Comparison of gadoteric acid and gadobutrol for detection as well as morphologic and dynamic characterization of lesions on breast dynamic contrast-enhanced magnetic resonance imaging

OBJECTIVE In contrast to conventional breast imaging techniques, one major diagnostic benefit of breast magnetic resonance imaging (MRI) is the simultaneous acquisition of morphologic and dynamic enhancement characteristics, which are based on angiogenesis and therefore provide insights into tumor pathophysiology. The aim of this investigation was to intraindividually compare 2 macrocyclic MRI contrast agents, with low risk for nephrogenic systemic fibrosis, in the morphologic and dynamic characterization of histologically verified mass breast lesions, analyzed by blinded human evaluation and a fully automatic computer-assisted diagnosis (CAD) technique. MATERIALS AND METHODS Institutional review board approval and patient informed consent were obtained. In this prospective, single-center study, 45 women with 51 histopathologically verified (41 malignant, 10 benign) mass lesions underwent 2 identical examinations at 1.5 T (mean time interval, 2.1 days) with 0.1-mmol kg doses of gadoteric acid and gadobutrol. All magnetic resonance images were visually evaluated by 2 experienced, blinded breast radiologists in consensus and by an automatic CAD system, whereas the morphologic and dynamic characterization as well as the final human classification of lesions were performed based on the categories of the Breast imaging reporting and data system MRI atlas. Lesions were also classified by defining their probability of malignancy (morpho-dynamic index; 0%-100%) by the CAD system. Imaging results were correlated with histopathology as gold standard. RESULTS The CAD system coded 49 of 51 lesions with gadoteric acid and gadobutrol (detection rate, 96.1%); initial signal increase was significantly higher for gadobutrol than for gadoteric acid for all and the malignant coded lesions (P < 0.05). Gadoteric acid resulted in more postinitial washout curves and fewer continuous increases of all and the malignant lesions compared with gadobutrol (CAD hot spot regions, P < 0.05). Morphologically, the margins of the malignancies were different between the 2 agents, whereas gadobutrol demonstrated more spiculated and fewer smooth margins (P < 0.05). Lesion classifications by the human observers and by the morpho-dynamic index compared with the histopathologic results did not significantly differ between gadoteric acid and gadobutrol. CONCLUSIONS Macrocyclic contrast media can be reliably used for breast dynamic contrast-enhanced MRI. However, gadoteric acid and gadobutrol differed in some dynamic and morphologic characterization of histologically verified breast lesions in an intraindividual, comparison. Besides the standardization of technical parameters and imaging evaluation of breast MRI, the standardization of the applied contrast medium seems to be important to receive best comparable MRI interpretation.

67P/Churyumov-Gerasimenko: Activity between March and June 2014 as observed from Rosetta/OSIRIS

Aims. 67P/Churyumov-Gerasimenko is the target comet of the ESA’s Rosetta mission. After commissioning at the end of March 2014, the Optical, Spectroscopic, and Infrared Remote Imaging System (OSIRIS) onboard Rosetta, started imaging the comet and its dust environment to investigate how they change and evolve while approaching the Sun. Methods. We focused our work on Narrow Angle Camera (NAC) orange images and Wide Angle Camera (WAC) red and visible-610 images acquired between 2014 March 23 and June 24 when the nucleus of 67P was unresolved and moving from approximately 4.3 AU to 3.8 AU inbound. During this period the 67P – Rosetta distance decreased from 5 million to 120 thousand km. Results. Through aperture photometry, we investigated how the comet brightness varies with heliocentric distance. 67P was likely already weakly active at the end of March 2014, with excess flux above that expected for the nucleus. The comet’s brightness was mostly constant during the three months of approach observations, apart from one outburst that occurred around April 30 and a second increase in flux after June 20. Coma was resolved in the profiles from mid-April. Analysis of the coma morphology suggests that most of the activity comes from a source towards the celestial north pole of the comet, but the outburst that occurred on April 30 released material in a different direction.

CHEOPS: a space telescope for ultra-high precision photometry of exoplanet transits

The CHaracterising ExOPlanet Satellite (CHEOPS) is a joint ESA-Switzerland space mission (expected to launch in 2017) dedicated to search for exoplanet transits by means of ultra-high precision photometry. CHEOPS will provide accurate radii for planets down to Earth size. Targets will mainly come from radial velocity surveys. The CHEOPS instrument is an optical space telescope of 30 cm clear aperture with a single focal plane CCD detector. The tube assembly is passively cooled and thermally controlled to support high precision, low noise photometry. The telescope feeds a re-imaging optic, which supports the straylight suppression concept to achieve the required Signal to Noise. © (2014) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE). Downloading of the abstract is permitted for personal use only.

Which side of the focal plane are you on?

Defocus blur is an indicator for the depth structure of a scene. However, given a single input image from a conventional camera one cannot distinguish between blurred objects lying in front or behind the focal plane, as they may be subject to exactly the same amount of blur. In this paper we address this limitation by exploiting coded apertures. Previous work in this area focuses on setups where the scene is placed either entirely in front or entirely behind the focal plane. We demonstrate that asymmetric apertures result in unique blurs for all distances from the camera. To exploit asymmetric apertures we propose an algorithm that can unambiguously estimate scene depth and texture from a single input image. One of the main advantages of our method is that, within the same depth range, we can work with less blurred data than in other methods. The technique is tested on both synthetic and real images.

AIV procedure for a CHEOPS demonstration model

The CHaracterizing ExOPlanet Satellite (CHEOPS) is an ESA Small Mission whose launch is planned for the end of 2017. It is a Ritchey-Chretien telescope with a 320 mm aperture providing a FoV of 0.32 degrees, which will target nearby bright stars already known to host planets, and measure, through ultrahigh precision photometry, the radius of exo-planets, allowing to determine their composition. This paper will present the details of the AIV plan for a demonstration model of the CHEOPS Telescope with equivalent structure but different CTEs. Alignment procedures, needed GSEs and devised verification tests will be described and a path for the AIV of the flight model, which will take place at industries premises, will be sketched. © (2014) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).

Time-trends in assisted and unassisted suicides completed with different methods: Swiss National Cohort.

OBJECTIVE The number of suicides assisted by right-to-die associations has increased in recent years in Switzerland. The aim of our study was to compare time trends in rates of assisted and unassisted suicide from 1991-2008. METHODS The Swiss National Cohort is a longitudinal study of mortality in the Swiss population; based on linkage of census data with mortality records up to 2008. The Federal Statistical Office coded suspected assisted suicides from 1998 onwards; and from 2003 onwards right-to-die associations reported the suicides they assisted. We used Poisson regression to analyse trends in rates of suicide per 100'000 person-years, by gender and age groups (15-34, 35-64, 65-94 years). RESULTS A total of 7'940'297 individuals and 24'842 suicides were included. In women, rates changed little in the younger age groups but increased in 65-94-year-olds, due to an increase in suicide by poisoning (from 5.1 to 17.2 per 100'000; p <0.001). An increase in suicides by poisoning was also observed in older men (from 8.6 to 18.2; p<0.001). Most suicides by poisoning were assisted. In men, suicide rates declined in all age groups, driven by declines in suicide with firearms. CONCLUSIONS Research is needed to gain a better understanding of the reasons for the tripling of assisted suicide rates in older women, and the doubling of rates in older men, of attitudes and vulnerabilities of those choosing assisted suicide, and of access to palliative care. Rates of assisted suicide should be monitored; including data on patient characteristics and underlying comorbidities.

Risk charts to guide targeted HIV-1 viral load monitoring of ART: development and validation in patients from resource-limited settings.

BACKGROUND HIV-1 RNA viral load (VL) testing is recommended to monitor antiretroviral therapy (ART) but not available in many resource-limited settings. We developed and validated CD4-based risk charts to guide targeted VL testing. METHODS We modeled the probability of virologic failure up to 5 years of ART based on current and baseline CD4 counts, developed decision rules for targeted VL testing of 10%, 20% or 40% of patients in seven cohorts of patients starting ART in South Africa, and plotted cut-offs for VL testing on colour-coded risk charts. We assessed the accuracy of risk chart-guided VL testing to detect virologic failure in validation cohorts from South Africa, Zambia and the Asia-Pacific. FINDINGS 31,450 adult patients were included in the derivation and 25,294 patients in the validation cohorts. Positive predictive values increased with the percentage of patients tested: from 79% (10% tested) to 98% (40% tested) in the South African, from 64% to 93% in the Zambian and from 73% to 96% in the Asia-Pacific cohorts. Corresponding increases in sensitivity were from 35% to 68% in South Africa, from 55% to 82% in Zambia and from 37% to 71% in Asia-Pacific. The area under the receiver-operating curve increased from 0.75 to 0.91 in South Africa, from 0.76 to 0.91 in Zambia and from 0.77 to 0.92 in Asia Pacific. INTERPRETATION CD4-based risk charts with optimal cut-offs for targeted VL testing may be useful to monitor ART in settings where VL capacity is limited.

SMARTnet: A Sensor for Monitoring the Geostationary Ring

As the number of space debris is increasing in the geostationary ring, it becomes mandatory for any satellite operator to avoid any collisions. Space debris in geosynchronous orbits may be observed with optical telescopes. Other than radar, that requires very large dishes and transmission powers for sensing high-altitude objects, optical observations do not depend on active illumination from ground and may be performed with notably smaller apertures. The detection size of an object depends on the aperture of the telescope, sky background and exposure time. With a telescope of 50 cm aperture, objects down to approximately 50 cm may be observed. This size is regarded as a threshold for the identification of hazardous objects and the prevention of potentially catastrophic collisions in geostationary orbits. In collaboration with the Astronomical Institute of the University of Bern (AIUB), the German Space Operations Center (GSOC) is building a small aperture telescope to demonstrate the feasibility of optical surveillance of the geostationary ring. The telescope will be located in the southern hemisphere and complement an existing telescope in the northern hemisphere already operated by AIUB. These two telescopes provide an optimum coverage of European GEO satellites and enable a continuous monitoring independent of seasonal limitations. The telescope will be operated completely automatically. The automated operations should be demonstrated covering the full range of activities including scheduling of observations, telescope and camera control as well as data processing.

In-vivo phase contrast magnetic resonance angiography of the cerebrovascular system: a comparative study with duplex sonography.

PURPOSE Assessment of the cerebral blood flow (CBF) is crucial in the evaluation of patients with steno-occlusive diseases of the arteries supplying the brain for prediction of stroke risk. Quantitative phase contrast magnetic resonance angiography (PC-MRA) can be utilised for noninvasive quantification of CBF. The aim of this study was to validate in-vivo PC-MRA data by comparing them with colour-coded duplex (CCD) sonography in patients with cerebrovascular disease. METHODS AND MATERIALS We examined 24 consecutive patients (mean age 63 years) with stenosis of arteries supplying the brain using PC-MRA and CCD. Velocities were measured in a total of 209 stenotic and healthy arterial segments (110 extra- and 99 intracranial). RESULTS Moderate to good correlation of velocity measurements between both techniques was observed in all six extracranial and five out of seven intracranial segments (p <0.05). Velocities measured with CCD sonography were generally higher than those obtained by PC-MRA. Reversal of flow direction was detected consistently with both methods. CONCLUSION PC-MRA represents a robust, standardised magnetic resonance imaging technique for blood flow measurements within a reasonable acquisition time, potentially evolving as valuable work-up tool for more precise patient stratification for revascularisation therapy. PC-MRA overcomes relevant weaknesses of CCD in being not operator-dependent and not relying on a bone window to assess the intracranial arteries.

Computational Tools for Stereo and Light Field Photography

This thesis covers a broad part of the field of computational photography, including video stabilization and image warping techniques, introductions to light field photography and the conversion of monocular images and videos into stereoscopic 3D content. We present a user assisted technique for stereoscopic 3D conversion from 2D images. Our approach exploits the geometric structure of perspective images including vanishing points. We allow a user to indicate lines, planes, and vanishing points in the input image, and directly employ these as guides of an image warp that produces a stereo image pair. Our method is most suitable for scenes with large scale structures such as buildings and is able to skip the step of constructing a depth map. Further, we propose a method to acquire 3D light fields using a hand-held camera, and describe several computational photography applications facilitated by our approach. As the input we take an image sequence from a camera translating along an approximately linear path with limited camera rotations. Users can acquire such data easily in a few seconds by moving a hand-held camera. We convert the input into a regularly sampled 3D light field by resampling and aligning them in the spatio-temporal domain. We also present a novel technique for high-quality disparity estimation from light fields. Finally, we show applications including digital refocusing and synthetic aperture blur, foreground removal, selective colorization, and others.

Quantifying the improvement in sepsis diagnosis, documentation, and coding: the marginal causal effect of year of hospitalization on sepsis diagnosis.

PURPOSE To quantify the coinciding improvement in the clinical diagnosis of sepsis, its documentation in the electronic health records, and subsequent medical coding of sepsis for billing purposes in recent years. METHODS We examined 98,267 hospitalizations in 66,208 patients who met systemic inflammatory response syndrome criteria at a tertiary care center from 2008 to 2012. We used g-computation to estimate the causal effect of the year of hospitalization on receiving an International Classification of Diseases, Ninth Revision, Clinical Modification discharge diagnosis code for sepsis by estimating changes in the probability of getting diagnosed and coded for sepsis during the study period. RESULTS When adjusted for demographics, Charlson-Deyo comorbidity index, blood culture frequency per hospitalization, and intensive care unit admission, the causal risk difference for receiving a discharge code for sepsis per 100 hospitalizations with systemic inflammatory response syndrome, had the hospitalization occurred in 2012, was estimated to be 3.9% (95% confidence interval [CI], 3.8%-4.0%), 3.4% (95% CI, 3.3%-3.5%), 2.2% (95% CI, 2.1%-2.3%), and 0.9% (95% CI, 0.8%-1.1%) from 2008 to 2011, respectively. CONCLUSIONS Patients with similar characteristics and risk factors had a higher of probability of getting diagnosed, documented, and coded for sepsis in 2012 than in previous years, which contributed to an apparent increase in sepsis incidence.

Temporal trends in the systemic inflammatory response syndrome, sepsis, and medical coding of sepsis.

BACKGROUND Recent reports using administrative claims data suggest the incidence of community- and hospital-onset sepsis is increasing. Whether this reflects changing epidemiology, more effective diagnostic methods, or changes in physician documentation and medical coding practices is unclear. METHODS We performed a temporal-trend study from 2008 to 2012 using administrative claims data and patient-level clinical data of adult patients admitted to Barnes-Jewish Hospital in St. Louis, Missouri. Temporal-trend and annual percent change were estimated using regression models with autoregressive integrated moving average errors. RESULTS We analyzed 62,261 inpatient admissions during the 5-year study period. 'Any SIRS' (i.e., SIRS on a single calendar day during the hospitalization) and 'multi-day SIRS' (i.e., SIRS on 3 or more calendar days), which both use patient-level data, and medical coding for sepsis (i.e., ICD-9-CM discharge diagnosis codes 995.91, 995.92, or 785.52) were present in 35.3 %, 17.3 %, and 3.3 % of admissions, respectively. The incidence of admissions coded for sepsis increased 9.7 % (95 % CI: 6.1, 13.4) per year, while the patient data-defined events of 'any SIRS' decreased by 1.8 % (95 % CI: -3.2, -0.5) and 'multi-day SIRS' did not change significantly over the study period. Clinically-defined sepsis (defined as SIRS plus bacteremia) and severe sepsis (defined as SIRS plus hypotension and bacteremia) decreased at statistically significant rates of 5.7 % (95 % CI: -9.0, -2.4) and 8.6 % (95 % CI: -4.4, -12.6) annually. All-cause mortality, SIRS mortality, and SIRS and clinically-defined sepsis case fatality did not change significantly during the study period. Sepsis mortality, based on ICD-9-CM codes, however, increased by 8.8 % (95 % CI: 1.9, 16.2) annually. CONCLUSIONS The incidence of sepsis, defined by ICD-9-CM codes, and sepsis mortality increased steadily without a concomitant increase in SIRS or clinically-defined sepsis. Our results highlight the need to develop strategies to integrate clinical patient-level data with administrative data to draw more accurate conclusions about the epidemiology of sepsis.

SMARTnet: First Experience of Setting Up a Telescope System to Survey the Geostationary Ring

Space debris in geostationary orbits may be detected with optical telescopes when the objects are illuminated by the Sun. The advantage compared to Radar can be found in the illumination: radar illuminates the objects and thus the detection sensitivity depletest proportional to the fourth power of the d istance. The German Space Operation Center, GSOC, together with the Astronomical Institute of the University of Bern, AIUB, are setting up a telescope system called SMARTnet to demonstrate the capability of performing geostationary surveillance. Such a telescope system will consist of two telescopes on one mount: a smaller telescope with an aperture of 20cm will serve for fast survey while the larger one, a telescope with an aperture of 50cm, will be used for follow-up observations. The telescopes will be operated by GSOC from Oberpfaffenhofen by the internal monitoring and control system called SMARTnetMAC. The observation plan will be generated by MARTnetPlanning seven days in advance by applying an optimized planning scheduler, taking into account fault time like cloudy nights, priority of objects etc. From each picture taken, stars will be identified and everything not being a star is treated as a possible object. If the same object can be identified on multiple pictures within a short time span, the trace is called a tracklet. In the next step, several tracklets will be correlated to identify individual objects, ephemeris data for these objects are generated and catalogued . This will allow for services like collision avoidance to ensure safe operations for GSOC’s satellites. The complete data processing chain is handled by BACARDI, the backbone catalogue of relational debris information and is presented as a poster.

PDB-Explorer: a web-based interactive map of the protein data bank in shape space

Background The RCSB Protein Data Bank (PDB) provides public access to experimentally determined 3D-structures of biological macromolecules (proteins, peptides and nucleic acids). While various tools are available to explore the PDB, options to access the global structural diversity of the entire PDB and to perceive relationships between PDB structures remain very limited. Methods A 136-dimensional atom pair 3D-fingerprint for proteins (3DP) counting categorized atom pairs at increasing through-space distances was designed to represent the molecular shape of PDB-entries. Nearest neighbor searches examples were reported exemplifying the ability of 3DP-similarity to identify closely related biomolecules from small peptides to enzyme and large multiprotein complexes such as virus particles. The principle component analysis was used to obtain the visualization of PDB in 3DP-space. Results The 3DP property space groups proteins and protein assemblies according to their 3D-shape similarity, yet shows exquisite ability to distinguish between closely related structures. An interactive website called PDB-Explorer is presented featuring a color-coded interactive map of PDB in 3DP-space. Each pixel of the map contains one or more PDB-entries which are directly visualized as ribbon diagrams when the pixel is selected. The PDB-Explorer website allows performing 3DP-nearest neighbor searches of any PDB-entry or of any structure uploaded as protein-type PDB file. All functionalities on the website are implemented in JavaScript in a platform-independent manner and draw data from a server that is updated daily with the latest PDB additions, ensuring complete and up-to-date coverage. The essentially instantaneous 3DP-similarity search with the PDB-Explorer provides results comparable to those of much slower 3D-alignment algorithms, and automatically clusters proteins from the same superfamilies in tight groups. Conclusion A chemical space classification of PDB based on molecular shape was obtained using a new atom-pair 3D-fingerprint for proteins and implemented in a web-based database exploration tool comprising an interactive color-coded map of the PDB chemical space and a nearest neighbor search tool. The PDB-Explorer website is freely available at www.​cheminfo.​org/​pdbexplorer and represents an unprecedented opportunity to interactively visualize and explore the structural diversity of the PDB.

Similarity Mapplet: Interactive Visualization of the Directory of Useful Decoys and ChEMBL in High Dimensional Chemical Spaces

An Internet portal accessible at www.gdb.unibe.ch has been set up to automatically generate color-coded similarity maps of the ChEMBL database in relation to up to two sets of active compounds taken from the enhanced Directory of Useful Decoys (eDUD), a random set of molecules, or up to two sets of user-defined reference molecules. These maps visualize the relationships between the selected compounds and ChEMBL in six different high dimensional chemical spaces, namely MQN (42-D molecular quantum numbers), SMIfp (34-D SMILES fingerprint), APfp (20-D shape fingerprint), Xfp (55-D pharmacophore fingerprint), Sfp (1024-bit substructure fingerprint), and ECfp4 (1024-bit extended connectivity fingerprint). The maps are supplied in form of Java based desktop applications called “similarity mapplets” allowing interactive content browsing and linked to a “Multifingerprint Browser for ChEMBL” (also accessible directly at www.gdb.unibe.ch) to perform nearest neighbor searches. One can obtain six similarity mapplets of ChEMBL relative to random reference compounds, 606 similarity mapplets relative to single eDUD active sets, 30 300 similarity mapplets relative to pairs of eDUD active sets, and any number of similarity mapplets relative to user-defined reference sets to help visualize the structural diversity of compound series in drug optimization projects and their relationship to other known bioactive compounds.