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  • 151.
    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    KTH, Superseded Departments, Microelectronics and Information Technology, IMIT.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.

  • 152. 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.

  • 153. 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.

  • 154. 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.

  • 155.
    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)
  • 156.
    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.

  • 157.
    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.

  • 158. 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.

  • 159. 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)
  • 160.
    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.

  • 161.
    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.

  • 162. 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.

  • 163.
    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.

  • 164. 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. 

  • 165. 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.

  • 166. 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)
  • 167. 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)
  • 168. 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.

  • 169. 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.

  • 170.
    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.

  • 171.
    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.

  • 172. 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.

  • 173.
    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.

  • 174.
    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.

  • 175. 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.

  • 176. 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.

  • 177. 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.

  • 178. 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.

  • 179. 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.

  • 180.
    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.

  • 181. 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.

  • 182. 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.

  • 183.
    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.

  • 184. Eissler, N.
    et al.
    Mao, Y.
    Brodin, D.
    Reuterswärd, Philippa
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Svahn Andersson, Helene
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology.
    Johnsen, J. I.
    Kiessling, R.
    Kogner, P.
    Combination Therapy of Anti-PD-1 Antibody and CSF-1R Inhibitor Reverses Induction of Suppressive Myeloid Cells and Controls Spontaneous Neuroblastoma Progression2016In: Pediatric Blood & Cancer, ISSN 1545-5009, E-ISSN 1545-5017, Vol. 63, p. S28-S28Article in journal (Refereed)
  • 185. Ekstrand, E. E.
    et al.
    Gustafsson, A. G.
    Norhammar, A. N.
    Näsman, Per N.
    KTH, School of Architecture and the Built Environment (ABE), Transport Science, Transport Planning, Economics and Engineering.
    Ryden, L. R.
    Kjellstrom, B. K.
    Periodontal disease: A potential risk factor for myocardial infarction in younger women2016In: EUROPEAN HEART JOURNAL, ISSN 0195-668X, Vol. 37, p. 350-350Article in journal (Refereed)
  • 186. Ekstrand, E
    et al.
    Gustafsson, A
    Norhammar, A
    Näsman, Per
    KTH, School of Architecture and the Built Environment (ABE), Centres, Centre for Transport Studies, CTS.
    Ryden, L
    Kjellström, B
    Periodontal disease - a potential risk factor for myocardial infarction in younger women.2016In: Svenska Hjärtförbundet, no 128Article in journal (Other academic)
  • 187.
    Elmstedt, Nina
    et al.
    KTH, School of Technology and Health (STH), Medical Engineering.
    Lind, Britta
    KTH, School of Technology and Health (STH), Medical Engineering.
    Ferm-Widlund, K.
    Westgren, M.
    Brodin, Lars-Åke
    KTH, School of Technology and Health (STH), Medical Engineering.
    Fetal heart contractile function and gestational age2012In: Cardiovascular Research, ISSN 0008-6363, E-ISSN 1755-3245, Vol. 93, p. S108-S108Article in journal (Other academic)
  • 188. Emri, M.
    et al.
    Opposits, G.
    Kis, S. A.
    Trón, L.
    Veres, P.
    Pányik, Á.
    Valastyán, I.
    Imrek, J.
    Moinar, J.
    Novák, D.
    Kerek, Andras
    KTH, School of Technology and Health (STH), Medical Engineering.
    Balkay, L.
    Software development framework supporting multimodal tomographic imaging2007In: 2006 IEEE Nuclear Science Symposium Conference Record, IEEE , 2007, p. 1857-1859Conference paper (Refereed)
    Abstract [en]

    Engineers specialized in multimodal tomography regularly face a wide scale of programming tasks requiring an integrated software system to ensure cost efficiency. Accordingly, a software development framework has been worked out comprising libraries for cluster-based data acquisition, image reconstruction, management of data files and complex multimodal volumetric visualization. This framework enabled us to develop complex software for our miniPET project [1]. This software contains a graphical application integrating data acquisition, cluster monitoring, event sorting, image reconstruction, interactive image processing tools for advanced multimodal visualization. It also contains utilities to solve these tasks without graphical user interface. The components of our acquisition program can run on embedded Linux systems making new ways to develop any other types of data acquisition software that uses embedded Linux systems. A versatile development framework is developed containing specific libraries and special file formats that support multimodal tomography. This framework was successfully used to elaborate our complex miniPET software.

  • 189.
    Enflo, Laura
    et al.
    KTH, School of Computer Science and Communication (CSC), Speech, Music and Hearing, TMH.
    Sundberg, Johan
    KTH, School of Computer Science and Communication (CSC), Speech, Music and Hearing, TMH.
    McAllister, Anita
    Collision and Phonation Threshold Pressures Before and After Loud, Prolonged Vocalization in Trained and Untrained Voices2013In: Journal of Voice, ISSN 0892-1997, E-ISSN 1873-4588, Vol. 27, no 5, p. 527-530Article in journal (Refereed)
    Abstract [en]

    The phonation threshold pressure (PTP) is defined as the lowest subglottal pressure needed for obtaining and sustaining vocal fold oscillation. It has been found to increase during vocal fatigue. In the present study, PTP is measured together with the threshold pressure needed for vocal fold collision; henceforth, the collision threshold pressure (CTP). PTP and CTP are compared before and after loud, prolonged vocalization in singer and nonsinger voices. Ten subjects repeated the vowel sequence /a, e, i, o, u/ at a Sound Pressure Level of at least 80 dB at 0.3 m for 20 minutes. Audio and electroglottography signals were recorded before and after this exercise. At the same time, oral pressure was registered while the subjects produced a diminuendo repeating the syllable /pa:/, thus acquiring an approximate of the subglottal pressure. CTP and PTP increased significantly after the vocal loading in the nonsinger subjects. On the other hand, singers reported no substantial effect of the exercise, and most singers had a mean after-to-before ratio close to 1 for both CTP and PTP.

  • 190.
    Engberg, L.
    et al.
    Raysearch Labs AB, Res Dept, Stockholm, Sweden..
    Eriksson, K.
    Raysearch Labs AB, Res Dept, Stockholm, Sweden..
    Forsgren, Anders
    KTH, School of Engineering Sciences (SCI), Mathematics (Dept.).
    Automated planning through explicit optimization of plan quality2018In: Radiotherapy and Oncology, ISSN 0167-8140, E-ISSN 1879-0887, Vol. 127, p. S1025-S1026Article in journal (Other academic)
  • 191.
    Engberg, Lovisa
    et al.
    KTH, School of Engineering Sciences (SCI), Mathematics (Dept.), Optimization and Systems Theory.
    Forsgren, Anders
    KTH, School of Engineering Sciences (SCI), Mathematics (Dept.), Optimization and Systems Theory.
    Eriksson, Kjell
    Hardemark, Bjorn
    Explicit optimization of plan quality measures in intensity-modulated radiation therapy treatment planning2017In: Medical physics (Lancaster), ISSN 0094-2405, Vol. 44, no 6, p. 2045-2053Article in journal (Refereed)
    Abstract [en]

    Purpose: To formulate convex planning objectives of treatment plan multicriteria optimization with explicit relationships to the dose-volume histogram (DVH) statistics used in plan quality evaluation. Methods: Conventional planning objectives are designed to minimize the violation of DVH statistics thresholds using penalty functions. Although successful in guiding the DVH curve towards these thresholds, conventional planning objectives offer limited control of the individual points on the DVH curve (doses-at-volume) used to evaluate plan quality. In this study, we abandon the usual penalty-function framework and propose planning objectives that more closely relate to DVH statistics. The proposed planning objectives are based on mean-tail-dose, resulting in convex optimization. We also demonstrate how to adapt a standard optimization method to the proposed formulation in order to obtain a substantial reduction in computational cost. Results: We investigated the potential of the proposed planning objectives as tools for optimizing DVH statistics through juxtaposition with the conventional planning objectives on two patient cases. Sets of treatment plans with differently balanced planning objectives were generated using either the proposed or the conventional approach. Dominance in the sense of better distributed doses-at-volume was observed in plans optimized within the proposed framework. Conclusion: The initial computational study indicates that the DVH statistics are better optimized and more efficiently balanced using the proposed planning objectives than using the conventional approach.

  • 192.
    Engfeldt, Torun
    et al.
    KTH, School of Biotechnology (BIO), Molecular Biotechnology.
    Orlova, Anna
    Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University.
    Tran, Thuy
    Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University.
    Bruskin, Alexander
    Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University.
    Widström, Charles
    Department of Hospital Physics, Uppsala University Hospital.
    Eriksson Karlström, Amelie
    KTH, School of Biotechnology (BIO), Molecular Biotechnology.
    Tolmachev, Vladimir
    Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University.
    Imaging of HER2-expressing tumours using a synthetic Affibody molecule containing the 99mTc-chelating mercaptoacetyl-glycyl-glycyl-glycyl (MAG3) sequence2007In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 34, no 5, p. 722-733Article in journal (Refereed)
    Abstract [en]

    Purpose  Expression of human epidermal growth factor receptor type 2 (HER2) in malignant tumours possesses well-documented prognostic and predictive value. Non-invasive imaging of expression can provide valuable diagnostic information, thereby influencing patient management. Previously, we reported a phage display selection of a small (about 7 kDa) protein, the Affibody molecule ZHER2:342, which binds HER2 with subnanomolar affinity, and demonstrated the feasibility of targeting of HER2-expressing xenografts using radioiodinated ZHER2:342. The goal of this study was to develop a method for 99mTc labelling of ZHER2:342 using the MAG3 chelator, which was incorporated into ZHER2:342 using peptide synthesis, and evaluate the targeting properties of the labelled conjugate. Methods  MAG3-ZHER2:342 was assembled using Fmoc/tBu solid phase peptide synthesis. Biochemical characterisation of the agent was performed using RP-HPLC, ESI-MS, biosensor studies and circular dichroism. A procedure for 99mTc labelling in the presence of sodium/potassium tartrate was established. Tumour targeting was evaluated by biodistribution study and gamma camera imaging in xenograft-bearing mice. Biodistribution of 99mTc-MAG3-ZHER2:342 and 125I-para-iodobenzoate -ZHER2:342 was compared 6 h p.i. Results  Synthetic MAG3-ZHER2:342 possessed an affinity of 0.2 nM for HER2 receptors. The peptide was labelled with 99mTc with an efficiency of about 75–80%. Labelled 99mTc-MAG3-ZHER2:342 retained capacity to bind specifically HER2-expressing SKOV-3 cells in vitro. 99mTc-MAG3-ZHER2:342 showed specific tumour targeting with a contrast similar to a radioiodinated analogue in mice bearing LS174T xenografts. Gamma camera imaging demonstrated clear and specific visualisation of HER2 expression. Conclusion  Incorporation of a mercaptoacetyl-containing chelating sequence during chemical synthesis enabled site-specific 99mTc labelling of the ZHER2:342 Affibody molecule with preserved targeting capacity.

  • 193.
    Engfeldt, Torun
    et al.
    KTH, School of Biotechnology (BIO).
    Tran, Thuy
    Unit of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University.
    Orlova, Anna
    Unit of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University.
    Widström, Charles
    Section of Hospital Physics, Department of Oncology, Uppsala University Hospital.
    Feldwisch, Joachim
    Unit of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University.
    Abrahmsén, Lars
    Affibody AB, Bromma.
    Wennborg, Anders
    Affibody AB, Bromma.
    Eriksson Karlström, Amelie
    KTH, School of Biotechnology (BIO).
    Tolmachev, Vladimir
    Unit of Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala University.
    99mTc-chelator engineering to improve tumour targeting properties of a HER2-specific Affibody molecule2007In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 34, no 11, p. 1843-1853Article in journal (Refereed)
    Abstract [en]

    Purpose  Monitoring HER2 expression is crucial for selection of breast cancer patients amenable to HER2-targeting therapy. The Affibody molecule ZHER2:342 binds to HER2 with picomolar affinity and enables specific imaging of HER2 expression. Previously, ZHER2:342 with the additional N-terminal mercaptoacetyl-glycyl-glycyl-glycyl (maGGG) sequence was labelled with 99mTc and demonstrated specific targeting of HER2-expressing xenografts. However, hepatobiliary excretion caused high radioactivity accumulation in the abdomen. We investigated whether the biodistribution of ZHER2:342 can be improved by substituting glycyl residues in the chelating sequence with more hydrophilic seryl residues.

    Methods  The Affibody molecule ZHER2:342, carrying the chelators mercaptoacetyl-glycyl-seryl-glycyl (maGSG), mercaptoacetyl-glycyl-D-seryl-glycyl [maG(D-S)G] and mercaptoacetyl-seryl-seryl-seryl (maSSS), were prepared by peptide synthesis and labelled with 99mTc. The differences in the excretion pathways were evaluated in normal mice. The tumour targeting capacity of 99mTc-maSSS-ZHER2:342 was studied in nude mice bearing SKOV-3 xenografts and compared with the capacity of radioiodinated ZHER2:342.

    Results  A shift towards renal excretion was obtained when glycine was substituted with serine in the chelating sequence. The radioactivity in the gastrointestinal tract was reduced threefold for the maSSS conjugate in comparison with the maGGG conjugate 4 h post injection (p.i.). The tumour uptake of 99mTc-maSSS-ZHER2:342 was 11.5 ± 0.5% IA/g 4 h p.i., and the tumour-to-blood ratio was 76. The pharmacokinetics and uptake characteristics of technetium-labelled ZHER2:342 were better than those of radioiodinated ZHER2:342.

    Conclusion  The introduction of serine residues in the chelator results in better tumour imaging properties of the Affibody molecule ZHER2:342 compared with glycyl-containing chelators and is favourable for imaging of tumours and metastases in the abdominal area.

  • 194.
    Engkvist, Inga-Lill
    et al.
    KTH, School of Technology and Health (STH), Ergonomics.
    Svensson, R.
    Eklund, Jörgen
    KTH, School of Technology and Health (STH), Ergonomics.
    Reported occupational injuries at Swedish recycling centres - based on official statistics2011In: Ergonomics, ISSN 0014-0139, E-ISSN 1366-5847, Vol. 54, no 4, p. 357-366Article in journal (Refereed)
    Abstract [en]

    Swedish recycling centres are manned facilities for waste collection. There is no special category in the official injury statistics for employees at recycling centres, which precludes a straightforward analysis of reported occupational injuries. This study aimed at identifying the frequency of reported accidents and diseases and the type of events that contribute to such injuries at recycling centres, based on official injury statistics. The employees were identified as being affected by more than three to five times as many accidents compared with the total workforce in Sweden. The reported accidents had occurred during a wide range of situations, but most frequently during manual handling of waste. Reported work-related diseases were mostly associated with musculoskeletal disorders, mainly due to heavy lifting. A more detailed classification of sanitation professions and workplaces in the official injury statistics would facilitate future studies of injuries in a specific professional category, e.g. employees at recycling centres. Suggestions for prevention are given. Statement of Relevance: The present article describes all reported work accidents and diseases among employees at recycling centres from 1992 to February 2005. It also highlights the problem of identifying new working groups in the official statistics and gives advice for a detailed classification to facilitate such future studies of injuries.

  • 195.
    Engström, Emma
    KTH, School of Architecture and the Built Environment (ABE), Land and Water Resources Engineering, Environmental Management and Assessment.
    Comparison of power spectra for tomosynthesis projections and reconstructed images2009In: Medical physics (Lancaster), ISSN 0094-2405, Vol. 36, no 5, p. 1753-1758Article in journal (Refereed)
    Abstract [en]

    Burgess [Med. Phys. 28, 419-437 (2001)] showed that the power spectrum of mammographic breast background follows a power law and that lesion detectability is affected by the power-law exponent beta which measures the amount of structure in the background. Following the study of Burgess , the authors measured and compared the power-law exponent of mammographic backgrounds in tomosynthesis projections and reconstructed slices to investigate the effect of tomosynthesis imaging on background structure. Our data set consisted of 55 patient cases. For each case, regions of interest (ROIs) were extracted from both projection images and reconstructed slices. The periodogram of each ROI was computed by taking the squared modulus of the Fourier transform of the ROI. The power-law exponent was determined for each periodogram and averaged across all ROIs extracted from all projections or reconstructed slices for each patient data set. For the projections, the mean beta averaged across the 55 cases was 3.06 (standard deviation of 0.21), while it was 2.87 (0.24) for the corresponding reconstructions. The difference in beta for a given patient between the projection ROIs and the reconstructed ROIs averaged across the 55 cases was 0.194, which was statistically significant (p < 0.001). The 95% CI for the difference between the mean value of beta for the projections and reconstructions was [0.170, 0.218]. The results are consistent with the observation that the amount of breast structure in the tomosynthesis slice is reduced compared to projection mammography and that this may lead to improved lesion detectability.

  • 196.
    Engström, Pähr
    et al.
    Karolinska Institutet, Dept. of Women's and Children's Health.
    Bartonek, Åsa
    Karolinska Institutet, Dept. of Women's and Child's Health.
    Tedroff, Kristina
    Karolinska Institutet, Dept. of Women's and Children's Health.
    Orefelt, Christina
    Karolinska Institutet, Dept. of Women's and Children's Health.
    Haglund-Åkerlind, Yvonne
    Karolinska Institutet, Dept. of Women's and Children's Health.
    Gutierrez-Farewik, Elena
    Department of Women’s and Children’s Health. Karolinska University Hospital, Sweden.
    Botulinum toxin A does not improve cast treatment for idiopathic toe-walking - a randomized controlled trial2013In: Journal of Bone and Joint Surgery. American volume, ISSN 0021-9355, E-ISSN 1535-1386, Vol. 95, no 5, p. 400-407Article in journal (Refereed)
    Abstract [en]

    Background: There are many treatments for idiopathic toe-walking, including casts with or without injection of botulinum toxin A. Combined treatment with casts and botulinum toxin A has become more common even though there have been few studies of its efficacy and safety problems. Our aims were to conduct a randomized controlled trial to test the hypotheses that combined treatment with casts and botulinum toxin A is more effective than casts alone in reducing toewalking by patients five to fifteen years of age, and that the treatment effect correlates with the extent of coexisting neuropsychiatric problems. Methods: All patients who had been consecutively admitted to the pediatric orthopaedics department of our institution because of idiopathic toe-walking between November 2005 and April 2010 were considered for inclusion in the study. Forty-seven children constituted the study population. The children were randomized to undergo four weeks of treatment with below-the-knee casts either as the sole intervention or to undergo the cast treatment one to two weeks after receiving injections of botulinum toxin A into the calves. Before treatment and three and twelve months after cast removal, all children underwent three-dimensional (3-D) gait analysis. The severity of the idiopathic toe-walking was classified on the basis of the gait analysis, and the parents rated the time that their child spent on his/her toes during barefoot walking. Passive hip, knee, and ankle motion as well as ankle dorsiflexor strength were measured. Before treatment, all children were evaluated with a screening questionnaire for neuropsychiatric problems. Results: No differences were found in any outcome parameter between the groups before treatment or at three or twelve months after cast removal. Several gait-analysis parameters, passive ankle motion, and ankle dorsiflexor strength were improved at both three and twelve months in both groups, even though many children still demonstrated some degree of toe-walking. The treatment outcomes were not correlated with coexisting neuropsychiatric problems. Conclusion: Adding botulinum toxin-A injections prior to cast treatment for idiopathic toe-walking does not improve the outcome of cast-only treatment. Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

  • 197.
    Engström, Pähr
    et al.
    Karolinska Institutet, Dept. of Women's and Children's Health.
    Gutierrez-Farewik, Elena
    KTH, School of Engineering Sciences (SCI), Mechanics, Biomechanics. KTH, School of Engineering Sciences (SCI), Mechanics, Structural Mechanics.
    Bartonek, Åsa
    Karolinska Institutet, Dept. of Women's and Child's Health.
    Tedroff, Kristina
    Karolinska Institutet, Dept. of Women's and Children's Health.
    Orefelt, Christina
    Karolinska Institutet, Dept. of Women's and Children's Health.
    Haglund-Åkerlind, Yvonne
    Karolinska Institutet, Dept. of Women's and Children's Health.
    Does Botulinum toxin A improve the walking pattern in children with idiopathic toe-walking?2010In: Journal of Children's Orthopaedics, ISSN 1863-2521, Vol. 4, no 4, p. 301-308Article in journal (Refereed)
    Abstract [en]

    Background: Numerous recommendations have been made for treating idiopathic toe-walking (ITW), but the treatment results have been questioned. The purpose of this study was to investigate whether botulinum toxin A (BTX) improves the walking pattern in ITW as examined with 3-D gait analysis. Participants and methods: A consecutive series of 15 children (aged 5-13 years) were enrolled in the study. The children underwent a 3-D gait analysis prior to treatment with a total of 6 units/kg bodyweight Botox® in the calf muscles and an exercise program. The gait analysis was repeated 3 weeks and 3, 6, and 12 months after treatment. A classification of toe-walking severity was made before treatment and after 12 months. The parents rated the perceived amount of toe-walking prior to treatment and 6 and 12 months after treatment. Results: Eleven children completed the 12-month follow-up. The gait analysis results displayed a significant improvement, indicating decreased plantarflexion angle at initial contact and during swing phase and increased dorsiflexion angle during midstance at all post-treatment testing instances. According to the parents' perception of toe-walking, 3/11 children followed for 12 months had ceased toe-walking completely, 4/11 decreased toe-walking, and 4/11 continued toe-walking. After 6-12 months, the toe-walking severity classification improved in 9 of the 14 children for whom data could be assessed. Conclusions: A single injection of BTX in combination with an exercise program can improve the walking pattern in children with ITW seen at gait analysis, but the obvious goal of ceasing toe-walking is only occasionally reached.

  • 198. Ercole, A.
    et al.
    Thelin, E. P.
    Holst, Anders
    KTH, School of Computer Science and Communication (CSC), Computational Science and Technology (CST).
    Bellander, B. M.
    Nelson, D. W.
    Kinetic modelling of serum S100b after traumatic brain injury2016In: BMC Neurology, ISSN 1471-2377, E-ISSN 1471-2377, Vol. 16, article id 93Article in journal (Refereed)
    Abstract [en]

    Background: An understanding of the kinetics of a biomarker is essential to its interpretation. Despite this, little kinetic modelling of blood biomarkers can be found in the literature. S100b is an astrocyte related marker of brain injury used primarily in traumatic brain injury (TBI). Serum levels are expected to be the net result of a multi-compartmental process. The optimal sample times for TBI prognostication, and to follow injury development, are unclear. The purpose of this study was to develop a kinetic model to characterise the temporal course of serum S100b concentration after primary traumatic brain injury. Methods: Data of serial serum S100b samples from 154 traumatic brain injury patients in a neurointensive care unit were retrospectively analysed, including only patients without secondary peaks of this biomarker. Additionally, extra-cranial S100b can confound samples earlier than 12 h after trauma and were therefore excluded. A hierarchical, Bayesian gamma variate kinetic model was constructed and the parameters estimated by Markov chain Monte Carlo sampling. Results: We demonstrated that S100b concentration changes dramatically over timescales that are clinically important for early prognostication with a peak at 27.2 h (95 % credible interval [25.6, 28.8]). Baseline S100b levels was found to be 0.11 mu g/L (95 % credible interval [0.10, 0.12]). Conclusions: Even small differences in injury to sample time may lead to marked changes in S100b during the first days after injury. This must be taken into account in interpretation. The model offers a way to predict the peak and trajectory of S100b from 12 h post trauma in TBI patients, and to identify deviations from this, possibly indicating a secondary event. Kinetic modelling, providing an equation for the peak and projection, may offer a way to reduce the ambiguity in interpretation of, in time, randomly sampled acute biomarkers and may be generally applicable to biomarkers with, in time, well defined hits.

  • 199.
    Erdman, William A.
    et al.
    MIDDLESEX GEN UNIV HOSP,RUTGERS MED SCH,NEW BRUNSWICK,NJ 08901 .
    Maguire Jr., Gerald Q.
    Columbia University, Department of Computer Science.
    Noz, Marilyn E.
    New York University.
    Stahl, T. J.
    MIDDLESEX GEN UNIV HOSP,RUTGERS MED SCH,NEW BRUNSWICK,NJ 08901 .
    A Picture Archiving and Communication System - Modus Operandi for a Filmless Nuclear Medicine Department1986In: Administrative Radiology, ISSN 0738-6974, Vol. 5, no 1, p. 34-38Article in journal (Refereed)
  • 200.
    Erdman, William A.
    et al.
    MIDDLESEX GEN UNIV HOSP,RUTGERS MED SCH,NEW BRUNSWICK,NJ 08901 .
    Stahl, T. J.
    MIDDLESEX GEN UNIV HOSP,RUTGERS MED SCH,NEW BRUNSWICK,NJ 08901 .
    Tokarz, R. J.
    MIDDLESEX GEN UNIV HOSP,RUTGERS MED SCH,NEW BRUNSWICK,NJ 08901 .
    Maguire Jr., Gerald Q.
    Columbia University, Department of Computer Science.
    Noz, Marilyn E.
    New York University.
    Development of a Digital Nuclear-Medicine System1983In: Proceedings of the Society of Photo-Optical Instrumentation Engineers, ISSN 0361-0748, Vol. 418, p. 100-102Article in journal (Refereed)
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