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  • 251. Batistuzzo, S.
    et al.
    Galvão, M. O.
    Duarte, E. S.
    Hoelzemann, J. J.
    Menezes Filho, J.
    Sadiktsis, Ioannis
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
    Westerholm, Roger
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
    Dreij, K.
    PAH exposure and relationship between buccal micronucleus cytome assay and urinary 1-hydroxypyrene levels among cashew nut roasting workers2016In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 258, p. S223-S224Article in journal (Refereed)
    Abstract [en]

    The present study conducted the first assessment of the occupational risk associated to artisanal cashew nut roasting by the use of exposure and effect biomarkers, as well as the characterization and dispersion analysis of the released particulate matter (PM). The PM concentrations in the exposed area were higher than in the non-exposed area. Furthermore, in the control area yielded a higher prevalence of coarse particles, while in the exposed area was observed fine particles. The morphological analysis showed a wide variety of particles. Biomass burning tracers K, Cl, S and Ca were the major inorganic compounds and polycyclic aromatic hydrocarbons (PAHs) with mutagenic and carcinogenic potential, such as benzo[a]pyrene, benzo[b]fluoranthene, benzo[a]anthracene, benzo[j]fluoranthene and indeno[1,2,3-c,d]pyrene were the most abundant PAHs. In addition, atmospheric modeling analysis suggest that these particles can reach regions higher than 40 kilometers. Occupational PAH exposure was confirmed by increases in 1-OHP levels in cashew nut workers. The frequencies of BMCyt biomarkers of genotoxic (micronuclei and nuclear bud) and cytotoxic (pyknosis, karyolysis, karyorrhexis and condensed chromatin) were higher in the exposed group (p < 0.0001) compared with the control group. The influence of factors such as age on the micronucleus was evidenced and a correlation between 1-OHP and MN was observed. It was the first study to found a correlation between these types of biomarkers. The uses of exposure and effect biomarkers were therefore efficient in assessing the occupational risk associated with artisanal cashew nut roasting and the high rates of PM2.5 are considered a potential contributor to this effect.

  • 252.
    Bauer, Florian
    Stockholm University, Faculty of Science, Department of Physics.
    Detector Considerations for Time-of-Flight in Positron Emission Tomography2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Positron-Emission-Tomography (PET) is a modern imaging technique in nuclear medicine providing quantitative 3D distribution of a radioactive tracer substance in the human body. The gamma-detector is the first link in the chain of components that constitutes a PET. It converts incoming radiation into optical light pulses, which are detected by photo multiplier tubes. Here the light is converted into electric pulses, to be further processed by the acquisition electronics. Improving detector sensitivity and resolution is of great value in research and in clinical practice.

    The focus of this work is to improve the detector to give it time-of-flight (TOF) capabilities, in order to further improve sensitivity, which in turn leads to increased image quality, faster scan time and/or reduced dose exposure for the patient.

    Image quality has improved over the years, but losses in image quality have been reported for heavy patients, due to increased attenuation, and more dispersed counts over a larger volume. Instrumentation limits are still significant in heavy patient images, but the incorporation of TOF information promises to alleviate some of the limitations.

    In order to improve the timing resolution of the detector fast photo-multipliers and a novel scheme to extract the event timing trigger from a detector by using the summed dynode signal were investigated.

    When designing new PET detectors, it is important to have detailed understanding and control of the light sharing mechanisms in the crystal arrays. Therefore it was necessary to perform optical simulations and single crystal light output measurements to derive a model for an LSO block detector.

    Another way to improve the image quality is to use the depth-of-interaction (DOI) of the gamma ray within the detector. It is shown that a multi-layer phoswich detector comprised of LSO with different decay times and TOF capability, combines the benefits of TOF and DOI in one detector, maximizing the effective sensitivity gain.

  • 253. Bauerschmidt, Christina
    et al.
    Woodcock, Michael
    Stevens, David L.
    Hill, Mark A.
    Rothkamm, Kai
    Helleday, Thomas
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Cohesin phosphorylation and mobility of SMC1 at ionizing radiation-induced DNA double-strand breaks in human cells2011In: Experimental Cell Research, ISSN 0014-4827, E-ISSN 1090-2422, Vol. 317, no 3, p. 330-337Article in journal (Refereed)
    Abstract [en]

    Cohesin, a hetero-tetrameric complex of SMC1, SMC3, Rad21 and Scc3, associates with chromatin after mitosis and holds sister chromatids together following DNA replication. Following DNA damage, cohesin accumulates at and promotes the repair of DNA double-strand breaks. In addition, phosphorylation of the SMC1/3 subunits contributes to DNA damage-induced cell cycle checkpoint regulation. The aim of this study was to determine the regulation and consequences of SMC1/3 phosphorylation as part of the cohesin complex. We show here that the ATM-dependent phosphorylation of SMC1 and SMC3 is mediated by H2AX, 53BP1 and MDC1. Depletion of RAD21 abolishes these phosphorylations, indicating that only the fully assembled complex is phosphorylated. Comparison of wild type SMC1 and SMC1S966A in fluorescence recovery after photo-bleaching experiments shows that phosphorylation of SMC1 is required for an increased mobility after DNA damage in G2-phase cells, suggesting that ATM-dependent phosphorylation facilitates mobilization of the cohesin complex after DNA damage.

  • 254.
    Baumgarten, Thomas
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Schlegel, Susan
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Wagner, Samuel
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Löw, Mirjam
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Eriksson, Jonas
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Bonde, Ida
    Herrgård, Markus J.
    Heipieper, Hermann J.
    Nørholm, Morten H. H.
    Slotboom, Dirk Jan
    de Gier, Jan-Willem
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Isolation and characterization of the E-coli membrane protein production strain Mutant56(DE3)2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 45089Article in journal (Refereed)
    Abstract [en]

    Membrane protein production is usually toxic to E. coli. However, using genetic screens strains can be isolated in which the toxicity of membrane protein production is reduced, thereby improving production yields. Best known examples are the C41(DE3) and C43(DE3) strains, which are both derived from the T7 RNA polymerase (P)-based BL21(DE3) protein production strain. In C41(DE3) and C43(DE3) mutations lowering t7rnap expression levels result in strongly reduced T7 RNAP accumulation levels. As a consequence membrane protein production stress is alleviated in the C41(DE3) and C43(DE3) strains, thereby increasing membrane protein yields. Here, we isolated Mutant56(DE3) from BL21(DE3) using a genetic screen designed to isolate BL21(DE3)-derived strains with mutations alleviating membrane protein production stress other than the ones in C41(DE3) and C43(DE3). The defining mutation of Mutant56(DE3) changes one amino acid in its T7 RNAP, which weakens the binding of the T7 RNAP to the T7 promoter governing target gene expression rather than lowering T7 RNAP levels. For most membrane proteins tested yields in Mutant56(DE3) were considerably higher than in C41(DE3) and C43(DE3). Thus, the isolation of Mutant56(DE3) shows that the evolution of BL21(DE3) can be promoted towards further enhanced membrane protein production.

  • 255. Bayat, Jari Taghavi
    et al.
    Hallberg, Ulrika
    Lindblad, Frank
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Uppsala University.
    Huggare, Jan
    Mohlin, Bengt
    Daily life impact of malocclusion in Swedish adolescents: A grounded theory study2013In: Acta Odontologica Scandinavica, ISSN 0001-6357, E-ISSN 1502-3850, Vol. 71, no 3-4, p. 792-798Article in journal (Refereed)
    Abstract [en]

    Objective. To explore how malocclusions affect daily life in adolescents and how adolescents cope with malocclusion-related distress. Materials and methods. Twelve strategically selected teenagers, seven girls and five boys aged 13-14 years, participated in this study. Open, tape-recorded in-depth interviews based on Focus Group Discussions (FGD) were performed using a theme guide and analyzed according to the qualitative method of classic grounded theory (GT). Results. A core category was identified and named 'Repeatedly reminded of the malocclusion'. Associated to the core category, five categories were generated and labeled 'Being directed by the media's ideal image', 'Monitoring others' teeth', 'Struggling with low self-esteem', 'Hiding one's teeth' and 'Striving for cure'. Low self-esteem appeared to be frequently reinforced through the concerns for the malocclusion and handled via different coping strategies, such as hiding the teeth and striving to receive orthodontic treatment. Such processes were further enforced through the influence of media. Low self-esteem could be associated to a visible malposition of teeth, according to the informants. Having to wait for orthodontic treatment was frustrating the adolescents. Conclusions. Adolescents with malocclusion are often reminded of their condition, which can lead to avoiding strategies to minimize the negative feelings associated with the teeth and low self-esteem. Clinicians may therefore need to be aware of potential irrational behaviors when interacting with adolescents with malocclusions. The findings also suggest that there might be a discrepancy of attitudes between professionals focusing on oral health aspects of malocclusions and the adolescents focusing on esthetic aspects.

  • 256. Beccaria, Franca
    et al.
    Rolando, Sara
    Törrönen, Jukka
    Stockholm University, Faculty of Social Sciences, Centre for Social Research on Alcohol and Drugs (SoRAD).
    Scavarda, Alice
    From housekeeper to status-oriented consumer and hyper-sexual imagery: images of alcohol targeted to Italian women from the 1960s to the 2000s2017In: Feminist Media Studies, ISSN 1468-0777, E-ISSN 1471-5902Article in journal (Refereed)
    Abstract [en]

    Advertisements not only mirror ideals of masculinity and femininity that prevail in a specific place and time, but also contribute to influencing them. This article analyses alcohol-related advertisements published in women’s magazines from 1967 to 2008 in Italy. The main aim is to understand cultural processes that underlie gender differences in drinking and more generally in Italian society. The sample consists of 376 direct and indirect advertisements collected from well-established women’s magazines. The study identifies continuities and changes in women’s subject positions in alcohol-related advertisements. Italian advertisements of the 1960s and 1970s still reflect a female condition that entails no recognition of women’s own desires and tastes. Advertisements from the 1980s and 1990s reflect a more complex representation of female consumers, associating them with their own desires and pleasures. In the 2000s, the focus on women’s physical appearance and social image has become the prevailing feature. In conclusion, the study shows that changes in female representations in advertisements in the last 50 years do not represent a shift toward a more balanced gender representation. The insistence on women’s appearance, with a correlated predominance of bodily pleasures and attractiveness, reproduces old stereotypes about drinking women.

  • 257. Beck, Ingela
    et al.
    Törnquist, Agneta
    Stockholm University, Faculty of Social Sciences, Department of Social Work.
    Broström, Linus
    Edberg, Anna-Karin
    Having to focus on doing rather than being: nurse assistants' experience of palliative care in municipal residential care settings2012In: International Journal of Nursing Studies, ISSN 0020-7489, E-ISSN 1873-491X, Vol. 49, no 4, p. 455-464Article in journal (Refereed)
    Abstract [en]

    Background

    Palliative care should be provided, irrespective of setting to all patients facing a life-threatening illness and to their families. The situation and needs of older people differ from those of younger people since they often have several co-existing diseases and health complaints. This implies an extensive need for care and for longer periods of palliative care. The main providers of palliative care for older people are nurse assistants, who are also those with the shortest education.

    Aim

    The aim of this study was to illuminate nurse assistants’ experience of palliative care for older people in residential care.

    Design

    The study had an explorative, descriptive design.

    Settings

    Thirteen residential care units in three different districts in a large city in southern Sweden.

    Participants

    Twenty-five nurse assistants selected to represent variations in age, gender workplace and work experience.

    Methods

    Data were collected from six focus-group interviews and subjected to content analysis to gain an understanding of the phenomenon.

    Results

    The nurse assistants described palliative care as a contrast to the everyday care they performed in that they had a legitimate possibility to provide the care needed and a clear assignment in relation to relatives. Palliative care also meant having to face death and dying while feeling simultaneous that it was unnatural to talk about death and having to deal with their own emotions. They emphasised that they were in need of support and experienced leadership as invisible and opaque, but gained strength from being recognized.

    Conclusion

    In order to support nurse assistants in providing high quality end-of-life care, more focus is needed on the trajectory of older peoples’ dying, on the importance of involving relatives throughout the period of care provision, and on support when encountering death and dying. There is also a need for engaged care leaders, both registered nurses and managers, to recognize the work of nurse assistants and to support care provision for older people within the framework of palliative care philosophy.

  • 258.
    Becker, Nina
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Max Planck Institute for Human Development, Germany.
    Kalpouzos, Grégoria
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Persson, Jonas
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Laukka, Erika J.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Brehmer, Yvonne
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Max Planck Institute for Human Development, Germany.
    Differential Effects of Encoding Instructions on Brain Activity Patterns of Item and Associative Memory2017In: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 29, no 3, p. 545-559Article in journal (Refereed)
    Abstract [en]

    Evidence from neuroimaging studies suggests a critical role of hippocampus and inferior frontal gyrus (IFG) in associative relative to item encoding. Here, we investigated similarities and differences in functional brain correlates for associative and item memory as a function of encoding instruction. Participants received either incidental (animacy judgments) or intentional encoding instructions while fMRI was employed during the encoding of associations and items. In a subsequent recognition task, memory performance of participants receiving intentional encoding instructions was higher compared with those receiving incidental encoding instructions. Furthermore, participants remembered more items than associations, regardless of encoding instruction. Greater brain activation in the left anterior hippocampus was observed for intentionally compared with incidentally encoded associations, although activity in this region was not modulated by the type of instruction for encoded items. Furthermore, greater activity in the left anterior hippocampus and left IFG was observed during intentional associative compared with item encoding. The same regions were related to subsequent memory of intentionally encoded associations and were thus task relevant. Similarly, connectivity of the anterior hippocampus to the right superior temporal lobe and IFG was uniquely linked to subsequent memory of intentionally encoded associations. Our study demonstrates the differential involvement of anterior hippocampus in intentional relative to incidental associative encoding. This finding likely reflects that the intent to remember triggers a specific binding process accomplished by this region.

  • 259.
    Becker, Nina
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Max Planck Institute for Human Development, Germany.
    Laukka, Erika J.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Kalpouzos, Gregoria
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Naveh-Benjamin, Moshe
    Bäckman, Lars
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Brehmer, Yvonne
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Max Planck Institute for Human Development, Germany.
    Structural brain correlates of associative memory in older adults2015In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 118, p. 146-153Article in journal (Refereed)
    Abstract [en]

    Associative memory involves binding two or more items into a coherent memory episode. Relative to memory for single items, associative memory declines greatly in aging. However, older individuals vary substantially in their ability to memorize associative information. Although functional studies link associative memory to the medial temporal lobe (MTL) and prefrontal cortex (PFC), little is known about how volumetric differences in MTL and PFC might contribute to individual differences in associative memory. We investigated regional gray-matter volumes related to individual differences in associative memory in a sample of healthy older adults (n = 54; age = 60 years). To differentiate item from associative memory, participants intentionally learned face-scene picture pairs before performing a recognition task that included single faces, scenes, and face-scene pairs. Gray-matter volumes were analyzed using voxel-based morphometry region-of-interest (ROI) analyses. To examine volumetric differences specifically for associative memory, item memory was controlled for in the analyses. Behavioral results revealed large variability in associative memory that mainly originated from differences in false-alarm rates. Moreover, associative memory was independent of individuals' ability to remember single items. Older adults with better associative memory showed larger gray-matter volumes primarily in regions of the left and right lateral PFC. These findings provide evidence for the importance of PFC in intentional learning of associations, likely because of its involvement in organizational and strategic processes that distinguish older adults with good from those with poor associative memory.

  • 260.
    Becker, Richard
    et al.
    Stockholm University, Faculty of Science, Department of Physical, Inorganic and Structural Chemistry.
    Johnsson, Mats
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Inorganic and Structural Chemistry.
    Berger, Helmuth
    Crystal Structure of the New Cobalt Tellurite Chloride Co5Te4O11Cl42007In: Zeitschrift für Anorganische und Allgemeines Chemie, ISSN 0044-2313, E-ISSN 1521-3749, Vol. 633, no 3, p. 422-424Article in journal (Refereed)
    Abstract [en]

    The crystal structure of the new compound Co5Te4O11Cl4 is described. It crystallizes in the triclinic system, space group P-1 with the unit cell parameters a = 822.26(8) pm, b = 1029.7(1) pm, c = 1031.1(1) pm, = 110.80(1)°, β = 97.950(9)°, = 98.260(9)° and Z = 2. The structure is layered along the bc–plane and built by [CoO5Cl], [CoO4Cl2] and [CoO4Cl] polyhedra sandwiched by [TeO3E] and [TeO4E] polyhedra. The layers can be regarded as infinite molecules without any net charge and only weak van der Waals forces connect them to each other. The halides and the lone-pair, E, of TeIV protrude from the layers.

  • 261. Beckers, Debby G J
    et al.
    Kompier, Michiel A J
    Kecklund, Göran
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Härmä, Mikko
    Worktime control: theoretical conceptualization, current empirical knowledge, and research agenda2012In: Scandinavian Journal of Work, Environment and Health, ISSN 0355-3140, E-ISSN 1795-990X, Vol. 38, no 4, p. 291-297Article in journal (Refereed)
  • 262.
    Beckley, Amber L.
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Sociology. Duke University, North Carolina.
    Caspi, Avshalom
    Broadbent, Jonathan
    Harrington, Honalee
    Houts, Renate M.
    Poulton, Richie
    Ramrakha, Sandhya
    Reuben, Aaron
    Moffitt, Terrie E.
    Association of Childhood Blood Lead Levels With Criminal Offending2017In: JAMA pediatrics, ISSN 2168-6203, E-ISSN 2168-6211Article in journal (Refereed)
    Abstract [en]

    Importance  Lead is a neurotoxin with well-documented effects on health. Research suggests that lead may be associated with criminal behavior. This association is difficult to disentangle from low socioeconomic status, a factor in both lead exposure and criminal offending.

    Objective  To test the hypothesis that a higher childhood blood lead level (BLL) is associated with greater risk of criminal conviction, recidivism (repeat conviction), conviction for violent offenses, and variety of self-reported criminal offending in a setting where BLL was not associated with low socioeconomic status.

    Design, Setting, and Participants  A total of 553 individuals participated in a prospective study based on a population-representative cohort born between April 1, 1972, and March 31, 1973, from New Zealand; the Dunedin Multidisciplinary Health and Development Study observed participants to age 38 years (December 2012). Statistical analysis was performed from November 10, 2016, to September 5, 2017.

    Exposures  Blood lead level measured at age 11 years.

    Main Outcomes and Measures  Official criminal conviction cumulative to age 38 years (data collected in 2013), single conviction or recidivism, conviction for nonviolent or violent crime, and self-reported variety of crime types at ages 15, 18, 21, 26, 32, and 38 years.

    Results  Participants included 553 individuals (255 female and 298 male participants) who had their blood tested for lead at age 11 years. The mean (SD) BLL at age 11 years was 11.01 (4.62) μg/dL. A total of 154 participants (27.8%) had a criminal conviction, 86 (15.6%) had recidivated, and 53 (9.6%) had a violent offense conviction. Variety scores for self-reported offending ranged from 0 to 10 offense types at each assessment; higher numbers indicated greater crime involvement. Self-reported offending followed the well-established age-crime curve (ie, the mean [SD] variety of self-reported offending increased from 1.99 [2.82] at age 15 years to its peak of 4.24 [3.15] at age 18 years and 4.22 [3.02] at age 21 years and declined thereafter to 1.10 [1.59] at age 38 years). Blood lead level was a poor discriminator between no conviction and conviction (area under the curve, 0.58). Overall, associations between BLL and conviction outcomes were weak. The estimated effect of BLL was lower for recidivism than for single convictions and lower for violent offending than for nonviolent offending. Sex-adjusted associations between BLL reached statistical significance for only 1 of the 6 self-reported offending outcomes at age 15 years (r = 0.10; 95% CI, 0.01-0.18; P = .02).

    Conclusions and Relevance  This study overcomes past limitations of studies of BLL and crime by studying the association in a place and time where the correlation was not confounded by childhood socioeconomic status. Findings failed to support a dose-response association between BLL and consequential criminal offending.

  • 263.
    Beckley, Amber L.
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Criminology.
    Kuja-Halkola, Ralf
    Lundholm, Lena
    Långström, Niklas
    Frisell, Thomas
    Association of height and violent criminality: results from a Swedish total population study2014In: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, Vol. 43, no 3, p. 835-842Article in journal (Refereed)
    Abstract [en]

    Background: Violent criminality is at least moderately heritable, but the mechanisms behind this remain largely unexplained. Height, a highly heritable trait, may be involved but no study has estimated the effect of height on crime while simultaneously accounting for important demographic, biological and other heritable confounders. Methods: We linked nationwide, longitudinal registers for 760 000 men who underwent mandatory military conscription from 1980 through 1992 in Sweden, to assess the association between height and being convicted of a violent crime. We used Cox proportional hazard modelling and controlled for three types of potential confounders: physical characteristics, childhood demographics and general cognitive ability (intelligence). Results: In unadjusted analyses, height had a moderate negative relationship to violent crime; the shortest of men were twice as likely to be convicted of a violent crime as the tallest. However, when simultaneously controlling for all measured confounders, height was weakly and positively related to violent crime. Intelligence had the individually strongest mitigating effect on the height-crime relationship. Conclusions: Although shorter stature was associated with increased risk of violent offending, our analyses strongly suggested that this relationship was explained by intelligence and other confounding factors. Hence, it is unlikely that height, a highly heritable physical characteristic, accounts for much of the unexplained heritability of violent criminality.

  • 264.
    Beckman, Marie
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Temporal events in neuronal differentiation and cell death: expression and processing of the Alzheimer's amyloid precursor protein family and a protein at the nuclear pore2003Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The present study had two major objectives: 1) to elucidate the involvement of Alzheimer’s amyloid precursor protein (APP) family in neuronal differentiation, and the effect of the Alzheimer’s disease (AD)-linked mutation APPV642I on signal transduction; 2) to investigate the fate of the nuclear pore complex protein POM121 during apoptosis and to examine the possibility of using green fluorescent protein (GFP)-labelled POM121 as a non-invasive sensor of apoptosis in living (non-fixed) cells.

    APP is the parent protein of the b-amyloid peptide, which is the major peptide constituent in the “senile plaques” of AD. APP and the homologous amyloid precursor-like proteins, APLP1 and APLP2, are members of the APP family. We compared the temporal expression patterns of these proteins during retinoic acid (RA)-induced neuronal differentiation of human neuroblastoma cells. To this end, we established a quantitative non-radioactive Northern blot assay for APLP1, APLP2 and APP. We found that the transcripts of all three APP family members were increased in response to RA. This occurred simultaneously with progressive neurite outgrowth and increased expression of neuronal markers. In addition, we observed that the increase in APLP2 mRNA was similar to that of APP mRNA, whereas the increase in APLP1 mRNA was significantly higher. The elevated mRNA levels also resulted in an in-creased protein expression of APLP1, APLP2 and the neuronal APP695 isoform. Studies using curcumin (diferuloylmethane), an inhibitor of the transcription factors NFkB/AP-1, and the mitogen-activated protein kinase (MAPK) JNK (c-Jun N-terminal kinase), revealed a diffe-rential regulation of APLP1 and APLP2. Curcumin suppressed the RA-induced mRNA expression of the APP family, in particular that of APLP1. On the protein level, curcumin also reduced the expression of APLP1. In contrast, curcumin induced an accumulation of APLP2, which we propose is due to inhibition of its proteolytic processing. Furthermore, curcumin induced neurite retraction in RA-differentiated cells without affecting their viability. Our results suggest that NFkB/AP-1 signal transduction pathways mediate a co-ordinated regula-tion of the mRNA expression of the APP family and that APLP1 processing is not regulated by the same mechanisms as the processing of APLP2 and APP. Our results are in agreement with important functions for APLP1, APLP2 and APP within the period of neurite extension and synaptic maturation, and a proposed role for these proteins in neuronal differentiation and synaptic plasticity.

    Using a doxycycline-controlled gene expression system (Tet-On), we investigated the effect of wild-type APP695 and the pathogenic familial AD-linked APPV642I mutant on signal transduction. Overexpression was induced at different levels in rat pheochromocytoma (PC12) Tet-On cells. We observed a nerve growth factor-dependent increase in the levels of phosphorylated extracellular regulated kinases 1 and 2 in response to expression of mutant APP. Our results support that increased signalling via MAPKs may have a role in the development of AD. In addition, we found that the inducing agent doxycycline in itself affected cell signalling and protected against oxidative stress. This information is critical for evaluation of the effects of transgene expression using Tet systems.

    Finally, we showed that POM121 is cleaved by a caspase-3-dependent mechanism at aspartate 531 during apoptosis. Characterising the degradation of POM121-GFP in relation to other apoptotic events, revealed that it can be applied as an early non-invasive sensor of nuc-lear apoptosis in living cells using fluorescence microscopy or fluorimetric analysis.

  • 265.
    Beckman, Marie
    et al.
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Kihlmark, Madeleine
    Södertörn University, Stockholm, Sweden.
    Hallberg, Einar
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Nucleus and Nuclear Envelope: Methods for Preparation2010Book (Other academic)
    Abstract [en]

    The cell nucleus of eukaryotic organisms contains the genome surrounded by a nuclear envelope consisting of a double-lipid membrane with embedded nuclear pores and an underlying nuclear lamina. The uniformity in size and density makes it possible to isolate pure intact nuclei at high yields from tissue homogenates by centrifugation through a sucrose cushion. Nuclear envelopes can be prepared from isolated nuclei by enzymatic degradation of their nucleic acid content. The resulting nuclear envelope preparations contain structurally well-conserved inner and outer nuclear membranes with attached ribosomes, nuclear pore complexes and nuclear lamina. Reliable methods for preparation of nuclei and nuclear envelopes play an important role in the successful identification of components that are located in nuclei and in nuclear subcompartments.

  • 266. Beelen, Rob
    et al.
    Hoek, Gerard
    Raaschou-Nielsen, Ole
    Stafoggia, Massimo
    Andersen, Zorana Jovanovic
    Weinmayr, Gudrun
    Hoffmann, Barbara
    Wolf, Kathrin
    Samoli, Evangelia
    Fischer, Paul H.
    Nieuwenhuijsen, Mark J.
    Xun, Wei W.
    Katsouyanni, Klea
    Dimakopoulou, Konstantina
    Marcon, Alessandro
    Vartiainen, Erkki
    Lanki, Timo
    Yli-Tuomi, Tarja
    Oftedal, Bente
    Schwarze, Per E.
    Nafstad, Per
    De Faire, Ulf
    Pedersen, Nancy L.
    Otstenson, Claes-Goran
    Fratiglioni, Laura
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Penell, Johanna
    Korek, Michal
    Pershagen, Goran
    Eriksen, Kirsten Thorup
    Overvad, Kim
    Sorensen, Mette
    Eeftens, Marloes
    Peeters, Petra H.
    Meliefste, Kees
    Wang, Meng
    Bueno-de-Mesquita, H. Bas
    Sugiri, Dorothea
    Kramer, Ursula
    Heinrich, Joachim
    de Hoogh, Kees
    Key, Timothy
    Peters, Annette
    Hampel, Regina
    Concin, Hans
    Nagel, Gabriele
    Jaensch, Andrea
    Ineichen, Alex
    Tsai, Ming-Yi
    Schaffner, Emmanuel
    Probst-Hensch, Nicole M.
    Schindler, Christian
    Ragettli, Martina S.
    Vilier, Alice
    Clavel-Chapelon, Francoise
    Declercq, Christophe
    Ricceri, Fulvio
    Sacerdote, Carlotta
    Galassi, Claudia
    Migliore, Enrica
    Ranzi, Andrea
    Cesaroni, Giulia
    Badaloni, Chiara
    Forastiere, Francesco
    Katsoulis, Michail
    Trichopoulou, Antonia
    Keuken, Menno
    Jedynska, Aleksandra
    Kooter, Ingeborg M.
    Kukkonen, Jaakko
    Sokhi, Ranjeet S.
    Vineis, Paolo
    Brunekreef, Bert
    Natural-Cause Mortality and Long-Term Exposure to Particle Components: An Analysis of 19 European Cohorts within the Multi-Center ESCAPE Project2015In: Journal of Environmental Health Perspectives, ISSN 0091-6765, E-ISSN 1552-9924, Vol. 123, no 6, p. 525-533Article, review/survey (Refereed)
    Abstract [en]

    Background: Studies have shown associations between mortality and long-term exposure to particulate matter air pollution. Few cohort studies have estimated the effects of the elemental composition of particulate matter on mortality. Objectives: Our aim was to study the association between natural-cause mortality and long-term exposure to elemental components of particulate matter. Methods: Mortality and confounder data from 19 European cohort studies were used. Residential exposure to eight a priori-selected components of particulate matter ( PM) was characterized following a strictly standardized protocol. Annual average concentrations of copper, iron, potassium, nickel, sulfur, silicon, vanadium, and zinc within PM size fractions <= 2.5 mu m (PM2.5) and <= 10 mu m (PM10) were estimated using land-use regression models. Cohort-specific statistical analyses of the associations between mortality and air pollution were conducted using Cox proportional hazards models using a common protocol followed by meta-analysis. Results: The total study population consisted of 291,816 participants, of whom 25,466 died from a natural cause during follow-up (average time of follow-up, 14.3 years). Hazard ratios were positive for almost all elements and statistically significant for PM2.5 sulfur (1.14; 95% CI: 1.06, 1.23 per 200ng/m(3)). In a two-pollutant model, the association with PM2.5 sulfur was robust to adjustment for PM2.5 mass, whereas the association with PM2.5 mass was reduced. Conclusions: Long-term exposure to PM2.5 sulfur was associated with natural-cause mortality. This association was robust to adjustment for other pollutants and PM2.5.

  • 267. Beelen, Rob
    et al.
    Raaschou-Nielsen, Ole
    Stafoggia, Massimo
    Andersen, Zorana Jovanovic
    Weinmayr, Gudrun
    Hoffmann, Barbara
    Wolf, Kathrin
    Samoli, Evangelia
    Fischer, Paul
    Nieuwenhuijsen, Mark
    Vineis, Paolo
    Xun, Wei W.
    Katsouyanni, Klea
    Dimakopoulou, Konstantina
    Oudin, Anna
    Forsberg, Bertil
    Modig, Lars
    Havulinna, Aki S.
    Lanki, Timo
    Turunen, Anu
    Oftedal, Bente
    Nystad, Wenche
    Nafstad, Per
    De Faire, Ulf
    Pedersen, Nancy L.
    Östenson, Claes-Göran
    Fratiglioni, Laura
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Penell, Johanna
    Korek, Michal
    Pershagen, Göran
    Eriksen, Kirsten Thorup
    Overvad, Kim
    Ellermann, Thomas
    Eeftens, Marloes
    Peeters, Petra H.
    Meliefste, Kees
    Wang, Meng
    Bueno-de-Mesquita, Bas
    Sugiri, Dorothea
    Kraemer, Ursula
    Heinrich, Joachim
    de Hoogh, Kees
    Key, Timothy
    Peters, Annette
    Hampel, Regina
    Concin, Hans
    Nagel, Gabriele
    Ineichen, Alex
    Schaffner, Emmanuel
    Probst-Hensch, Nicole
    Kuenzli, Nino
    Schindler, Christian
    Schikowski, Tamara
    Adam, Martin
    Phuleria, Harish
    Vilier, Alice
    Clavel-Chapelon, Francoise
    Declercq, Christophe
    Grioni, Sara
    Krogh, Vittorio
    Tsai, Ming-Yi
    Ricceri, Fulvio
    Sacerdote, Carlotta
    Galassi, Claudia
    Migliore, Enrica
    Ranzi, Andrea
    Cesaroni, Giulia
    Badaloni, Chiara
    Forastiere, Francesco
    Tamayo, Ibon
    Amiano, Pilar
    Dorronsoro, Miren
    Katsoulis, Michail
    Trichopoulou, Antonia
    Brunekreef, Bert
    Hoek, Gerard
    Effects of long-term exposure to air pollution on natural-cause mortality: an analysis of 22 European cohorts within the multicentre ESCAPE project2014In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 383, no 9919, p. 785-795Article in journal (Refereed)
    Abstract [en]

    Background Few studies on long-term exposure to air pollution and mortality have been reported from Europe. Within the multicentre European Study of Cohorts for Air Pollution Effects (ESCAPE), we aimed to investigate the association between natural-cause mortality and long-term exposure to several air pollutants. Methods We used data from 22 European cohort studies, which created a total study population of 367 251 participants. All cohorts were general population samples, although some were restricted to one sex only. With a strictly standardised protocol, we assessed residential exposure to air pollutants as annual average concentrations of particulate matter (PM) with diameters of less than 2.5 mu m (PM2.5), less than 10 mu m (PM10), and between 10 mu m and 2.5 mu m (PMcoarse), PM2.5 absorbance, and annual average concentrations of nitrogen oxides (NO2 and NOx), with land use regression models. We also investigated two traffic intensity variables-traffic intensity on the nearest road (vehicles per day) and total traffic load on all major roads within a 100 m buff er. We did cohort-specific statistical analyses using confounder models with increasing adjustment for confounder variables, and Cox proportional hazards models with a common protocol. We obtained pooled effect estimates through a random-effects meta-analysis. Findings The total study population consisted of 367 251 participants who contributed 5 118 039 person-years at risk (average follow-up 13.9 years), of whom 29 076 died from a natural cause during follow-up. A significantly increased hazard ratio (HR) for PM2.5 of 1.07 (95% CI 1.02-1.13) per 5 mu g/m(3) was recorded. No heterogeneity was noted between individual cohort effect estimates (I-2 p value=0.95). HRs for PM2.5 remained significantly raised even when we included only participants exposed to pollutant concentrations lower than the European annual mean limit value of 25 mu g/m(3) (HR 1.06, 95% CI 1.00-1.12) or below 20 mu g/m(3) (1.07, 1.01-1.13). Interpretation Long-term exposure to fine particulate air pollution was associated with natural-cause mortality, even within concentration ranges well below the present European annual mean limit value.

  • 268. Beelen, Rob
    et al.
    Stafoggia, Massimo
    Raaschou-Nielsen, Ole
    Andersen, Zorana Jovanovic
    Xun, Wei W.
    Katsouyanni, Klea
    Dimakopoulou, Konstantina
    Brunekreef, Bert
    Weinmayr, Gudrun
    Hoffmann, Barbara
    Wolf, Kathrin
    Samoli, Evangelia
    Houthuijs, Danny
    Nieuwenhuijsen, Mark
    Oudin, Anna
    Forsberg, Bertil
    Olsson, David
    Salomaa, Veikko
    Lanki, Timo
    Yli-Tuomi, Tarja
    Oftedal, Bente
    Aamodt, Geir
    Nafstad, Per
    De Faire, Ulf
    Pedersen, Nancy L.
    Östenson, Claes-Göran
    Fratiglioni, Laura
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Penell, Johanna
    Korek, Michal
    Pyko, Andrei
    Thorup Eriksen, Kirsten
    Tjonneland, Anne
    Becker, Thomas
    Eeftens, Marloes
    Bots, Michiel
    Meliefste, Kees
    Wang, Meng
    Bueno-de-Mesquita, Bas
    Sugiri, Dorothea
    Kraemer, Ursula
    Heinrich, Joachim
    de Hoogh, Kees
    Key, Timothy
    Peters, Annette
    Cyrys, Josef
    Concin, Hans
    Nagel, Gabriele
    Ineichen, Alex
    Schaffner, Emmanuel
    Probst-Hensch, Nicole
    Dratva, Julia
    Ducret-Stich, Regina
    Vilier, Alice
    Clavel-Chapelon, Francoise
    Stempfelet, Morgane
    Grioni, Sara
    Krogh, Vittorio
    Tsai, Ming-Yi
    Marcon, Alessandro
    Ricceri, Fulvio
    Sacerdote, Carlotta
    Galassi, Claudia
    Migliore, Enrica
    Ranzi, Andrea
    Cesaroni, Giulia
    Badaloni, Chiara
    Forastiere, Francesco
    Tamayo, Ibon
    Amiano, Pilar
    Dorronsoro, Miren
    Katsoulis, Michail
    Trichopoulou, Antonia
    Vineis, Paolo
    Hoek, Gerard
    Long-term Exposure to Air Pollution and Cardiovascular Mortality An Analysis of 22 European Cohorts2014In: Epidemiology, ISSN 1044-3983, E-ISSN 1531-5487, Vol. 25, no 3, p. 368-378Article in journal (Refereed)
    Abstract [en]

    Background: Air pollution has been associated with cardiovascular mortality, but it remains unclear as to whether specific pollutants are related to specific cardiovascular causes of death. Within the multicenter European Study of Cohorts for Air Pollution Effects (ESCAPE), we investigated the associations of long-term exposure to several air pollutants with all cardiovascular disease (CVD) mortality, as well as with specific cardiovascular causes of death. Methods: Data from 22 European cohort studies were used. Using a standardized protocol, study area-specific air pollution exposure at the residential address was characterized as annual average concentrations of the following: nitrogen oxides (NO2 and NOx); particles with diameters of less than 2.5 mu m (PM2.5), less than 10 mu m (PM10), and 10 mu m to 2.5 mu m (PMcoarse); PM2.5 absorbance estimated by land-use regression models; and traffic indicators. We applied cohort-specific Cox proportional hazards models using a standardized protocol. Random-effects meta-analysis was used to obtain pooled effect estimates. Results: The total study population consisted of 367,383 participants, with 9994 deaths from CVD (including 4,992 from ischemic heart disease, 2264 from myocardial infarction, and 2484 from cerebrovascular disease). All hazard ratios were approximately 1.0, except for particle mass and cerebrovascular disease mortality; for PM2.5, the hazard ratio was 1.21 (95% confidence interval = 0.87-1.69) per 5 mu g/m(3) and for PM10, 1.22 (0.91-1.63) per 10 mu g/m(3). Conclusion: In a joint analysis of data from 22 European cohorts, most hazard ratios for the association of air pollutants with mortality from overall CVD and with specific CVDs were approximately 1.0, with the exception of particulate mass and cerebrovascular disease mortality for which there was suggestive evidence for an association.

  • 269. Been, Frederic
    et al.
    Bifisma, Lubertus
    Benaglia, Lisa
    Berset, Jean-Daniel
    Botero-Coy, Ana M.
    Castiglioni, Sara
    Kraus, Ludwig
    Stockholm University, Faculty of Social Sciences, Centre for Social Research on Alcohol and Drugs (SoRAD). IFT Institut für Therapieforschung, Germany.
    Zobel, Frank
    Schaub, Michael P.
    Buecheli, Alexander
    Hernandez, Felix
    Delemont, Olivier
    Esseiva, Pierre
    Ort, Christoph
    Assessing geographical differences in illicit drug consumption-A comparison of results from epidemiological and wastewater data in Germany and Switzerland2016In: Drug And Alcohol Dependence, ISSN 0376-8716, E-ISSN 1879-0046, Vol. 161, p. 189-199Article in journal (Refereed)
    Abstract [en]

    Background: Wastewater analysis is an innovative approach that allows monitoring illicit drug use at the community level. This study focused on investigating geographical differences in drug consumption by comparing epidemiological, crime and wastewater data. Methods: Wastewater samples were collected in 19 cities across Germany and Switzerland during one week, covering a population of approximately 8.1 million people. Self-report data and consumption offences for the investigated areas were used for comparison and to investigate differences between the indicators. Results: Good agreement between data sources was observed for cannabis and amphetamine-type stimulants, whereas substantial discrepancies were observed for cocaine. In Germany, an important distinction could be made between Berlin, Dortmund and Munich, where cocaine and particularly amphetamine were more prevalent, and Dresden, where methamphetamine consumption was clearly predominant. Cocaine consumption was relatively homogenous in the larger urban areas of Switzerland, although prevalence and offences data suggested a more heterogeneous picture. Conversely, marked regional differences in amphetamine and methamphetamine consumption could be highlighted. Conclusions: Combining the available data allowed for a better understanding of the geographical differences regarding prevalence, typology and amounts of substances consumed. For cannabis and amphetamine-type stimulants, the complementarity of survey, police and wastewater data could be highlighted, although notable differences could be identified when considering more stigmatised drugs (i.e. cocaine and heroin). Understanding illicit drug consumption at the national scale remains a difficult task, yet this research illustrates the added value of combining complementary data sources to obtain a more comprehensive and accurate picture of the situation.

  • 270. Beer, Netta
    et al.
    Ali, Abdullah S.
    Eskilsson, Helena
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Jansson, Andreas
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Abdul-Kadir, Faiza M.
    Rotllant-Estelrich, Guida
    Abass, Ali K.
    Wabwire-Mangen, Fred
    Björkman, Anders
    Kallander, Karin
    A qualitative study on caretakers' perceived need of bed-nets after reduced malaria transmission in Zanzibar, Tanzania2012In: BMC Public Health, ISSN 1471-2458, E-ISSN 1471-2458, Vol. 12, p. 606-Article in journal (Refereed)
    Abstract [en]

    Background: The elimination of malaria in Zanzibar is highly dependent on sustained effective coverage of bed-nets to avoid malaria resurgence. The Health Belief Model (HBM) framework was used to explore the perceptions of malaria and bed-net use after a noticeable reduction in malaria incidence. Methods: Nineteen in-depth interviews were conducted with female and male caretakers of children under five in North A district, Zanzibar. Deductive content analysis was used to identify meaning units that were condensed, coded and assigned to pre-determined elements of the HBM. Results: Awareness of malaria among caretakers was high but the illness was now seen as easily curable and uncommon. In addition to the perceived advantage of providing protection against malaria, bed-nets were also thought to be useful for avoiding mosquito nuisance, especially during the rainy season when the malaria and mosquito burden is high. The discomfort of sleeping under a net during the hot season was the main barrier that interrupted consistent bed-net usage. The main cue to using a bed-net was high mosquito density, and children were prioritized when it came to bed-net usage. Caretakers had high perceived self-efficacy and did not find it difficult to use bed-nets. Indoor Residual Spraying (IRS), which was recognized as an additional means of mosquito prevention, was not identified as an alternative for bed-nets. A barrier to net ownership was the increasingly high cost of bed-nets. Conclusions: Despite the reduction in malaria incidence and the resulting low malaria risk perceptions among caretakers, the benefit of bed-nets as the most proficient protection against mosquito bites upholds their use. This, in combination with the perceived high self-efficacy of caretakers, supports bed-net usage, while seasonality interrupts consistent use. High effective coverage of bed-nets could be further improved by reinforcing the benefits of bed-nets, addressing the seasonal heat barrier by using nets with larger mesh sizes and ensuring high bed-net ownership rates through sustainable and affordable delivery mechanisms.

  • 271. Beghini, Alessandro
    et al.
    Corlazzoli, Francesca
    Del Giacco, Luca
    Re, Matteo
    Lazzaroni, Francesca
    Brioschi, Matteo
    Valentini, Giorgio
    Ferrazzi, Fulvia
    Ghilardi, Anna
    Righi, Marco
    Turrini, Mauro
    Mignardi, Marco
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Cesana, Clara
    Bronte, Vincenzo
    Nilsson, Mats
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Morra, Enrica
    Cairoli, Roberto
    Regeneration-associated WNT Signaling Is Activated in Long-term Reconstituting AC133(bright) Acute Myeloid Leukemia Cells2012In: Neoplasia, ISSN 1522-8002, E-ISSN 1476-5586, Vol. 14, no 12, p. 1236-+Article in journal (Refereed)
    Abstract [en]

    Acute myeloid leukemia (AML) is a genetically heterogeneous clonal disorder characterized by two molecularly distinct self-renewing leukemic stem cell (LSC) populations most closely related to normal progenitors and organized as a hierarchy. A requirement for WNT/beta-catenin signaling in the pathogenesis of AML has recently been suggested by a mouse model. However, its relationship to a specific molecular function promoting retention of self-renewing leukemia-initiating cells (LICs) in human remains elusive. To identify transcriptional programs involved in the maintenance of a self-renewing state in LICs, we performed the expression profiling in normal (n = 10) and leukemic (n = 33) human long-term reconstituting AC133(+) cells, which represent an expanded cell population in most AML patients. This study reveals the ligand-dependent WNT pathway activation in AC133(bright) AML cells and shows a diffuse expression and release of WNT 10B, a hematopoietic stem cell regenerative-associated molecule. The establishment of a primary AC133(+) AML cell culture (A46) demonstrated that leukemia cells synthesize and secrete WNT ligands, increasing the levels of dephosphorylated beta-catenin in vivo. We tested the LSC functional activity in AC133(+) cells and found significant levels of engraftment upon transplantation of A46 cells into irradiated Rag2(-/-)gamma c(-/-) mice. Owing to the link between hematopoietic regeneration and developmental signaling, we transplanted A46 cells into developing zebrafish. This system revealed the formation of ectopic structures by activating dorsal organizer markers that act downstream of the WNT pathway. In conclusion, our findings suggest that AC133(bright) LSCs are promoted by misappropriating homeostatic WNT programs that control hematopoietic regeneration. Neoplasia (2012) 14, 1236-1248

  • 272.
    Behm, Mikaela
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Stockholms universitet.
    Regulation of RNA Editing: The impact of inosine on the neuronal transcriptome2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The transcriptome of the mammalian brain is extensively modified by adenosine to inosine (A-to-I) nucleotide conversion by two adenosine deaminases (ADAR1 and ADAR2). As adenosine and inosine have different base pairing properties, A-to-I RNA editing shapes the functional output of both coding and non-coding RNAs (ncRNAs) in the brain. The aim of this thesis was to identify editing events in small regulatory ncRNAs (miRNAs) and to determine their temporal and spatial editing status in the developing and adult mouse brain. To do this, we initially analyzed the editing status of miRNAs from different developmental time points of the mouse brain. We detected novel miRNA substrates subjected to A-to-I editing and found a general increase in miRNA editing during brain development, implicating a more stringent control of miRNAs as the brain matures. Most of the edited miRNAs were found to be transcribed as a single long consecutive transcript from a large gene cluster. However, maturation from this primary miRNA (pri-miRNA) transcript into functional forms of miRNAs is regulated individually, and might be influenced by the ADAR proteins in an editing independent matter. We also found that edited miRNAs were highly expressed at the synapse, implicating a role as local regulators of synaptic translation. We further show that the increase in editing during development is explained by a gradual accumulation of the ADAR enzymes in the nucleus. Specifically for ADAR2, we found a developmentally increasing interaction with two factors, importin-α4 and Pin1, that facilitate nuclear localization of the editing enzyme. We have also found that selectively edited stem loops often are flanked by other long stem loop structures that induce editing in cis. This may explain why multiple pri-miRNAs are edited within the same cluster. In conclusion, this thesis has significantly increased the understanding of the dynamics of both editing substrates and enzymes in the developing and mature brain.

  • 273.
    Behm, Mikaela
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Wahlstedt, Helene
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Widmark, Albin
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Eriksson, Maria
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Öhman, Marie
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Accumulation of nuclear ADAR2 regulates A-to-I RNA editing during neuronal development2017In: Journal of Cell Science, ISSN 0021-9533, E-ISSN 1477-9137, Vol. 130, p. 745-753Article in journal (Refereed)
    Abstract [en]

    Adenosine to inosine (A-to-I) RNA editing is important for a functional brain, and most known sites that are subject to selective RNA editing have been found to result in diversified protein isoforms that are involved in neurotransmission. In the absence of the active editing enzymes ADAR1 or ADAR2 (also known as ADAR and ADARB1, respectively), mice fail to survive until adulthood. Nuclear A-to-I editing of neuronal transcripts is regulated during brain development, with low levels of editing in the embryo and a dramatic increase after birth. Yet, little is known about the mechanisms that regulate editing during development. Here, we demonstrate lower levels of ADAR2 in the nucleus of immature neurons than in mature neurons. We show that importin-a4 (encoded by Kpna3), which increases during neuronal maturation, interacts with ADAR2 and contributes to the editing efficiency by bringing it into the nucleus. Moreover, we detect an increased number of interactions between ADAR2 and the nuclear isomerase Pin1 as neurons mature, which contribute to ADAR2 protein stability. Together, these findings explain how the nuclear editing of substrates that are important for neuronal function can increase as the brain develops. 

  • 274. Beijer, Ulla
    et al.
    Scheffel Birath, Christina
    DeMartinis, Valerie
    af Klinteberg, Britt
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS). Stockholm University, Faculty of Social Sciences, Department of Psychology, Biological psychology. Karolinska Institutet, Sweden.
    Facets of male violence against women with Substance Abuse Problems: Women with residence and homeless women2016In: Journal of Interpersonal Violence, ISSN 0886-2605, E-ISSN 1552-6518Article in journal (Refereed)
    Abstract [en]

    The aims of this study were to investigate the type and extent to which women with substance abuse problems have been exposed to male violence during their lifetime, and to examine possible differences between women with a residence (WR) and homeless women (HW). The total sample included 79 women (WR, n = 35; HW, n = 44; M age = 47.8 years). Of the total sample, 72 women (91%) had experienced different kinds of male violence, 88% from former partners, and 26% from male friends or acquaintances. Of the 72 women, 71% further reported “Countless occasions of violent events,” and 36% had been forced to commit criminal acts. Abused women who had been forced to commit criminal acts were significantly more frequently found to be homeless, have reported parental alcohol and/or drug problems, have witnessed domestic violence in childhood, have been victims of sexual violence, have used illicit drugs as a dominant preparation, and have injected illicit drugs. Almost half of the abused women (46%) met criteria for posttraumatic stress disorder (PTSD), where HW showed an almost 4-time higher risk (RR 3.78) than WR. In conclusion there is a particular vulnerability in women with substance abuse to male violence, which has an important impact on their health status. Thus, from a public health perspective, it is suggested that for those women who have experienced male violence, treatment protocols need to include both assessing and addressing the impact of such experience in relation to substance abuse as well as concomitant health concerns.

  • 275. Beishuizen, Cathrien R. L.
    et al.
    Stephan, Blossom C. M.
    van Gool, Willem A.
    Brayne, Carol
    Peters, Ron J. G.
    Andrieu, Sandrine
    Kivipelto, Miia
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Soininen, Hilkka
    Busschers, Wim B.
    van Charante, Eric P. Moll
    Richard, Edo
    Web-Based Interventions Targeting Cardiovascular Risk Factors in Middle-Aged and Older People: A Systematic Review and Meta-Analysis2016In: Journal of Medical Internet Research, ISSN 1438-8871, E-ISSN 1438-8871, Vol. 18, no 3, article id e55Article, review/survey (Refereed)
    Abstract [en]

    Background: Web-based interventions can improve single cardiovascular risk factors in adult populations. In view of global aging and the associated increasing burden of cardiovascular disease, older people form an important target population as well.

    Objective: In this systematic review and meta-analysis, we evaluated whether Web-based interventions for cardiovascular risk factor management reduce the risk of cardiovascular disease in older people.

    Methods: Embase, Medline, Cochrane and CINAHL were systematically searched from January 1995 to November 2014. Search terms included cardiovascular risk factors and diseases (specified), Web-based interventions (and synonyms) and randomized controlled trial. Two authors independently performed study selection, data-extraction and risk of bias assessment. In a meta-analysis, outcomes regarding treatment effects on cardiovascular risk factors (blood pressure, glycated hemoglobin A1c (HbA1C), low-density lipoprotein (LDL) cholesterol, smoking status, weight and physical inactivity) and incident cardiovascular disease were pooled with random effects models.

    Results: A total of 57 studies (N=19,862) fulfilled eligibility criteria and 47 studies contributed to the meta-analysis. A significant reduction in systolic blood pressure (mean difference -2.66 mmHg, 95% CI -3.81 to -1.52), diastolic blood pressure (mean difference -1.26 mmHg, 95% CI -1.92 to -0.60), HbA1c level (mean difference -0.13%, 95% CI -0.22 to -0.05), LDL cholesterol level (mean difference -2.18 mg/dL, 95% CI -3.96 to -0.41), weight (mean difference -1.34 kg, 95% CI -1.91 to -0.77), and an increase of physical activity (standardized mean difference 0.25, 95% CI 0.10-0.39) in the Web-based intervention group was found. The observed effects were more pronounced in studies with short (<12 months) follow-up and studies that combined the Internet application with human support (blended care). No difference in incident cardiovascular disease was found between groups (6 studies).

    Conclusions: Web-based interventions have the potential to improve the cardiovascular risk profile of older people, but the effects are modest and decline with time. Currently, there is insufficient evidence for an effect on incident cardiovascular disease. A focus on long-term effects, clinical endpoints, and strategies to increase sustainability of treatment effects is recommended for future studies.

  • 276. Bejerot, Susanne
    et al.
    Nilsonne, Gustav
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Humble, Mats B.
    Subcortical brain volume differences in participants with attention deficit hyperactivity disorder in children and adults2017In: Lancet psychiatry, ISSN 2215-0374, E-ISSN 2215-0366, Vol. 4, no 6, p. 437-437Article in journal (Refereed)
  • 277. Belenky, G
    et al.
    Åkerstedt, Torbjörn
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Occupational Sleep Medicine, introduction2011In: Principle and Practice of Sleep Medicine / [ed] Kryger MH, Roth T, Dement WC, St. Louise: Elisevier Saunders , 2011, p. 1723-Chapter in book (Refereed)
  • 278. Belenky, Gregory
    et al.
    Åkerstedt, Torbjörn
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Wasensten, Nancy J.
    Introduction. Occupational Sleep Medicin2016In: Principles and Practice of Sleep Medicine / [ed] Meir H. Kryger, Thomas Roth, William C. Dement, Elsevier, 2016, 6 uppl., p. 679-681Chapter in book (Other academic)
  • 279. Bell, J. Simon
    et al.
    Johnell, Kristina
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Wimmer, Barbara C.
    Wiese, Michael D.
    Multidose drug dispensing and optimising drug use in older people2013In: Age and Ageing, ISSN 0002-0729, E-ISSN 1468-2834, Vol. 42, no 5, p. 556-558Article in journal (Refereed)
  • 280. Bell, Thomas J.
    et al.
    Eiríksdóttir, Emelía
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Langel, Ülo
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Eberwine, James
    PAIR technology: exon-specific RNA binding protein isolation in live cells2011In: Cell-penetrating peptides: Methods and Protocols / [ed] Ülo Langel, New York: Humana Press, 2011, p. 473-486Chapter in book (Refereed)
    Abstract [en]

    RNA-binding proteins (RBPs) are fundamental regulatory proteins for all forms of transcriptional and posttranscriptional control of gene expression. However, isolating RBPs is technically challenging for investigators. Currently, the most widely used techniques to isolate RBPs are in vitro biochemical approaches. Although these approaches have been useful, they have several limitations. One key limitation to using in vitro biochemical approaches is that RBP–RNA interactions are isolated under nonbiological conditions. Here we review a novel experimental approach to identify RBPs called peptide nucleic acid (PNA)-assisted identification of RBPs (PAIR) technology (Zielinski et al., Proc Natl Acad Sci USA 103:1557–1562, 2006). This technology has two significant advantages over traditional approaches. (1) It overcomes the in vitro limitation of biochemical approaches by allowing investigators to isolate RBP–RNA interactions under in vivo conditions. (2) This technology is highly mRNA specific; it isolates RBPs in an exon-specific manner. By selectively targeting alternatively spliced exons with PAIR technology, investigators can isolate splice variant-specific and mRNA region-specific (5-UTR and 3-UTR) RBP complexes for any mRNA of interest.

  • 281.
    Bellander, Martin
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Berggren, Rasmus
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Mårtensson, Johan
    Brehmer, Yvonne
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Max Planck Institute for Human Development, Germany.
    Wenger, Elisabeth
    Li, Tie-Qiang
    Bodammer, Nils C.
    Shing, Yee-Lee
    Werkle-Bergner, Markus
    Lövdén, Martin
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Behavioral correlates of changes in hippocampal gray matter structure during acquisition of foreign vocabulary2016In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 131, p. 205-213Article in journal (Refereed)
    Abstract [en]

    Experience can affect human gray matter volume. The behavioral correlates of individual differences in such brain changes are not well understood. In a group of Swedish individuals studying Italian as a foreign language, we investigated associations among time spent studying, acquired vocabulary, baseline performance on memory tasks, and gray matter changes. As a way of studying episodic memory training, the language learning focused on acquiring foreign vocabulary and lasted for 10 weeks. T-1-weighted structural magnetic resonance imaging and cognitive testing were performed before and after the studies. Learning behavior was monitored via participants' use of a smartphone application dedicated to the study of vocabulary. A whole-brain analysis showed larger changes in gray matter structure of the right hippocampus in the experimental group (N = 33) compared to an active control group (N = 23). A first path analyses revealed that time spent studying rather than acquired knowledge significantly predicted change in gray matter structure. However, this association was not significant when adding performance on baseline memory measures into the model, instead only the participants' performance on a short-term memory task with highly similar distractors predicted the change. This measure may tap similar individual difference factors as those involved in gray matter plasticity of the hippocampus.

  • 282.
    Bellander, Martin
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Eschen, Anne
    Lövdén, Martin
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Martin, Mike
    Bäckman, Lars
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Brehmer, Yvonne
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Max Planck Institute for Human Development, Germany.
    No Evidence for Improved Associative Memory Performance Following Process-Based Associative Memory Training in Older Adults2017In: Frontiers in Aging Neuroscience, ISSN 1663-4365, E-ISSN 1663-4365, Vol. 8, article id 326Article in journal (Refereed)
    Abstract [en]

    Studies attempting to improve episodic memory performance with strategy instructions and training have had limited success in older adults: their training gains are limited in comparison to those of younger adults and do not generalize to untrained tasks and contexts. This limited success has been partly attributed to age-related impairments in associative binding of information into coherent episodes. We therefore investigated potential training and transfer effects of process-based associative memory training (i.e., repeated practice). Thirty-nine older adults (M-age = 68.8) underwent 6 weeks of either adaptive associative memory training or item recognition training. Both groups improved performance in item memory, spatial memory (object-context binding) and reasoning. A disproportionate effect of associative memory training was only observed for item memory, whereas no training-related performance changes were observed for associative memory. Self-reported strategies showed no signs of spontaneous development of memory-enhancing associative memory strategies. Hence, the results do not support the hypothesis that process-based associative memory training leads to higher associative memory performance in older adults.

  • 283.
    Bellavia, Andrea
    et al.
    Karolinska Inst, Inst Environm Med, Unit Nutr Epidemiol.
    Åkerstedt, Torbjörn
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Bottai, Matteo
    Wolk, Alicja
    Karolinska Inst, Inst Environm Med, Unit Nutr Epidemiol.
    Orsini, Nicola
    Karolinska Inst, Inst Environm Med, Unit Nutr Epidemiol.
    Sleep Duration and Survival Percentiles Across Categories of Physical Activity2014In: American Journal of Epidemiology, ISSN 0002-9262, E-ISSN 1476-6256, Vol. 179, no 4, p. 484-491Article in journal (Refereed)
    Abstract [en]

    The association between long sleep duration and death is not fully understood. Long sleep is associated with low physical activity, which is a strong predictor of death. Our aim was to investigate the association between sleep duration and death across categories of total physical activity in a large prospective cohort of Swedish men and women. We followed a population-based cohort of 70,973 participants (37,846 men and 33,127 women), aged 45-83 years, from January 1998 to December 2012. Sleep duration and physical activity levels were assessed through a questionnaire. We evaluated the association of interest in terms of mortality rates by estimating hazard ratios with Cox regression and in terms of survival by evaluating 15th survival percentile differences with Laplace regression. During 15 years of follow-up, we recorded 14,575 deaths (8,436 men and 6,139 women). We observed a significant interaction between sleep duration and physical activity in predicting death (P < 0.001). Long sleep duration (>8 hours) was associated with increased mortality risk (hazard ratio = 1.24; 95% confidence interval: 1.11, 1.39) and shorter survival (15th percentile difference = -20 months; 95% confidence interval: -30, -11) among only those with low physical activity. The association between long sleep duration and death might be partly explained by comorbidity with low physical activity.

  • 284.
    Beltran-Pardo, Eliana
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Jonsson, K. Ingemar
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Kristianstad University, Sweden.
    Harms-Ringdahl, Mats
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Haghdoost, Siamak
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Wojcik, Andrzej
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Tolerance to Gamma Radiation in the Tardigrade Hypsibius dujardini from Embryo to Adult Correlate Inversely with Cellular Proliferation2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 7, article id e0133658Article in journal (Refereed)
    Abstract [en]

    Tardigrades are highly tolerant to desiccation and ionizing radiation but the mechanisms of this tolerance are not well understood. In this paper, we report studies on dose responses of adults and eggs of the tardigrade Hypsibius dujardini exposed to gamma radiation. In adults the LD50/48h for survival was estimated at similar to 4200 Gy, and doses higher than 100 Gy reduced both fertility and hatchability of laid eggs drastically. We also evaluated the effect of radiation (doses 50 Gy, 200 Gy, 500 Gy) on eggs in the early and late embryonic stage of development, and observed a reduced hatchability in the early stage, while no effect was found in the late stage of development. Survival of juveniles from irradiated eggs was highly affected by a 500 Gy dose, both in the early and the late stage. Juveniles hatched from eggs irradiated at 50 Gy and 200 Gy developed into adults and produced offspring, but their fertility was reduced compared to the controls. Finally we measured the effect of low temperature during irradiation at 4000 Gy and 4500 Gy on survival in adult tardigrades, and observed a slight delay in the expressed mortality when tardigrades were irradiated on ice. Since H. dujardini is a freshwater tardigrade with lower tolerance to desiccation compared to limno-terrestrial tardigrades, the high radiation tolerance in adults, similar to limno-terrestrial tardigrades, is unexpected and seems to challenge the idea that desiccation and radiation tolerance rely on the same molecular mechanisms. We suggest that the higher radiation tolerance in adults and late stage embryos of H. dujardini (and in other studied tardigrades) compared to early stage embryos may partly be due to limited mitotic activity, since tardigrades have a low degree of somatic cell division (eutely), and dividing cells are known to be more sensitive to radiation.

  • 285. Bengtsson, Camilla
    et al.
    Theorell, Töres
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Klareskog, Lars
    Alfredsson, Lars
    Psychosocial Stress at Work and the Risk of Developing Rheumatoid Arthritis: Results from the Swedish EIRA Study.2009In: Psychotherapy and psychosomatics, ISSN 1423-0348, Vol. 78, no 3, p. 193-194Article in journal (Refereed)
  • 286.
    Bengtsson, Emil
    Stockholm University, Faculty of Science, Medical Radiation Physics (together with KI).
    Doseplanning ocular tumors with 125I-seeds2006Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Since 1986 patients with ocular malignant melanoma have been treated with Ru-106 plaques at S:t Erik Eye Hospital. In 1998 I-125 radioactive seed plaques was presented as an alternative to Ru-106 when treating tumors with an apical height greater than 7 mm. Until June 2005 the doseplanning of these plaques was based on a depth-dose curve made in the dose planning system Cadplan supplied by Varian Medical Systems. In the recent years the capabilities of computerized 3D dose planning system has increased greatly. The number of types of seeds on the market has also increased.

    In order to implement the modern 3D dose planning system Brachy Vision 7.3.10 in planning the I-125 plaques, a review of the dose planning process have been done.

    The ultra sound equipment used by the ophthalmologist to determine the apical height of the tumor has been investigated in terms of accuracy. A phantom has been developed for this task.

    As new seeds entered the market a comparision have been made comparing the Amersham 6711 seed with the Bebig I25.S06 seed. A method for measuring the activity of the single seeds has also been developed.

    The dose planning system Brachy Vision 7.3.10 have been compared to the old dose planning method, and an implementation of the plaques into Brachy Vision have been made.

    The ultra sound equipment was accurate in the regions of interest. It was also discovered that the Bebig I25.S06 seed gave slightly higher dose compared to the Amersham 6711 with the same activity. The difference between the seeds is however small. The results indicate that the old dose planning method gave a slight underdosage.

  • 287.
    Bengtsson, Johanna
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    The impact of cytochrome P4501-inhibitors on aryl hydrocarbon receptor signaling2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The aryl hydrocarbon receptor (AHR) best known as a ligand-activated transcription factor that mediates toxic responses to xenobiotics such as dioxins, is also activated by certain endogenous compounds. Activation of the AHR up-regulates transcription of a large number of genes, including those encoding members of the cytochrome P450 1 family of enzymes (CYP1s). Although the AHR has been shown to be involved in several normal processes, its physiological role remains elusive. The endogenous ligand 6-formylindolo[3,2-b]carbazole (FICZ), formed from tryptophan, is present in cell culture media and biological specimens. FICZ is an excellent substrate for CYP1 enzymes and together FICZ/AHR/CYP1A1 interactions constitute an auto regulatory feedback loop that controls AHR signaling. A vast number of compounds that inhibit CYP1 enzymes have been reported to be AHR activators, even though they have little or no affinity for the receptor. We hypothesized, that their agonistic effects are dependent on the presence of background levels of FICZ. To test this, AHR signaling in different cell systems exposed to FICZ and/or inhibitors was assessed by measuring EROD activity and CYP1A1 transcription. In addition to a commercial culture medium, a medium free of background levels of FICZ was used. Activation of AHR by of a diverse set of CYP1A1 inhibitors did require FICZ in the culture medium. Furthermore, the compounds tested both prolonged and potentiated FICZ-induced receptor signaling. On the basis of these observations we propose that a compound may activate AHR signaling indirectly by inhibiting CYP1A1 and thereby attenuating the metabolism of FICZ. This mechanism was confirmed for certain polyphenols and pharmaceuticals. Surprisingly, the activating capacity and potentiating effect of two pharmaceuticals on AHR signaling could not be explained by the mechanism proposed, and we speculated that in these cases the agonistic effect might involve interactions of the cellular antioxidant response with the basic transcription machinery. Together, our observations provide a mechanistic explanation as to how compounds that inhibit CYP1A1 can activate AHR signaling. They also indicate that the general perception of the binding pocket of AHR as promiscuous, is probably wrong. The fact that indirect activation of AHR may cause sustained signaling requires further studies in vivo not least, in order to prevent toxicity.

  • 288. Bengtsson, Linus
    et al.
    Lu, Xin
    Liljeros, Fredrik
    Stockholm University, Faculty of Social Sciences, Department of Sociology. The Institute for Futures Studies, Sweden.
    Thanh, Hoang Huy
    Thorson, Anna
    Strong propensity for HIV transmission among men who have sex with men in Vietnam: behavioural data and sexual network modelling2014In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 4, no 1, article id e003526Article in journal (Refereed)
    Abstract [en]

    Objectives Survey data from men who have sex with men (MSM) in Asian cities indicate ongoing and drastic increases in HIV prevalence. It is unknown which behavioural factors are most important in driving these epidemics. We aimed to analyse detailed sexual behaviour data among MSM in Vietnam and to model HIV transmission using improved assumptions on sexual network structure. Setting Vietnam. Participants Internet-using men who had ever had sex (any type) with a man, aged 18years and living in Vietnam. The study was cross-sectional, population-based and performed in 2012, using online respondent-driven sampling. The Internet-based survey instrument was completed by 982 participants, of which 857 were eligible. Questions included sociodemography and retrospective sexual behaviour, including number of unprotected anal sex (UAS) acts per partner. Primary and secondary outcome measures Estimated basic reproductive number over 3months as a function of transmission risk per UAS act; frequency distributions of number of UAS partners and UAS acts during last 3months. Results 36% (CI 32% to 42%) reported UAS at least once during the last 3months. 36% (CI 32% to 41%) had ever taken an HIV test and received the result. UAS partner numbers and number of UAS acts were both highly skewed and positively correlated. Using a weighted configuration model, taking into account partner numbers, frequency of UAS and their correlations, we estimated the basic reproductive number (R0) over 3months. The results indicated rapid transmission over a wide range of values of per-act transmissibility. Conclusions Men with multiple partners had unexpectedly high UAS frequency per partner, paired with low HIV testing rates. The study highlights the importance of collecting data on frequency of UAS acts and indicates the need to rapidly scale-up HIV prevention services and testing opportunities for MSM in Vietnam.

  • 289. Bengtsson, Linus
    et al.
    Lu, Xin
    Stockholm University, Faculty of Social Sciences, Department of Sociology.
    Thorson, Anna
    Garfield, Richard
    von Schreeb, Johan
    Improved Response to Disasters and Outbreaks by Tracking Population Movements with Mobile Phone Network Data: A Post-Earthquake Geospatial Study in Haiti2011In: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 8, no 8, p. e1001083-Article in journal (Refereed)
    Abstract [en]

    Background: Population movements following disasters can cause important increases in morbidity and mortality. Without knowledge of the locations of affected people, relief assistance is compromised. No rapid and accurate method exists to track population movements after disasters. We used position data of subscriber identity module (SIM) cards from the largest mobile phone company in Haiti (Digicel) to estimate the magnitude and trends of population movements following the Haiti 2010 earthquake and cholera outbreak. Methods and Findings: Geographic positions of SIM cards were determined by the location of the mobile phone tower through which each SIM card connects when calling. We followed daily positions of SIM cards 42 days before the earthquake and 158 days after. To exclude inactivated SIM cards, we included only the 1.9 million SIM cards that made at least one call both pre-earthquake and during the last month of study. In Port-au-Prince there were 3.2 persons per included SIM card. We used this ratio to extrapolate from the number of moving SIM cards to the number of moving persons. Cholera outbreak analyses covered 8 days and tracked 138,560 SIM cards. An estimated 630,000 persons (197,484 Digicel SIM cards), present in Port-au-Prince on the day of the earthquake, had left 19 days post-earthquake. Estimated net outflow of people (outflow minus inflow) corresponded to 20% of the Port-au-Prince pre-earthquake population. Geographic distribution of population movements from Port-au-Prince corresponded well with results from a large retrospective, population-based UN survey. To demonstrate feasibility of rapid estimates and to identify areas at potentially increased risk of outbreaks, we produced reports on SIM card movements from a cholera outbreak area at its immediate onset and within 12 hours of receiving data. Conclusions: Results suggest that estimates of population movements during disasters and outbreaks can be delivered rapidly and with potentially high validity in areas with high mobile phone use.

  • 290. Bengtsson-Palme, Johan
    et al.
    Angelin, Martin
    Huss, Mikael
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Kjellqvist, Sanela
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Kristiansson, Erik
    Palmgren, Helena
    Larsson, D. G. Joakim
    Johansson, Anders
    The Human Gut Microbiome as a Transporter of Antibiotic Resistance Genes between Continents2015In: Antimicrobial Agents and Chemotherapy, ISSN 0066-4804, E-ISSN 1098-6596, Vol. 59, no 10, p. 6551-6560Article in journal (Refereed)
    Abstract [en]

    Previous studies of antibiotic resistance dissemination by travel have, by targeting only a select number of cultivable bacterial species, omitted most of the human microbiome. Here, we used explorative shotgun metagenomic sequencing to address the abundance of >300 antibiotic resistance genes in fecal specimens from 35 Swedish students taken before and after exchange programs on the Indian peninsula or in Central Africa. All specimens were additionally cultured for extended-spectrum beta-lactamase (ESBL)-producing enterobacteria, and the isolates obtained were genome sequenced. The overall taxonomic diversity and composition of the gut microbiome remained stable before and after travel, but there was an increasing abundance of Proteobacteria in 25/35 students. The relative abundance of antibiotic resistance genes increased, most prominently for genes encoding resistance to sulfonamide (2.6-fold increase), trimethoprim (7.7-fold), and beta-lactams (2.6-fold). Importantly, the increase observed occurred without any antibiotic intake. Of 18 students visiting the Indian peninsula, 12 acquired ESBL-producing Escherichia coli, while none returning from Africa were positive. Despite deep sequencing efforts, the sensitivity of metagenomics was not sufficient to detect acquisition of the low-abundant genes responsible for the observed ESBL phenotype. In conclusion, metagenomic sequencing of the intestinal microbiome of Swedish students returning from exchange programs in Central Africa or the Indian peninsula showed increased abundance of genes encoding resistance to widely used antibiotics.

  • 291.
    Benmakhlouf, Hamza
    et al.
    Stockholm University, Faculty of Science, Department of Physics. Karolinska University Hospital, Sweden.
    Johansson, J.
    Paddick, I.
    Andreo, Pedro
    Stockholm University, Faculty of Science, Department of Physics. Karolinska University Hospital, Sweden.
    Monte Carlo calculated and experimentally determined output correction factors for small field detectors in Leksell Gamma Knife Perfexion beams2015In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 60, no 10, p. 3959-3973Article in journal (Refereed)
    Abstract [en]

    The measurement of output factors (OF) for the small photon beams generated by Leksell Gamma Knife (R) (LGK) radiotherapy units is a challenge for the physicist due to the under or over estimation of these factors by a vast majority of the detectors commercially available. Output correction factors, introduced in the international formalism published by Alfonso (2008 Med. Phys. 35 5179-86), standardize the determination of OFs for small photon beams by correcting detector-reading ratios to yield OFs in terms of absorbed-dose ratios. In this work output correction factors for a number of detectors have been determined for LGK Perfexion (TM) Co-60 gamma-ray beams by Monte Carlo (MC) calculations and measurements. The calculations were made with the MC system PENELOPE, scoring the energy deposited in the active volume of the detectors and in a small volume of water; the detectors simulated were two silicon diodes, one liquid ionization chamber (LIC), alanine and TLD. The calculated LIC output correction factors were within +/- 0.4%, and this was selected as the reference detector for experimental determinations where output correction factors for twelve detectors were measured, normalizing their readings to those of the LIC. The MC-calculated and measured output correction factors for silicon diodes yielded corrections of up to 5% for the smallest LGK collimator size of 4 mm diameter. The air ionization chamber measurements led to extremely large output correction factors, caused by the well-known effect of partial volume averaging. The corrections were up to 7% for the natural diamond detector in the 4 mm collimator, also due to partial volume averaging, and decreased to within about +/- 0.6% for the smaller synthetic diamond detector. The LIC, showing the smallest corrections, was used to investigate machine-to-machine output factor differences by performing measurements in four LGK units with different dose rates. These resulted in OFs within +/- 0.6% and +/- 0.2% for the 4 mm and 8 mm collimators, respectively, providing evidence for the use of generic OFs for these LGK beams. Using the experimentally derived output correction factors, OFs can be measured using a wide range of commercially available detectors.

  • 292.
    Benmakhlouf, Hamza
    et al.
    Stockholm University, Faculty of Science, Department of Physics. Karolinska Institutet, Sweden.
    Sempau, Josep
    Andreo, Pedro
    Stockholm University, Faculty of Science, Department of Physics. Karolinska Institutet, Sweden.
    Output correction factors for nine small field detectors in 6 MV radiation therapy photon beams: A PENELOPE Monte Carlo study2014In: Medical physics (Lancaster), ISSN 0094-2405, Vol. 41, no 4, p. 041711-Article in journal (Refereed)
    Abstract [en]

    Purpose: To determine detector-specific output correction factors, k(Qclin,Qmsr)(fclin,fmsr) in 6 MV small photon beams for air and liquid ionization chambers, silicon diodes, and diamond detectors from two manufacturers. Methods: Field output factors, defined according to the international formalism published by Alfonso et al. [Med. Phys. 35, 5179-5186 (2008)], relate the dosimetry of small photon beams to that of the machine-specific reference field; they include a correction to measured ratios of detector readings, conventionally used as output factors in broad beams. Output correction factors were calculated with the PENELOPE Monte Carlo (MC) system with a statistical uncertainty (type-A) of 0.15% or lower. The geometries of the detectors were coded using blueprints provided by the manufacturers, and phase-space files for field sizes between 0.5 x 0.5 cm(2) and 10 x 10 cm(2) from a Varian Clinac iX 6 MV linac used as sources. The output correction factors were determined scoring the absorbed dose within a detector and to a small water volume in the absence of the detector, both at a depth of 10 cm, for each small field and for the reference beam of 10 x 10 cm(2). Results: The Monte Carlo calculated output correction factors for the liquid ionization chamber and the diamond detector were within about +/- 1% of unity even for the smallest field sizes. Corrections were found to be significant for small air ionization chambers due to their cavity dimensions, as expected. The correction factors for silicon diodes varied with the detector type (shielded or un-shielded), confirming the findings by other authors; different corrections for the detectors from the two manufacturers were obtained. The differences in the calculated factors for the various detectors were analyzed thoroughly and whenever possible the results were compared to published data, often calculated for different accelerators and using the EGSnrc MC system. The differences were used to estimate a type-B uncertainty for the correction factors. Together with the type-A uncertainty from the Monte Carlo calculations, an estimation of the combined standard uncertainty was made, assigned to the mean correction factors from various estimates. Conclusions: The present work provides a consistent and specific set of data for the output correction factors of a broad set of detectors in a Varian Clinac iX 6 MV accelerator and contributes to improving the understanding of the physics of small photon beams. The correction factors cannot in general be neglected for any detector and, as expected, their magnitude increases with decreasing field size. Due to the reduced number of clinical accelerator types currently available, it is suggested that detector output correction factors be given specifically for linac models and field sizes, rather than for a beam quality specifier that necessarily varies with the accelerator type and field size due to the different electron spot dimensions and photon collimation systems used by each accelerator model. (C) 2014 American Association of Physicists in Medicine.

  • 293. Bennett, Alexander
    et al.
    Gnjidic, Danijela
    Gillett, Mark
    Carroll, Peter
    Matthews, Slade
    Johnell, Kristina
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Fastbom, Johan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Hilmer, Sarah
    Prevalence and Impact of Fall-Risk-Increasing Drugs, Polypharmacy, and Drug-Drug Interactions in Robust Versus Frail Hospitalised Falls Patients: A Prospective Cohort Study2014In: Drugs & Aging, ISSN 1170-229X, E-ISSN 1179-1969, Vol. 31, no 3, p. 225-232Article in journal (Refereed)
    Abstract [en]

    Background Several measures of medication exposure are associated with adverse outcomes in older people. Exposure to and the clinical outcomes of these measures in robust versus frail older inpatients are not known. Objective In older robust and frail patients admitted to hospital after a fall, we investigated the prevalence and clinical impact of fall-risk-increasing drugs (FRIDs), total number of medications, and drug-drug interactions (DDIs). Methods Patients >= 60 years of age admitted with a fall to a tertiary referral teaching hospital in Sydney were recruited and frailty was assessed. Data were collected at admission, discharge, and 2 months after admission. Results A total of 204 patients were recruited (mean age 80.5 +/- 8.3 years), with 101 robust and 103 frail. On admission, compared with the robust, frail participants had significantly higher mean +/- SD number of FRIDs (frail 3.4 +/- 2.2 vs. robust 1.6 +/- 1.5, P < 0.0001), total number of medications (9.8 +/- 4.3 vs. 4.4 +/- 3.3, P < 0.0001), and DDI exposure (35 vs. 5 %, P = 0.001). Number of FRIDs on discharge was significantly associated with recurrent falls [odds ratio (OR) 1.7 (95 % confidence interval [CI] 1.3-2.1)], which were most likely to occur with 1.5 FRIDs in the frail and 2.5 FRIDs in the robust. Number of medications on discharge was also associated with recurrent falls [OR 1.2 (1.0-1.3)], but DDIs were not. Conclusion Exposure to FRIDs and other measures of high-risk medication exposures is common in older people admitted with falls, especially the frail. Number of FRIDs and to a lesser extent total number of medicines at discharge were associated with recurrent falls.

  • 294. Benson, Rebecca
    et al.
    Glaser, Karen
    Corna, Laurie M
    Platts, Loretta G
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Di Gessa, Giorgio
    Worts, Diana
    Price, Debora
    McDonough, Peggy
    Sacker, Amanda
    Do work and family care histories predict health in older women?2017In: European Journal of Public Health, ISSN 1101-1262, E-ISSN 1464-360X, Vol. 27, no 6, p. 1010-1015Article in journal (Refereed)
    Abstract [en]

    Background: Social and policy changes in the last several decades have increased women's options for combining paid work with family care. We explored whether specific combinations of work and family care over the lifecourse are associated with variations in women's later life health.

    Methods: We used sequence analysis to group women in the English Longitudinal Study of Ageing according to their work histories and fertility. Using logistic regression, we tested for group differences in later life disability, depressive symptomology and mortality, while controlling for childhood health and socioeconomic position and a range of adult socio-economic circumstances and health behaviours.

    Results: Women who transitioned from family care to either part-time work after a short break from the labour force, or to full-time work, reported lower odds of having a disability compared with the reference group of women with children who were mostly employed full-time throughout. Women who shifted from family care to part-time work after a long career break had lower odds of mortality than the reference group. Depressive symptoms were not associated with women's work and family care histories.

    Conclusion: Women's work histories are predictive of their later life disability and mortality. This relationship may be useful in targeting interventions aimed at improving later life health. Further research is necessary to explore the mechanisms linking certain work histories to poorer later life health and to design interventions for those affected.

  • 295.
    Beramendi, Ana
    Stockholm University, Faculty of Science, Department of Zoology.
    Morphologican and functional studies on the Drosophila neuromuscular system during postembryonic stages2005Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The nervous system of the fruit fly Drosophila melanogaster has emerged as an excellent model for fundamental neuroscience as well as for biomedical research of human neurological diseases. In this thesis, two aspects of the neuromuscular system have been investigated: the role of the IkB-protein Cactus in the larval neuromuscular junction and the morphology of motor terminals throughout adult life.

    We found that cactus mutant larvae have poor locomotion, morphological abnormalities at the presynaptic site of motor terminals and impaired mechanical and electrophysiological properties, demonstrating that Cactus is clearly involved in the normal functioning of Drosophila neuromuscular system. In the adult, we show that cactus, dorsal and dif are expressed in the brain but are not redistributed between cytoplasm and nucleus in a circadian manner as expected from a previous finding in larval brain. Both Cactus and Dif immunoreactivity was strong in mushroom bodies and antennal lobes, suggesting a putative role in olfactory memory. In the rat, proteins of the same family are involved in the regulation of sleep but we found no indication of such regulation in flies subjected to 6 hrs of sleep deprivation.

    We found that neuromuscular junctions continue to change throughout adult life. Two types of long-term changes in the morphology of neuromuscular junctions are demonstrated here: a daily change in the size of synaptic boutons and long-term changes in bouton size developing over several weeks. By careful morphological studies of flight neuromuscular terminals in clock-gene mutants and wild type flies of different ages we demonstrate that the daily changes depend on the biological clock and disappear in the old fly. Moreover, we show that light is necessary for the motor neurons studied to reach maximum size of synaptic boutons. Lastly, we found that the two clock genes period and timeless are also necessary to control axonal branching.

    Transmission electron microscopy revealed several ultrastructural features distinct of the aging fly and indicative of reduced plasticity. We used a temperature-sensitive allele of shibire that rapidly and reversibly blocks vesicle recycling to investigate whether the morphological phenotype found in neuromuscular junctions of aging flies could be explained by impairment of endocytotic mechanisms. Our results show a clear reduction of the time required for complete paralysis and an increased recovery time in old flies, indicating that aging correlates with impaired endocytosis and membrane dynamics.

  • 296.
    Berg, Lisa
    et al.
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS).
    Bäck, Karin
    Vinnerljung, Bo
    Stockholm University, Faculty of Social Sciences, Department of Social Work.
    Hjern, Anders
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS). Karolinska Institutet, Sweden.
    Parental alcohol-related disorders and school performance in 16 year olds - a national cohort study2016In: Addiction, ISSN 0965-2140, E-ISSN 1360-0443, Vol. 111, no 10, p. 1795-1803Article in journal (Refereed)
    Abstract [en]

    To study the links between parental alcohol-related disorders and offspring school performance and, specifically, whether associations vary by gender of parent or child and whether associations are mediated by other adverse psychosocial circumstances commonly appearing together with parental alcohol problems, such as parental mental health problems or criminal behaviour.

    Register study in a national cohort.

    Setting

    Sweden.

    740 618 individuals born in Sweden in 1990-1996.

    Parental hospital admissions for alcohol-related disorders and school performance in their offspring, in the final year of compulsory school at age 15-16, was analysed in relation to sociodemographic confounders and psychosocial covariates, using linear and logistic regressions.

    Both mothers’ and fathers’ alcohol-related hospital admissions were associated with lower z-scores of grades and national mathematic tests scores. After adjustment for parental education and sociodemographic confounders, beta-coefficients of z-scores of grades were -0.42 (95% CI -0.45, -0.39) and -0.42 (95 % CI -0.43,-0.40), and beta-coefficients of mathematic tests scores were -0.36 (95% CI -0.39, -0.33) and -0.31 (95% CI -0.33, -0.29), for mothers’ and fathers’ alcohol-related disorders, respectively. Adjusted ORs for not being eligible for secondary school were 1.99 (95% CI 1.84-2.15) and 2.04 (95% CI 1.95-2.15) for mothers’ and fathers’ alcohol-related disorders, respectively. Adjusting the analyses for psychosocial factors in the family almost eradicated the statistical effects of parental alcohol-related disorders on offspring school performance to beta-coefficients of 0.03 to -0.10 and ORs of 0.89 to 1.15. The effect of a mother's alcohol-related hospital admission on school performance was stronger in girls than in boys, whereas no gender differences were seen for a father's alcohol-related hospital admission.

    Conclusions

    In Sweden, alcohol-related disorders in both mothers and fathers are associated with lower school performance in their children at age 15-16, with most of the statistical effects being attributed to psychosocial circumstances of the family, such as parental psychiatric disorders, drug use, and criminality and receipt of social or child welfare interventions.

  • 297.
    Berg, Lisa
    et al.
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS). Stockholm University, Faculty of Social Sciences, Department of Social Work.
    Hjern, Anders
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS). Stockholm University, Faculty of Social Sciences, Department of Social Work.
    Barn till föräldrar med cancer – hur många berörs och vilka är konsekvenserna i ett livsloppsperspektiv?2016Report (Other academic)
  • 298.
    Berg, Lisa
    et al.
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS).
    Hjern, Anders
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS).
    Barn till separerade föräldrar: Hälsa, utbildning och sociala levnadsförhållanden i ett livsloppsperspektiv2016Report (Other academic)
  • 299.
    Berg, Lisa
    et al.
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS).
    Rostila, Mikael
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS).
    Hjern, Anders
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS). Karolinska Institutet, Sweden.
    Parental death during childhood and depression in young adults – a national cohort study2016In: Journal of Child Psychology and Psychiatry and Allied Disciplines, ISSN 0021-9630, E-ISSN 1469-7610, Vol. 57, no 9, p. 1092-1098Article in journal (Refereed)
    Abstract [en]

    Background

    There are few prospective, population-based studies on childhood parental death and psychiatric disorders in adulthood, and previous findings are inconclusive. This study investigated the association between parental death from natural and external (suicides, accidents or homicides) causes before 18 years and the risk of clinical depression in young adults, in relation to age at loss and gender of both child and parent.

    Methods

    In this register-based study, a national cohort born in Sweden during 1973–1982 (n = 862,554) was followed with regard to hospital admissions and outpatient care for depression during 2006–2013. Multivariate Cox proportional hazards models were used to estimate the impact of parental death, taking sociodemographic and parental psychosocial covariates into account.

    Results

    Maternal death from natural causes was associated with a hazard ratio (HR) of outpatient care for depression of 1.19 [95% confidence interval (CI), 1.02–1.40] in men and 1.15 (1.01–1.31) in women, after adjustment for sociodemographic confounders, with similar effect sizes for paternal natural death. Death from external causes consistently had higher effect size compared with natural deaths, in particular in relation to risk of hospital admissions for depression where they were as high as HR 3.23 (2.38–4.38) for men, and 1.79 (1.30–2.47) for women after a loss of a mother. Losing a parent in preschool age, compared with losing a parent as a teenager, was associated with higher risks of both hospitalization (p = .006) and outpatient care (p = .001) for depression.

    Conclusions

    This study indicates that parental loss to death from natural causes during childhood is associated with a small increased risk of long-term consequences for psychological health. Children who lose their parents to death from external causes, that is suicides, accidents or homicides, and children losing a parent in young ages are, however, at particular risk and should be given priority in preventive interventions after parental loss.

  • 300.
    Berg, Lisa
    et al.
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS).
    Rostila, Mikael
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS).
    Saarela, Jan
    Hjern, Anders
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS). Karolinska Institutet, Sweden.
    Parental Death During Childhood and Subsequent School Performance2014In: Pediatrics, ISSN 0031-4005, E-ISSN 1098-4275, Vol. 133, no 4, p. 682-689Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Parental death during childhood has been linked to increased mortality and mental health problems in adulthood. School failure may be an important mediator in this trajectory. We investigated the association between parental death before age 15 years and school performance at age 15 to 16 years, taking into account potentially contributing factors such as family socioeconomic position (SEP) and parental substance abuse, mental health problems, and criminality.

    METHODS: This was a register-based national cohort study of 772117 subjects born in Sweden between 1973 and 1981. Linear and logistic regression models were used to analyze school performance as mean grades (scale: 1-5; SD: 0.70) and school failure (finished school with incomplete grades). Results are presented as -coefficients and odds ratios (ORs) with 95% confidence intervals (CIs).

    RESULTS: Parental death was associated with lower grades (ORs: -0.21 [95% CI: -0.23 to -0.20] and -0.17 [95% CI: -0.19 to -0.15]) for paternal and maternal deaths, respectively. Adjustment for SEP and parental psychosocial factors weakened the associations, but the results remained statistically significant. Unadjusted ORs of school failure were 2.04 (95% CI: 1.92 to 2.17) and 1.51 (95% CI: 1.35 to 1.69) for paternal and maternal deaths. In fully adjusted models, ORs were 1.40 (95% CI: 1.31 to 1.49) and 1.18 (95% CI: 1.05 to 1.32). The higher crude impact of death due to external causes (ie, accident, violence, suicide) (OR: -0.27 [90% CI: -0.28 to -0.26]), compared with natural deaths (OR: -0.16 [95% CI: -0.17 to -0.15]), was not seen after adjustment for SEP and psychosocial situation of the family.

    CONCLUSIONS: Parental death during childhood was associated with lower grades and school failure. Much of the effect, especially for deaths by external causes, was associated with socially adverse childhood exposures.

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