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  • 151. Cederström, B.
    et al.
    Fredenberg, E.
    Berggren, Karl
    KTH, School of Engineering Sciences (SCI), Physics, Physics of Medical Imaging. Mammography Solutions, Philips, Sweden.
    Erhard, K.
    Danielsson, Mats
    KTH, School of Engineering Sciences (SCI), Physics, Physics of Medical Imaging.
    Wallis, M.
    Lesion characterization in spectral photon-counting tomosynthesis2017In: Medical Imaging 2017: Physics of Medical Imaging, SPIE - International Society for Optical Engineering, 2017, Vol. 10132, article id 1013205Conference paper (Refereed)
    Abstract [en]

    It has previously been shown that 2D spectral mammography can be used to discriminate between (likely benign) cystic and (potentially malignant) solid lesions in order to reduce unnecessary recalls in mammography. One limitation of the technique is, however, that the composition of overlapping tissue needs to be interpolated from a region surrounding the lesion. The purpose of this investigation was to demonstrate that lesion characterization can be done with spectral tomosynthesis, and to investigate whether the 3D information available in tomosynthesis can reduce the uncertainty from the interpolation of surrounding tissue. A phantom experiment was designed to simulate a cyst and a tumor, where the tumor was overlaid with a structure that made it mimic a cyst. In 2D, the two targets appeared similar in composition, whereas spectral tomosynthesis revealed the exact compositional difference. However, the loss of discrimination signal due to spread from the plane of interest was of the same strength as the reduction of anatomical noise. Results from a preliminary investigation on clinical tomosynthesis images of solid lesions yielded results that were consistent with the phantom experiments, but were still to some extent inconclusive. We conclude that lesion characterization is feasible in spectral tomosynthesis, but more data, as well as refinement of the calibration and discrimination algorithms, are needed to draw final conclusions about the benefit compared to 2D.

  • 152.
    Cederström, Björn
    et al.
    KTH, School of Engineering Sciences (SCI), Physics.
    Fredenberg, Erik
    KTH, School of Engineering Sciences (SCI), Physics.
    The influence of anatomical noise on optimal beam quality in mammography2014In: Medical physics (Lancaster), ISSN 0094-2405, Vol. 41, no 12, p. 121903-Article in journal (Refereed)
    Abstract [en]

    Purpose: Beam-quality optimization in digital mammography traditionally considers detection of a target obscured by quantum noise in a homogeneous background. This does not correspond well to the clinical imaging task because real mammographic images contain a complex superposition of anatomical structures, resulting in anatomical noise that may dominate over quantum noise. The purpose of this paper is to assess the influence on optimal beam quality in mammography when anatomical noise is taken into account. Methods: The detectability of microcalcifications and masses was quantified using a theoretical ideal-observer model that included quantum noise as well as anatomical noise and a simplified model of a photon-counting mammography system. The outcome was experimentally verified using two types of simulated tissue phantoms. Results: The theoretical model showed that the detectability of tumors and microcalcifications behaves differently with respect to beam quality and dose. The results for small microcalcifications were similar to what traditional optimization methods yield, which is to be expected because quantum noise dominates over anatomical noise at high spatial frequencies. For larger tumors, however, low-frequency anatomical noise was the limiting factor. Because anatomical structure noise has similar energy dependence as tumor contrast, the optimal x-ray energy was found to be higher and the useful energy region was wider than traditional methods suggest. A simplified scalar model was able to capture this behavior using a fitted noise mixing parameter. The phantom measurements confirmed these theoretical results. Conclusions: It was shown that since quantum noise constitutes only a small fraction of the noise, the dose could be reduced substantially without sacrificing tumor detectability. Furthermore, when anatomical noise is included, the tube voltage can be increased well beyond what is conventionally considered optimal and used clinically, without loss of image quality. However, no such conclusions can be drawn for the more complex mammographic imaging task as a whole. (C) 2014 American Association of Physicists in Medicine.

  • 153.
    Chandra, Ramesh
    et al.
    New York University.
    Lo, S.
    Noz, Marilyn E.
    New York University.
    Maguire Jr., Gerald Q.
    University of Utah, Department of Computer Science.
    Absorbed Fractions for Radionuclides Uniformly Distributed in the Myocardium1976In: Proceedings of the Radiopharmaceutical Dosimetry Symposium, Rockville, MD, USA: HEW Radiopharmaceutical Dosimetry Symposium , 1976, p. 199-207Conference paper (Refereed)
  • 154.
    Chapnick, Jeffrey V
    et al.
    New York University.
    Noz, Marilyn E.
    New York University, Department of Radiology.
    Kramer, Elissa L.
    New York University, Department of Radiology.
    Sanger, Joseph J.
    New York University.
    Birnbaum, Bernard A.
    New York University.
    Maguire Jr., Gerald Q.
    Columbia University, Computer Science.
    Megibow, Alec J.
    New York University.
    Oratz, R.
    New York University, Department of Radiology.
    Weinreb, Jeffrey C.
    New York University.
    Martino, J.
    New York University.
    Structural, Functional Image Fusion in Cancer Patients1990In: Radiology, ISSN 0033-8419, E-ISSN 1527-1315, Vol. 177, p. P377-Article in journal (Refereed)
  • 155.
    Chapnick, Jeffrey V
    et al.
    New York University.
    Noz, Marilyn E.
    New York University, Department of Radiology.
    Maguire Jr., Gerald Q.
    Columbia University, Department of Computer Science.
    Sanger, Joseph J.
    New York University.
    Megibow, Alec J.
    New York University.
    Kramer, Elissa L.
    New York University, Department of Radiology.
    Oratz, R.
    New York University.
    Birnbaum, Bernard A.
    New York University.
    Martino, J.
    New York University.
    Fusion of Functional and Structural Images1990In: Radiology, ISSN 0033-8419, E-ISSN 1527-1315, Vol. 177, p. P223-Article in journal (Refereed)
  • 156.
    Chapnick, Jeffrey V
    et al.
    New York University.
    Noz, Marilyn E.
    New York University, Department of Radiology.
    Maguire Jr., Gerald Q.
    Columbia University, Department of Computer Science.
    Sanger, Joseph J.
    New York University.
    Megibow, Alec J.
    New York University.
    Kramer, Elissa L.
    New York University, Department of Radiology.
    Oratz, R.
    New York University, Department of Radiology.
    Birnbaum, Bernard A.
    New York University.
    Martino, J.
    New York University, Department of Radiology.
    Fusion of Functional Spect Images with Structural CT/MRI Images1991In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 32, p. 1135-Article in journal (Refereed)
  • 157. Checa, A.
    et al.
    Idborg, H.
    Zandian, Arash
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Sar, D. Garcia
    Surowiec, I.
    Trygg, J.
    Svenungsson, E.
    Jakobsson, P-J
    Nilsson, Peter
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Gunnarsson, I.
    Wheelock, C. E.
    Dysregulations in circulating sphingolipids associate with disease activity indices in female patients with systemic lupus erythematosus: a cross-sectional study2017In: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 26, no 10, p. 1023-1033Article in journal (Refereed)
    Abstract [en]

    Objective The objective of this study was to investigate the association of clinical and renal disease activity with circulating sphingolipids in patients with systemic lupus erythematosus. Methods We used liquid chromatography tandem mass spectrometry to measure the levels of 27 sphingolipids in plasma from 107 female systemic lupus erythematosus patients and 23 controls selected using a design of experiment approach. We investigated the associations between sphingolipids and two disease activity indices, the Systemic Lupus Activity Measurement and the Systemic Lupus Erythematosus Disease Activity Index. Damage was scored according to the Systemic Lupus International Collaborating Clinics damage index. Renal activity was evaluated with the British Island Lupus Activity Group index. The effects of immunosuppressive treatment on sphingolipid levels were evaluated before and after treatment in 22 female systemic lupus erythematosus patients with active disease. Results Circulating sphingolipids from the ceramide and hexosylceramide families were increased, and sphingoid bases were decreased, in systemic lupus erythematosus patients compared to controls. The ratio of C-16:0-ceramide to sphingosine-1-phosphate was the best discriminator between patients and controls, with an area under the receiver-operating curve of 0.77. The C-16:0-ceramide to sphingosine-1-phosphate ratio was associated with ongoing disease activity according to the Systemic Lupus Activity Measurement and the Systemic Lupus Erythematosus Disease Activity Index, but not with accumulated damage according to the Systemic Lupus International Collaborating Clinics Damage Index. Levels of C-16:0- and C-24:1-hexosylceramides were able to discriminate patients with current versus inactive/no renal involvement. All dysregulated sphingolipids were normalized after immunosuppressive treatment. Conclusion We provide evidence that sphingolipids are dysregulated in systemic lupus erythematosus and associated with disease activity. This study demonstrates the utility of simultaneously targeting multiple components of a pathway to establish disease associations.

  • 158.
    Chen, Han
    et al.
    KTH, School of Engineering Sciences (SCI), Physics, Physics of Medical Imaging.
    Cederström, Björn
    KTH, School of Engineering Sciences (SCI), Physics, Physics of Medical Imaging.
    Xu, Cheng
    KTH, School of Engineering Sciences (SCI), Physics, Physics of Medical Imaging.
    Persson, Mats
    KTH, School of Engineering Sciences (SCI), Physics, Physics of Medical Imaging.
    Karlsson, Staffan
    KTH, School of Engineering Sciences (SCI), Physics, Physics of Medical Imaging.
    Danielsson, Mats
    KTH, School of Engineering Sciences (SCI), Physics, Physics of Medical Imaging.
    A photon-counting silicon-strip detector for digital mammography with an ultrafast 0.18-mu m CMOS ASIC2014In: Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, ISSN 0168-9002, E-ISSN 1872-9576, Vol. 749, p. 1-6Article in journal (Refereed)
    Abstract [en]

    We have evaluated a silicon-strip detector with a 0.18-mu m CMOS application specific integrated circuits (ASIC) containing 160 channels for use in photon-counting digital mammography. Measurements were performed at the Elettra light source using monochromatic X-ray beams with different energies and intensities. Energy resolution, Delta E/E-in, was measured to vary between 0.10 and 0.23 in the energy range of 15-40 keV. Pulse pileup has shown little effect on energy resolution.

  • 159.
    Chen, Han
    et al.
    KTH, School of Engineering Sciences (SCI), Physics, Physics of Medical Imaging.
    Danielsson, Mats
    KTH, School of Engineering Sciences (SCI), Physics, Physics of Medical Imaging.
    Cederström, Björn
    KTH, School of Engineering Sciences (SCI), Physics, Physics of Medical Imaging.
    On imaging with or without grid in digital mammography2014In: Proceedings of SPIE, the International Society for Optical Engineering, ISSN 0277-786X, E-ISSN 1996-756X, Vol. 9033, p. 903346-Article in journal (Refereed)
    Abstract [en]

    The grids used in digital mammography to reduce scattered radiation from the breast are not perfect and lead to partial absorption of primary radiation at the same time as not all of the scattered radiation is absorbed. It has therefore lately been suggested to remove the grids and correct for effects of scattered radiation by post-processing the images. In this paper, we investigated the dose reduction that might be achieved if the gird were to be removed. Dose reduction is determined as a function of PMMA thickness by comparing the contrast-to-noise ratios (CNRs) of images acquired with and without grid at a constant exposure. We used a theoretical model validated with Monte Carlo simulations and phantom studies. To evaluate the CNR, we applied aluminum filters of two different sizes, 4x8 cm2 and 1x1 cm 2. When the large Al filter was used, the resulting CNR value for the grid-less images was overestimated as a result of a difference in amount of scattered radiation in the background region and of the region covered by the filter, a difference that could be eliminated by selecting a region of interest close to the edge of the filter. The optimal CNR when the PMMA thickness was above about 4 cm was obtained with a grid, whereas removing the grid leaded to a dose saving in thinner PMMAs. The results suggest not removing grids in breast cancer screening.

  • 160.
    Chen, Han
    et al.
    KTH, School of Engineering Sciences (SCI), Physics, Physics of Medical Imaging.
    Danielsson, Mats
    KTH, School of Engineering Sciences (SCI), Physics, Physics of Medical Imaging.
    Xu, Cheng
    KTH, School of Engineering Sciences (SCI), Physics, Physics of Medical Imaging.
    Size-dependent scanning parameters (kVp and mAs) for photon-counting spectral CT system in pediatric imaging: simulation study2016In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 61, no 11Article in journal (Refereed)
    Abstract [en]

    We are developing a photon-counting spectral CT detector with small pixel size of 0.40.5 mm2, o ering a potentialadvantage for better visualization of small structures in pediatric patients. The purpose of this study is to determinethe patient size dependent scanning parameters (kVp and mAs) for pediatric CT in two imaging cases: adipose imagingand iodinated blood imaging.Cylindrical soft-tissue phantoms of diameters between 10-25 cm were used to mimic patients of di erent ages from 0-15 y. For adipose imaging, a 5-mm-diameter adipose sphere was assumed as an imaging target, while an iodinated bloodsphere of 1 mm in diameter was assumed in the case of iodinated imaging. By applying the geometry of a commercial CTscanner (GE LightSpeed VCT), simulations were carried out to calculate the detectability index,d02, with tube potentialsvarying from 40 to 140 kVp. The optimal kVp for each phantom in each imaging case was determined such that the dose-normalized detectability index,d02=dose, is maximized. With the assumption that image quality in pediatric imagingis required the same as in typical adult imaging, the value of mAs at optimal kVp for each phantom was selected toachieve a reference detectability index that was obtained by scanning an adult phantom (30 cm in diameter) in a typicaladult CT procedure (120 kVp and 200 mAs) using a modeled energy-integrating system.For adipose imaging, the optimal kVps are 50, 60, 80, and 120 kVp, respectively, for phantoms of 10, 15, 20, and25-cm in diameter. The corresponding mAs values required to achieve the reference detectability index are only 9%,23%, 24%, and 54% of the mAs that is used for adult patients at 120 kVp, for 10, 15, 20, and 25-cm-diameter phantoms,respectively. In the case of iodinated imaging, a tube potential of 60 kVp was found optimal for all phantoms investigated,and the mAs values required to achieve the reference detectability index are 2%, 9%, 37%, and 109% of the adult mAs.The results also indicate that with the use of respective optimal kVps, the photon-counting spectral system o ers up to30% higherd02=dose than the modeled energy-integrating system for adipose imaging, and 70% for iodinated imaging.

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  • 161. Cheng, W.
    et al.
    Rolls, E. T.
    Qiu, J.
    Liu, W.
    Tang, Y.
    Huang, C. -C
    Wang, X.
    Zhang, J.
    Lin, W.
    Zheng, Lirong
    KTH.
    Pu, J.
    Tsai, S. -J
    Yang, A. C.
    Lin, C. -P
    Wang, F.
    Xie, P.
    Feng, J.
    Medial reward and lateral non-reward orbitofrontal cortex circuits change in opposite directions in depression2016In: Brain, ISSN 0006-8950, E-ISSN 1460-2156, Vol. 139, no 12, p. 3296-3309Article in journal (Refereed)
    Abstract [en]

    The first brain-wide voxel-level resting state functional connectivity neuroimaging analysis of depression is reported, with 421 patients with major depressive disorder and 488 control subjects. Resting state functional connectivity between different voxels reflects correlations of activity between those voxels and is a fundamental tool in helping to understand the brain regions with altered connectivity and function in depression. One major circuit with altered functional connectivity involved the medial orbitofrontal cortex Brodmann area 13, which is implicated in reward, and which had reduced functional connectivity in depression with memory systems in the parahippocampal gyrus and medial temporal lobe, especially involving the perirhinal cortex Brodmann area 36 and entorhinal cortex Brodmann area 28. The Hamilton Depression Rating Scale scores were correlated with weakened functional connectivity of the medial orbitofrontal cortex Brodmann area 13. Thus in depression there is decreased reward-related and memory system functional connectivity, and this is related to the depressed symptoms. The lateral orbitofrontal cortex Brodmann area 47/12, involved in non-reward and punishing events, did not have this reduced functional connectivity with memory systems. Second, the lateral orbitofrontal cortex Brodmann area 47/12 had increased functional connectivity with the precuneus, the angular gyrus, and the temporal visual cortex Brodmann area 21. This enhanced functional connectivity of the non-reward/punishment system (Brodmann area 47/12) with the precuneus (involved in the sense of self and agency), and the angular gyrus (involved in language) is thus related to the explicit affectively negative sense of the self, and of self-esteem, in depression. A comparison of the functional connectivity in 185 depressed patients not receiving medication and 182 patients receiving medication showed that the functional connectivity of the lateral orbitofrontal cortex Brodmann area 47/12 with these three brain areas was lower in the medicated than the unmedicated patients. This is consistent with the hypothesis that the increased functional connectivity of the lateral orbitofrontal cortex Brodmann area 47/12 is related to depression. Relating the changes in cortical connectivity to our understanding of the functions of different parts of the orbitofrontal cortex in emotion helps to provide new insight into the brain changes related to depression. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved.

  • 162. Chew, M S
    et al.
    Brandberg, J
    Bjarum, S
    Baek-Jensen, K
    Sloth, E
    Ask, P
    Hasenkam, J M
    Janerot-Sjöberg, B
    Hälsouniversitetet, Linköping University.
    Pediatric cardiac output measurement using surface integration of velocity vectors: an in vivo validation study.2000In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 28, no 11, p. 3664-71Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To test the accuracy and reproducibility of systemic cardiac output (CO) measurements using surface integration of velocity vectors (SIVV) in a pediatric animal model with hemodynamic instability and to compare SIVV with traditional pulsed-wave Doppler measurements.

    DESIGN: Prospective, comparative study.

    SETTING: Animal research laboratory at a university medical center.

    SUBJECTS: Eight piglets weighing 10-15 kg.

    INTERVENTIONS: Hemodynamic instability was induced by using inhalation of isoflurane and infusions of colloid and dobutamine.

    MEASUREMENTS: SIVV CO was measured at the left ventricular outflow tract, the aortic valve, and ascending aorta. Transit time CO was used as the reference standard.

    RESULTS: There was good agreement between SIVV and transit time CO. At high frame rates, the mean difference +/- 2 SD between the two methods was 0.01+/-0.27 L/min for measurements at the left ventricular outflow tract, 0.08+/-0.26 L/min for the ascending aorta, and 0.06+/-0.25 L/min for the aortic valve. At low frame rates, measurements were 0.06+/-0.25, 0.19+/-0.32, and 0.14+/-0.30 L/min for the left ventricular outflow tract, ascending aorta, and aortic valve, respectively. There were no differences between the three sites at high frame rates. Agreement between pulsed-wave Doppler and transit time CO was poorer, with a mean difference +/- 2 SD of 0.09+/-0.93 L/min. Repeated SIVV measurements taken at a period of relative hemodynamic stability differed by a mean difference +/-2 SD of 0.01+/-0.22 L/min, with a coefficient of variation = 7.6%. Intraobserver coefficients of variation were 5.7%, 4.9%, and 4.1% at the left ventricular outflow tract, ascending aorta, and aortic valve, respectively. Interobserver variability was also small, with a coefficient of variation = 8.5%.

    CONCLUSIONS: SIVV is an accurate and reproducible flow measurement technique. It is a considerable improvement over currently used methods and is applicable to pediatric critical care.

  • 163. Cornelio, Roberto Belloti
    et al.
    Wikant, Aksel
    Mjosund, Hanne
    Kopperud, Hilde Molvig
    Haasum, Johan
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology.
    Gedde, Ulf
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology.
    Ortengren, Ulf Thore
    The influence of bis-EMA vs bis GMA on the degree of conversion and water susceptibility of experimental composite materials2014In: Acta Odontologica Scandinavica, ISSN 0001-6357, E-ISSN 1502-3850, Vol. 72, no 6, p. 440-447Article in journal (Refereed)
    Abstract [en]

    Objective. The aim of this work was to assess the influence of the bis-EMA content on the degree of conversion (DC) and its effect on the water sorption and solubility. Materials and methods. In a polytetrafluorethylene (PTFE) mould, 30 samples (O = 5 mm, height = 2 mm) of four experimental dental composite resins were cured for 10 s, 20 s and 40 s. The DC was analysed by Fourier Transform (FT)-Raman spectroscopy. To analyse sorption and solubility, six samples (O = 15 mm and thickness = 1 mm) of each composite (n = 72) were stored in water at 37 degrees C for different storage periods: 24 h, 7 days and 30 days. Results. When cured for 20 or 40 s the DC increased with the increasing content of bis-EMA. However, the presence of 15 wt% of bis-GMA did not affect the DC, except when cured with 10 s irradiation time. This study also found a correlation between the content of bis-EMA and the reduced values for sorption and solubility, for all storage times used, when the materials were cured with 20 s. Conclusions. The DC of mixtures with higher content of bis-EMA is affected by the presence of bis-GMA at lower energy density delivered from the curing device, suggesting that the restrictions caused by the presence of hydrogen bonds is dependent of the irradiation time used.

  • 164.
    Crafoord, Joakim
    et al.
    Karolinska Hospital, Department of Radiology.
    Mahmoud, Faaiza
    New York University, Department of Radiology.
    Kramer, Elissa L.
    New York University, Department of Radiology.
    Maguire Jr., Gerald Q.
    KTH, Superseded Departments, Microelectronics and Information Technology, IMIT.
    Noz, Marilyn E.
    New York University, Department of Radiology.
    Zeleznik, Michael P.
    RAHD Oncology Products, St. Lois, MO, USA.
    Comparison of two landmark based image registration methods for use with a body atlas2000In: Physica medica (Testo stampato), ISSN 1120-1797, E-ISSN 1724-191X, Vol. 16, no 2, p. 75-82Article in journal (Refereed)
    Abstract [en]

    We describe preliminary work registering abdominal MRI images from three healthy male volunteers. Anatomically selected 3D homologous point pairs (landmarks), from which eigenvalues were generated to form the basis for a 3D non-affine polynomial transformation, were placed on axial slices alone and on axial, coronal and sagittal slices. Registration accuracy was judged visually by comparing superimposed 3D isosurfaces from the reference, untransformed, and transformed volume data and by comparing merged 2D slices projected fi om the transformed and reference volume data superimposed with 2D isolines. The squared sum of intensity differences between the transformed/untransformed and the reference volume was significant at the 0.05 (p >0.05) confidence level. The correlation coefficient improved by an average of 38% and the cross correlation between pixel values improved by an average of 22%. In each trial, the standard deviation of the landmarks after transformation was within one voxel and the standard error of the mean was not significantly different from zero at the 0.05 confidence level. Abdominal isosurface volume differences (between individuals) changed from an average of 14.5% before registration to 2.9% after registration. This experiment shows that it is possible to choose landmarks such that abdominal data from different subject volumes can be mapped to a common reference, and thus that it is possible to use this combined volume both to form an atlas and to warp abdominal data from an atlas to a patient volume.

  • 165. Crook, S. M.
    et al.
    Bednar, J. A.
    Berger, S.
    Cannon, R.
    Davison, A. P.
    Djurfeldt, Mikael
    KTH, School of Computer Science and Communication (CSC), Centres, Centre for High Performance Computing, PDC.
    Eppler, J.
    Kriener, B.
    Furber, S.
    Graham, B.
    Plesser, H. E.
    Schwabe, L.
    Smith, L.
    Steuber, V.
    Van Albada, S.
    Creating, documenting and sharing network models2012In: Network, ISSN 0954-898X, E-ISSN 1361-6536, Vol. 23, no 4, p. 131-149Article, review/survey (Refereed)
    Abstract [en]

    As computational neuroscience matures, many simulation environments are available that are useful for neuronal network modeling. However, methods for successfully documenting models for publication and for exchanging models and model components among these projects are still under development. Here we briefly review existing software and applications for network model creation, documentation and exchange. Then we discuss a few of the larger issues facing the field of computational neuroscience regarding network modeling and suggest solutions to some of these problems, concentrating in particular on standardized network model terminology, notation, and descriptions and explicit documentation of model scaling. We hope this will enable and encourage computational neuroscientists to share their models more systematically in the future.

  • 166. Crosbie, J. C.
    et al.
    Rogers, P. A. W.
    Stevenson, A. W.
    Hall, C. J.
    Lye, J. E.
    Nordström, Terese
    KTH.
    Midgley, S. M.
    Lewis, R. A.
    Reference dosimetry at the Australian Synchrotron's imaging and medical beamline using free-air ionization chamber measurements and theoretical predictions of air kerma rate and half value layer2013In: Medical physics (Lancaster), ISSN 0094-2405, Vol. 40, no 6, p. 062103-Article in journal (Refereed)
    Abstract [en]

    Purpose: Novel, preclinical radiotherapy modalities are being developed at synchrotrons around the world, most notably stereotactic synchrotron radiation therapy and microbeam radiotherapy at the European Synchrotron Radiation Facility in Grenoble, France. The imaging and medical beamline (IMBL) at the Australian Synchrotron has recently become available for preclinical radiotherapy and imaging research with clinical trials, a distinct possibility in the coming years. The aim of this present study was to accurately characterize the synchrotron-generated x-ray beam for the purposes of air kerma-based absolute dosimetry. Methods: The authors used a theoretical model of the energy spectrum from the wiggler source and validated this model by comparing the transmission through copper absorbers (0.1-3.0 mm) against real measurements conducted at the beamline. The authors used a low energy free air ionization chamber (LEFAC) from the Australian Radiation Protection and Nuclear Safety Agency and a commercially available free air chamber (ADC-105) for the measurements. The dimensions of these two chambers are different from one another requiring careful consideration of correction factors. Results: Measured and calculated half value layer (HVL) and air kerma rates differed by less than 3% for the LEFAC when the ion chamber readings were corrected for electron energy loss and ion recombination. The agreement between measured and predicted air kerma rates was less satisfactory for the ADC-105 chamber, however. The LEFAC and ADC measurements produced a first half value layer of 0.405 ± 0.015 and 0.412 ± 0.016 mm Cu, respectively, compared to the theoretical prediction of 0.427 ± 0.012 mm Cu. The theoretical model based upon a spectrum calculator derived a mean beam energy of 61.4 keV with a first half value layer of approximately 30 mm in water. Conclusions: The authors showed in this study their ability to verify the predicted air kerma rate and x-ray attenuation curve on the IMBL using a simple experimental method, namely, HVL measurements. The HVL measurements strongly supports the x-ray beam spectrum, which in turn has a profound effect on x-ray dosimetry.

  • 167. Damangir, Soheil
    et al.
    Manzouri, Amirhossein
    Oppedal, Ketil
    Carlsson, Stefan
    KTH, School of Computer Science and Communication (CSC), Computer Vision and Active Perception, CVAP.
    Firbank, Michael J.
    Sonnesyn, Hogne
    Tysnes, Ole-Bjorn
    O'Brien, John T.
    Beyer, Mona K.
    Westman, Eric
    Aarsland, Dag
    Wahlund, Lars-Olof
    Spulber, Gabriela
    Multispectral MRI segmentation of age related white matter changes using a cascade of support vector machines2012In: Journal of the Neurological Sciences, ISSN 0022-510X, E-ISSN 1878-5883, Vol. 322, no 1-2, p. 211-216Article in journal (Refereed)
    Abstract [en]

    White matter changes (WMC) are the focus of intensive research and have been linked to cognitive impairment and depression in the elderly. Cumbersome manual outlining procedures make research on WMC labor intensive and prone to subjective bias. We present a fast, fully automated method for WMC segmentation using a cascade of reduced support vector machines (SVMs) with active learning. Data of 102 subjects was used in this study. Two MRI sequences (T1-weighted and FLAIR) and masks of manually outlined WMC from each subject were used for the image analysis. The segmentation framework comprises pre-processing, classification (training and core segmentation) and post-processing. After pre-processing, the model was trained on two subjects and tested on the remaining 100 subjects. The effectiveness and robustness of the classification was assessed using the receiver operating curve technique. The cascade of SVMs segmentation framework outputted accurate results with high sensitivity (90%) and specificity (99.5%) values, with the manually outlined WMC as reference. An algorithm for the segmentation of WMC is proposed. This is a completely competitive and fast automatic segmentation framework, capable of using different input sequences, without changes or restrictions of the image analysis algorithm.

  • 168.
    Danielsson, Mats
    KTH, School of Engineering Sciences (SCI), Physics, Physics of Medical Imaging.
    MAMMOGRAPHY SHIFTS TOWARD SPECTRAL IMAGING-Photon counting is an intuitive way to detect x-rays, which by nature are digital and have a color spectrum2009In: Diagnostic Imaging, Vol. 25, no 7Article in journal (Refereed)
  • 169.
    Danielsson, Mats
    KTH, School of Engineering Sciences (SCI), Physics, Physics of Medical Imaging.
    MO‐D‐210A‐01: Photon Counting Detectors for Mammography2009In: Medical physics (Lancaster), ISSN 0094-2405, Vol. 36, no 6, p. 2699-2699Article in journal (Refereed)
    Abstract [en]

    Mammography is currently one of the most common x‐ray imaging examinations. More than 100 million women worldwide are screened every year and early detection of breast cancer through mammography has proven to be a key to significantly reduced mortality. The requirement on spatial resolution as well as contrast resolution is very high in order to detect and diagnose the cancer. Moreover, because of the large number of women going through this procedure and the fact that more than 99 % are healthy, it also becomes very important to minimize the radiation dose. Photon counting may be one way to meet the demands and mammography is the first modality in x‐ray imaging to implement photon counting detectors. FDA approval is still pending but they are currently in routine clinical use in more than 15 countries. The photon counting enables a discrimination of all electronic noise and a more optimum use of the information in each x‐ray. The absence of electronic noise is particularly important in low dose applications, in for example tomosynthesis a number of exposures from different angles are required and since the dose in each projection is just a fraction of the total dose for a mammogram the sensitivity to electronic noise will increase. Using the spectral information for each x‐ray it is in principle possible to deduce the elemental composition of an object in the breast. This could for example be used to enhance microcalcifications relative to soft tissue and differentiate water from fat in cysts. Recently contrast mammography has attracted significant attention. In this application Iodine is used as a contrast media to visualize the vascular structure. As in breast MRI the cancer stand out because of the leaky vessels resulting from its angiogenesis. A photon counting detector gives a unique opportunity to image the Iodine through spectral imaging by adjusting one of the thresholds to its K‐edge. Challenges for photon counting in mammography are high rates of x‐rays, both to generate the required flux at the source and to handle the rates at the detector without pile‐up. Even more difficult to handle are the charge sharing between detector pixels which, if not corrected for, will compromise the energy information. The current status of photon counting detectors in mammography will be described together with strategies to overcome the pit‐falls. Also future possibilities with spectral imaging in mammography will be investigated and examples from ongoing clinical trials will be given. Learning Objectives: 1. Status of photon counting detectors in mammography 2. Pit‐falls and opportunities with photon counting detectors for mammography 3. Future applications based on spectral detectors for mammography.

  • 170.
    Danielsson, Mats
    KTH, School of Engineering Sciences (SCI), Physics, Physics of Medical Imaging.
    TH‐A‐217BCD‐01: Challenges and Opportunities with Photon Counting CT2012In: Medical physics (Lancaster), ISSN 0094-2405, Vol. 39, no 6, p. 3989-3989Article in journal (Refereed)
    Abstract [en]

    There is currently a large interest in photon counting CT detector research in both academia and industry. There are several detector systems and strategies to handle major challenges such as the very high count‐rate, while the energy information for each photon is retained. Another challenge is cross talk, which may compromise the energy estimation for the photons and can cause double counts, which gets worse with smaller pixel size. If implemented in the clinic, photon counting CT will likely enable a dose reduction when this is important, as for example in pediatric CT. Photon counting CT will also make possible quantitative measurements, energy weighting and/or tissue decomposition techniques that can be of great importance for a number of imaging tasks.

  • 171. Daub, Jennifer
    et al.
    Gardner, Paul P.
    Tate, John
    Ramsköld, Daniel
    KTH.
    Manske, Magnus
    Scott, William G.
    Weinberg, Zasha
    Griffiths-Jones, Sam
    Bateman, Alex
    The RNA WikiProject: Community annotation of RNA families2008In: RNA: A publication of the RNA Society, ISSN 1355-8382, E-ISSN 1469-9001, Vol. 14, no 12, p. 2462-2464Article in journal (Refereed)
    Abstract [en]

    The online encyclopedia Wikipedia has become one of the most important online references in the world and has a substantial and growing scientific content. A search of Google with many RNA-related keywords identifies a Wikipedia article as the top hit. We believe that the RNA community has an important and timely opportunity to maximize the content and quality of RNA information in Wikipedia. To this end, we have formed the RNA WikiProject (http://en.wikipedia.org/wiki/Wikipedia: WikiProject_RNA) as part of the larger Molecular and Cellular Biology WikiProject. We have created over 600 new Wikipedia articles describing families of noncoding RNAs based on the Rfam database, and invite the community to update, edit, and correct these articles. The Rfam database now redistributes this Wikipedia content as the primary textual annotation of its RNA families. Users can, therefore, for the first time, directly edit the content of one of the major RNA databases. We believe that this Wikipedia/Rfam link acts as a functioning model for incorporating community annotation into molecular biology databases.

  • 172. Dawed, A. Y.
    et al.
    Mari, A.
    McDonald, T. J.
    Hong, Mun-Gwan
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Sharma, S.
    Robertson, N. R.
    Mahajan, A.
    Walker, M.
    Gough, S.
    Zhou, K.
    Forgie, I.
    Ruetten, H.
    Jones, A. G.
    Pearson, E. R.
    GLP-1 receptor variants markedly differentiate glycaemic response to GLP-1 receptor agonists: a DIRECT study2017In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 60, p. S393-S393Article in journal (Refereed)
  • 173. Dembrower, K.
    et al.
    Liu, Yue
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Azizpour, Hossein
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Robotics, Perception and Learning, RPL.
    Eklund, M.
    Smith, Kevin
    KTH, School of Electrical Engineering and Computer Science (EECS), Computer Science, Computational Science and Technology (CST). KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Lindholm, P.
    Strand, F.
    Comparison of a deep learning risk score and standard mammographic density score for breast cancer risk prediction2020In: Radiology, ISSN 0033-8419, E-ISSN 1527-1315, Vol. 294, no 2, p. 265-272Article in journal (Refereed)
    Abstract [en]

    Background: Most risk prediction models for breast cancer are based on questionnaires and mammographic density assessments. By training a deep neural network, further information in the mammographic images can be considered. Purpose: To develop a risk score that is associated with future breast cancer and compare it with density-based models. Materials and Methods: In this retrospective study, all women aged 40-74 years within the Karolinska University Hospital uptake area in whom breast cancer was diagnosed in 2013-2014 were included along with healthy control subjects. Network development was based on cases diagnosed from 2008 to 2012. The deep learning (DL) risk score, dense area, and percentage density were calculated for the earliest available digital mammographic examination for each woman. Logistic regression models were fitted to determine the association with subsequent breast cancer. False-negative rates were obtained for the DL risk score, age-adjusted dense area, and age-adjusted percentage density. Results: A total of 2283 women, 278 of whom were later diagnosed with breast cancer, were evaluated. The age at mammography (mean, 55.7 years vs 54.6 years; P< .001), the dense area (mean, 38.2 cm2 vs 34.2 cm2; P< .001), and the percentage density (mean, 25.6% vs 24.0%; P< .001) were higher among women diagnosed with breast cancer than in those without a breast cancer diagnosis. The odds ratios and areas under the receiver operating characteristic curve (AUCs) were higher for age-adjusted DL risk score than for dense area and percentage density: 1.56 (95% confidence interval [CI]: 1.48, 1.64; AUC, 0.65), 1.31 (95% CI: 1.24, 1.38; AUC, 0.60), and 1.18 (95% CI: 1.11, 1.25; AUC, 0.57), respectively (P< .001 for AUC). The false-negative rate was lower: 31% (95% CI: 29%, 34%), 36% (95% CI: 33%, 39%; P = .006), and 39% (95% CI: 37%, 42%; P< .001); this difference was most pronounced for more aggressive cancers. Conclusion: Compared with density-based models, a deep neural network can more accurately predict which women are at risk for future breast cancer, with a lower false-negative rate for more aggressive cancers.

  • 174.
    Dewyngaert, J. Keith
    et al.
    New York University.
    Noz, Marilyn E.
    New York University, Department of Radiology.
    Ellerin, B.
    New York University.
    Kramer, Elissa L.
    New York University, Department of Radiology.
    Maguire Jr., Gerald Q.
    KTH, Superseded Departments, Microelectronics and Information Technology, IMIT.
    Zeleznik, Michael P.
    RAHD Oncology Products, St. Louis, MO, USA.
    Procedure for unmasking localization information from ProstaScint scans for prostate radiation therapy treatment planning2004In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 60, no 2, p. 654-662Article in journal (Refereed)
    Abstract [en]

    Purpose: To demonstrate a method to extract the meaningful biologic information from In-111-radiolabeled capromab pendetide (ProstaScint) SPECT scans for use in radiation therapy treatment planning by removing that component of the In-111 SPECT images associated with normal structures. Methods and Materials: We examined 20 of more than 80 patients who underwent simultaneous Tc-99m/In-111 SPECT scans, which were subsequently registered to the corresponding CT/MRI scans. A thresholding algorithm was used to identify Tc-99m uptake associated with blood vessels and CT electron density associated with bone marrow. Corresponding voxels were removed from the In-111 image set. Results: No single threshold value was found to be associated with the Tc-99m uptake that corresponded to the blood vessels. Intensity values were normalized to a global maximum and, as such, were dependent upon the quantity of Tc-99m pooled in the bladder. The reduced ProstaScint volume sets were segmented by use of a thresholding feature of the planning system and superimposed on the CT/MRI scans. Conclusions: ProstaScint images are now closer to becoming a biologically and therapeutically useful and accurate image set. After known sources of normal intensity are stripped away, the remaining areas that demonstrate uptake may be segmented and superimposed on the treatment-planning CT/MRI volume.

  • 175.
    Deyev, Sergey M.
    et al.
    Russian Acad Sci, Mol Immunol Lab, Shemyakin & Ovchinnikov Inst Bioorgan Chem, Moscow, Russia.;Res Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Tomsk, Russia.;Sechenov Univ, Ctr Biomed Engn, Moscow, Russia..
    Vorobyeva, Anzhelika
    Res Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Tomsk, Russia.;Uppsala Univ, Dept Immunol Genet & Pathol, SE-75185 Uppsala, Sweden..
    Schulga, Alexey
    Russian Acad Sci, Mol Immunol Lab, Shemyakin & Ovchinnikov Inst Bioorgan Chem, Moscow, Russia.;Res Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Tomsk, Russia..
    Abouzayed, Ayman
    Uppsala Univ, Dept Med Chem, Uppsala, Sweden..
    Gunther, Tyran
    Uppsala Univ, Dept Immunol Genet & Pathol, SE-75185 Uppsala, Sweden..
    Garousi, Javad
    Uppsala Univ, Dept Immunol Genet & Pathol, SE-75185 Uppsala, Sweden..
    Konovalova, Elena
    Russian Acad Sci, Mol Immunol Lab, Shemyakin & Ovchinnikov Inst Bioorgan Chem, Moscow, Russia..
    Ding, Haozhong
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Protein Engineering.
    Gräslund, Torbjörn
    KTH, School of Biotechnology (BIO), Centres, Albanova VinnExcellence Center for Protein Technology, ProNova. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Protein Engineering.
    Orlova, Anna
    Res Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Tomsk, Russia.;Uppsala Univ, Dept Med Chem, Uppsala, Sweden.;Uppsala Univ, Sci Life Lab, Uppsala, Sweden..
    Tolmachev, Vladimir
    Res Tomsk Polytech Univ, Res Sch Chem & Appl Biomed Sci, Tomsk, Russia.;Uppsala Univ, Dept Immunol Genet & Pathol, SE-75185 Uppsala, Sweden..
    Effect of a radiolabel biochemical nature on tumor-targeting properties of EpCAM-binding engineered scaffold protein DARPin Ec12020In: International Journal of Biological Macromolecules, ISSN 0141-8130, E-ISSN 1879-0003, Vol. 145, p. 216-225Article in journal (Refereed)
    Abstract [en]

    Radionuclide-based imaging of molecular therapeutic targets might facilitate stratifying patients for specific biotherapeutics. New type of imaging probes, based on designed ankyrin repeat proteins (DARPins), have demonstrated excellent contrast of imaging of human epidermal growth factor type 2 (HER2) expression in preclinical models. We hypothesized that labeling approaches, which result in lipophilic radiometabolites (non-residualizing labels), would provide the best imaging contrast for DARPins that internalize slowly after binding to cancer cells. The hypothesis was tested using DARPin Ec1 that binds to epithelial cell adhesion molecule (EpCAM). EpCAM is a promising therapeutic target. Ec1 was labeled with I-125 using two methods to obtain the non-residualizing labels, while residualizing labels were obtained by labeling it with Tc-99m. All labeled Ec1 variants preserved target specificity and picomolar binding affinity to EpCAM-expressing pancreatic adenocarcinoma BxPC-3 cells. In murine models, all the variants provided similar tumor uptake. However, I-125-PIB-H-6-Ec1 had noticeably lower retention in normal tissues, which provided appreciably higher tumor-to-organ ratios. Furthermore, I-125-PIB-H-6-Ec1 demonstrated the highest imaging contrast in preclinical models than any other EpCAM-imaging agent tested so far. In conclusion, DARPin Ec1 in combination with a non-residualizing label is a promising probe for imaging EpCAM expression a few hours after injection.

  • 176.
    Dickmann, Jannis
    et al.
    KTH. German Canc Res Ctr, Div Xray Imaging & CT, Neuenheimer Feld 280, Heidelberg, Germany.;Tech Univ Darmstadt, Karolinenpl 4, Darmstadt, Germany..
    Maier, Joscha
    German Canc Res Ctr, Div Xray Imaging & CT, Neuenheimer Feld 280, Heidelberg, Germany.;Ruprecht Karls Univ Heidelberg, Dept Phys & Astron, Neuenheimer Feld 226, Heidelberg, Germany..
    Sawall, Stefan
    German Canc Res Ctr, Div Xray Imaging & CT, Neuenheimer Feld 280, Heidelberg, Germany.;Ruprecht Karls Univ Heidelberg, Med Fac, Neuenheimer Feld 672, Heidelberg, Germany..
    Thuering, Thomas
    Dectris Ltd, Tafernweg 1, Baden, Switzerland..
    Gkoumas, Spyridon
    Dectris Ltd, Tafernweg 1, Baden, Switzerland..
    Broennimann, Christian
    Dectris Ltd, Tafernweg 1, Baden, Switzerland..
    Kachelriess, Marc
    German Canc Res Ctr, Div Xray Imaging & CT, Neuenheimer Feld 280, Heidelberg, Germany.;Ruprecht Karls Univ Heidelberg, Med Fac, Neuenheimer Feld 672, Heidelberg, Germany..
    A Count Rate-Dependent Method for Spectral Distortion Correction in Photon Counting CT2018In: Medical Imaging 2018: Physics Of Medical Imaging / [ed] Lo, JY Schmidt, TG Chen, GH, SPIE - International Society for Optical Engineering, 2018, article id UNSP 1057311Conference paper (Refereed)
    Abstract [en]

    Rawdata-based material decomposition in spectral CT using photon-counting energy-selective detectors relies on a precise forward model that predicts a count-rate given intersection lengths for each material. This requires extensive system-specific measurements or calibration techniques. Existing calibrations either estimate a detected spectrum and are able to account for spectrally distorted assumptions or correct the predicted count rate using a correction function and can accommodate for count rate-dependent effects such as pulse pileup. We propose a calibration method that uses transmission measurements to optimize a correction function that, unlike existing methods, depends both on the photon energy and the count rate. It is thus able to correct for both kinds of distortions. In a simulated material decomposition into water and iodine, the error was reduced by 96% compared to the best performing reference method if only pulse pileup was present and reduced by 23% if additionally spectral distortions were taken into account. In phantom measurements using a Dectris SANTIS prototype detector, the proposed method allowed to reduce the error by 29% compared to the best performing reference method. Artifacts were below the noise level for the proposed method, while the reference methods either showed an offset in the water region or ring artifacts.

  • 177. Dijksterhuis, Jacomijn P.
    et al.
    Arthofer, Elisa
    Marinescu, Voichita D.
    Nelander, Sven
    Uhlen, Mathias
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Ponten, Frederik
    Mulder, Jan
    Schulte, Gunnar
    High levels of WNT-5A in human glioma correlate with increased presence of tumor-associated microglia/monocytes2015In: Experimental Cell Research, ISSN 0014-4827, E-ISSN 1090-2422, Vol. 339, no 2, p. 280-288Article in journal (Refereed)
    Abstract [en]

    Malignant gliomas are among the most severe types of cancer, and the most common primary brain tumors. Treatment options are limited and the prognosis is poor. WNT-5A, a member of the WNT family of lipoglycoproteins, plays a role in oncogenesis and tumor progression in various cancers, whereas the role of WNT-5A in glioma remains obscure. Based on the role of WNT-5A as an oncogene, its potential to regulate microglia cells and the glioma-promoting capacities of microglia cells, we hypothesize that WNT-5A has a role in regulation of immune functions in glioma. We investigated WNT-5A expression by in silico analysis of the cancer genome atlas (TCGA) transcript profiling of human glioblastoma samples and immunohistochemistry experiments of human glioma tissue microarrays (TMA). Our results reveal higher WNT-5A protein levels and mRNA expression in a subgroup of gliomas (WNT-5A(high)) compared to non-malignant control brain tissue. Furthermore, we show a significant correlation between WNT-5A in the tumor and presence of major histocompatibility complex Class II-positive microglia/monocytes. Our data pinpoint a positive correlation between WNT-5A and a proinflammatory signature in glioma. We identify increased presence of microglia/monocytes as an important aspect in the inflammatory transformation suggesting a novel role for WNT-5A in human glioma.

  • 178.
    Dimarogonas, Dimos V.
    et al.
    KTH, School of Electrical Engineering (EES), Automatic Control.
    Kyriakopoulos, Kostas J.
    Inverse agreement algorithms with application to swarm dispersion for multiple nonholonomic agents2008In: 2008 IEEE INTERNATIONAL CONFERENCE ON ROBOTICS AND AUTOMATION, 2008, p. 1973-1978Conference paper (Other academic)
    Abstract [en]

    We propose an inverse agreement control strategy for multiple nonholonomic agents that forces the team members to disperse in the workspace in a distributed manner. Both the cases of an unbounded and a circular bounded workspace are considered. In the first case, we show that the closed loop system reaches a configuration in which the minimum distance between any pair of agents is larger than a specific lower bound. It is proved that this lower bound coincides with the agents' sensing radius. In the case of a bounded workspace, the control law is modified to force the agents to remain within the workspace boundary throughout the closed loop system evolution. Moreover the proposed control guarantees collision avoidance between the team members. The results are supported through relevant computer simulations.

  • 179. Djureinovic, D.
    et al.
    Dodig-Crnkovic, Tea
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Hellström, Cecilia
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics.
    Holgersson, G.
    Bergqvist, M.
    Mattsson, J. S. M.
    Pontén, F.
    Ståhle, E.
    Schwenk, Jochen M.
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics.
    Micke, P.
    Detection of autoantibodies against cancer-testis antigens in non-small cell lung cancer2018In: Lung Cancer, ISSN 0169-5002, E-ISSN 1872-8332, Vol. 125, p. 157-163Article in journal (Refereed)
    Abstract [en]

    Objectives: Cancer-testis antigens (CTAs) are defined as proteins that are specifically expressed in testis or placenta and their expression is frequently activated in cancer. Due to their ability to induce an immune response, CTAs may serve as suitable targets for immunotherapy. The aim of this study was to evaluate if there is reactivity against CTAs in the plasma of non-small cell lung cancer (NSCLC) patients through the detection of circulating antibodies. Materials and methods: To comprehensively analyze autoantibodies against CTAs the multiplexing capacities of suspension bead array technology was used. Bead arrays were created with 120 protein fragments, representing 112 CTAs. Reactivity profiles were measured in plasma samples from 133 NSCLC patients and 57 cases with benign lung diseases. Results: Altogether reactivity against 69 antigens, representing 81 CTAs, was demonstrated in at least one of the analyzed samples. Twenty-nine of the antigens (45 CTAs) demonstrated exclusive reactivity in NSCLC samples. Reactivity against cancer-testis antigen family 47; member A (CT47A) genes, P antigen family member 3 (PAGE3), variable charge X-linked (VCX), melanoma antigen family B1 (MAGEB1), lin-28 homolog B (LIN28B) and chromosome 12 open reading frame 54 (C12orf54) were only found in NSCLC patients at a frequency of 1%–4%. The presence of autoantibodies towards these six antigens was confirmed in an independent group of 34 NSCLC patients. Conclusion: We identified autoantibodies against CTAs in the plasma of lung cancer patients. The reactivity pattern of autoantibodies was higher in cancer patients compared to the benign group, stable over time, but low in frequency of occurrence. The findings suggest that some CTAs are immunogenic and that these properties can be utilized as immune targets. 

  • 180.
    Djureinovic, D.
    et al.
    Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden..
    Hellström, Cecilia
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Dodig-Crnkovic, Tea
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Ponten, F.
    Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden..
    Bergqvist, M.
    Gavle Cent Hosp, Dept Oncol, Gavle, Sweden..
    Holgersson, G.
    Gavle Cent Hosp, Dept Oncol, Gavle, Sweden..
    Schwenk, Jochen M.
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Micke, P.
    Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden..
    Autoantibody Profiles of Cancer-Testis Genes in Non-Small Cell Lung Cancer2017In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 12, no 11, p. S2002-S2002Article in journal (Other academic)
  • 181. Djureinovic, Dijana
    et al.
    Hallström, Björn M.
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Horie, Masafumi
    Mattsson, Johanna Sofia Margareta
    La Fleur, Linnea
    Fagerberg, Linn
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Brunnstrom, Hans
    Lindskog, Cecilia
    Madjar, Katrin
    Rahnenfuehrer, Joerg
    Ekman, Simon
    Stahle, Elisabeth
    Koyi, Hirsh
    Branden, Eva
    Edlund, Karolina
    Hengstler, Jan G.
    Lambe, Mats
    Saito, Akira
    Botling, Johan
    Ponten, Fredrik
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Micke, Patrick
    Profiling cancer testis antigens in non-small-cell lung cancer2016In: JCI INSIGHT, ISSN 2379-3708, Vol. 1, no 10, article id e86837Article in journal (Refereed)
    Abstract [en]

    Cancer testis antigens (CTAs) are of clinical interest as biomarkers and present valuable targets for immunotherapy. To comprehensively characterize the CTA landscape of non-small-cell lung cancer (NSCLC), we compared RNAseq data from 199 NSCLC tissues to the normal transcriptome of 142 samples from 32 different normal organs. Of 232 CTAs currently annotated in the Caner Testis Database (CTdatabase), 96 were confirmed in NSCLC. To obtain an unbiased CTA profile of NSCLC, we applied stringent criteria on our RNAseq data set and defined 90 genes as CTAs, of which 55 genes were not annotated in the CTdatabase, thus representing potential new CTAs. Cluster analysis revealed that CTA expression is histology dependent and concurrent expression is common. IHC confirmed tissue-specific protein expression of selected new CTAs (TKTL1, TGIF2LX, VCX, and CXORF67). Furthermore, methylation was identified as a regulatory mechanism of CTA expression based on independent data from The Cancer Genome Atlas. The proposed prognostic impact of CTAs in lung cancer was not confirmed, neither in our RNAseq cohort nor in an independent meta-analysis of 1,117 NSCLC cases. In summary, we defined a set of 90 reliable CTAs, including information on protein expression, methylation, and survival association. The detailed RNAseq catalog can guide biomarker studies and efforts to identify targets for immunotherapeutic strategies.

  • 182. Djureinovic, Dijana
    et al.
    Hallström, Björn
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Mattsson, Johanna Sofia Margareta
    La Fleur, Linnea
    Botling, Johan
    Fagerberg, Linn
    Brunnstrom, Hans
    Ekman, Simon
    Stahle, Elisabeth
    Koyi, Hirsh
    Lambe, Mats
    Branden, Eva
    Lindskog, Cecilia
    Ponten, Fredrik
    Uhlen, Mathias
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Micke, Patrick
    The Identification of Therapeutic Targets in Lung Cancer Based on Transcriptomic and Proteomic Characterization of Cancer-Testis Antigens2015In: Journal of Thoracic Oncology, ISSN 1556-0864, E-ISSN 1556-1380, Vol. 10, no 9, p. S256-S256Article in journal (Other academic)
  • 183. Dolan, R. T.
    et al.
    Penny, S.
    Kelly, C. M.
    Brennan, D. J.
    Rexhepaj, E.
    Jirstrom, K.
    Ponten, F.
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics.
    Gallagher, W. M.
    Kell, M. R.
    Development of immunohistochemical surrogates for prediction of breast cancer patient outcome via high-throughput antibody generation and validation using tissue microarray technology2011In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 98, p. 28-28Article in journal (Refereed)
  • 184. Dong, Li
    et al.
    Kong, Jiangping
    Sundberg, Johan
    KTH, School of Computer Science and Communication (CSC), Speech, Music and Hearing, TMH.
    Long-term-average spectrum characteristics of Kunqu Opera singers' speaking, singing and stage speech2014In: Logopedics, Phoniatrics, Vocology, ISSN 1401-5439, E-ISSN 1651-2022, Vol. 39, no 2, p. 72-80Article in journal (Refereed)
    Abstract [en]

    Long-term-average spectrum (LTAS) characteristics were analyzed for ten Kunqu Opera singers, two in each of five roles. Each singer performed singing, stage speech, and conversational speech. Differences between the roles and between their performances of these three conditions are examined. After compensating for Leq difference LTAS characteristics still differ between the roles but are similar for the three conditions, especially for Colorful face (CF) and Old man roles, and especially between reading and singing. The curves show no evidence of a singer's formant cluster peak, but the CF role demonstrates a speaker's formant peak near 3 kHz. The LTAS characteristics deviate markedly from non-singers' standard conversational speech as well as from those of Western opera singing.

  • 185. Dong, Li
    et al.
    Sundberg, Johan
    KTH, School of Computer Science and Communication (CSC), Speech, Music and Hearing, TMH.
    Kong, Jiangping
    Loudness and Pitch of Kunqu Opera2014In: Journal of Voice, ISSN 0892-1997, E-ISSN 1873-4588, Vol. 28, no 1, p. 14-19Article in journal (Refereed)
    Abstract [en]

    Equivalent sound level (Leq), sound pressure level (SPL), and fundamental frequency (F-0) are analyzed in each of five Kunqu Opera roles, Young girl and Young woman, Young man, Old man, and Colorful face. Their pitch ranges are similar to those of some western opera singers (alto, alto, tenor, baritone, and baritone, respectively). Differences among tasks, conditions (stage speech, singing, and reading lyrics), singers, and roles are examined. For all singers, Leq of stage speech and singing were considerably higher than that of conversational speech. Interrole differences of Leq among tasks and singers were larger than the intrarole differences. For most roles, time domain variation of SPL differed between roles both in singing and stage speech. In singing, as compared with stage speech, SPL distribution was more concentrated and variation of SPL with time was smaller. With regard to gender and age, male roles had higher mean Leq and lower average F-0, MF0, as compared with female roles. Female singers showed a wider F-0 distribution for singing than for stage speech, whereas the opposite was true for male singers. The Leq of stage speech was higher than in singing for young personages. Younger female personages showed higher Leq, whereas older male personages had higher Leq. The roles performed with higher Leq tended to be sung at a lower MF0.

  • 186.
    Donker, Dirk W.
    et al.
    Univ Utrecht, Dept Intens Care Med, Univ Med Ctr Utrecht, Utrecht, Netherlands..
    Brodie, Daniel
    Columbia Univ, Coll Phys & Surg, New York Presbyterian Hosp, Div Pulm Allergy & Crit Care Med, New York, NY USA..
    Henriques, Jose P. S.
    Univ Amsterdam, Dept Cardiol, Acad Med Ctr, Amsterdam UMC, Amsterdam, Netherlands..
    Broomé, Michael
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging.
    Left ventricular unloading during veno-arterial ECMO: a review of percutaneous and surgical unloading interventions2019In: Perfusion, ISSN 0267-6591, E-ISSN 1477-111X, Vol. 34, no 2, p. 98-105Article, review/survey (Refereed)
    Abstract [en]

    Short-term mechanical support by veno-arterial extracorporeal membrane oxygenation (VA ECMO) is more and more applied in patients with severe cardiogenic shock. A major shortcoming of VA ECMO is its variable, but inherent increase of left ventricular (LV) mechanical load, which may aggravate pulmonary edema and hamper cardiac recovery. In order to mitigate these negative sequelae of VA ECMO, different adjunct LV unloading interventions have gained a broad interest in recent years. Here, we review the whole spectrum of percutaneous and surgical techniques combined with VA ECMO reported to date.

  • 187.
    Donker, Dirk W.
    et al.
    Univ Utrecht, Univ Med Ctr Utrecht, Dept Intens Care Med, Utrecht, Netherlands..
    Brodie, Daniel
    Columbia Univ, Coll Phys & Surg, New York Presbyterian Hosp, Div Pulm Allergy & Crit Care Med, New York, NY USA..
    Henriques, Jose P. S.
    Univ Amsterdam, Acad Med Ctr, Dept Cardiol, Amsterdam, Netherlands..
    Broomé, Michael
    KTH, School of Technology and Health (STH), Medical Engineering, Medical Imaging. Karolinska Univ Hosp, ECMO Dept, SE-17176 Stockholm, Sweden.;Karolinska Inst, Dept Physiol & Pharmacol, Anaesthesiol & Intens Care, Stockholm, Sweden.
    Left Ventricular Unloading During Veno-Arterial ECMO: A Simulation Study2019In: ASAIO journal (1992), ISSN 1058-2916, E-ISSN 1538-943X, Vol. 65, no 1, p. 11-20Article in journal (Refereed)
    Abstract [en]

    Veno-arterial extracorporeal membrane oxygenation (VA ECMO) is widely used in cardiogenic shock. It provides systemic perfusion, but left ventricular (LV) unloading is suboptimal. Using a closed-loop, real-time computer model of the human cardiovascular system, cardiogenic shock supported by peripheral VA ECMO was simulated, and effects of various adjunct LV unloading interventions were quantified. After VA ECMO initiation (4 L/min) in cardiogenic shock (baseline), hemodynamics improved (increased to 85 mm Hg), while LV overload occurred (10% increase in end-diastolic volume [EDV], and 5 mm Hg increase in pulmonary capillary wedge pressure [PCWP]). Decreasing afterload (65 mm Hg mean arterial pressure) and circulating volume (-800 mL) reduced LV overload (12% decrease in EDV and 37% decrease in PCWP) compared with baseline. Additional intra-aortic balloon pumping only marginally decreased cardiac loading. Instead, adjunct Impella T enhanced LV unloading (23% decrease in EDV and 41% decrease in PCWP). Alternative interventions, for example, left atrial/ventricular venting, yielded substantial unloading. We conclude that real-time simulations may provide quantitative clinical measures of LV overload, depending on the degree of VA ECMO support and adjunct management. Simulations offer insights into individualized LV unloading interventions in cardiogenic shock supported by VA ECMO as a proof of concept for potential future applications in clinical decision support, which may help to improve individualized patient management in complex cardiovascular disease.

  • 188. Downs, J.
    et al.
    Velupillai, Sumithra
    KTH, School of Electrical Engineering and Computer Science (EECS), Theoretical Computer Science, TCS.
    George, G.
    Holden, R.
    Kikoler, M.
    Dean, H.
    Fernandes, A.
    Dutta, R.
    Detection of Suicidality in Adolescents with Autism Spectrum Disorders: Developing a Natural Language Processing Approach for Use in Electronic Health Records2017In: Advances in Printing and Media Technology, ISSN 0892-2284, E-ISSN 1942-597X, Vol. 2017, p. 641-649Article in journal (Refereed)
    Abstract [en]

    Over 15% of young people with autism spectrum disorders (ASD) will contemplate or attempt suicide during adolescence. Yet, there is limited evidence concerning risk factors for suicidality in childhood ASD. Electronic health records (EHRs) can be used to create retrospective clinical cohort data for large samples of children with ASD. However systems to accurately extract suicidality-related concepts need to be developed so that putative models of suicide risk in ASD can be explored. We present a systematic approach to 1) adapt Natural Language Processing (NLP) solutions to screen with high sensitivity for reference to suicidal constructs in a large clinical ASD EHR corpus (230,465 documents), and 2) evaluate within a screened subset of 500 patients, the performance of an NLP classification tool for positive and negated suicidal mentions within clinical text. When evaluated, the NLP classification tool showed high system performance for positive suicidality with precision, recall, and F1 scores all > 0.85 at a document and patient level. The application therefore provides accurate output for epidemiological research into the factors contributing to the onset and recurrence of suicidality, and potential utility within clinical settings as an automated surveillance or risk prediction tool for specialist ASD services.

  • 189.
    Drobin, Kimi
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Assadi, Ghazaleh
    Karolinska Inst, Dept Biosci & Nutr, Stockholm, Sweden..
    Hong, Mun-Gwan
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Anggraeni Andersson, Margaretha
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Fredolini, Claudia
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics. KTH, Centres, Science for Life Laboratory, SciLifeLab. Royal Inst Technol, KTH, Sch Biotechnol, Affin Prote,SciLifeLab, Stockholm, Sweden..
    Forsström, Björn
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Reznichenko, Anna
    Karolinska Inst, Dept Biosci & Nutr, Stockholm, Sweden..
    Akhter, Tahmina
    Karolinska Inst, Dept Biosci & Nutr, Stockholm, Sweden..
    Ek, Weronica E.
    Karolinska Inst, Dept Biosci & Nutr, Stockholm, Sweden.;Uppsala Univ, Sci Life Lab, Dept Immunol Genet & Pathol, Uppsala, Sweden..
    Bonfiglio, Ferdinando
    Karolinska Inst, Dept Biosci & Nutr, Stockholm, Sweden.;Biodonostia Hlth Res Inst, Dept Gastrointestinal & Liver Dis, San Sebastian, Spain..
    Hansen, Mark Berner
    AstraZeneca R&D, Innovat & Global Med, Molndal, Sweden.;Univ Copenhagen, Bispebjerg Hosp, Ctr Digest Dis, Copenhagen, Denmark..
    Sandberg, Kristian
    Uppsala Univ, Sci Life Lab, Drug Discovery & Dev Platform, Uppsala, Sweden.;Uppsala Univ, Uppsala Biomed Ctr, Dept Med Chem, Organ Pharmaceut Chem, Uppsala, Sweden.;Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden..
    Greco, Dario
    Univ Helsinki, Inst Biotechnol, Helsinki, Finland..
    Repsilber, Dirk
    Orebro Univ, Sch Med Sci, Orebro, Sweden..
    Schwenk, Jochen M.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    D'Amato, Mauro
    Karolinska Inst, Dept Biosci & Nutr, Stockholm, Sweden.;BioDonostia Hlth Res Inst, San Sebastian, Spain.;Ikerbasque, Basque Fdn Sci, Bilbao, Spain..
    Halfvarson, Jonas
    Orebro Univ, Fac Med & Hlth, Dept Gastroenterol, SE-70182 Orebro, Sweden..
    Targeted Analysis of Serum Proteins Encoded at Known Inflammatory Bowel Disease Risk Loci2019In: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 25, no 2, p. 306-316Article in journal (Refereed)
    Abstract [en]

    Few studies have investigated the blood proteome of inflammatory bowel disease (IBD). We characterized the serum abundance of proteins encoded at 163 known IBD risk loci and tested these proteins for their biomarker discovery potential. Based on the Human Protein Atlas (HPA) antibody availability, 218 proteins from genes mapping at 163 IBD risk loci were selected. Targeted serum protein profiles from 49 Crohns disease (CD) patients, 51 ulcerative colitis (UC) patients, and 50 sex- and age-matched healthy individuals were obtained using multiplexed antibody suspension bead array assays. Differences in relative serum abundance levels between disease groups and controls were examined. Replication was attempted for CD-UC comparisons (including disease subtypes) by including 64 additional patients (33 CD and 31 UC). Antibodies targeting a potentially novel risk protein were validated by paired antibodies, Western blot, immuno-capture mass spectrometry, and epitope mapping. By univariate analysis, 13 proteins mostly related to neutrophil, T-cell, and B-cell activation and function were differentially expressed in IBD patients vs healthy controls, 3 in CD patients vs healthy controls and 2 in UC patients vs healthy controls (q < 0.01). Multivariate analyses further differentiated disease groups from healthy controls and CD subtypes from UC (P < 0.05). Extended characterization of an antibody targeting a novel, discriminative serum marker, the laccase (multicopper oxidoreductase) domain containing 1 (LACC1) protein, provided evidence for antibody on-target specificity. Using affinity proteomics, we identified a set of IBD-associated serum proteins encoded at IBD risk loci. These candidate proteins hold the potential to be exploited as diagnostic biomarkers of IBD.

  • 190.
    Dusart, Philip
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Cellular and Clinical Proteomics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Hallström, Björn M.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Renne, Thomas
    Univ Med Ctr Hamburg Eppendorf, Inst Clin Chem & Lab Med, D-20246 Hamburg, Germany..
    Odeberg, Jacob
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Uhlén, Mathias
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
    Butler, Lynn M.
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Cellular and Clinical Proteomics.
    A Systems-Based Map of Human Brain Cell-Type Enriched Genes and Malignancy-Associated Endothelial Changes2019In: Cell reports, ISSN 2211-1247, E-ISSN 2211-1247, Vol. 29, no 6, p. 1690-+Article in journal (Refereed)
    Abstract [en]

    Changes in the endothelium of the cerebral vasculature can contribute to inflammatory, thrombotic, and malignant disorders. The importance of defining cell-type-specific genes and their modification in disease is increasingly recognized. Here, we develop a bioinformatics-based approach to identify normal brain cell-enriched genes, using bulk RNA sequencing (RNA-seq) data from 238 normal human cortex samples from 2 independent cohorts. We compare endothelial cell-enriched gene profiles with astrocyte, oligodendrocyte, neuron, and microglial cell profiles. Endothelial changes in malignant disease are explored using RNA-seq data from 516 lower-grade gliomas and 401 glioblastomas. Lower-grade gliomas appear to be an "endothelial intermediate'' between normal brain and glioblastoma. We apply our method for the prediction of glioblastoma-specific endothelial biomarkers, providing potential diagnostic or therapeutic targets. In summary, we provide a roadmap of endothelial cell identity in normal and malignant brain, using a method developed to resolve bulk RNA-seq into constituent cell-type-enriched profiles.

  • 191.
    Dyczynski, Matheus
    et al.
    Karolinska Inst, Dept Oncol Pathol, Canc Ctr Karolinska, Stockholm, Sweden..
    Yu, Yasmin
    Karolinska Inst, Dept Oncol Pathol, Canc Ctr Karolinska, Stockholm, Sweden.;Sprint Biosci, Huddinge, Sweden..
    Otrocka, Magdalena
    Karolinska Inst, Dept Med Biochem & Biophys, Sci Life Lab Stockholm, Chem Biol Consortium Sweden, Solna, Sweden..
    Parpal, Santiago
    Sprint Biosci, Huddinge, Sweden..
    Braga, Tiago
    Sprint Biosci, Huddinge, Sweden..
    Henley, Aine Brigette
    Sprint Biosci, Huddinge, Sweden..
    Zazzi, Henric
    KTH, School of Electrical Engineering and Computer Science (EECS), Centres, Centre for High Performance Computing, PDC.
    Lerner, Mikael
    Karolinska Inst, Dept Oncol Pathol, Canc Ctr Karolinska, Stockholm, Sweden..
    Wennerberg, Krister
    Univ Helsinki, Inst Mol Med Finland, FIMM, Helsinki, Finland..
    Viklund, Jenny
    Sprint Biosci, Huddinge, Sweden..
    Martinsson, Jessica
    Sprint Biosci, Huddinge, Sweden..
    Grander, Dan
    Karolinska Inst, Dept Oncol Pathol, Canc Ctr Karolinska, Stockholm, Sweden..
    De Milito, Angelo
    Karolinska Inst, Dept Oncol Pathol, Canc Ctr Karolinska, Stockholm, Sweden.;Sprint Biosci, Huddinge, Sweden..
    Tamm, Katja Pokrovskaja
    Karolinska Inst, Dept Oncol Pathol, Canc Ctr Karolinska, Stockholm, Sweden..
    Targeting autophagy by small molecule inhibitors of vacuolar protein sorting 34 (Vps34) improves the sensitivity of breast cancer cells to Sunitinib2018In: Cancer Letters, ISSN 0304-3835, E-ISSN 1872-7980, Vol. 435, p. 32-43Article in journal (Refereed)
    Abstract [en]

    Resistance to chemotherapy is a challenging problem for treatment of cancer patients and autophagy has been shown to mediate development of resistance. In this study we systematically screened a library of 306 known anti-cancer drugs for their ability to induce autophagy using a cell-based assay. 114 of the drugs were classified as autophagy inducers; for 16 drugs, the cytotoxicity was potentiated by siRNA-mediated knock-down of Atg7 and Vps34. These drugs were further evaluated in breast cancer cell lines for autophagy induction, and two tyrosine kinase inhibitors, Sunitinib and Erlotinib, were selected for further studies. For the pharmacological inhibition of autophagy, we have characterized here a novel highly potent selective inhibitor of Vps34, SB02024. SB02024 blocked autophagy in vitro and reduced xenograft growth of two breast cancer cell lines, MDA-MB-231 and MCF-7, in vivo. Vps34 inhibitor significantly potentiated cytotoxicity of Sunitinib and Erlotinib in MCF-7 and MDA-MB-231 in vitro in monolayer cultures and when grown as multicellular spheroids. Our data suggests that inhibition of autophagy significantly improves sensitivity to Sunitinib and Erlotinib and that Vps34 is a promising therapeutic target for combination strategies in breast cancer.

  • 192. Echternach, Matthias
    et al.
    Dippold, Sebastian
    Sundberg, Johan
    KTH, School of Computer Science and Communication (CSC), Speech, Music and Hearing, TMH, Music Acoustics.
    Arndt, Susan
    Zander, Mark F.
    Richter, Bernhard
    High-Speed Imaging and Electroglottography Measurements of the Open Quotient in Untrained Male Voices' Register Transitions2010In: Journal of Voice, ISSN 0892-1997, E-ISSN 1873-4588, Vol. 24, no 6, p. 644-650Article in journal (Refereed)
    Abstract [en]

    Vocal fold oscillation patterns in vocal register transitions are still unclarified. The vocal fold oscillations and the open quotient were analyzed with high-speed digital imaging (HSDI) and electroglottography (EGG) in 18 male untrained subjects singing a glissando from modal to the falsetto register. Results reveal that the open quotient changed with register in both HSDI. and EGG. The in-class correlations for different HSDI and EGG determinations of the open quotient were high. However, we found only weak interclass correlations between both methods. In ID subjects, irregularities of vocal fold vibration occurred during the register transition. Our results confirm previous observations that falsetto register is associated with a higher open quotient compared with modal register. These data suggest furthermore that irregularities typically observed in audio and electroglottographic signals during register transitions are caused by irregularities in vocal fold vibration.

  • 193. Echternach, Matthias
    et al.
    Sundberg, Johan
    KTH, School of Computer Science and Communication (CSC), Speech, Music and Hearing, TMH, Music Acoustics.
    Arndt, Susan
    Breyer, Tobias
    Markl, Michael
    Schumacher, Martin
    Richter, Bernhard
    Vocal tract and register changes analysed by real-time MRI in male professional singers - a pilot study2008In: Logopedics, Phoniatrics, Vocology, ISSN 1401-5439, E-ISSN 1651-2022, Vol. 33, no 2, p. 67-73Article in journal (Refereed)
    Abstract [en]

    Changes of vocal tract shape accompanying changes of vocal register and pitch in singing have remained an unclear field. Dynamic real-time magnetic resonance imaging (MRI) was applied to two professional classical singers (a tenor and a baritone) in this pilot study. The singers sang ascending scales from B3 to G#4 on the vowel /a/, keeping the modal register throughout or shifting to falsetto register for the highest pitches. The results show that these singers made few and minor modifications of vocal tract shape when they changed from modal to falsetto and some clear modifications when they kept the register. In this case the baritone increased his tongue dorsum height, widened his jaw opening, and decreased his jaw protrusion, while the tenor merely lifted his uvula. The method used seems promising and should be applied to a greater number of singer subjects in the future.

  • 194. Echternach, Matthias
    et al.
    Sundberg, Johan
    KTH, School of Computer Science and Communication (CSC), Speech, Music and Hearing, TMH.
    Arndt, Susan
    Markl, Michael
    Schumacher, Martin
    Richter, Bernhard
    Vocal Tract in Female Registers: A Dynamic Real-Time MRI Study2010In: Journal of Voice, ISSN 0892-1997, E-ISSN 1873-4588, Vol. 24, no 2, p. 133-139Article in journal (Refereed)
    Abstract [en]

    The area of vocal registers is still unclarified. In a previous investigation, dynamic real-time magnetic resonance imaging (MRI), which is able to produce up to 10 frames per second, was successfully applied for examinations of vocal tract modifications in register transitions in male singers. In the present study, the same MRI technique was used to study vocal tract shapes during four professional young sopranos' lower and upper register transitions. The subjects were asked to sing a scale on the vowel /a/ across their transitions. The transitions were acoustically identified by four raters. In neither of these transitions, clear vocal tract changes could be ascertained. However, substantial changes, that is, widening of the lips, opening of the jaw, elevation of the tongue dorsum, and continuous widening of the pharynx, were observed when the singers reached fundamental frequencies that were close to the frequency of the first formant of the vowel sung. These findings suggest that in these subjects register transition was not primarily the result of modifications of the vocal tract.

  • 195. Echternach, Matthias
    et al.
    Sundberg, Johan
    KTH, School of Computer Science and Communication (CSC), Speech, Music and Hearing, TMH.
    Markl, Michael
    Richter, Bernhard
    Professional Opera Tenors' Vocal Tract Configurations in Registers2010In: Folia Phoniatrica et Logopaedica, ISSN 1021-7762, E-ISSN 1421-9972, Vol. 62, no 6, p. 278-287Article in journal (Refereed)
    Abstract [en]

    Objective: Tenor singers may reach their top pitch range either by shifting from modal to falsetto register or by using their so-called 'voix mixte'. Material and Methods: In this study, dynamic real-time MRI of 8 frames per second was used to analyze the vocal tract profile in 10 professional opera tenors, who sang an ascending scale from C4 (262 Hz) to A4 (440 Hz) on the vowel /a/. The scale included their register transition and the singers applied both register techniques in different takes. Results: Modal to falsetto register changes were associated with only minor vocal tract modifications, including elevation and tilting of the larynx and a lifted tongue dorsum. Transitions to voix mixte, by contrast, were associated with major vocal tract modifications. Under these conditions, the subjects widened their pharynges, their lip and jaw openings, and increased their jaw protrusion. These modifications were stronger in more 'heavy' tenors than in more 'light' tenors. The acoustic consequences of these articulatory changes are discussed.

  • 196. Echternach, Matthias
    et al.
    Sundberg, Johan
    KTH, School of Computer Science and Communication (CSC), Speech, Music and Hearing, TMH.
    Zander, Mark F.
    Richter, Bernhard
    Perturbation Measurements in Untrained Male Voices' Transitions From Modal to Falsetto Register2011In: Journal of Voice, ISSN 0892-1997, E-ISSN 1873-4588, Vol. 25, no 6, p. 663-669Article in journal (Refereed)
    Abstract [en]

    Purpose. Voice periodicity during transitions from modal to falsetto register still remains an unclarified question. Method. We examined the acoustic and electroglottographic signals of 20 healthy untrained male voices' transitions from modal to falsetto register on the vowels /a, e, i, o, u, and ae/. Results. In addition to discontinuities in fundamental frequency (F0), an independent increase of jitter, relative average perturbation, and shimmer was observed during and apparently caused by the register transition. In falsetto, the jitter was higher than in the modal register. The contact quotient derived from the electroglottographic signal tended to be lower for higher than for lower F0. Conclusion. Register transitions are associated with increase of perturbation.

  • 197.
    Edeling, Madita
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH).
    Target Volume Delineation In Hypoxia Dose Painting2019Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Purpose: Tumour hypoxia is the result of uncontrolled growth of the tumour and its vasculature and is often found in solid tumours. It has been known for some time that tumour hypoxia is associated with increased radio resistance and poorer treatment outcomes. While there are several techniques to image the tumour’s oxygenation, no metric or guideline exists that helps in automatically delineating those hypoxic cells into target volumes. Even though several hypoxic biomarkers have been developed and tested to detect visualise and localise hypoxic areas, most of these delineated areas show volumes that are not immediately suitable for dose planning (i.e. a speckled hypoxia distribution). This work deals with 18 cases of tumour hypoxia in patients with non-small cell lung cancer (NSCLC) and presents a method that gives guidance on how to construct hypoxic target volumes feasible for dose planning.

    Materials and Methods: PET-CT scans have been taken with the hypoxic biomarker 18F-HX4. Hypoxic volumes have been extracted using a threshold of 10mmHg. A region growing algorithm was used to develop the HTV delineation method. Individually calculated doses based on the pO2-distribution within the hypoxic target volume have been used for the construction of dose plans with 24 fractions.

    Results: Treatment plans that boost the hypoxic target volume whilst sparing surrounding organs at risk were possible to construct for those tumours lying outside the mediastinum. Tumours which volumes were partially or fully overlapping with the mediastinum showed conflicts with delivering the dose necessary for a tumour control probability (TCP) of at least 95% and not exceeding the dose constraints set for the mediastinum.

    Download full text (pdf)
    Madita_Edeling_Student_Theses
  • 198. Ehlén, Å.
    et al.
    Nodin, B.
    Rexhepaj, E.
    Brändstedt, J.
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics (closed 20130101). KTH, School of Biotechnology (BIO), Centres, Albanova VinnExcellence Center for Protein Technology, ProNova.
    Alvarado-Kristensson, M.
    Pontén, F.
    Brennan, D. J.
    Jirström, K.
    RBM3-regulated genes promote DNA integrity and affect clinical outcome in epithelial ovarian cancer2011In: Translational Oncology, ISSN 1936-5233, Vol. 4, no 4, p. 202-211Article in journal (Refereed)
    Abstract [en]

    The RNA-binding motif protein 3 (RBM3) was initially discovered as a putative cancer biomarker based on its differential expression in various cancer forms in the Human Protein Atlas (HPA). We previously reported an association between high expression of RBM3 and prolonged survival in breast and epithelial ovarian cancer (EOC). Because the function of RBM3 has not been fully elucidated, the aim of this study was to use gene set enrichment analysis to identify the underlying biologic processes associated with RBM3 expression in a previously analyzed EOC cohort (cohort 1, n = 267). This revealed an association between RBM3 expression and several cellular processes involved in the maintenance of DNA integrity. RBM3-regulated genes were subsequently screened in the HPA to select for putative prognostic markers, and candidate proteins were analyzed in the ovarian cancer cell line A2780, whereby an up-regulation of Chk1, Chk2, and MCM3 was demonstrated in siRBM3-treated cells compared to controls. The prognostic value of these markers was assessed at the messenger RNA level in cohort 1 and the protein level in an independent EOC cohort (cohort 2, n = 154). High expression levels of Chk1, Chk2, and MCM3 were associated with a significantly shorter survival in both cohorts, and phosphorylated Chk2 was an adverse prognostic marker in cohort 2. These results uncover a putative role for RBM3 in DNA damage response, which might, in part, explain its cisplatin-sensitizing properties and good prognostic value in EOC. Furthermore, it is demonstrated that Chk1, Chk2, and MCM3 are poor prognostic markers in EOC.

  • 199. Ehrentraut, Claudia
    et al.
    Ekholm, Markus
    KTH.
    Tanushi, Hideyuki
    Tiedemann, Jörg
    Dalianis, Hercules
    Detecting hospital-acquired infections: A document classification approach using support vector machines and gradient tree boosting2018In: Health Informatics Journal, ISSN 1460-4582, E-ISSN 1741-2811, Vol. 24, no 1, p. 24-42Article in journal (Refereed)
    Abstract [en]

    Hospital-acquired infections pose a significant risk to patient health, while their surveillance is an additional workload for hospital staff. Our overall aim is to build a surveillance system that reliably detects all patient records that potentially include hospital-acquired infections. This is to reduce the burden of having the hospital staff manually check patient records. This study focuses on the application of text classification using support vector machines and gradient tree boosting to the problem. Support vector machines and gradient tree boosting have never been applied to the problem of detecting hospital-acquired infections in Swedish patient records, and according to our experiments, they lead to encouraging results. The best result is yielded by gradient tree boosting, at 93.7percent recall, 79.7percent precision and 85.7percent F1 score when using stemming. We can show that simple preprocessing techniques and parameter tuning can lead to high recall (which we aim for in screening patient records) with appropriate precision for this task.

  • 200.
    Eiken, Ola
    et al.
    KTH, School of Technology and Health (STH), Environmental Physiology.
    Kölegård, Roger
    KTH, School of Technology and Health (STH), Environmental Physiology.
    Repeated exposures to moderately increased intravascular pressure increases stiffness in human arteries and arterioles2011In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 29, no 10, p. 1963-1971Article in journal (Refereed)
    Abstract [en]

    The aim was to investigate whether repeated exposures to moderate pressure elevations in the blood vessels of the arms (pressure training; PT) affect pressure distension in arteries/arterioles of healthy subjects (n=11). PT and vascular pressure-distension determinations were conducted with the subject seated in a pressure chamber with one arm slipped through a hole in the chamber door. Increased intravascular pressure was accomplished by increasing chamber pressure. Before PT, one arm was investigated (control arm) during stepwise increases in chamber pressure to 180 mmHg. Artery diameter and flow were measured in the brachial artery using ultrasonography/Doppler techniques. Thereafter, the contralateral arm underwent a PT regimen consisting of three 40 min sessions/ week during 5 weeks. Chamber pressure was increased during PT from 65 mmHg during the first week to 105 mmHg during the last week. After PT, pressure-distension relationships were examined in both the trained arm and the control arm. Prior to and following PT, endothelium-dependent and endothelium-independent dilatations of the brachial artery were studied. PT reduced (p<0.01) arterial pressure distension by 46 ± 18%. Likewise, the pressure-induced increase in arterial flow was less pronounced after (350 ± 249%) compared with before (685 ± 216 %) PT. The PT-induced reductions in arterial/arteriolar pressure distension were reversed 5 weeks post-PT. Neither endothelium-dependent nor endothelium-independent arterial dilatation were affected by PT. It thus appears that the in vivo wall stiffness in arteries and arterioles increases markedly in response to intermittent, moderate increments of transmural pressure during 5 weeks. The increases in arterial/arteriolar stiffness are reversible and do not reflect a reduced capacity to dilate the vessels. The findings are compatible with the notion that local load serves as “ a prime mover” in the development of vascular changes in hypertension.

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Output format
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  • asciidoc
  • rtf