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  • 1.
    Allard, Per
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Eriksson, K
    Ross, S B
    Marcusson, J O
    [3H]GBR-12935 binding to dopamine uptake sites in rat striatum.1990In: Neuropsychobiology, ISSN 0302-282X, E-ISSN 1423-0224, Vol. 23, no 4, p. 177-81Article in journal (Refereed)
    Abstract [en]

    The binding of the selective dopamine uptake inhibitor [3H]GBR-12935 to rat striatum was studied. Competition by mazindol and dopamine against [3H]GBR-12935 binding revealed monophasic binding curves. The addition of 100 microM dopamine to the mazindol competition inhibited only 80% of the binding, indicating more than one [3H]GBR-12935 binding site in rat striatum. When a binding fraction that could be discriminated by 1 microM mazindol or 1 mM dopamine was defined as specific binding, a single site binding model was obtained. The [3H]GBR-12935 binding was of protein nature, since it was abolished after protease treatment. Drug inhibition studies with the addition of low concentrations of mazindol and dopamine resulted in alterations in apparent Kd values only, suggesting competitive inhibition by these compounds against [3H]GBR-12935 binding. It is concluded that the [3H]GBR-12935 binding to rat striatum discriminated by 1 microM mazindol reflects binding to the substrate recognition site for the dopamine uptake.

  • 2.
    Allard, Per
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Norlén, M
    Caudate nucleus dopamine D(2) receptors in depressed suicide victims.2001In: Neuropsychobiology, ISSN 0302-282X, E-ISSN 1423-0224, Vol. 44, no 2, p. 70-3Article in journal (Refereed)
    Abstract [en]

    Several lines of evidence indicate the involvement of the dopamine system in depressive states. In this post-mortem study, the binding of [(3)H]raclopride to dopamine D(2) receptors in the caudate nucleus was investigated in 13 depressed suicide victims and 19 controls. There were no differences in B(max) or K(d) between the two groups. A subgroup consisting of individuals with major depression, however, had significantly higher K(d) values than controls. Previous findings regarding changes in dopamine metabolism in depression and antidepressant effects of dopamine agonists seem, according to the present study, not to be reflected by alterations in density or affinity of dopamine D(2) receptors in depressed suicide victims.

  • 3. Börjesson, A
    et al.
    Karlsson, T
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Rönnlund, Michael
    Nilsson, L
    Linopirdine (DUP 996): cholinergic treatment of older adults using successive and non-successive tests.1999In: Neuropsychobiology, ISSN 0302-282X, E-ISSN 1423-0224, Vol. 40, no 2, p. 78-85Article in journal (Refereed)
    Abstract [en]

    The purpose of this study was to examine whether cholinergic treatment of age-associated memory impairment with Linopirdine (DUP 996), a derivate of phenylindoline, affects explicit memory, implicit memory, and primary memory. We also assessed cognitive decision making in a reaction time test. Explicit memory was assessed by face recognition, word recall and a word recognition test, being part of a successive test paradigm. Implicit memory was assessed by primed word fragment completion in the same successive test paradigm. Primary memory was studied by means of digit recall. Thirty-eight elderly subjects fulfilled the criteria for memory impairment. Four groups of subjects were given 10, 20 or 30 mg of DUP 996 or placebo during 4 weeks. A double-blind procedure was applied. No significant treatment effects for recognition memory and priming were obtained in the successive test paradigm. Analysis of dependence/independence between tests did not show any clear pattern of treatment effects. The other explicit memory tests and the reaction time test showed no effect with DUP 996. Because of the range of the different tests used here, the result and the general evidence in other investigations of the cholinergic depletion among aged people, the conclusion is that DUP 996 does not improve memory performance either in explicit, implicit or primary tests.

  • 4.
    Chotai, Jayanti
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Asberg, M
    Variations in CSF monoamine metabolites according to the season of birth.1999In: Neuropsychobiology, ISSN 0302-282X, E-ISSN 1423-0224, Vol. 39, no 2, p. 57-62Article in journal (Refereed)
    Abstract [en]

    The cerebrospinal fluid (CSF) concentrations of the monoamine metabolites 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) as well as their ratios and correlations were analyzed in relation to the season of birth. The sample consisted of 241 drug-free patients participating in psychobiological programs and comprising the DSM-III-R diagnoses of mood, anxiety and adjustment disorders. Significant season-of-birth variations were found even after adjusting for sex, age, height, the diagnostic category and the month of lumbar puncture. Those born during February to April had significantly lower values of 5-HIAA. Values of HVA and of the ratios HVA/5-HIAA and HVA/MHPG were significantly higher for those born during October to January. Correlation coefficients also showed season-of-birth variations. These results may provide an important link for the season-of-birth variations reported for several neuropsychiatric disorders.

  • 5.
    Chotai, Jayanti
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Forsgren, Tomas
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Nilsson, L G
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Season of birth variations in the temperament and character inventory of personality in a general population.2001In: Neuropsychobiology, ISSN 0302-282X, E-ISSN 1423-0224, Vol. 44, no 1, p. 19-26Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Since several studies show season of birth variations in morbidity, suicidal behavior and CSF (cerebrospinal fluid) monoamine metabolites, we investigated season of birth variations in personality in the population. METHODS: We analyzed by multiple logistic regressions the Temperament and Character Inventory (TCI) for 2,130 individuals taking part in the Betula prospective random cohort study of Umeå, Sweden. RESULTS: The personality dimensions were correlated significantly with age and gender. We stratified the data according to age, gender and the season of TCI measurement. By the median split in each stratum, a high-value group and a low-value group were obtained for each of the personality dimensions. Those born during February to April were significantly more likely than those born during October to January to have high NS (novelty seeking) among women, particularly the subscale NS2 (impulsiveness vs. reflection), and to have high PS (persistence) among men. Temperament profiles also showed season of birth variations. CONCLUSIONS: We discuss the associations in the literature between personality and the monoamines serotonin and dopamine, and suggest that our results are compatible with a hypothesis of season of birth variation in the monoamine turnover. The personality traits are likely to be influenced by several genetic and environmental factors, one of them being the season of birth.

  • 6.
    Chotai, Jayanti
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Kullgren, Gunnar
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Asberg, M
    CSF monoamine metabolites in relation to the diagnostic interview for borderline patients (DIB).1998In: Neuropsychobiology, ISSN 0302-282X, E-ISSN 1423-0224, Vol. 38, no 4, p. 207-12Article in journal (Refereed)
    Abstract [en]

    The cerebrospinal fluid concentrations of the monoamine metabolites 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), 3-methoxy-4-hydroxyphenylglycol, and their ratios were studied in relation to the Diagnostic Interview for Borderline patients (DIB) evaluated retrospectively from hospital records for a sample of 202 patients participating in psychobiological programs on mood disorders. No correlations with the total DIB score were significant. Patients with borderline personality disorder (BPD) defined by a total DIB score of at least 7 or 6, respectively, did not differ significantly from non-BPD regarding the metabolites. However, for section II (impulse action pattern) of the DIB, those with an intermediate value of the section score had significantly higher levels of 5-HIAA and HVA, suggesting that such higher than normal concentrations may be protective against impulsive or suicidal behavior generated by an underlying psychiatric morbidity due to other risk factors.

  • 7.
    Chotai, Jayanti
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Salander Renberg, Ellinor
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Kullgren, Gunnar
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Asberg, M
    Season of birth variations in dimensions of functioning evaluated by the diagnostic interview for borderline patients.2000In: Neuropsychobiology, ISSN 0302-282X, E-ISSN 1423-0224, Vol. 41, no 3, p. 132-8Article in journal (Refereed)
    Abstract [en]

    In view of recent reports showing that cerebrospinal fluid (CSF) levels of monoamine metabolites exhibit season of birth variations, and that they are also associated with section II (impulse action patterns) of the diagnostic interview for borderline patients (DIB), we analyzed two samples of data to investigate the relationship between the season of birth and the DIB. The first sample comprised 202 patients participating in psychobiological research in Stockholm, and the second sample comprised 130 patients who had committed suicide in Västerbotten in northern Sweden. Those with intermediate score for section II (impulse action patterns) were significantly more likely to have been born during the season October to January in the pooled data, and this tendency persisted in separate analyses for the two samples and for the two diagnostic groups mood disorders and schizophrenia, respectively. Those with high score for section IV (psychosis) were significantly more likely to have been born during February to April in the pooled sample and in the nonschizophrenic group. In the group with schizophrenia, those born during February to April had significantly high scores for section III (affects). These results throw further light on the role of season of birth in suicidology and in psychiatric morbidity.

  • 8.
    Chotai, Jayanti
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Serretti, Alessandro
    Lorenzi, Cristina
    Interaction between the tryptophan hydroxylase gene and the serotonin transporter gene in schizophrenia but not in bipolar or unipolar affective disorders.2005In: Neuropsychobiology, ISSN 0302-282X, E-ISSN 1423-0224, Vol. 51, no 1, p. 3-9Article in journal (Refereed)
    Abstract [en]

    Increasing focus is being given to identify possible combinations of genes related to specific clinical phenotypes. In our sample of 814 patients comprising 114 with schizophrenia, 416 with bipolar affective disorder and 284 with unipolar affective disorder, we studied interactions between the tryptophan hydroxylase (TPH), the serotonin transporter (5-HTTLPR), and the dopamine receptor (DRD4) genes in relation to five major psychiatric symptomatology scores. There was significant interaction between the TPH and the 5-HTTLPR genes. With an increasing number of short (s) alleles of 5-HTTLPR, the scores for delusions, disorganization and negative symptoms were significantly decreasing among subjects having the TPH genotype AA but increasing among subjects having the TPH genotype AC, yielding the highest scores for the combinations AA x ll and AC x ss. Since high scores on just delusions, disorganization and negative symptoms but low scores on excitement and depression were found among subjects with schizophrenia, we conducted comparisons among the three diagnostic categories and controls as regards the combined TPH x 5-HTTLPR genotype distribution. Schizophrenia subjects had a significantly different distribution of the genotype combination for TPH x 5-HTTLPR as compared to 241 controls or to unipolar or bipolar subjects, and had significantly higher frequencies of AA x ll and of AC x ss. Thus, an interaction between TPH and 5-HTTLPR genes constitutes susceptibility to schizophrenia, thereby yielding apparent relationships between the major psychiatric symptomatology scores and genotype combinations in samples that are obtained by pooling schizophrenia with other diagnostic categories.

  • 9.
    Gustafsson, Per E
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Gustafsson, PA
    Ivarsson, T
    Nelson, N
    Diurnal cortisol levels and cortisol response in youths with obsessive-compulsive disorder.2008In: Neuropsychobiology, ISSN 0302-282X, E-ISSN 1423-0224, Vol. 57, no 1-2, p. 14-21Article in journal (Refereed)
  • 10. Hellgren, Charlotte
    et al.
    Akerud, Helena
    Skalkidou, Alkistis
    Bäckström, Torbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Sundstrom-Poromaa, Inger
    Low Serum Allopregnanolone Is Associated with Symptoms of Depression in Late Pregnancy2014In: Neuropsychobiology, ISSN 0302-282X, E-ISSN 1423-0224, Vol. 69, no 3, p. 147-153Article in journal (Refereed)
    Abstract [en]

    Background: Allopregnanolone (3 alpha-hydroxy-5 alpha-pregnan-20-one) is a neurosteroid which has an inhibitory function through interaction with the GABA(A) receptor. This progesterone metabolite has strong sedative and anxiolytic properties, and low endogenous levels have been associated with depressed mood. This study aimed to investigate whether the very high serum allopregnanolone levels in late pregnancy covary with concurrent self-rated symptoms of depression and anxiety. Methods: Ninety-six women in pregnancy weeks 37-40 rated symptoms of depression and anxiety with the Montgomery-Asberg Depression Rating Scale (MADRS-S) and Spielberger State-Trait Anxiety Inventory. Their serum allopregnanolone was analyzed by Celite chromatography and radioinnmunoassay. Results: Ten women had elevated depression scores (MADRS-S >= 13), and this group had significantly lower allopregnanolone levels compared to women with MADRS-S scores in the normal range (39.0 +/- 17.9 vs. 54.6 +/- 18.7 nmol/l, p = 0.014). A significant negative correlation was found between self-rated depression scores and allopregnanolone concentrations (Pearson's correlation coefficient = -0.220, p = 0.031). The linear association between self-rated depression scores and allopregnanolone serum concentrations remained significant when adjusted for gestational length, progesterone levels, and parity. Self-rated anxiety, however, was not associated with allopregnanolone serum concentrations during pregnancy. Conclusion: High allopregnanolone serum concentrations may protect against depressed mood during pregnancy. (C) 2014 S. Karger AG, Basel

  • 11.
    Löfgren, Magnus
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Bengtsson, Sara K
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Johansson, Maja
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Bäckström, Torbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Allopregnanolone promotes success in food competition in subordinate male rats2013In: Neuropsychobiology, ISSN 0302-282X, E-ISSN 1423-0224, Vol. 68, no 1, p. 15-23Article in journal (Refereed)
    Abstract [en]

    Background/Aims: Allopregnanolone or 3 alpha-hydroxy-5 alpha-pregnan-20-one (AlloP) is normally sedative and anxiolytic, but can under provoking circumstances paradoxically induce aggressive behavior. Therefore, it is of particular interest to determine if there is a relationship between an anxiolytic effect and aggressive behavior following AlloP administration.

    Method: Male Wistar rats were housed in triads comprising of 1 young rat (35 days) and 2 older rats (55 days), with the intent of producing a social hierarchy. The triads were sampled for total serum testosterone and submitted to a social challenge in the form of a food competition test (FCT), where the rats competed for access to drinking sweetened milk. At baseline, the younger rats were identified as subordinates. To test for the behavioral effect of AlloP, the subordinate rats were given intravenous AlloP injections of 0.5 and 1 mg/kg. To assess the optimal AlloP effect, 6 intervals (5, 10, 15, 20, 30 and 40 min) between injection and the FCT were used. In separate studies, AlloP was also given by subcutaneous and intraperitoneal administration at 10 and 17 mg/kg.

    Results: AlloP (1 mg/kg, i.v.) increased drinking time and aggressive behavior in subordinate rats, with a positive correlation between these behaviors. The subcutaneous injection (17 mg/kg) also increased drinking time in subordinate animals. Serum testosterone concentration was higher in dominant compared to subordinate rats, and correlated with drinking time and weight.

    Conclusions: AlloP increased drinking time and aggressive behavior, and the correlation indicates a relationship between an anxiolytic effect and aggressive behavior. Copyright (c) 2013 S. Karger AG, Basel

  • 12. Natale, Vicenzo
    et al.
    Adan, Ana
    Chotai, Jayanti
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Further results on the association between morningness-eveningness preference and the season of birth in human adults2002In: Neuropsychobiology, ISSN 0302-282X, E-ISSN 1423-0224, Vol. 46, no 4, p. 209-214Article in journal (Refereed)
    Abstract [en]

    Morningness-eveningness preference by the self-rated Morningness-Eveningness Questionnaire (MEQ) has earlier been shown to be associated with the subjects' season of birth. Here, we obtain this result for a new sample of 2,125 university students and for the sample obtained by pooling the data with the earlier study, yielding totally 3,709 Italian and Spanish subjects. An nonlinear regression of MEQ as a cosine curve according to the month of birth, adjusting for age and gender, gave a maximum (morningness) around the transition between the birth months December and January, and a minimum (eveningness) around the transition between the birth months June and July. Multiple logistic regressions showed that for females as well as for males, the group born during the half-year April to September containing summer had a significantly lower proportion of morning types as compared with the group born during the half-year October to March containing winter. This was more pronounced for males. Moreover, a significantly higher proportion of morning types among females compared with males was found only in the group born during April to September, but not in the group born during October to March. There was a weak but statistically significant positive correlation between MEQ and age in the sample's limited age range of 17-30 years. We discuss the results in terms of the mutually inhibitory systems of melatonin and dopamine, and find further support for a hypothesis that it is the variation in the length of photoperiod during the gestational or perinatal period that contributes significantly to the season of birth variation found in the morningness-eveningness preference among adults.

  • 13.
    Sigurdh, Jeanette
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Spigset, O
    Allard, Per
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Mjörndal, T
    Hägglöf, Bruno
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Child and Adolescent Psychiatry.
    Binding of [(3)H]lysergic acid diethylamide to serotonin 5-HT(2A) receptors and of [(3)H]paroxetine to serotonin uptake sites in platelets from healthy children, adolescents and adults.1999In: Neuropsychobiology, ISSN 0302-282X, E-ISSN 1423-0224, Vol. 40, no 4, p. 183-7Article in journal (Refereed)
    Abstract [en]

    Possible age effects on binding of [(3)H]lysergic acid diethylamide ([(3)H]LSD) to serotonin 5-HT(2A) receptors and of [(3)H]paroxetine to serotonin uptake sites were studied in platelets from healthy children (11-12 years of age), adolescents (16-17 years of age) and adults. Significant overall age effects were found both for the number of binding sites (B(max)) for [(3)H]LSD binding (p < 0.001), the affinity constant (K(d)) for [(3)H]LSD binding (p < 0.001), B(max) for [(3)H]paroxetine binding (p < 0.001) and K(d) for [(3)H] paroxetine binding (p = 0.006). In general, there was a decrease in B(max) with increasing age, which predominantly occurred between the ages 11-12 years and 16-17 years for the 5-HT(2A) receptor, and after 16-17 years of age for the serotonin uptake site. These developmental changes might have an impact on the effect of treatment with serotonergic drugs in children and adolescents. When the platelet serotonin variables investigated are employed in studies in children or adolescents, age matching or, alternatively, introduction of age control in the statistical analysis should be performed.

  • 14.
    Sundman, Ingrid
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Allard, Per
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Eriksson, A
    Marcusson, J
    GABA uptake sites in frontal cortex from suicide victims and in aging.1997In: Neuropsychobiology, ISSN 0302-282X, E-ISSN 1423-0224, Vol. 35, no 1, p. 11-5Article in journal (Refereed)
    Abstract [en]

    The binding of [3H]nipecotic acid to GABA uptake sites was studied in post mortem human frontal cortex from 17 suicide victims and 21 controls without known neurological or psychiatric disorder. The suicide victims were subclassified according to the use of violent or non-violent methods and to the presence or absence of a known history of a depressive disorder. No difference was found between the suicide victims and the controls with regard to [3H]nipecotic acid binding to GABA uptake sites (Bmax) and apparent affinity (Kd). No differences were found either with regard to method of suicide or whether a depressive symptom existed or not. The binding of [3H]nipecotic acid to GABA uptake sites was also studied in post mortem human frontal cortex with regard to aging. The age of the subjects ranged from 16 to 84 years. No significant difference in either Bmax or Kd was found. The present findings suggest that the GABA uptake sites in the human frontal cortex are not subjected to regulation or degenerative changes in conditions investigated.

  • 15. von Knorring, L
    et al.
    Perris, C
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Jacobsson, Lars
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Rosenberg, B
    Multi-aspects classification of mental disorders (MACM). A solution to the present confusion in the international classification mental disorders.1980In: Neuropsychobiology, ISSN 0302-282X, E-ISSN 1423-0224, Vol. 6, no 2, p. 101-108Article in journal (Refereed)
    Abstract [en]

    The international classification of mental disorders (ICD-8) presented by the WHO has not been accepted in all countries and where it is used, local adjustments are made and sometimes parallel classification models are used. The diagnostic system has also been criticized as lacking in exactness and consistency and the reliability between diagnosticians has been shown to be low. As a consequence, international communication is made difficult and research is hampered. This problem is particularly relevant in the field of biological research. In fact, it can be suspected that most inconsistencies as regards results obtained in different places might depend upon an inconsistent use of the current diagnostic labels. A possible solution of this problem can be the use of a multiaspect classification model. Such a multiaspect model (MACM) including four variables - symptomatology, severity, course and supposed etiopathogenesis - has been tested for several years at Umeå. MACM is shown to be easly to communicate both in undergraduate training and in ternational communication. The reliability between diagnosticians is found to range from 56 to 82% as compared to 22-36% as concerns ICD-8. It is also shown that fairly homogeneous groups, both regarding course, supposed etiopathogenesis and biological basis, can be formed and that MACM seems to bear temporal stability. Computer programming of MACM diagnoses is as possible as with ICD-8 diagnoses. Furthermore, when Macm is used in clinical routine work, much more information valid in administrative routines is stored than what is possible when ICD-8 is used.

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