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Browall, S., Backhaus, E., Naucler, P., Galanis, I., Sjöström, K., Karlsson, D., . . . Henriques-Normark, B. (2014). Clinical manifestations of invasive pneumococcal disease by vaccine and non-vaccine types. European Respiratory Journal, 44(6), 1646-1657
Open this publication in new window or tab >>Clinical manifestations of invasive pneumococcal disease by vaccine and non-vaccine types
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2014 (English)In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 44, no 6, p. 1646-1657Article in journal (Refereed) Published
Place, publisher, year, edition, pages
European Respiratory Society, 2014
National Category
Infectious Medicine
Research subject
Natural sciences; Infection Biology
Identifiers
urn:nbn:se:his:diva-10438 (URN)10.1183/09031936.00080814 (DOI)000347267500027 ()25323223 (PubMedID)2-s2.0-84916220535 (Scopus ID)
Available from: 2014-12-17 Created: 2014-12-17 Last updated: 2018-11-15Bibliographically approved
Handlin, L., Nilsson, A., Ejdebäck, M., Hydbring-Sandberg, E. & Uvnäs-Moberg, K. (2012). Associations between the Psychological Characteristics of the Human-Dog Relationship and Oxytocin and Cortisol Levels. Anthrozoos, 25(2), 215-228
Open this publication in new window or tab >>Associations between the Psychological Characteristics of the Human-Dog Relationship and Oxytocin and Cortisol Levels
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2012 (English)In: Anthrozoos, ISSN 0892-7936, E-ISSN 1753-0377, Vol. 25, no 2, p. 215-228Article in journal (Refereed) Published
Abstract [en]

The aim of the present study was to explore possible correlations between dog owners' relationships with their dogs, as measured with the Monash Dog Owner Relationship Scale (MDORS), and oxytocin and cortisol levels in both the owners and their dogs. Ten female owners of male Labrador Retrievers completed the MDORS. The scores obtained from the single items, subscales, and total score of the MDORS were calculated. Ten blood samples were collected from each dog owner and her dog during a 60-minute interaction. Blood samples were analyzed for oxytocin and cortisol by Enzyme Immuno Assay (EIA) and mean values of oxytocin and cortisol were calculated in both owners and dogs. The MDORS scores obtained were correlated with basal and mean oxytocin and cortisol levels. The correlation analysis revealed some relationships between the scores of items in the MDORS that reflect the character of the dog-owner-relationship and the owners' hormone levels. For example, higher oxytocin levels in the owners were associated with greater frequency in kissing their dogs (rs = 0.864, p = 0.001). Lower cortisol levels in the owners were associated with their perception that it will be more traumatic when their dog dies (rs = -0.730, p = 0.025). The correlation analysis also revealed some relationships between the scores of items in the MDORS and the dogs' hormone levels. For example, greater frequency in owners kissing their dogs was associated with higher oxytocin levels in the dogs (rs = 0.753, p = 0.029). Six items in the subscale Perceived Costs, as well as the subscale itself, correlated significantly with the dogs' oxytocin levels (rs = 0.820, p = 0.007), that is, the lower the perceived cost, the higher the dogs' oxytocin levels. In addition, significant correlations between the oxytocin levels of the owners and the dogs were demonstrated. Possible mechanisms behind these correlations are discussed. In conclusion, the scores of some items and the subscales of the MDORS correlated with oxytocin, and to a lesser extent cortisol, levels in both the owners and dogs.

Place, publisher, year, edition, pages
Berg Publishers, 2012
Keywords
cortisol, dog, dog owner, MDORS, oxytocin
National Category
Natural Sciences
Research subject
Natural sciences
Identifiers
urn:nbn:se:his:diva-5929 (URN)10.2752/175303712X13316289505468 (DOI)000304287700007 ()2-s2.0-84859540616 (Scopus ID)
Available from: 2012-06-05 Created: 2012-06-05 Last updated: 2017-12-07Bibliographically approved
Handlin, L., Hydbring-Sandberg, E., Nilsson, A., Ejdebäck, M., Jansson, A. & Uvnäs-Moberg, K. (2011). Short-Term Interaction between Dogs and Their Owners: Effects on Oxytocin, Cortisol, Insulin and Heart Rate-An Exploratory Study. Anthrozoos, 24(3), 301-315
Open this publication in new window or tab >>Short-Term Interaction between Dogs and Their Owners: Effects on Oxytocin, Cortisol, Insulin and Heart Rate-An Exploratory Study
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2011 (English)In: Anthrozoos, ISSN 0892-7936, E-ISSN 1753-0377, Vol. 24, no 3, p. 301-315Article in journal (Refereed) Published
Abstract [en]

The aim of this exploratory study was to determine heart rate and the levels of oxytocin, cortisol, and insulin in dogs and their owners in response to a short-term interaction. In addition, the dogs' behavior was studied. The owners' responses were compared with those obtained from a control group. Ten female volunteers and their own male Labrador dogs participated in an experiment during which the owner stroked, petted, and talked with her dog during the first 3 minutes. Blood samples were collected from both dog and owner before (0) and at 1, 3, 5, 15, 30, and 60 minutes after the start of the interaction. Blood samples were analyzed by EIA. Heart rate was monitored telemetrically. The data were analyzed using linear mixed models and paired t-tests. The dogs' oxytocin levels were significantly increased 3 minutes after the start of the interaction (p = 0.027). Cortisol levels were significantly increased after 15 and 30 minutes (p = 0.004 and p = 0.022, respectively), and heart rate was significantly decreased after 55 minutes (p = 0.008). The dogs displayed normal behaviors during the experiment. The owners' oxylocin levels peaked between 1 and 5 minutes after interaction (p = 0.026). No such effect was seen in the controls. Cortisol levels displayed a significant decrease at 15 or 30 minutes in both owners and controls, and insulin levels did so at 60 minutes (p = 0.030, p = 0.002 and p = 0.002, p < 0.0001, respectively). Heart rate decreased significantly in the owners at 55 and 60 minutes (p = 0.0008) but not in the controls. In conclusion, short-term sensory interaction between dogs and their owners influences hormonal levels and heart rate. However, further studies need to be performed in order to better understand the effects of interaction between dogs and their owners.

Place, publisher, year, edition, pages
Berg Publishers, 2011
Keywords
cortisol, heart rate, human dog interaction, insulin, oxytocin
National Category
Natural Sciences
Research subject
Natural sciences
Identifiers
urn:nbn:se:his:diva-5520 (URN)10.2752/175303711X13045914865385 (DOI)000295154400006 ()2-s2.0-79960721263 (Scopus ID)
Available from: 2012-03-22 Created: 2012-03-01 Last updated: 2017-12-07Bibliographically approved
Verma, D., Eriksson, P., Sahdo, B., Persson, A., Ejdebäck, M., Särndahl, E. & Söderkvist, P. (2010). Two Adult Siblings with Atypical Cryopyrin Associated Periodic Syndrome (CAPS) due to a Novel M299V Mutation in the NLRP3 Gene.. Arthritis and Rheumatism, 62(7), 2138-2143
Open this publication in new window or tab >>Two Adult Siblings with Atypical Cryopyrin Associated Periodic Syndrome (CAPS) due to a Novel M299V Mutation in the NLRP3 Gene.
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2010 (English)In: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 62, no 7, p. 2138-2143Article in journal (Refereed) Published
Abstract [en]

Objective: The NALP3 inflammasome is a multiprotein complex that triggers caspase 1–mediated interleukin-1β (IL-1β) release. Mutations in the gene encoding NALP3 (NLRP3) underlie the cryopyrin-associated periodic syndrome (CAPS). The aim of this study was to report a novel NLRP3 mutation in 2 siblings of Swedish descent in whom symptoms first presented in adulthood.

Methods: Mutation analysis of NLRP3 was performed on DNA from patients with CAPS and 100 control subjects. For assessment of caspase 1 and IL-1β, blood was collected from patients and age- and sex-matched healthy control subjects. Genetic constructs containing mutant or wild-type NLRP3 were transduced into THP-1 cells, followed by assessment of IL-1β levels in cell supernatant.

Results: Both siblings carried a novel M299V mutation in NLRP3, which was not present in the control population. The samples obtained from the patients displayed increased caspase 1 activity and elevated IL-1β levels at basal conditions as compared with healthy control subjects. THP-1 cells expressing mutated M299V revealed almost 10-fold higher IL-1β production compared with the wild-type construct.

Conclusion: M299V is an activating mutation in NLRP3 resulting in elevated spontaneous caspase 1 activity and IL-1β levels. The classic CAPS phenotype was lacking in these adult siblings. Whereas one sibling displayed a milder phenotype that has so far responded satisfactorily to oral nonsteroidal antiinflammatory drugs in combination with low-dose corticosteroids, the inflammatory symptoms in the sibling with the more severe case responded well to IL-1β blockade. Understanding the pathogenic mechanism underlying such disorders can be helpful for the physician. Our study reinforces the importance of genetic testing and laboratory investigations in combination with careful phenotypic evaluation for the diagnosis of such patients.

Place, publisher, year, edition, pages
American College of Rheumatology, 2010
Keywords
NALP3, NLRP3, CAPS, IL-1β, Anakinra
National Category
Natural Sciences
Research subject
Natural sciences
Identifiers
urn:nbn:se:his:diva-4507 (URN)10.1002/art.27489 (DOI)000282758500034 ()20506209 (PubMedID)2-s2.0-77954229474 (Scopus ID)
Available from: 2010-12-28 Created: 2010-12-28 Last updated: 2017-12-11Bibliographically approved
Jonas, W., Johansson, L. M., Nissen, E., Ejdebäck, M., Ransjö-Arvidson, A. B. & Uvnäs-Moberg, K. (2009). Effects of Intrapartum Oxytocin Administration and Epidural Analgesia on the Concentration of Plasma Oxytocin and Prolactin, in Response to Suckling During the Second Day Postpartum. Breastfeeding Medicine, 4(2), 71-82
Open this publication in new window or tab >>Effects of Intrapartum Oxytocin Administration and Epidural Analgesia on the Concentration of Plasma Oxytocin and Prolactin, in Response to Suckling During the Second Day Postpartum
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2009 (English)In: Breastfeeding Medicine, ISSN 1556-8253, E-ISSN 1556-8342, Vol. 4, no 2, p. 71-82Article in journal (Refereed) Published
Abstract [en]

Background: Oxytocin and prolactin stimulate milk ejection and milk production during breastfeeding. The aim of the present study was to make a detailed analysis of maternal release of oxytocin and prolactin in response to breastfeeding during the second day postpartum in mothers who had received oxytocin either intravenously for stimulation of labor or intramuscularly for prevention of postpartum hemorrhage and/or epidural analgesia or those who had received no such treatment in connection with birth.

Methods: In a descriptive comparative study plasma oxytocin and prolactin concentrations were measured in response to suckling during the second day postpartum in women who had received intravenous intrapartum oxytocin (n = 8), intramuscular postpartum oxytocin (n = 13), or epidural analgesia, either with (n = 14) or without (n = 6) intrapartum oxytocin infusion, and women who received none of these interventions (n = 20). Hormone levels were analyzed by enzyme immunoassay.

Results: All mothers showed a pulsatile oxytocin pattern during the first 10 minutes of breastfeeding. Women who had received epidural analgesia with oxytocin infusion had the lowest endogenous median oxytocin levels. The more oxytocin infusion the mothers had received during labor, the lower their endogenous oxytocin levels were during a breastfeeding during the second day postpartum. A significant rise of prolactin was observed after 20 minutes in all women, but after 10 minutes in mothers having received oxytocin infusion during labor. In all women, oxytocin variability and the rise of prolactin levels between 0 and 20 minutes correlated significantly with median oxytocin and prolactin levels.

Conclusion: Oxytocin, released in a pulsatile way, and prolactin were released by breastfeeding during the second day postpartum. Oxytocin infusion decreased endogenous oxytocin levels dose-dependently. Furthermore, oxytocin infusion facilitated the release of prolactin. Epidural analgesia in combination with oxytocin infusion influenced endogenous oxytocin levels negatively.

Place, publisher, year, edition, pages
Mary Ann Liebert, 2009
National Category
Natural Sciences
Research subject
Natural sciences
Identifiers
urn:nbn:se:his:diva-3292 (URN)10.1089/bfm.2008.0002 (DOI)000276674000004 ()19210132 (PubMedID)2-s2.0-67649939196 (Scopus ID)
Available from: 2009-07-09 Created: 2009-07-09 Last updated: 2018-05-03Bibliographically approved
Handlin, L., Jonas, W., Petersson, M., Ejdebäck, M., Ransjö-Arvidsson, A.-B., Nissen, E. & Uvnäs-Moberg, K. (2009). Effects of Sucking and Skin-to-Skin Contact on Maternal ACTH and Cortisol Levels During the Second Day Postpartum - Influence of Epidural Analgesia and Oxytocin in the Perinatal Period. Breastfeeding Medicine, 4(4), 207-220
Open this publication in new window or tab >>Effects of Sucking and Skin-to-Skin Contact on Maternal ACTH and Cortisol Levels During the Second Day Postpartum - Influence of Epidural Analgesia and Oxytocin in the Perinatal Period
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2009 (English)In: Breastfeeding Medicine, ISSN 1556-8253, E-ISSN 1556-8342, Vol. 4, no 4, p. 207-220Article in journal (Refereed) Published
Abstract [en]

Background and Aims: In this study we made a detailed analysis of the mothers' release pattern of adreno-corticotropic hormone (ACTH) and cortisol during a breastfeeding session during the second day postpartum and related these patterns to maternal oxytocin levels as well to the duration of sucking and the duration of skin-to-skin contact before sucking the breast. Furthermore, we investigated if epidural analgesia and oxytocin administration during and after labor influenced the release pattern of ACTH and cortisol.

Methods: Sixty-three primiparae were included in the study. Fourteen received oxytocin intramuscularly postpartum, nine received oxytocin infusion, 14 received epidural analgesia combined with oxytocin infusion, and six received epidural analgesia alone. Twenty mothers did not receive any of these medical interventions. Blood samples were analyzed for ACTH and cortisol by enzyme-linked immunoassay.

Results: Both ACTH and cortisol levels fell significantly during the breastfeeding session. A significant negative relationship was found between oxytocin and ACTH levels, but not between oxytocin and cortisol levels. A contact before onset of sucking was significantly and negatively associated with lower cortisol levels, but not with ACTH levels. Cortisol levels differed significantly between mothers having received epidural analgesia with and without oxytocin.

Conclusions: Breastfeeding is associated with a decrease of ACTH and cortisol levels. Skin-to-skin contact contributes to this effect. ACTH correlated negatively with the duration of sucking and median oxytocin levels, whereas cortisol levels correlated inversely with the duration of skin-to-skin contact preceding sucking, suggesting a partial dissociation between the mechanisms regulating ACTH and cortisol release. In addition, medical interventions in connection with birth influence the activity of the hypothalamic-pituitary-adrenal axis 2 days after birth.

Place, publisher, year, edition, pages
Mary Ann Liebert, 2009
National Category
Natural Sciences
Research subject
Natural sciences
Identifiers
urn:nbn:se:his:diva-3470 (URN)10.1089/bfm.2009.0001 (DOI)000276798300005 ()19731998 (PubMedID)2-s2.0-70350339335 (Scopus ID)
Available from: 2009-11-02 Created: 2009-11-02 Last updated: 2018-05-03Bibliographically approved
Hardy, M. P., Owczarek, C. M., Jermiin, L. S., Ejdebäck, M. & Hertzog, P. J. (2004). Characterization of the type I interferon locus and identification of novel genes. Genomics, 84(2), 331-345
Open this publication in new window or tab >>Characterization of the type I interferon locus and identification of novel genes
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2004 (English)In: Genomics, ISSN 0888-7543, E-ISSN 1089-8646, Vol. 84, no 2, p. 331-345Article in journal (Refereed) Published
Abstract [en]

The human type I interferon (IFN) genes are clustered on human chromosome 9p21 and the mouse genes are located in the region of conserved synteny on mouse chromosome 4. We have identified two novel mouse Ifna genes (Ifna12, Ifna13) and Ifnl2 (IFN-like 2, a homologue of Limitin/IFN-like 1). Another type I IFN gene was designated Ifne1. Mouse Ifne1 was expressed in ovaries and uterus but not in tissues of hematopoietic origin. IFN-epsilon1 has general structural characteristics of a type I IFN. These studies represent the first detailed annotation of the mouse type I IFN locus, and the products of these novel genes may have important functions in reproduction and host defense.

Place, publisher, year, edition, pages
Elsevier, 2004
National Category
Biochemistry and Molecular Biology
Research subject
Medical sciences; Natural sciences
Identifiers
urn:nbn:se:his:diva-9894 (URN)10.1016/j.ygeno.2004.03.003 (DOI)000222665200010 ()15233997 (PubMedID)2-s2.0-2542420686 (Scopus ID)
Available from: 2014-09-05 Created: 2014-09-05 Last updated: 2017-12-05Bibliographically approved
Svensson, M., Lundh, D., Ejdebäck, M. & Mandal, A. (2004). Functional prediction of a T-DNA tagged gene of Arabidopsis thalianaby in silico analysis. Journal of Molecular Modeling, 10(2), 130-138
Open this publication in new window or tab >>Functional prediction of a T-DNA tagged gene of Arabidopsis thalianaby in silico analysis
2004 (English)In: Journal of Molecular Modeling, ISSN 1610-2940, E-ISSN 0948-5023, Vol. 10, no 2, p. 130-138Article in journal (Refereed) Published
Abstract [en]

We have employed a gene-knockout approach using T-DNA tagging and in vivo gene fusion in Arabidopsis thaliana for identification and isolation of specific plant genes. Screening of about 3,000 T-DNA tagged lines resulted in identification of a mutant line (no. 197) exhibiting a significant delay in flowering. From this line a 600-bp plant DNA fragment downstream of the left T-DNA junction was cloned by inverse PCR. BLAST searching in the A. thaliana genomic database indicated a putative gene, frf (flowering regulating factor), with unknown function downstream of the T-DNA insert. Bioinformatic tools were used to predict possible protein structure and function. The protein structure predicted by fold recognition indicates that frf is a transcriptional regulator, a ligand-binding receptor responsive to steroids and hormones. Analyzing the predicted results and the phenotype of the T-DNA tagged plant we hypothesized that FRF might be involved in hormone response in A. thaliana. For verification of this hypothesis we exposed the plants of line no. 197 to gibberellic acid (GA3), a potential growth regulator in higher plants. This treatment resulted in an earlier onset of flowering, almost similar to that in wild type control plants.

Place, publisher, year, edition, pages
Springer, 2004
National Category
Botany
Identifiers
urn:nbn:se:his:diva-2382 (URN)10.1007/s00894-003-0176-3 (DOI)
Available from: 2008-11-25 Created: 2008-11-25 Last updated: 2017-12-20Bibliographically approved
O'Neill, L. A. J., Dunne, A., Ejdebäck, M., Gray, P., Jefferies, C. & Wietek, C. (2003). Mal and MyD88: adapter proteins involved in signal transduction by Toll-like receptors. Paper presented at 7th Biennial Conference of the International-Endotoxin-Society, Arlington, Virginia, July 18-21, 2002. Journal of Endotoxin Research, 9(1), 55-59
Open this publication in new window or tab >>Mal and MyD88: adapter proteins involved in signal transduction by Toll-like receptors
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2003 (English)In: Journal of Endotoxin Research, ISSN 0968-0519, E-ISSN 1743-2839, Vol. 9, no 1, p. 55-59Article in journal (Refereed) Published
Abstract [en]

Signal transduction processes activated by Toll-like receptors (TLRs) include the important transcription factor NF-kappaB and 2 MAP kinases, p38 and Jun N-terminal kinase. These signals ultimately give rise to increased expression of a multitude of pro-inflammatory proteins. Receptor-proximal proteins involved in signalling by all TLRs include the adapter MyD88, 3 IRAKs (IRAK-4, IRAK and IRAK-2), Tollip, Traf-6 and TAK-1. Differences between signals generated by TLRs are emerging, with both TLR4 and TLR2 signalling requiring an additional adapter termed MyD88-adapter-like (Mal; also known as TIRAP). MyD88 and Mal both have a homologous Toll/IL-1 receptor (TIR) domain although they differ in their N-termini, with MyD88 possessing a death domain. In addition, structural models reveal marked differences in surface charges which, when taken with surface charge differences between TLR2 and TLR4 TIR domains, may indicate that TLR4 but not TLR2 recruits Mal directly. Another difference is that Mal can become phosphorylated. Future studies on Mal will reveal specificities in signal transduction by different TLRs, which may ultimately provide molecular explanations for specificities in the innate immune response to infection.

Place, publisher, year, edition, pages
Maney Publishing, 2003
National Category
Biochemistry and Molecular Biology
Research subject
Natural sciences; Medical sciences
Identifiers
urn:nbn:se:his:diva-9893 (URN)10.1177/09680519030090010701 (DOI)000181702400007 ()12691620 (PubMedID)2-s2.0-0037226672 (Scopus ID)
Conference
7th Biennial Conference of the International-Endotoxin-Society, Arlington, Virginia, July 18-21, 2002
Available from: 2014-09-05 Created: 2014-09-05 Last updated: 2017-12-05Bibliographically approved
Dunne, A., Ejdebäck, M., Ludidi, P. L., O'Neill, L. A. J. & Gay, N. J. (2003). Structural complementarity of Toll/interleukin-1 receptor domains in Toll-like receptors and the adaptors Mal and MyD88. Journal of Biological Chemistry, 278(42), 41443-41451
Open this publication in new window or tab >>Structural complementarity of Toll/interleukin-1 receptor domains in Toll-like receptors and the adaptors Mal and MyD88
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2003 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 278, no 42, p. 41443-41451Article in journal (Refereed) Published
Abstract [en]

The Toll/interleukin 1 receptor (TIR) domain is a region found in the cytoplasmic tails of members of the Toll-like receptor/interleukin-1 receptor superfamily. The domain is essential for signaling and is also found in the adaptor proteins Mal (MyD88 adaptor-like) and MyD88, which function to couple activation of the receptor to downstream signaling components. Experimental structures of two Toll/interleukin 1 receptor domains reveal a alpha-beta-fold similar to that of the bacterial chemotaxis protein CheY, and other evidence suggests that the adaptors can make heterotypic interactions with both the receptors and themselves. Here we show that the purified TIR domains of Mal and MyD88 can form stable heterodimers and also that Mal homodimers and oligomers are dissociated in the presence of ATP. To identify structural features that may contribute to the formation of signaling complexes, we produced models of the TIR domains from human Toll-like receptor 4 (TLR4), Mal, and MyD88. We found that although the overall fold is conserved the electrostatic surface potentials are quite distinct. Docking studies of the models suggest that Mal and MyD88 bind to different regions in TLRs 2 and 4, a finding consistent with a cooperative role of the two adaptors in signaling. Mal and MyD88 are predicted to interact at a third non-overlapping site, suggesting that the receptor and adaptors may form heterotetrameric complexes. The theoretical model of the interactions is supported by experimental data from glutathione S-transferase pull-downs and co-immunoprecipitations. Neither theoretical nor experimental data suggest a direct role for the conserved proline in the BB-loop in the association of TLR4, Mal, and MyD88. Finally we show a sequence relationship between the Drosophila protein Tube and Mal that may indicate a functional equivalence of these two adaptors in the Drosophila and vertebrate Toll pathways.

Place, publisher, year, edition, pages
American Society for Biochemistry and Molecular Biology, 2003
National Category
Biochemistry and Molecular Biology
Research subject
Medical sciences; Natural sciences
Identifiers
urn:nbn:se:his:diva-9895 (URN)10.1074/jbc.M301742200 (DOI)000185847200124 ()12888566 (PubMedID)2-s2.0-16744364738 (Scopus ID)
Available from: 2014-09-05 Created: 2014-09-05 Last updated: 2017-12-05Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-3053-4543

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