulated by NAME was generally consistent with the observed ash layers, although the layers in the simulated ash clouds that are identified with observed ash layers are about twice the depth of the observed layers. The structure of the simulated ash clouds were sensitive to the profile of ash emissions that was assumed. In terms of horizontal and vertical structure the best results were obtained by assuming that the emission occurred at the top of the eruption plume, consistent with the observed structure of eruption plumes. However, early in the period when the intensity of the eruption was low, assuming that the emission of ash was uniform with height gives better guidance on the horizontal and vertical structure of the ash cloud. Comparison of the lidar concentrations with those from NAME show that 2–5% of the total mass erupted by the volcano remained in the ash cloud over the United Kingdom.

A comparative performance analysis of TRMM 3B42 (TMPA) versions 6 and 7 for hydrological applications over Andean-Amazon river basins

The Tropical Rainfall Measuring Mission 3B42 precipitation estimates are widely used in tropical regions for hydrometeorological research. Recently, version 7 of the product was released. Major revisions to the algorithm involve the radar refl ectivity - rainfall rates relationship, surface clutter detection over high terrain, a new reference database for the passive microwave algorithm, and a higher quality gauge analysis product for monthly bias correction. To assess the impacts of the improved algorithm, we compare the version 7 and the older version 6 product with data from 263 rain gauges in and around the northern Peruvian Andes. The region covers humid tropical rainforest, tropical mountains, and arid to humid coastal plains. We and that the version 7 product has a significantly lower bias and an improved representation of the rainfall distribution. We further evaluated the performance of versions 6 and 7 products as forcing data for hydrological modelling, by comparing the simulated and observed daily streamfl ow in 9 nested Amazon river basins. We find that the improvement in the precipitation estimation algorithm translates to an increase in the model Nash-Sutcliffe effciency, and a reduction in the percent bias between the observed and simulated flows by 30 to 95%.

The three-dimensional morphology of simulated and observed convective storms over southern England

A set of high-resolution radar observations of convective storms has been collected to evaluate such storms in the UK Met Office Unified Model during the DYMECS project (Dynamical and Microphysical Evolution of Convective Storms). The 3-GHz Chilbolton Advanced Meteorological Radar was set up with a scan-scheduling algorithm to automatically track convective storms identified in real-time from the operational rainfall radar network. More than 1,000 storm observations gathered over fifteen days in 2011 and 2012 are used to evaluate the model under various synoptic conditions supporting convection. In terms of the detailed three-dimensional morphology, storms in the 1500-m grid-length simulations are shown to produce horizontal structures a factor 1.5–2 wider compared to radar observations. A set of nested model runs at grid lengths down to 100m show that the models converge in terms of storm width, but the storm structures in the simulations with the smallest grid lengths are too narrow and too intense compared to the radar observations. The modelled storms were surrounded by a region of drizzle without ice reflectivities above 0 dBZ aloft, which was related to the dominance of ice crystals and was improved by allowing only aggregates as an ice particle habit. Simulations with graupel outperformed the standard configuration for heavy-rain profiles, but the storm structures were a factor 2 too wide and the convective cores 2 km too deep.

ESR and EISCAT observations of the response of the cusp and cleft to IMF orientation changes

We report observations of the cusp/cleft ionosphere made on December 16th 1998 by the EISCAT (European incoherent scatter) VHF radar at Tromso and the EISCAT Svalbard radar (ESR). We compare them with observations of the dayside auroral luminosity, as seen by meridian scanning photometers at Ny Alesund and of HF radar backscatter, as observed by the CUTLASS radar. We study the response to an interval of about one hour when the interplanetary magnetic field (IMF), monitored by the WIND and ACE spacecraft, was southward. The cusp/cleft aurora is shown to correspond to a spatially extended region of elevated electron temperatures in the VHF radar data. Initial conditions were characterised by a northward-directed IMF and cusp/cleft aurora poleward of the ESR. A strong southward turning then occurred, causing an equatorward motion of the cusp/cleft aurora. Within the equatorward expanding, southward-IMF cusp/cleft, the ESR observed structured and elevated plasma densities and ion and electron temperatures. Cleft ion fountain upflows were seen in association with elevated ion temperatures and rapid eastward convection, consistent with the magnetic curvature force on newly opened held lines for the observed negative IMF B-y. Subsequently, the ESR beam remained immediately poleward of the main cusp/cleft and a sequence of poleward-moving auroral transients passed over it. After the last of these, the ESR was in the polar cap and the radar observations were characterised by extremely low ionospheric densities and downward field-aligned flows. The IMF then turned northward again and the auroral oval contracted such that the ESR moved back into the cusp/cleft region. For the poleward-retreating northward-IMF cusp/cleft, the convection flows were slower, upflows were weaker and the electron density and temperature enhancements were less structured. Following the northward turning, the bands of high electron temperature and cusp/cleft aurora bifurcated, consistent with both subsolar and lobe reconnection taking place simultaneously. The present paper describes the large-scale behaviour of the ionosphere during this interval, as observed by a powerful combination of instruments. Two companion papers, by Lockwood et al. (2000) and Thorolfsson et al. (2000), both in this issue, describe the detailed behaviour of the poleward-moving transients observed during the interval of southward B-z, and explain their morphology in the context of previous theoretical work.

Short-term variability of solar wind number density, speed and dynamic pressure as a function of the interplanetary magnetic field components: A survey over two solar cycles

The variability of hourly values of solar wind number density, number density variation, speed, speed variation and dynamic pressure with IMF Bz and magnitude |B| has been examined for the period 1965–1986. We wish to draw attention to a strong correlation in number density and number density fluctuation with IMF Bz characterised by a symmetric increasing trend in these quantities away from Bz = 0 nT. The fluctuation level in solar wind speed is found to be relatively independent of Bz. We infer that number density and number density variability dominate in controlling solar wind dynamic pressure and dynamic pressure variability. It is also found that dynamic pressure is correlated with each component of IMF and that there is evidence of morphological differences between the variation with each component. Finally, we examine the variation of number density, speed, dynamic pressure and fluctuation level in number density and speed with IMF magnitude |B|. Again we find that number density variation dominates over solar wind speed in controlling dynamic pressure.