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  • 301.
    Green, Henrik
    et al.
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab. Linköping University, Sweden; National Board of Forensic Medicine, Sweden.
    Hasmats, Johanna
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Kupershmidt, Ilya
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab. NextBio, USA.
    Edsgärd, Daniel
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    de Petris, Luigi
    Lewensohn, Rolf
    Blackhall, Fiona
    Vikingsson, Svante
    Besse, Benjamin
    Lindgren, Andrea
    Branden, Eva
    Koyi, Hirsh
    Peterson, Curt
    Lundeberg, Joakim
    KTH, School of Biotechnology (BIO), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Using Whole-Exome Sequencing to Identify Genetic Markers for Carboplatin and Gemcitabine-Induced Toxicities2016In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 22, no 2, p. 366-373Article in journal (Refereed)
    Abstract [en]

    Purpose: Chemotherapies are associated with significant interindividual variability in therapeutic effect and adverse drug reactions. In lung cancer, the use of gemcitabine and carboplatin induces grade 3 or 4 myelosuppression in about a quarter of the patients, while an equal fraction of patients is basically unaffected in terms of myelosuppressive side effects. We therefore set out to identify genetic markers for gemcitabine/carboplatin-induced myelosuppression. Experimental Design: We exome sequenced 32 patients that suffered extremely high neutropenia and thrombocytopenia (grade 3 or 4 after first chemotherapy cycle) or were virtually unaffected (grade 0 or 1). The genetic differences/polymorphism between the groups were compared using six different bioinformatics strategies: (i) whole-exome nonsynonymous single-nucleotide variants association analysis, (ii) deviation from Hardy-Weinberg equilibrium, (iii) analysis of genes selected by a priori biologic knowledge, (iv) analysis of genes selected from gene expression meta-analysis of toxicity datasets, (v) Ingenuity Pathway Analysis, and (vi) FunCoup network enrichment analysis. Results: A total of 53 genetic variants that differed among these groups were validated in an additional 291 patients and were correlated to the patients' myelosuppression. In the validation, we identified rs1453542 in OR4D6 (P = 0.0008; OR, 5.2; 95% CI, 1.8-18) as a marker for gemcitabine/carboplatin-induced neutropenia and rs5925720 in DDX53 (P = 0.0015; OR, 0.36; 95% CI, 0.17-0.71) as a marker for thrombocytopenia. Patients homozygous for the minor allele of rs1453542 had a higher risk of neutropenia, and for rs5925720 the minor allele was associated with a lower risk for thrombocytopenia. Conclusions: We have identified two new genetic markers with the potential to predict myelosuppression induced by gemcitabine/ carboplatin chemotherapy.

  • 302. Gremel, Gabriela
    et al.
    Djureinovic, Dijana
    Niinivirta, Marjut
    Laird, Alexander
    Ljungqvist, Oscar
    Johannesson, Henrik
    Bergman, Julia
    Edqvist, Per-Henrik
    Navani, Sanjay
    Khan, Naila
    Patil, Tushar
    Sivertsson, Åsa
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Harrison, David J.
    Ullenhag, Gustav J.
    Stewart, Grant D.
    Ponten, Fredrik
    A systematic search strategy identifies cubilin as independent prognostic marker for renal cell carcinoma2017In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 17, article id 9Article in journal (Refereed)
    Abstract [en]

    Background: There is an unmet clinical need for better prognostic and diagnostic tools for renal cell carcinoma (RCC). Methods: Human Protein Atlas data resources, including the transcriptomes and proteomes of normal and malignant human tissues, were searched for RCC-specific proteins and cubilin (CUBN) identified as a candidate. Patient tissue representing various cancer types was constructed into a tissue microarray (n = 940) and immunohistochemistry used to investigate the specificity of CUBN expression in RCC as compared to other cancers. Two independent RCC cohorts (n = 181; n = 114) were analyzed to further establish the sensitivity of CUBN as RCC-specific marker and to explore if the fraction of RCCs lacking CUBN expression could predict differences in patient survival. Results: CUBN was identified as highly RCC-specific protein with 58% of all primary RCCs staining positive for CUBN using immunohistochemistry. In venous tumor thrombi and metastatic lesions, the frequency of CUBN expression was increasingly lost. Clear cell RCC (ccRCC) patients with CUBN positive tumors had a significantly better prognosis compared to patients with CUBN negative tumors, independent of T-stage, Fuhrman grade and nodal status (HR 0.382, CI 0.203-0.719, P = 0.003). Conclusions: CUBN expression is highly specific to RCC and loss of the protein is significantly and independently associated with poor prognosis. CUBN expression in ccRCC provides a promising positive prognostic indicator for patients with ccRCC. The high specificity of CUBN expression in RCC also suggests a role as a new diagnostic marker in clinical cancer differential diagnostics to confirm or rule out RCC.

  • 303. Gremel, Gabriela
    et al.
    Wanders, Alkwin
    Cedernaes, Jonathan
    Fagerberg, Linn
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Hallström, Björn
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Edlund, Karolina
    Sjostedt, Evelina
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Ponten, Fredrik
    The human gastrointestinal tract-specific transcriptome and proteome as defined by RNA sequencing and antibody-based profiling2015In: Journal of gastroenterology, ISSN 0944-1174, E-ISSN 1435-5922, Vol. 50, no 1, p. 46-57Article in journal (Refereed)
    Abstract [en]

    The gastrointestinal tract (GIT) is subdivided into different anatomical organs with many shared functions and characteristics, but also distinct differences. We have combined a genome-wide transcriptomics analysis with immunohistochemistry-based protein profiling to describe the gene and protein expression patterns that define the human GIT. RNA sequencing data derived from stomach, duodenum, jejunum/ileum and colon specimens were compared to gene expression levels in 23 other normal human tissues analysed with the same method. Protein profiling based on immunohistochemistry and tissue microarrays was used to sub-localize the corresponding proteins with GIT-specific expression into sub-cellular compartments and cell types. Approximately 75 % of all human protein-coding genes were expressed in at least one of the GIT tissues. Only 51 genes showed enriched expression in either one of the GIT tissues and an additional 83 genes were enriched in two or more GIT tissues. The list of GIT-enriched genes with validated protein expression patterns included various well-known but also previously uncharacterised or poorly studied genes. For instance, the colon-enriched expression of NXPE family member 1 (NXPE1) was established, while NLR family, pyrin domain-containing 6 (NLRP6) expression was primarily found in the human small intestine. We have applied a genome-wide analysis based on transcriptomics and antibody-based protein profiling to identify genes that are expressed in a specific manner within the human GIT. These genes and proteins constitute important starting points for an improved understanding of the normal function and the different states of disease associated with the GIT.

  • 304.
    Grishenkov, Dmitry
    KTH, School of Engineering Sciences (SCI), Aeronautical and Vehicle Engineering, Marcus Wallenberg Laboratory MWL.
    Polymer-shelled Ultrasound Contrast Agents: Characterization and Application2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Ultrasound-based imaging technique is probably the most used approach for rapid investigationand monitoring of anatomical and physiological conditions of internal organs and tissues.Ultrasound-based techniques do not require the use of ionizing radiation making the tests anexceptionally safe and painless. Operating in the frequency range between 1 to 15 MHz, medicalultrasound provides reliable visual and quantitative information from both superficial structuressuch as muscles and tendons, and also deeper organs such as liver and kidney. From the technicalpoint of view medical ultrasound has a good spatial and temporal resolution. Ultrasound machineis mobile or even portable, which makes it truly bedside modality. And last but not the least,ultrasound investigations are cheaper in comparison to other real time imaging techniques.

    Ultrasound imaging techniques can be greatly improved by the use of contrast agents to enhancethe signal from the area of interest (e.g. cardiac or liver tissues) relative to the background.Typically ultrasound contrast agent (UCA) is a suspension of the microbubbles consisting of agas core encapsulated within the solid shell. Generally these devices are injected systemically andfunction to passively enhance the ultrasound echo. In recent years, the UCAs have evolved frombeing just a visualization tool to become a new multifunctional and complex device for drug orgene therapy and targeted imaging.

    The overall objective of the project is to test novel polymer shelled microbubbles (MBs) as apossible new generation of ultrasound contrast agents.

    During the first year of the project an innovative criterion based on cross-correlation analysis toassess the pressure threshold at which ultrasonic waves fracture the polymer shell of microbubblehas been developed. In addition, acoustic properties of these microbubbles which are relevant totheir use both as contrast agents and drug carriers for localized delivery have been preliminarytested. Furthermore, in order to reconstruct viscoelastic properties of the shell the originalChurch’s model (1995) has been implemented. In collaboration with Karolinska Institutet, imagesof the microbubbles have been acquired with conventional imaging system. These imagesdemonstrate the potential of the novel polymer-shelled microbubbles to be used as contractenhancing agents.

    The objective of the second year was to describe the acoustic and mechanical properties ofdifferent types of microbubbles synthesised under varied conditions. This task was divided in twointerrelated parts. In the first part acoustic characterization has been completed in low intensityregion with the study of backscattered power, attenuation and phase velocity. In order torecalculate mechanical properties of the shell existing theoretical model has been furtheriimodified to accommodate the frequency dependence of viscoelastic properties andsimultaneously fit the attenuation and phase velocity data. The results concerning acoustic andmechanical properties of the microbubbles have been sent as a feedback to the manufacture inorder to optimize fabrication protocol for effective image acquisition. In the second part acousticcharacterization has been performed in high intensity region under varied parameters ofexperimental set-up. The results that illustrate the dependence of the fracture pressure thresholdon the system parameters allows us to discuss the potential role of polymer-shelled UCAs as drugcarriers and formulate the protocol for save, localized, cavitation-mediated drug delivery.

    For the third year the major task was to move on from the bulk volume in vitro tests towards themicrocapillary study and even further to incorporate the microcapillary into the tissue mimickingultrasound phantom. The last study has the objective to take into account the wave propagationthrough tissue. And last but not the least, the application of the polymer-shelled microbubblesfor evaluation of perfusion characteristics, i.e. capillary volume and velocity of the flow, has beenperformed. Similar tests are carried out with commercially available phospholipid-shelled UCA.Using destruction/replenishment technique it is suggested that the novel polymer-shelledmicrobubbles have a potential for a more accurate perfusion evaluation compared to that ofcommercially available phospholipid-shelled UCA.

    In conclusion, proposed polymer-shelled gas-core microbubbles provide a viable system to beused among the next generation of ultrasound contrast agents, which facilitate not only imageenhancement relevant to diagnostics but also localized and specific drug delivery for non-invasivetherapy even in acute conditions.

  • 305.
    Grishenkov, Dmitry
    et al.
    KTH, School of Engineering Sciences (SCI), Aeronautical and Vehicle Engineering, MWL Ultrasound.
    Kari, Leif
    KTH, School of Engineering Sciences (SCI), Aeronautical and Vehicle Engineering, Marcus Wallenberg Laboratory MWL.
    Brismar, Torkel B.
    Karolinska University Hospital.
    Paradossi, Gaio
    Università di Roma Tor Vergata.
    Acoustic properties of polymer-shelled ultrasound contrast agents. Bulk volume vs. microcapillary2009In: 16th International Congress on Sound and Vibration 2009, ICSV 2009, Krakow, 2009, p. 2515-2522Conference paper (Refereed)
    Abstract [en]

    The focus of contrast-enhanced ultrasound research has developed beyond detecting the blood pool to new areas such as perfusion imaging, drug and gene therapy, and targeted imaging. Polymer-shelled microbubbles are proposed as a new generation of ultrasound contrast agents (UCAs) which fulfil the requirements of these applications. With a shelf-life of several months and possibility to conjugate pharmacological molecules to their surface, these UCAs will allow not only to enhance the contrast of ultrasound images, but also to function as carriers of drugs to be delivered locally. In this study, the results of an experimental investigation of three types of UCAs stabilized by thick poly vinyl alcohol (PVA) shell are presented. These UCAs are synthesized from a PVA aqueous solution under varied pH values and temperature. The UCAs differ from each other in their average diameter, shell thickness and polydispersity. Knowledge of the peak negative pressure at which the solid shell fractures is paramount for a proper use of UCAs. Therefore, the dependence of this quantity on temperature and number of cycles in the incident pulse is examined. Much of the blood volume resides in the microcirculation, with capillaries playing a particularly important role in patho-physiology and drug delivery. In this sense in vitro characterization of the UCAs oscillation was moved from bulk volume to the capillary scale, where tissue-bubble interaction takes place. The main conclusion to be drawn from these results is that the shell of the UCAs begin to fracture at values of mechanical index (MI) approved for clinical applications. The fatigue, i.e. the accumulation of damage within the shell of the UCAs, is found to play an important role in fracturing the shell. Finally adhesion of the UCAs to the elastic wall is studied and correlated with estimates of the shell’s visco-elastic constants. Open questions arising from this comparison are briefly discussed.

  • 306.
    Grosso, Giorgia
    et al.
    Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, Unit Rheumatol, Stockholm, Sweden..
    Sippl, Natalie
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Kjellstrom, Barbro
    Karolinska Inst, Karolinska Univ Hosp, Cardiol Unit, Dept Med Solna, Stockholm, Sweden..
    Amara, Khaled
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    de Faire, Ulf
    Karolinska Inst, Div Cardiovasc Epidemiol IMM, Stockholm, Sweden..
    Elvin, Kerstin
    Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, Unit Rheumatol, Stockholm, Sweden.;Karolinska Inst, Karolinska Univ Hosp, Unit Clin Immunol, Dept Clin Immunol & Transfus Med, Stockholm, Sweden..
    Lindahl, Bertil
    Uppsala Univ, Dept Med Sci, Uppsala, Sweden..
    Näsman, Per
    KTH.
    Ryden, Lars
    Karolinska Inst, Dept Med Solna, Cardiol Unit, Stockholm, Sweden..
    Norrhammar, Anna
    Karolinska Inst, Dept Med Solna, Cardiol Unit, Stockholm, Sweden.;Capio St Gorans Hosp, Stockholm, Sweden..
    Svenungsson, Elisabet
    Karolinska Inst, Dept Med, Div Rheumatol, Stockholm, Sweden..
    IgG Antiphospholipid Antibodies, -a Common but Neglected Finding in Patients with Myocardial Infarction2018In: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 70Article in journal (Other academic)
  • 307.
    Grosso, Giorgia
    et al.
    Karolinska Univ Hosp, Karolinska Inst, Stockholm, Sweden..
    Sippl, Natalie
    Karolinska Univ Hosp, Karolinska Inst, Stockholm, Sweden..
    Kjellström, Barbro
    Karolinska Univ Hosp, Karolinska Inst, Stockholm, Sweden..
    Amara, Khaled
    Karolinska Univ Hosp, Karolinska Inst, Stockholm, Sweden..
    de Faire, Ulf
    Karolinska Univ Hosp, Karolinska Inst, Stockholm, Sweden..
    Elvin, Kerstin
    Karolinska Univ Hosp, Karolinska Inst, Stockholm, Sweden..
    Lindahl, Bertil
    Uppsala Univ, Uppsala, Sweden..
    Näsman, Per
    KTH, School of Architecture and the Built Environment (ABE), Real Estate and Construction Management, Building and Real Estate Economics.
    Ryden, Lars
    Karolinska Univ Hosp, Karolinska Inst, Stockholm, Sweden..
    Norhammar, Anna
    Karolinska Univ Hosp, Karolinska Inst, Stockholm, Sweden.;Capio St Gorans Hosp, Stockholm, Sweden..
    Svenungsson, Elisabet
    Karolinska Univ Hosp, Karolinska Inst, Stockholm, Sweden..
    Antiphospholipid Antibodies in Patients With Myocardial Infarction2019In: Annals of Internal Medicine, ISSN 0003-4819, E-ISSN 1539-3704, Vol. 170, no 4, p. 277-280Article in journal (Refereed)
  • 308.
    Grönkvist, Mikael
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Environmental Physiology.
    LaPelusa, M.
    Univ Texas Rio Grande Valley, Sch Med, Edinburg, TX USA..
    Gennser, Mikael
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Environmental Physiology. Royal Inst Technol, Environm Physiol, Stockholm, Sweden..
    Machado-Moreira, Christiano Antonio
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Environmental Physiology.
    Postural and Daily Variations in the Single-Breath Diffusion Capacity of the Lungs for Carbon Monoxide2018In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 197Article in journal (Other academic)
  • 309.
    Guala, Dimitri
    et al.
    Stockholm Univ, Dept Biochem & Biophys, Stockholm Bioinformat Ctr, Sci Life Lab, Box 1031, S-17121 Solna, Sweden..
    Bernhem, Kristoffer
    KTH, School of Engineering Sciences (SCI), Applied Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Blal, Hammou Ait
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Biotechnology (BIO).
    Jans, Daniel
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences (SCI), Applied Physics.
    Lundberg, Emma
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Biotechnology (BIO).
    Brismar, Hjalmar
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences (SCI), Applied Physics.
    Sonnhammer, Erik L. L.
    Stockholm Univ, Dept Biochem & Biophys, Stockholm Bioinformat Ctr, Sci Life Lab, Box 1031, S-17121 Solna, Sweden..
    Experimental validation of predicted cancer genes using FRET2018In: METHODS AND APPLICATIONS IN FLUORESCENCE, ISSN 2050-6120, Vol. 6, no 3, article id 035007Article in journal (Refereed)
    Abstract [en]

    Huge amounts of data are generated in genome wide experiments, designed to investigate diseases with complex genetic causes. Follow up of all potential leads produced by such experiments is currently cost prohibitive and time consuming. Gene prioritization tools alleviate these constraints by directing further experimental efforts towards the most promising candidate targets. Recently a gene prioritization tool called MaxLink was shown to outperform other widely used state-of-the-art prioritization tools in a large scale in silico benchmark. An experimental validation of predictions made by MaxLink has however been lacking. In this study we used Fluorescence Resonance Energy Transfer, an established experimental technique for detection of protein-protein interactions, to validate potential cancer genes predicted by MaxLink. Our results provide confidence in the use of MaxLink for selection of new targets in the battle with polygenic diseases.

  • 310. Gunes, I.
    et al.
    Kucuk, A.
    Comu, F. M.
    Sivgin, V.
    Alkan, M.
    Arslan, M.
    Unal, Y.
    I kappa B Kinase 2 impairs Platelet Activation2017In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 221, p. 248-250Article in journal (Other academic)
  • 311. Gunther, A. C.
    et al.
    Schandl, A. R.
    Berhardsson, J.
    Bjärtå, A.
    Wållgren, M.
    Sundin, O.
    Alvarsson, Jesper
    KTH, School of Engineering Sciences (SCI), Aeronautical and Vehicle Engineering, Marcus Wallenberg Laboratory MWL.
    Bottai, M.
    Martling, C. -R
    Sackey, P. V.
    Pain rather than induced emotions and ICU sound increases skin conductance variability in healthy volunteers2016In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 60, no 8, p. 1111-1120Article in journal (Refereed)
    Abstract [en]

    BackgroundAssessing pain in critically ill patients is difficult. Skin conductance variability (SCV), induced by the sympathetic response to pain, has been suggested as a method to identify pain in poorly communicating patients. However, SCV, a derivate of conventional skin conductance, could potentially also be sensitive to emotional stress. The purpose of the study was to investigate if pain and emotional stress can be distinguished with SCV. MethodsIn a series of twelve 1-min sessions with SCV recording, 18 healthy volunteers were exposed to standardized electric pain stimulation during blocks of positive, negative, or neutral emotion, induced with pictures from the International Affective PictureSystem (IAPS). Additionally, authentic intensive care unit (ICU) sound was included in half of the sessions. All possible combinations of pain and sound occurred in each block of emotion, and blocks were presented in randomized order. ResultsPain stimulation resulted in increases in the number of skin conductance fluctuations (NSCF) in all but one participant. During pain-free baseline sessions, the median NSCF was 0.068 (interquartile range 0.013-0.089) and during pain stimulation median NSCF increased to 0.225 (interquartile range 0.146-0.3175). Only small increases in NSCF were found during negative emotions. Pain, assessed with the numeric rating scale, during the sessions with pain stimulation was not altered significantly by other ongoing sensory input. ConclusionIn healthy volunteers, NSCF appears to reflect ongoing autonomous reactions mainly to pain and to a lesser extent, reactions to emotion induced with IAPS pictures or ICU sound.

  • 312. Gustafsson, J.
    et al.
    Ternström, Sten
    KTH, School of Computer Science and Communication (CSC), Speech, Music and Hearing, TMH.
    Södersten, M.
    Schalling, E.
    Motor-Learning-Based Adjustment of Ambulatory Feedback on Vocal Loudness for Patients With Parkinson's Disease2016In: Journal of Voice, ISSN 0892-1997, E-ISSN 1873-4588, Vol. 30, no 4, p. 407-415Article in journal (Refereed)
    Abstract [en]

    Objectives: To investigate how the direct biofeedback on vocal loudness administered with a portable voice accumulator (VoxLog) should be configured, to facilitate an optimal learning outcome for individuals with Parkinson's disease (PD), on the basis of principles of motor learning. Study Design: Methodologic development in an experimental study. Methods: The portable voice accumulator VoxLog was worn by 20 participants with PD during habitual speech during semistructured conversations. Six different biofeedback configurations were used, in random order, to study which configuration resulted in a feedback frequency closest to 20% as recommended on the basis of previous studies. Results: Activation of feedback when the wearer speaks below a threshold level of 3dB below the speaker's mean voice sound level in habitual speech combined with an activation time of 500ms resulted in a mean feedback frequency of 21.2%. Conclusions: Settings regarding threshold and activation time based on the results from this study are recommended to achieve an optimal learning outcome when administering biofeedback on vocal loudness for individuals with PD using portable voice accumulators.

  • 313.
    Gustafsson, Joakim Körner
    et al.
    Karolinska Institutet.
    Södersten, Maria
    Karolinska Institutet.
    Ternström, Sten
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Speech, Music and Hearing, TMH, Speech Communication and Technology.
    Schalling, Ellika
    Karolinska Institutet.
    Voice use in daily life studied with a portable voice accumulator in individuals with Parkinson’s disease and matched healthy controls2019In: Journal of Speech, Language and Hearing Research, ISSN 1092-4388, E-ISSN 1558-9102, Vol. 62, no 12, p. 4324-4334Article in journal (Refereed)
    Abstract [en]

    Purpose: The purpose of this work was to study how voice use in daily life is impacted by Parkinson’s disease (PD), specifically if there is a difference in voice sound level and phonation ratio during everyday activities for individuals with PD and matched healthy controls. A further aim was to study how variations in environmental noise impact voice use. Method: Long-term registration of voice use during 1 week in daily life was performed for 21 participants with PD (11 male, 10 female) and 21 matched healthy controls using the portable voice accumulator VoxLog. Voice use was assessed through registrations of spontaneous speech in different ranges of environmental noise in daily life and in a controlled studio recording setting. Results: Individuals with PD use their voice 50%-60% less than their matched healthy controls in daily life. The difference increases in high levels of environmental noise. Individuals with PD used an average voice sound level in daily life that was 8.11 dB (female) and 6.7 dB (male) lower than their matched healthy controls. Difference in mean voice sound level for individuals with PD and controls during spontaneous speech during a controlled studio registration was 3.0 dB for the female group and 4.1 dB for the male group. Conclusions: The observed difference in voice use in daily life between individuals with PD and matched healthy controls is a 1st step to objectively quantify the impact of PD on communicative participation. The variations in voice use in different levels of environmental noise and when comparing controlled and variable environments support the idea that the study of voice use should include methods to assess function in less controlled situations outside the clinical setting.

  • 314.
    Gutierrez, Elena
    Karolinska Institutet.
    Kinetics of compensatory gait in persons with myelomeningocele2005In: Gait & Posture, ISSN 0966-6362, E-ISSN 1879-2219, Vol. 21, no 1, p. 12-23Article in journal (Refereed)
    Abstract [en]

    This study investigated the kinetic strategy and compensatory mechanisms during self-ambulatory gait in children with lumbo-sacral myelomeningocele. Thirty-one children with mid-lumbar to low-sacral myelomeningocele who walked without aids and 21 control children were evaluated by three-dimensional gait analysis. Joint moments in all planes at the hip and knee and sagittal moments at the ankle, as well as joint power and work done at all three joints, were analyzed. Joint moment capacity lost due to plantarflexor and dorsiflexor weakness was provided instead by orthotic support, but other joints were loaded more to compensate for the weakness at the ankles and restricted ankle motion. Subjects with total plantarflexor and dorsiflexor paresis and strength in the hip abductors had more knee extensor loading due to plantarflexor weakness and dorsiflexion angle of the orthotic ankle joint. The subjects with orthoses also generated more power at the hip to supplement the power generation lost to plantarflexor weakness and fixed ankles. The most determinant muscle whose paresis changes gait kinetics was the hip abductor. Hip abductor weakness resulted in a characteristic pattern where the hips displayed an eccentric adduction moment, mediating energy transfer into the lower limbs, and the hips replaced the knees as power absorbers in early stance. Joint moment, power and work analyses complement a kinematic analysis to provide a complete picture of how children who have muscle paresis recruit stronger muscle groups to compensate for weaker ones.

  • 315.
    Gutierrez, Elena M
    et al.
    Karolinska Institutet, Dept. of Surgical Sciences, Orthopedics Section.
    Bartonek, Åsa
    Karolinska Institutet, Dept. of Women's and Child's Health.
    Haglund-Åkerlind, Yvonne
    Karolinska Institutet, Dept. of Women's and Children's Health.
    Saraste, Helena
    Karolinska Institutet, Dept. of Surgical Sciences, Orthopedics Section.
    Kinetics of compensatory gait in persons with myelomeningocele2005In: Gait & Posture, ISSN 0966-6362, E-ISSN 1879-2219, Vol. 21, no 1, p. 12-23Article in journal (Refereed)
    Abstract [en]

    This study investigated the kinetic strategy and compensatory mechanisms during self-ambulatory gait in children with lumbo-sacral myelomeningocele. Thirty-one children with mid-lumbar to low-sacral myelomeningocele who walked without aids and 21 control children were evaluated by three-dimensional gait analysis. Joint moments in all planes at the hip and knee and sagittal moments at the ankle, as well as joint power and work done at all three joints, were analyzed. Joint moment capacity lost due to plantarflexor and dorsiflexor weakness was provided instead by orthotic support, but other joints were loaded more to compensate for the weakness at the ankles and restricted ankle motion. Subjects with total plantarflexor and dorsiflexor paresis and strength in the hip abductors had more knee extensor loading due to plantarflexor weakness and dorsiflexion angle of the orthotic, ankle joint. The subjects with orthoses also generated more power at the hip to supplement the power generation lost to plantarflexor weakness and fixed ankles. The most determinant muscle whose paresis changes gait kinetics was the hip abductor. Hip abductor weakness resulted in a characteristic pattern where the hips displayed an eccentric adduction moment, mediating energy transfer into the lower limbs, and the hips replaced the knees as power absorbers in early stance. Joint moment, power and work analyses complement a kinematic analysis to provide a complete picture of how children who have muscle paresis recruit stronger muscle groups to compensate for weaker ones.

  • 316.
    Gutierrez-Farewik, Elena
    Karolinska Institutet, Department of Women's and Children's Health.
    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]

    ACKGROUND:

    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 toe-walking 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.

    TRIAL REGISTRATION: ClinicalTrials.gov NCT01590693.

  • 317. Gyllencreutz, Erika
    et al.
    Lu, Ke
    KTH, School of Technology and Health (STH), Medical Engineering.
    Abtahi, Farhad
    KTH, School of Technology and Health (STH), Medical Engineering, Computer and Electronic Engineering.
    Lindecrantz, Kaj
    KTH, School of Technology and Health (STH), Medical Engineering, Computer and Electronic Engineering.
    Nordström, Lennart
    Lindqvist, Pelle
    Holzmann, Malin
    Characteristics of variable decelerations and prediction of fetal acidemia2017In: American Journal of Obstetrics and Gynecology, ISSN 0002-9378, E-ISSN 1097-6868, Vol. 216, no 1, p. S507-S507Article in journal (Other academic)
  • 318.
    Gyllencreutz, Erika
    et al.
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.;Ostersund Hosp, Dept Obstet & Gynecol, S-83183 Region Jamtland Harjedal, Ostersund, Sweden..
    Lu, Ke
    KTH, School of Technology and Health (STH).
    Lindecrantz, Kaj
    KTH, School of Technology and Health (STH). Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden..
    Lindqvist, Pelle G.
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.;Karolinska Univ Hosp, Pregnancy & Delivery Care, Stockholm, Sweden..
    Nordström, Lennart
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.;Karolinska Univ Hosp, Pregnancy & Delivery Care, Stockholm, Sweden..
    Holzmann, Malin
    Karolinska Inst, Dept Womens & Childrens Hlth, Stockholm, Sweden.;Karolinska Univ Hosp, Pregnancy & Delivery Care, Stockholm, Sweden..
    Abtahi, Farhad
    Karolinska Inst, Inst Environm Med, Stockholm, Sweden.;Karolinska Univ Hosp Huddinge, Dept Clin Physiol, Stockholm, Sweden..
    Validation of a computerized algorithm to quantify fetal heart rate deceleration area2018In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 97, no 9, p. 1137-1147Article in journal (Refereed)
    Abstract [en]

    IntroductionReliability in visual cardiotocography interpretation is unsatisfying, which has led to the development of computerized cardiotocography. Computerized analysis is well established for antenatal fetal surveillance but has yet not performed sufficiently during labor. We aimed to investigate the capacity of a new computerized algorithm compared with visual assessment in identifying intrapartum fetal heart rate baseline and decelerations. Material and methodsIn all, 312 intrapartum cardiotocography tracings with variable decelerations were analyzed by the computerized algorithm and visually examined by two observers, blinded to each other and the computer analysis. The width, depth and area of each deceleration was measured. Four cases (>100 variable decelerations) were subjected to in-depth detailed analysis. The outcome measures were bias in seconds (width), beats per minute (depth), and beats (area) between computer and observers using Bland-Altman analysis. Interobserver reliability was determined by calculating intraclass correlation and Spearman rank analysis. ResultsThe analysis (312 cases) showed excellent intraclass correlation (0.89-0.95) and very strong Spearman correlation (0.82-0.91). The detailed analysis of >100 decelerations in four cases revealed low bias between the computer and the two observers; width 1.4 and 1.4 seconds, depth 5.1 and 0.7 beats per minute, and area 0.1 and -1.7 beats. This was comparable to the bias between the two observers: 0.3 seconds (width), 4.4 beats per minute (depth) and 1.7 beats (area). The intraclass correlation was excellent (0.90-.98). ConclusionA novel computerized algorithm for intrapartum cardiotocography analysis is as accurate as gold standard visual assessment, with high correlation and low bias.

  • 319. Hadimeri, Ursula
    et al.
    Smedby, Örjan
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Biomedical Engineering and Health Systems, Medical Imaging.
    Fransson, Sven-Göran
    Stegmayr, Bernd
    Hadimeri, Henrik
    Fistula diameter correlates with echocardiographic characteristics in stable hemodialysis patients2015In: Nephrology@ Point of Care, ISSN 2059-3007, Vol. 1, no 1Article in journal (Refereed)
    Abstract [en]

    Aims and background: Left ventricular hypertrophy (LVH) is a common finding in hemodialysis patients. The aim of the present study was to investigate if the diameter of the distal radiocephalic fistula could influence left ventricular variables in stable hemodialysis patients. Methods: Nineteen patients were investigated. Measurements of the diameter of the arteriovenous (AV) fistula were performed in 4 different locations. The patients were investigated using M-mode recordings and measurements in the 2D image. Doppler ultrasound was also performed. Transonic measurements were performed after ultrasound investigation. Results: Fistula mean and maximal diameter correlated with left ventricular characteristics. Fistula flow correlated neither with the left ventricular characteristics nor with fistula diameters. Conclusions: The maximal diameter of the distal AV fistula seems to be a sensitive marker of LVH in stable hemodialysis patients.

  • 320. Haglund, Felix
    et al.
    Hallström, Björn M.
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Nilsson, Inga-Lena
    Hoog, Anders
    Juhlin, C. Christofer
    Larsson, Catharina
    Inflammatory infiltrates in parathyroid tumors2017In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 177, no 6, p. 445-453Article in journal (Refereed)
    Abstract [en]

    Context: Inflammatory infiltrates are sometimes present in solid tumors and may be coupled to clinical behavior or etiology. Infectious viruses contribute to tumorigenesis in a significant fraction of human neoplasias. Objective: Characterize inflammatory infiltrates and possible viral transcription in primary hyperparathyroidism. Design: From the period 2007 to 2016, a total of 55 parathyroid tumors (51 adenomas and 4 hyperplasias) with prominent inflammatory infiltrates were identified from more than 2000 parathyroid tumors in the pathology archives, and investigated by immunohistochemistry for CD4, CD8, CD20 and CD45 and scored as +0, +1 or +2. Clinicopathological data were compared to 142 parathyroid adenomas without histological evidence of inflammation. Transcriptome sequencing was performed for 13 parathyroid tumors (four inflammatory, 9 non-inflammatory) to identify potential viral transcripts. Results: Tumors had prominent germinal center-like nodular (+2) lymphocytic infiltrates consisting of T and B lymphocytes (31%) and/or diffuse (+1-2) infiltrates of predominantly CD8+T lymphocytes (84%). In the majority of cases with adjacent normal parathyroid tissue, the normal rim was unaffected by the inflammatory infiltrates (96%). Presence of inflammatory infiltrates was associated with higher levels of serum-PTH (P = 0.007) and oxyphilic differentiation (P = 0.002). Co-existent autoimmune disease was observed in 27% of patients with inflammatory infiltrates, which in turn was associated with oxyphilic differentiation (P = 0.041). Additionally, prescription of anti-inflammatory drugs was associated with lower serum ionized calcium (P = 0.037). Conclusions: No evidence of virus-like sequences in the parathyroid tumors could be found by transcriptome sequencing, suggesting that other factors may contribute to attract the immune system to the parathyroid tumor tissue.

  • 321. Haider, J. M.
    et al.
    Kramer, Elissa L.
    New York University, Department of Radiology.
    Maguire Jr., Gerald Q.
    KTH, School of Information and Communication Technology (ICT), Microelectronics and Information Technology, IMIT.
    Millan, Evelyn
    New York University.
    Noz, Marilyn E.
    New York University, Department of Radiology.
    Orbach, D. B.
    Zeleznik, Michael P.
    Saya Systems Inc., Salt Lake City, UT, USA.
    Problems with two automatic methods for SPECT-SPECT and SPECT-MRI Volume Matching2002In: Medical physics (Lancaster), ISSN 0094-2405, Vol. 29, no 8, p. 1944-Article in journal (Refereed)
  • 322.
    Halvorsen, Kjartan
    et al.
    The Swedish School of Sport and Health Sciences.
    Arndt, Anton
    Karolinska Institute.
    Lundberg, Arne
    Karolinska Institute.
    Estimating the directions of the talar and subtalar axes2007In: Proceedings of the International Society of Biomechanics XXI Congress, 2007Conference paper (Refereed)
  • 323.
    Hambardzumyan, K.
    et al.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Hamsten, C.
    Karolinska Inst, Dept Med, Unit Immunol & Allergy, Stockholm, Sweden..
    Idborg, H.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Lourido, Lucia Maria
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Saevarsdottir, S.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Nilsson, Peter
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    van Vollenhoven, R. F.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.;Amsterdam Rheumatol & Immunol Ctr, Amsterdam, Netherlands..
    Jakobsson, P. -J
    EVALUATION OF SERUM PROTEIN LEVELS AT BASELINE AS PREDICTORS OF RESPONSE TO METHOTREXATE IN PATIENTS WITH EARLY RHEUMATOID ARTHRITIS: RESULTS FROM SWEFOT TRIAL POPULATION2018In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 77, p. 569-570Article in journal (Other academic)
  • 324.
    Hambardzumyan, K.
    et al.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.;Karolinska Univ Hosp Solna, Stockholm, Sweden..
    Hamsten, C.
    Karolinska Univ Hosp Solna, Stockholm, Sweden.;Karolinska Inst, Dept Med, Unit Immunol & Allergy, Stockholm, Sweden..
    Idborg, H.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.;Karolinska Univ Hosp Solna, Stockholm, Sweden..
    Lourido, Lucia
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Saevarsdottir, S.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.;Karolinska Univ Hosp Solna, Stockholm, Sweden..
    Nilsson, Peter
    KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Affinity Proteomics.
    van Vollenhoven, R.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.;Karolinska Univ Hosp Solna, Stockholm, Sweden..
    Jakobsson, P.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden.;Karolinska Univ Hosp Solna, Stockholm, Sweden..
    Evaluation of serum protein levels at baseline as predictors of response to methotrexate in patients with early rheumatoid arthritis: results from the SWEFOT trial population2018In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 47, p. 31-31Article in journal (Other academic)
  • 325.
    Hansson, Sven Ove
    Philosophy and History, KTH, School of Architecture and the Built Environment (ABE), Philosophy and History of Technology, Philosophy.
    The Ethics of Cranial Nerve Implants2020In: Otolaryngologic clinics of North America, ISSN 0030-6665, E-ISSN 1557-8259, Vol. 53, no 1, p. 21-30Article in journal (Refereed)
    Abstract [en]

    This overview of ethical and social issues pertaining to cranial nerve implants covers informed consent; risk-benefit assessments; security against unauthorized reprogramming or privacy intrusion; explantation; psychological side effects; equity and social distribution, cultural effects, for instance, on the deaf subculture; enhancement; and research ethics.

  • 326.
    Harjama, Liisa
    et al.
    Univ Helsinki, ERN Skin, Dept Dermatol & Allergol, Helsinki, Finland..
    Kettunen, Kaisa
    Univ Helsinki, Lab Genet, Helsinki, Finland.;Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki Inst Life Sci HiLIFE, Helsinki, Finland..
    Elomaa, Outi
    Folkhalsan Res Ctr, Helsinki, Finland.;Univ Helsinki, Stem Cells & Metab Res Program, Res Programs Unit, Helsinki, Finland..
    Einarsdottir, Elisabet
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Gene Technology. KTH, Centres, Science for Life Laboratory, SciLifeLab. Folkhalsan Res Ctr, Helsinki, Finland.;Univ Helsinki, Stem Cells & Metab Res Program, Res Programs Unit, Helsinki, Finland.;Karolinska Inst, Dept Biosci & Nutr, Huddinge, Sweden..
    Heikkila, Hannele
    Univ Helsinki, ERN Skin, Dept Dermatol & Allergol, Helsinki, Finland..
    Kivirikko, Sirpa
    Univ Helsinki, Dept Clin Genet, Helsinki, Finland.;Univ Helsinki, Dept Med & Clin Genet, Helsinki, Finland.;Univ Helsinki, Cent Hosp, Helsinki, Finland..
    Lappalainen, Katriina
    Univ Helsinki, ERN Skin, Dept Dermatol & Allergol, Helsinki, Finland..
    Saarela, Janna
    Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki Inst Life Sci HiLIFE, Helsinki, Finland.;Univ Oslo, NCMM, Oslo, Norway..
    Alby, Caroline
    Univ Paris 05, Sorbonne Paris Cite, Dept Genet, Paris, France..
    Ranki, Annamari
    Univ Helsinki, ERN Skin, Dept Dermatol & Allergol, Helsinki, Finland..
    Kere, Juha
    Folkhalsan Res Ctr, Helsinki, Finland.;Univ Helsinki, Stem Cells & Metab Res Program, Res Programs Unit, Helsinki, Finland.;Karolinska Inst, Dept Biosci & Nutr, Huddinge, Sweden..
    Hadj-Rabia, Smail
    Univ Paris, Hop Univ Necker Enfants Malad, Inst Imagine, Dept Dermatol,APHP5,INSERM,U1163, Paris, France.;Univ Paris, Hop Univ Necker Enfants Malad, Reference Ctr Genodermatoses & Rare Skin Dis MAGE, FIMARAD,ERN Skin,Inst Imagine,APHP5,INSERM,U1163, Paris, France..
    Hannula-Jouppi, Katariina
    Univ Helsinki, ERN Skin, Dept Dermatol & Allergol, Helsinki, Finland.;Folkhalsan Res Ctr, Helsinki, Finland.;Univ Helsinki, Stem Cells & Metab Res Program, Res Programs Unit, Helsinki, Finland..
    Phenotypic Variability with SLURP1 Mutations and Diffuse Palmoplantar Keratoderma2020In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 100, no 2, article id adv00060Article in journal (Other academic)
  • 327.
    Hashemi, Nashmil
    et al.
    Danderyd Hosp, Unit Cardiol, Dept Clin Sci, Karolinska Inst, Stockholm, Sweden.;Capio St Gorans Hosp, Dept Clin Physiol, S-11281 Stockholm, Sweden..
    Brodin, Lars-Åke
    KTH, School of Technology and Health (STH), Medical Engineering.
    Hedman, Anders
    Soder Sjukhuset, Sect Cardiol, Dept Clin Sci, Karolinska Inst, Stockholm, Sweden..
    Samad, Bassem A.
    Danderyd Hosp, Unit Cardiol, Dept Clin Sci, Karolinska Inst, Stockholm, Sweden..
    Alam, Mahbubul
    Danderyd Hosp, Unit Cardiol, Dept Clin Sci, Karolinska Inst, Stockholm, Sweden..
    Improved right ventricular index of myocardial performance in the assessment of right ventricular function after coronary artery bypass grafting2018In: Interactive Cardiovascular and Thoracic Surgery, ISSN 1569-9293, E-ISSN 1569-9285, Vol. 26, no 5, p. 798-804Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Decreased right ventricular (RV) longitudinal function following coronary artery bypass grafting (CABG), as assessed by tricuspid annular systolic excursion (TAPSE) and RV peak systolic velocity (RVS') is a known condition. We aimed to explore the feasibility of the right ventricular index of myocardial performance (RIMP) in the assessment of RV function after CABG at rest and during peak dobutamine stress echocardiography (DSE). METHODS: Forty-two patients indicated for CABG were included in this study. Coronary angiography, DSE and exercise bicycle test were performed within 6 weeks before and 3 months after CABG. The RIMP, RVS' and TAPSE at the lateral tricuspid annulus were also assessed. The results were presented as mean +/- standard deviation. RESULTS: The RIMP improved after CABG both at rest (0.45 +/- 0.11 before vs 0.38 +/- 0.08 after CABG, P= 0.013) and during DSE (0.75 +/- 0.23 vs 0.49 +/- 0.14, P < 0.001). TAPSE declined significantly when comparing the values from before CABG to after CABG both at rest (23.9 +/- 4.46 vs 14.6 +/- 3.67, P < 0.001) and during DSE (20.9 +/- 4.16 vs 11.9 +/- 3.60, P < 0.001). RVS' also decreased after CABG both at rest (11.9 +/- 2.40 vs 8.5 +/- 1.93, P < 0.001) and during DSE (15.6 +/- 4.30 vs 10.5 +/- 3.21, P <0.001). On the other hand, exercise capacity improved after CABG compared with baseline (128.4 +/- 40.12 W vs 142.1 +/- 46.73 W, P = 0.014). CONCLUSIONS: RIMP improved after CABG both at rest and during DSE. The reduction in TAPSE and RVS' after CABG indicate reduced regional mechanical RV function along the long axis rather than reduced global RV function.

  • 328.
    Hashemi, Nashmil
    et al.
    Karolinska Inst, Danderyd Univ Hosp, Dept Clin Sci, Unit Cardiol, Stockholm, Sweden.;Capio St Gorans Hosp, Dept Clin Physiol, Stockholm, Sweden..
    Johnson, Jonas
    KTH, School of Technology and Health (STH), Medical Engineering.
    Brodin, Lars-Åke
    KTH, School of Technology and Health (STH), Medical Engineering.
    Gomes-Bernardes, Andrei A.
    Capio St Gorans Hosp, Dept Clin Physiol, Stockholm, Sweden..
    Sartipy, Ulrik
    Karolinska Univ Hosp, Heart & Vasc Theme, Stockholm, Sweden.;Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Svenarud, Peter
    Karolinska Univ Hosp, Heart & Vasc Theme, Stockholm, Sweden.;Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Dalen, Magnus
    Karolinska Univ Hosp, Heart & Vasc Theme, Stockholm, Sweden.;Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden..
    Back, Magnus
    Karolinska Univ Hosp, Dept Cardiol, Stockholm, Sweden..
    Alam, Mahbubul
    Karolinska Inst, Danderyd Univ Hosp, Dept Clin Sci, Unit Cardiol, Stockholm, Sweden..
    Winter, Reidar
    Karolinska Inst, Danderyd Univ Hosp, Dept Clin Sci, Unit Cardiol, Stockholm, Sweden..
    Right ventricular mechanics and contractility after aortic valve replacement surgery: a randomised study comparing minimally invasive versus conventional approach2018In: Open heart, E-ISSN 2053-3624, Vol. 5, no 2, article id UNSP e000842Article in journal (Refereed)
    Abstract [en]

    Objective Minimally invasive aortic valve replacementsurgery (MIAVR) is an alternative surgical technique to conventional aortic valve replacement surgery (AVR) in selected patients. The randomised study Cardiac Function after Minimally Invasive Aortic Valve Implantation (CMILE) showed that right ventricular (RV) longitudinal function was reduced after both MIAVR and AVR, but the reduction was more pronounced following AVR. However, postoperative global RV function was equally impaired in both groups. The purpose of this study was to explore alterations in RV mechanics and contractility following MIAVR as compared with AVR. Methods A predefined post hoc analysis of CMILE consisting of 40 patients with severe aortic valve stenosis who were eligible for isolated surgical aortic valve replacement were randomised to MIAVR or AVR. RV function was assessed by echocardiography prior to surgery and 40 days post-surgery. Results Comparing preoperative to postoperative values, RV longitudinal strain rate was preserved following MIAVR (-1.5 +/- 0.5 vs -1.5 +/- 0.4 1/s, p=0.84) but declined following AVR (-1.7 +/- 0.3 vs -1.4 +/- 0.3 its, p<0.01). RV longitudinal strain reduced following AVR (-27.4 +/- 2.9% vs -18.8%+/- 4.7%, p<0.001) and MIAVR (-26.5 +/- 5.3% vs -20.7%+/- 4.5%, p<0.01). Peak systolic velocity of the lateral tricuspid annulus reduced by 36.6% in the AVR group (9.3 +/- 2.1 vs 5.9 +/- 1.5 cm/s, p<0.01) and 18.8% in the MIAVR group (10.1 +/- 2.9 vs 8.2 +/- 1.4 cm/s, p<0.01) when comparing preoperative values with postoperative values. Conclusions RV contractility was preserved following MIAVR but was deteriorated following AVR. RV longitudinal function reduced substantially following AVR. A decline in RV longitudinal function was also observed following MIAVR, however, to a much lesser extent.

  • 329.
    Hassel, Ivon
    et al.
    Laboratory of Structural Function, Research Institute for Sustainable Humanosphere, Kyoto University.
    Berard, Pierre
    Laboratory of Sustainable Materials, Research Institute for Sustainable Humanosphere, Kyoto University.
    Modén, Carl S.
    KTH, School of Engineering Sciences (SCI), Aeronautical and Vehicle Engineering, Lightweight Structures.
    Berglund, Lars
    KTH, School of Chemical Science and Engineering (CHE), Fibre and Polymer Technology, Biocomposites.
    The single cube apparatus for shear testing: Full-field strain data and finite element analysis of wood in transverse shear2009In: Composites Science And Technology, ISSN 0266-3538, E-ISSN 1879-1050, Vol. 69, no 7-8, p. 877-882Article in journal (Refereed)
    Abstract [en]

    The design and analysis of wood structures require accurate data for shear properties, where transverse shear in particular has been neglected in the past. The single cube apparatus (SCA) was applied to transverse shear of Norway spruce (Picea Abies), due to the importance of this species in wood structures, such as glulam, and also its allegedly low value of GRT . Full-field strain data and FEA were used to analyze the potential of the method. The presence of a large central region of homogeneous and close to pure shear strain was confirmed. The SCA method is therefore a strong candidate for improved shear test procedures in wood and other materials, where porosity (gripping problems), heterogeneity on mm-scale and polar orthotropy (annual ring curvature) may cause particular difficulties. In contrast to many other shear test studies, the accuracy of the present GRT data is supported by documented large and homogeneous specimen stress- and strain-fields in almost pure shear, direct measurements of strain field, and careful stress analysis based on FEA.

  • 330.
    Hatherly, Robert
    et al.
    Department of Nuclear Medicine, Karolinska University Hospital, Stockholm, Sweden .
    Brolin, Fredrik
    Department of Nuclear Medicine, Karolinska University Hospital, Stockholm, Sweden .
    Oldner, Asa
    Department of Nuclear Medicine, Karolinska University Hospital, Stockholm, Sweden .
    Sundin, Anders
    Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden .
    Lundblad, Henrik
    Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden .
    Maguire Jr., Gerald Q.
    KTH, School of Information and Communication Technology (ICT), Communication Systems, CoS, Radio Systems Laboratory (RS Lab).
    Jonsson, Cathrine
    Department of Medical Physics, Karolinska University Hospital, Stockholm, Sweden.
    Jacobsson, Hans
    Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden .
    Noz, Marilyn E.
    New York University, Department of Radiology.
    Technical Requirements for Na18F PET Bone Imaging of Patients Being Treated Using a Taylor Spatial Frame.2014In: Journal of nuclear medicine technology, ISSN 1535-5675Article in journal (Refereed)
    Abstract [en]

    Diagnosis of new bone growth in patients with compound tibia fractures or deformities treated using a Taylor spatial frame is difficult with conventional radiography because the frame obstructs the images and creates artifacts. The use of Na(18)F PET studies may help to eliminate this difficulty.

    METHODS: Patients were positioned on the pallet of a clinical PET/CT scanner and made as comfortable as possible with their legs immobilized. One bed position covering the site of the fracture, including the Taylor spatial frame, was chosen for the study. A topogram was performed, as well as diagnostic and attenuation correction CT. The patients were given 2 MBq of Na(18)F per kilogram of body weight. A 45-min list-mode acquisition was performed starting at the time of injection, followed by a 5-min static acquisition 60 min after injection. The patients were examined 6 wk after the Taylor spatial frame had been applied and again at 3 mo to assess new bone growth.

    RESULTS: A list-mode reconstruction sequence of 1 × 1,800 and 1 × 2,700 s, as well as the 5-min static scan, allowed visualization of regional bone turnover.

    CONCLUSION: With Na(18)F PET/CT, it was possible to confirm regional bone turnover as a means of visualizing bone remodeling without the interference of artifacts from the Taylor spatial frame. Furthermore, dynamic list-mode acquisition allowed different sequences to be performed, enabling, for example, visualization of tracer transport from blood to the fracture site.

  • 331. Hau, Sofie Olsson
    et al.
    Karnevi, Emelie
    Lundgren, Sebastian
    Li, Bo
    Lynch, Seodhna
    Elebro, Jacob
    Heby, Margareta
    Nodin, Bjorn
    Eberhard, Jakob
    Uhlén, Mathias
    KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Moran, Bruce
    Gallagher, William M.
    Jirstrom, Karin
    A translational effort to identify prognostic and predictive biomarkers in pancreatic cancer among RBM3-regulated genes.2018In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 36, no 4Article in journal (Other academic)
  • 332.
    Hauser, Janosch
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Stemme, Göran
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    Roxhed, Niclas
    KTH, School of Electrical Engineering and Computer Science (EECS), Intelligent systems, Micro and Nanosystems.
    A blood hematocrit test strip2019Conference paper (Other academic)
    Abstract [en]

    This paper reports a self-propelled microfluidichematocrit (HCT) test that uses the correlation betweenblood hematocrit and wicking distance of blood in a specialpaper matrix. The enabling feature is a novel blood volumemetering method that allows sampling from the fingertipand reliably generates a highly precise blood volume of47.7 ± 1.9 μl (CV 4%) that is transferred into a porouspaper matrix. A dissolvable valve ensures a relaxed timewindow for blood sampling, making it highly user-friendlyand resilient to overfilling. The presented hematocrit teststrip poses a simple, cheap, equipment-free solution forpatient-centric hematocrit measurements.

  • 333.
    Hauser, Janosch
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Stemme, Göran
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    Roxhed, Niclas
    KTH, School of Electrical Engineering and Computer Science (EECS), Micro and Nanosystems.
    AN AUTONOMOUS BLOOD MICROSAMPLING DEVICE ENABLING METERED LARGE-VOLUME DRIED PLASMA SPOTS (DPS)2018Conference paper (Other academic)
    Abstract [en]

    This work introduces a novel principle for volume metering of passively separated blood plasma, empowered by an air pinch-off structure and the high capillary force of a paper matrix. The presented microfluidic device enables the autonomous generation of large-volume dried plasma spots (DPS) with 16 μl of plasma from 50-100 μl of human whole blood within less than 10 minutes. Providing large-volume DPS increases the confidence level of detecting low concentration analytes and constitutes a step towards using blood microsampling in the everyday blood analysis routine.

  • 334. Havel, M.
    et al.
    Sundberg, Johan
    KTH, School of Computer Science and Communication (CSC), Speech, Music and Hearing, TMH.
    Contribution of paranasal sinuses to the acoustical properties of the nasal tract2013In: Proceedings and Report - 8th International Workshop on Models and Analysis of Vocal Emissions for Biomedical Applications, MAVEBA 2013, Firenze University Press , 2013, p. 47-50Conference paper (Refereed)
    Abstract [en]

    The contribution of the nasal and paranasal cavities to vocal tract resonator properties is unclear. Here we investigate resonance phenomena of paranasal sinuses with and without selective occlusion of the middle meatus, and the sphenoidal as well as the maxillary ostium in a cadaveric situs. Nasal and paranasal cavities of the thiel-embalmed cadaver were excited by sine-tone sweeps from a earphone in the epipharynx. A microphone at the nostrils picked up the response. Different conditions with blocked and unblocked middle meatus and sphenoidal ostium were tested. Additionally, infundibulotomy was performed allowing direct access to and selective occlusion of the maxillary ostium. Response curves showed high reproducibility. A marked dip was observed after removing single sided occlusion of the middle meatus and the sphenoidal ostium. A marked low frequency dip was also detected after removal of occlusion of maxillary ostium following infundibulotomy. Reproducible frequency responses of nasal tract can be derived from cadaver measurements. Marked acoustic effects of the maxillary sinus appeared only after direct exposure of the maxillary ostium following infundibulotomy.

  • 335. Havel, Miriam
    et al.
    Becker, Sven
    Schuster, Maria
    Johnson, Thorsten
    Maier, Andreas
    Sundberg, Johan
    KTH, School of Computer Science and Communication (CSC), Speech, Music and Hearing, TMH.
    Effects of functional endoscopic sinus surgery on the acoustics of the sinonasal tract2017In: Rhinology, ISSN 0300-0729, E-ISSN 1996-8604, Vol. 55, no 1, p. 81-89Article in journal (Refereed)
    Abstract [en]

    Background: Nasal and paranasal cavities are supposed to contribute substantially to the vocal tract resonator properties. However, their acoustical effects as well as the effects of sinus surgery on the voice remain unclear. In this work we investigate resonance phenomena of paranasal sinuses prior to and after various rhinosurgical procedures in cadaveric human sinonasal tracts and corresponding 3D casts. Methodology: Nasal and paranasal cavities of formalin-preserved cadavers and corresponding 3D replicas were excited by sine tone sweeps from an earphone placed in the epipharynx.The response was picked up by a microphone at the nostrils. Different FESS procedures were performed and the acoustical responses following excitation were recorded.The measured acoustical changes in the obtained transfer functions were then evaluated. Results: Marked low frequency dips were detected in the transfer functions when sinus cavities were included in the nasal resonator system. These dips showed a significant correlation with sinus volumes. Following FESS procedures they moved upwards in frequency depending on the extent of the surgical intervention. Conclusions: The transfer functions obtained in cadaveric situs and 3D replicas showed dips at the resonance frequencies of the paranasal cavities. Marked acoustic effects in terms of increase in dip frequency following FESS procedures were reproducibly documented.

  • 336. Havel, Miriam
    et al.
    Ertl, Lena
    Bauer, Daniel
    Schuster, Maria
    Stelter, Klaus
    Sundberg, Johan
    KTH, School of Computer Science and Communication (CSC), Speech, Music and Hearing, TMH, Speech Communication and Technology.
    Resonator properties of paranasal sinuses: preliminary results of an anatomical study2014In: Rhinology, ISSN 0300-0729, E-ISSN 1996-8604, Vol. 52, no 2, p. 178-182Article in journal (Refereed)
    Abstract [en]

    Background: The contribution of the nasal and paranasal cavities to vocal tract resonator properties is unclear as are voice effects of sinus surgery. Here we investigate resonance phenomena of paranasal sinuses with and without selective occlusion of the middle meatus and maxillary ostium in a cadaver. Methodology: Nasal and paranasal cavities of a Thiel-embalmed cadaver were excited by sine-tone sweeps from an earphone in the epipharynx.The response was picked up by a microphone at the nostrils. Different conditions with blocked and unblocked middle meatus were tested. Additionally, infundibulotomy was performed allowing direct access to and selective occlusion of the maxillary ostium. Results: Responses showed high reproducibility. Minor effects appeared after removal of meatal occlusion. A marked low frequency dip was detected after removal of occlusion of maxillary ostium following infundibulotomy. Conclusion: Reproducible frequency responses of nasal tract can be derived from cadaver measurements. Marked acoustic effects of the maxillary sinus appeared only after direct exposure of the maxillary ostium following infundibulotomy.

  • 337. Havel, Miriam
    et al.
    Kornes, Tanja
    Weitzberg, Eddie
    Lundberg, Jon O.
    Sundberg, Johan
    KTH, School of Computer Science and Communication (CSC), Speech, Music and Hearing, TMH. University College of Music Education, Sweden.
    Eliminating paranasal sinus resonance and its effects on acoustic properties of the nasal tract2016In: Logopedics, Phoniatrics, Vocology, ISSN 1401-5439, E-ISSN 1651-2022, Vol. 41, no 1, p. 33-40Article in journal (Refereed)
    Abstract [en]

    The significance of nasal resonance and anti-resonance to voice production is a classical issue in vocal pedagogy and voice research. The complex structure of the nasal tract produces a complex frequency response. This complexity must be heavily influenced by the morphology of the paranasal cavities, but their contributions are far from being entirely understood. Detailed analyses of these cavities are difficult because of their limited accessibility. Here we test different methods aiming at documenting the acoustical properties of the paranasal tract. The first set of experiments was performed under in vivo conditions, where the middle meatus was occluded by means of targeted application of a maltodextrin mass under endoscopic control. The efficiency of this occlusion method was verified by measuring the nasal nitric oxide (NO) output during humming. In another experiment the frequency responses to sine sweep excitation of an epoxy mould of a nasal cavity were measured, with and without elimination of paranasal sinuses. The third experiment was conducted in a cadaveric situs, with and without maltodextrin occlusion of the middle meatus and the sphenoidal ostia. The results show that some nasal tract resonances were unaffected by the manipulation of the paranasal cavities. Providing access to a maxillary sinus resulted in marked dips in the response curve while access to the sphenoidal ostium caused only minor effects.

  • 338.
    Haylock, A.
    et al.
    Uppsala Univ, Dept Immunol Genet & Pathol, Dept Surg Sci, Uppsala, Sweden..
    Nilvebrant, Johan
    KTH, School of Biotechnology (BIO), Protein Technology.
    Mortensen, A. C.
    Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden..
    Velikyan, I.
    Uppsala Univ, Dept Med Chem, Uppsala, Sweden..
    Falk, R.
    Karolinska Inst, Dept Neurosci, Stockholm, Sweden..
    Nestor, M.
    Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden..
    Generation and evaluation of single chain fragments for molecular imaging of CD44v6-expressing cancers2017In: European Journal of Nuclear Medicine and Molecular Imaging, ISSN 1619-7070, E-ISSN 1619-7089, Vol. 44, p. S553-S554Article in journal (Other academic)
  • 339. Haylock, Anna-Karin
    et al.
    Nilvebrant, Johan
    KTH, School of Biotechnology (BIO), Protein Technology.
    Mortensen, Anja
    Velikyan, Irina
    Nestor, Marika
    Falk, Ronny
    Generation and evaluation of antibody agents for molecular imaging of CD44v6-expressing cancers2017In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 8, no 39, p. 65152-65170Article in journal (Refereed)
    Abstract [en]

    Aim: The aim of this study was to generate and characterize scFv antibodies directed to human CD44v6, as well as to radiolabel and evaluate top candidates in vitro and in vivo for their potential use in CD44v6-targeted molecular imaging in cancer patients. Materials and methods: Phage display selections were used to isolate CD44v6-specific scFvs. A chain shuffling strategy was employed for affinity maturation based on a set of CD44v6-specific first-generation clones. Two second-generation scFv clones were then chosen for labeling with 111In or 125I and assessed for CD44v6-specific binding on cultured tumor cells. In vivo uptake and distribution was evaluated in tumor-bearing mice using a dual tumor model. Finally, a proof-of-concept small animal PET-CT study was performed on one of the candidates labeled with 124I. Results: Two affinity-matured clones, CD44v6-scFv-A11 and CD44v6-scFv-H12, displayed promising binding kinetics. Seven out of eight radiolabeled conjugates demonstrated CD44v6-specific binding. In vivo studies on selected candidates demonstrated very advantageous tumor-to-organ ratios, in particular for iodinated conjugates, where 125I-labeled scFvs exhibited favorable kinetics and tumor-to-blood ratios above five already at 24 hours p. i.. The small animal PET-CT study using 124I-labeled CD44v6-scFv-H12 was in line with the biodistribution data, clearly visualizing the high CD44v6-expressing tumor. Conclusion: The single chain fragments, CD44v6-scFv-A11 and CD44v6-scFv-H12 specifically bind to CD44v6, and the radiolabeled counterparts provide high tumor-to-blood ratios and fast clearance from organs and blood. We conclude that radioiodinated CD44v6-scFv-A11 and CD44v6-scFv-H12 possess features highly suitable for stringent molecular imaging.

  • 340. He, Qinggang
    et al.
    Wang, Ying
    KTH, School of Biotechnology (BIO), Theoretical Chemistry and Biology.
    Alfeazi, Ines
    Sadeghi, Saman
    Electrochemical nucleophilic synthesis of di-tert-butyl-(4-[F-18]fluoro-1,2-phenylene)-dicarbonate2014In: Applied Radiation and Isotopes, ISSN 0969-8043, E-ISSN 1872-9800, Vol. 92, p. 52-57Article in journal (Refereed)
    Abstract [en]

    An electrochemical method with the ability to conduct F-18-fluorination of aromatic molecules through direct nucleophilic fluorination of cationic intermediates is presented in this paper. The reaction was performed on a remote-controlled automatic platform. Nucleophilic electrochemical fluorination of tert-butyloxycarbonyl (Boc) protected catechol, an intermediate model molecule for the positron emission tomography (PET) probe (3,4-dihydroxy-6-[F-18]fluoro-L-phenylalanine), was performed. Fluorination was achieved under potentiostatic anodic oxidation in acetonitrile containing Et3N center dot 3HF and other supporting electrolytes. Radiofluorination efficiency was influenced by a number of variables, including the concentration of the precursor, concentration of Et3N center dot 3HF, type of supporting electrolyte, temperature and time, as well as applied potentials. Radiofluorination efficiency of 10.4 +/- 0.6% (n=4) and specific activity of up to 43 GBq/mmol was obtained after 1 h electrolysis of 0.1 M of 4-tert-butyl-diboc-catechol in the acetonitrile solution of Et3N center dot 3HF (0.033 M) and NBu4PF6 (0.05 M). Density functional theory (DFT) was employed to explain the tert-butyl functional group facilitation of electrochemical oxidation and subsequent fluorination.

  • 341. He, Zehui
    et al.
    Lo Martire, Riccardo
    KTH, School of Engineering Sciences (SCI), Aeronautical and Vehicle Engineering. Guangzhou University of Chinese Medicine Second Affiliated Hospital, China.
    Lu, Chuanjian
    Liu, Hongxia
    Ma, Lin
    Huang, Ying
    Li, Yongmei
    Sun, Liyun
    Bai, Yanping
    Liu, Wali
    Zha, Xushan
    Rasch Analysis of the Dermatology Life Quality Index Reveals Limited Application to Chinese Patients with Skin Disease2018In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 98, no 1, p. 59-64Article in journal (Refereed)
    Abstract [en]

    The objective of this study was to examine the psychometric properties of the Chinese version of the Dermatology Life Quality Index (DLQI) and to assess the invariance of its items with respect to several patient parameters via Rasch analysis. Data were aggregated from 9,845 patients with various skin diseases across 9 hospitals in different regions of China. The response structure, local independence, and reliability of the DLQI scale were analysed in a partial credit model, and differential item functioning (DIF) across region, disease, sex, and age were assessed with a Mantel-Haenszel procedure. Although acceptable scale reliability (Person Separation Index=2.3) was obtained, several problems were revealed, including disordered response thresholds, misfitting items, DIF by geographical region and disease, and mis-targeting patients with mild impairment regarding health-related quality of life (HRQL). In conclusion, the DLQI provides inadequate information on patients' impairments in HRQL, and the application of the DLQI in Chinese patients with skin disease is limited.

  • 342.
    Hedberg, Yolanda S.
    et al.
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Surface and Corrosion Science. Karolinska Institutet, Sweden.
    Liden, Carola
    Lindberg, Magnus
    Chromium Dermatitis in a Metal Worker Due to Leather Gloves and Alkaline Coolant2016In: Acta Dermato-Venereologica, ISSN 0001-5555, E-ISSN 1651-2057, Vol. 96, no 1, p. 104-105Article in journal (Refereed)
  • 343.
    Hedberg, Yolanda S.
    et al.
    KTH, School of Chemical Science and Engineering (CHE), Chemistry. Karolinska Institutet, Sweden .
    Liden, Carola
    Wallinder, Inger Odnevall
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Surface and Corrosion Science.
    Chromium released from leather - I: exposure conditions that govern the release of chromium(III) and chromium(VI)2015In: Contact Dermatitis, ISSN 0105-1873, E-ISSN 1600-0536, Vol. 72, no 4, p. 206-215Article in journal (Refereed)
    Abstract [en]

    Background. Approximately 1-3% of the adult population in Europe is allergic to chromium (Cr). Anew restriction in REACH(Registration, Evaluation, Authorization and Restriction of Chemicals) based on the ISO 17075 standard has recently been adopted in the EU to limit Cr(VI) in consumer and occupational leather products. Objectives. The aim of this study was to critically assess key experimental parameters in this standard on the release of Cr(III) and Cr(VI) and their relevance for skin exposure. Material and methods. Four differently tanned, unfinished, leather samples were systematically investigated for their release of Cr(III) and Cr(VI) in relation to surface area, key exposure parameters, temperature, ultraviolet irradiation, and time. Results. Although the total release of Cr was largely unaffected by all investigated parameters, except exposure duration and temperature, the Cr oxidation state was highly dynamic, with reduced amounts of released Cr(VI) with time, owing to the simultaneous release of reducing agents from the leather. Significantly more Cr(III) than Cr(VI) was released from the Cr-tanned leather for all conditions tested, and it continued to be released in artificial sweat up to at least 1 week of exposure. Conclusions. Several parameters were identified that influenced the outcome of the ISO 17075 test.

  • 344.
    Hedberg, Yolanda S.
    et al.
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Surface and Corrosion Science.
    Qian, Bin
    Shen, Zhijian
    Virtanen, Sannakaisa
    Odnevall Wallinder, Inger
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Surface and Corrosion Science.
    In vitro biocompatibility of CoCrMo dental alloys fabricated by selective laser melting2014In: Dental Materials, ISSN 0109-5641, E-ISSN 1879-0097, Vol. 30, no 5, p. 525-534Article in journal (Refereed)
    Abstract [en]

    Objective. Selective laser melting (SLM) is increasingly used for the fabrication of customized dental components made of metal alloys such as CoCrMo. The main aim of the present study is to elucidate the influence of the non-equilibrium microstructure obtained by SLM on corrosion susceptibility and extent of metal release (measure of biocompatibility). Methods. A multi-analytical approach has been employed by combining microscopic and bulk compositional tools with electrochemical techniques and chemical analyses of metals in biologically relevant fluids for three differently SLM fabricated CoCrMo alloys and one cast CoCrMo alloy used for comparison. Results. Rapid cooling and strong temperature gradients during laser melting resulted in the formation of a fine cellular structure with cell boundaries enriched in Mo (Co depleted), and suppression of carbide precipitation and formation of a martensitic epsilon (hcp) phase at the surface. These features were shown to decrease the corrosion and metal release susceptibility of the SLM alloys compared with the cast alloy. Unique textures formed in the pattern of the melting pools of the three different laser melted CoCrMo alloys predominantly explain observed small, though significant, differences. The susceptibility for corrosion and metal release increased with an increased number (area) of laser melt pool boundaries. Significance. This study shows that integrative and interdisciplinary studies of microstructural characteristics, corrosion, and metal release are essential to assess and consider during the design and fabrication of CoCrMo dental components of optimal biocompatibility. The reason is that the extent of metal release from CoCrMo is dependent on fabrication procedures.

  • 345.
    Hedberg, Yolanda
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemistry, Surface and Corrosion Science.
    Uter, Wolfgang
    Univ Erlangen Nurnberg, Dept Med Informat Biometry & Epidemiol, Erlangen, Germany..
    Banerjee, Piu
    Guys Hosp, St Johns Inst Dermatol, London, England.;Lewisham & Greenwich NHS Trust, London, England..
    Lind, Marie-Louise
    Stockholm Cty Council, Ctr Occupat & Environm Med, Stockholm, Sweden..
    Steengaard, Sanne Skovvang
    Univ Hosp Herlev Gentofte, Natl Allergy Res Ctr, Hellerup, Denmark..
    Teo, Ying
    Guys Hosp, St Johns Inst Dermatol, London, England..
    Liden, Carola
    Karolinska Inst, Inst Environm Med, Box 210, SE-17177 Stockholm, Sweden..
    Non-oxidative hair dye products on the European market: What do they contain?2018In: Contact Dermatitis, ISSN 0105-1873, E-ISSN 1600-0536, Vol. 79, no 5, p. 281-287Article in journal (Refereed)
    Abstract [en]

    Background: Hair dyeing is very common and may cause allergic contact dermatitis. Oxidative (often termed permanent or semi-permanent) hair dye products have constituted the focus of market surveys and toxicological risk assessments, while non-oxidative (semi-permanent, temporary or direct) products have not been assessed. Objectives: To identify the hair dye substances presently used in non-oxidative hair dye products in Europe. Methods: Ingredient label data on eligible products in 5 European countries were collected, and 289 different non-oxidative hair dye products were included in this study. Results: Up to 9 hair dye substances were present in each product. Sixty-eight individual hair dye substances were identified on the 289 product labels, and their occurrence ranged from 0.3% to 34%. There were differences concerning substances used and their number per product between products of different consistency and colour. Conclusions: The hair dye substances in non-oxidative hair dye products are different from those in oxidative hair dye products, and are currently not covered by patch test series. The toxicological and skin-sensitizing profile of the substances in non-oxidative hair dye products, as well as their concentrations, should be further investigated.

  • 346.
    Hedberg, Yolanda
    et al.
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemistry, Surface and Corrosion Science. KTH Royal Inst Technol, Sch Engn Sci Chem Biotechnol & Hlth, Div Surface & Corros Sci, Dept Chem, SE-10044 Stockholm, Sweden..
    Wei, Zheng
    KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Chemistry, Surface and Corrosion Science.
    Matura, Mihaly
    Stockholm Cty Council, Unit Occupat & Environm Dermatol, Ctr Occupat & Environm Med, Stockholm, Sweden.;Skaraborgs Hosp Skovde, Unit Dermatol, Skovde, Sweden..
    High release of hexavalent chromium into artificial sweat in a case of leather shoe-induced contact dermatitis2020In: Contact Dermatitis, ISSN 0105-1873, E-ISSN 1600-0536, Vol. 82, no 3, p. 179-+Article in journal (Other academic)
  • 347. Hedner, Charlotta
    et al.
    Gaber, Alexander
    Korkocic, Dejan
    Nodin, Bjorn
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Kuteeva, Eugenia
    Johannesson, Henrik
    Jirstrom, Karin
    Eberhard, Jakob
    SATB1 is an independent prognostic factor in radically resected upper gastrointestinal tract adenocarcinoma2014In: Virchows Archiv, ISSN 0945-6317, E-ISSN 1432-2307, Vol. 465, no 6, p. 649-659Article in journal (Refereed)
    Abstract [en]

    Gastric cancer is the second most common cause of cancer-related death worldwide, and the incidence of esophageal adenocarcinoma is rising. While some progress has been made in treatment strategies, overall survival remains very poor for patients with adenocarcinoma in the upper gastrointestinal tract. Special AT-rich sequence binding protein 1 (SATB1) is a global genome organizer that has been demonstrated to promote aggressive tumor behavior in several different types of cancer, including gastric cancer. The prognostic value of SATB1 expression in esophageal cancer has, however, not yet been described. In this study, expression of SATB1 was examined by immunohistochemistry on tissue microarrays prepared from tissue samples from 175 patients with adenocarcinoma of the esophagus, cardia, or stomach and containing normal tissue, intestinal metaplasia, primary tumors, and metastases. A well-validated antibody was used. We found SATB1 to be an independent prognostic factor in patients with a radically resected tumor, correlating with shorter overall survival as well as with shorter recurrence-free survival. SATB1 expression was also found to be significantly lower in primary tumors associated with intestinal metaplasia than those without intestinal metaplasia. This observation is of potential biological interest as it has been proposed that intestinal metaplasia-associated tumors constitute a less aggressive phenotype.

  • 348. Heinonen, Sini
    et al.
    Muniandy, Maheswary
    Buzkova, Jana
    Mardinoglu, Adil
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab. Chalmers University of Technology, Sweden.
    Rodriguez, Amaia
    Fruhbeck, Gema
    Hakkarainen, Antti
    Lundbom, Jesper
    Lundbom, Nina
    Kaprio, Jaakko
    Rissanen, Aila
    Pietilainen, Kirsi H.
    Mitochondria-related transcriptional signature is downregulated in adipocytes in obesity: a study of young healthy MZ twins2017In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 60, no 1, p. 169-181Article in journal (Refereed)
    Abstract [en]

    Low mitochondrial activity in adipose tissue is suggested to be an underlying factor in obesity and its metabolic complications. We aimed to find out whether mitochondrial measures are downregulated in obesity also in isolated adipocytes. We studied young adult monozygotic (MZ) twin pairs discordant (n = 14, intrapair difference Delta BMI ae<yen> 3 kg/m(2)) and concordant (n = 5, Delta BMI < 3 kg/m(2)) for BMI, identified from ten birth cohorts of 22- to 36-year-old Finnish twins. Abdominal body fat distribution (MRI), liver fat content (magnetic resonance spectroscopy), insulin sensitivity (OGTT), high-sensitivity C-reactive protein, serum lipids and adipokines were measured. Subcutaneous abdominal adipose tissue biopsies were obtained to analyse the transcriptomics patterns of the isolated adipocytes as well as of the whole adipose tissue. Mitochondrial DNA transcript levels in adipocytes were measured by quantitative real-time PCR. Western blots of oxidative phosphorylation (OXPHOS) protein levels in adipocytes were performed in obese and lean unrelated individuals. The heavier (BMI 29.9 +/- 1.0 kg/m(2)) co-twins of the discordant twin pairs had more subcutaneous, intra-abdominal and liver fat and were more insulin resistant (p < 0.01 for all measures) than the lighter (24.1 +/- 0.9 kg/m(2)) co-twins. Altogether, 2538 genes in adipocytes and 2135 in adipose tissue were significantly differentially expressed (nominal p < 0.05) between the co-twins. Pathway analysis of these transcripts in both isolated adipocytes and adipose tissue revealed that the heavier co-twins displayed reduced expression of genes relating to mitochondrial pathways, a result that was replicated when analysing the pathways behind the most consistently downregulated genes in the heavier co-twins (in at least 12 out of 14 pairs). Consistently upregulated genes in adipocytes were related to inflammation. We confirmed that mitochondrial DNA transcript levels (12S RNA, 16S RNA, COX1, ND5, CYTB), expression of mitochondrial ribosomal protein transcripts and a major mitochondrial regulator PGC-1 alpha (also known as PPARGC1A) were reduced in the heavier co-twins' adipocytes (p < 0.05). OXPHOS protein levels of complexes I and III in adipocytes were lower in obese than in lean individuals. Subcutaneous abdominal adipocytes in obesity show global expressional downregulation of oxidative pathways, mitochondrial transcripts and OXPHOS protein levels and upregulation of inflammatory pathways. The datasets analysed and generated during the current study are available in the figshare repository.

  • 349. Herbst, Christian
    et al.
    Ternström, Sten
    KTH, School of Computer Science and Communication (CSC), Speech, Music and Hearing, TMH, Music Acoustics.
    A comparison of different methods to measure the EGG contact quotient2006In: Logopedics, Phoniatrics, Vocology, ISSN 1401-5439, E-ISSN 1651-2022, Vol. 31, no 3, p. 126-138Article in journal (Refereed)
    Abstract [en]

    The results from six published electroglottographic (EGG-based) methods for calculating the EGG contact quotient (CQEGG) were compared to closed quotients derived from simultaneous videokymographic imaging (CQKYM). Two trained male singers phonated in falsetto and in chest register, with two degrees of adduction in both registers. The maximum difference between methods in the CQEGG was 0.3 (out of 1.0). The CQEGG was generally lower than the CQKYM. Within subjects, the CQEGG co-varied with the CQkym, but with changing offsets depending on method. The CQEGG cannot be calculated for falsetto phonation with little adduction, since there is no complete glottal closure. Basic criterion-level methods with thresholds of 0.2 or 0.25 gave the best match to the CQKYM data. The results suggest that contacting and de-contacting in the EGG might not refer to the same physical events as do the beginning and cessation of airflow.

  • 350.
    Herling, L.
    et al.
    Karolinska Inst, Dept Clin Sci Intervent & Technol CLINTEC, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Obstet & Gynecol, Ctr Fetal Med, Stockholm, Sweden..
    Johnson, Jonas
    KTH, School of Technology and Health (STH), Medical Engineering. Karolinska Univ Hosp, Dept Obstet & Gynecol, Ctr Fetal Med, Stockholm, Sweden.
    Ferm-Widlund, K.
    Karolinska Univ Hosp, Dept Obstet & Gynecol, Ctr Fetal Med, Stockholm, Sweden..
    Bergholm, Fredrik
    KTH, School of Technology and Health (STH), Medical Engineering.
    Lindgren, P.
    Karolinska Univ Hosp, Dept Obstet & Gynecol, Ctr Fetal Med, Stockholm, Sweden..
    Sonesson, S. -E
    Acharya, G.
    Karolinska Inst, Dept Clin Sci Intervent & Technol CLINTEC, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Obstet & Gynecol, Ctr Fetal Med, Stockholm, Sweden.;UiT Arctic Univ Norway, Dept Clin Med, Womens Hlth & Perinatol Res Grp, Tromso, Norway..
    Westgren, M.
    Karolinska Inst, Dept Clin Sci Intervent & Technol CLINTEC, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Obstet & Gynecol, Ctr Fetal Med, Stockholm, Sweden..
    Automated analysis of fetal cardiac function using color tissue Doppler imaging2018In: Ultrasound in Obstetrics and Gynecology, ISSN 0960-7692, E-ISSN 1469-0705, Vol. 52, no 5, p. 599-608Article in journal (Refereed)
    Abstract [en]

    Objective To evaluate the feasibility of automated analysis of fetal myocardial velocity recordings obtained by color tissue Doppler imaging (cTDI). Methods This was a prospective cross-sectional observational study of 107 singleton pregnancies >= 41 weeks of gestation. Myocardial velocity recordings were obtained by cTDI in a long-axis four-chamber view of the fetal heart. Regions of interest were placed in the septum and the right (RV) and left (LV) ventricular walls at the level of the atrioventricular plane. Peak myocardial velocities and mechanical cardiac time intervals were measured both manually and by an automated algorithm and agreement between the two methods was evaluated. Results In total, 321 myocardial velocity traces were analyzed using each method. It was possible to analyze all velocity traces obtained from the LV, RV and septal walls with the automated algorithm, and myocardial velocities and cardiac mechanical time intervals could be measured in 96% of all traces. The same results were obtained when the algorithm was run repeatedly. The myocardial velocities measured using the automated method correlated significantly with those measured manually. The agreement between methods was not consistent and some cTDI parameters had considerable bias and poor precision. Conclusions Automated analysis of myocardial velocity recordings obtained by cTDI was feasible, suggesting that this technique could simplify and facilitate the use of cTDI in the evaluation of fetal cardiac function, both in research and in clinical practice.

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