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  • 251.
    Bajinskis, Ainars
    et al.
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Lindegren, Helene
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Johansson, Lotta
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Harms-Ringdahl, Mats
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Forsby, Anna
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Low-Dose/Dose-Rate gamma Radiation Depresses Neural Differentiation and Alters Protein Expression Profiles in Neuroblastoma SH-SY5Y Cells and C17.2 Neural Stem Cells2011In: Radiation Research, ISSN 0033-7587, E-ISSN 1938-5404, Vol. 175, no 2, p. 185-192Article in journal (Refereed)
    Abstract [en]

    The effects of low doses of ionizing radiation on cellular development in the nervous system are presently unclear. The focus of the present study was to examine low-dose gamma-radiation-induced effects on the differentiation of neuronal cells and on the development of neural stem cells to glial cells. Human neuroblastoma SH-SY5Y cells were exposed to (137)Cs gamma rays at different stages of retinoic acid-induced neuronal differentiation, and neurite formation was determined 6 days after exposure. When SH-SY5Y cells were exposed to low-dose-rate gamma rays at the onset of differentiation, the number of neurites formed per cell was significantly less after exposure to either 10, 30 or 100 mGy compared to control cells. Exposure to 10 and 30 mGy attenuated differentiation of immature C17.2 mouse-derived neural stem cells to glial cells, as verified by the diminished expression of glial fibrillary acidic protein. Proteomic analysis of the neuroblastoma cells by 2D-PAGE after 30 mGy irradiation showed that proteins involved in neuronal development were downregulated. Proteins involved in cell cycle and proliferation were altered in both cell lines after exposure to 30 mGy; however, the rate of cell proliferation was not affected in the low-dose range. The radiation-induced attenuation of differentiation and the persistent changes in protein expression is indicative of an epigenetic rather than a cytotoxic mechanism. (C) 2011 by Radiation Research Society

  • 252.
    Bajinskis, Ainars
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Natarajan, Adayapalam T.
    Erixon, Klaus
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Harms-Ringdahl, Mats
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    DNA double strand breaks induced by the indirect effect of radiation are more efficiently repaired by non-homologous end joining compared to homologous recombination repair2013In: Mutation research. Genetic toxicology and environmental mutagenesis, ISSN 1383-5718, E-ISSN 1879-3592, Vol. 756, no 1-2, p. 21-29Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to investigate the relative involvement of three major DNA repair pathways, i.e., non-homologous end joining (NHEJ), homologous recombination (HRR) and base excision (BER) in repair of DNA lesions of different complexity induced by low- or high-LET radiation with emphasis on the contribution of the indirect effect of radiation for these radiation qualities. A panel of DNA repair-deficient CHO cell lines was irradiated by Cs-137 gamma-rays or radon progeny alpha-particles. Irradiation was also performed in the presence of 2 M DMSO to reduce the indirect effect of radiation and the complexity of the DNA damage formed. Clonogenic survival and micronucleus assays were used to estimate efficiencies of the different repair pathways for DNA damages produced by direct and indirect effects. Removal of the indirect effect of low-LET radiation by DMSO increased clonogenic survival and decreased MN formation for all cell lines investigated. A direct contribution of the indirect effect of radiation to DNA base damage was suggested by the significant protection by DMSO seen for the BER deficient cell line. Lesions formed by the indirect effect are more readily repaired by the NHEJ pathway than by HRR after irradiation with gamma-rays or alpha-particles as evaluated by cell survival and the yields of MN. The results obtained with BER- and NHEJ-deficient cells suggest that the indirect effect of radiation contributes significantly to the formation of repair substrates for these pathways.

  • 253.
    Bakali, Amin
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Herman, Maria Dolores
    Johnson, Kenneth A.
    Kelly, Amélie A.
    Wieslander, Åke
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Hallberg, B. M.
    Nordlund, Pär
    Crystal structure of YegS, a homologue to the mammalian diacylglycerol kinases, reveals a novel regulatory metal binding site2007In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 282, no 27, p. 19644-19652Article in journal (Refereed)
    Abstract [en]

    The human lipid kinase family controls cell proliferation, differentiation, and tumorigenesis and includes diacylglycerol kinases, sphingosine kinases, and ceramide kinases. YegS is an Escherichia coli protein with significant sequence homology to the catalytic domain of the human lipid kinases. We have solved the crystal structure of YegS and shown that it is a lipid kinase with phosphatidylglycerol kinase activity. The crystal structure reveals a two-domain protein with significant structural similarity to a family of NAD kinases. The active site is located in the interdomain cleft formed by four conserved sequence motifs. Surprisingly, the structure reveals a novel metal binding site composed of residues conserved in most lipid kinases.

  • 254. Ball, Frank
    et al.
    Britton, Tom
    Stockholm University, Faculty of Science, Department of Mathematics.
    House, Thomas
    Isham, Valerie
    Mollison, Denis
    Pellis, Lorenzo
    Tomba, Gianpaolo Scalia
    Seven challenges for metapopulation models of epidemics, including households models2015In: Epidemics, ISSN 1755-4365, E-ISSN 1878-0067, Vol. 10, p. 63-67Article in journal (Refereed)
    Abstract [en]

    This paper considers metapopulation models in the general sense, i.e. where the population is partitioned into sub-populations (groups, patches,...), irrespective of the biological interpretation they have, e.g. spatially segregated large sub-populations, small households or hosts themselves modelled as populations of pathogens. This framework has traditionally provided an attractive approach to incorporating more realistic contact structure into epidemic models, since it often preserves analytic tractability (in stochastic as well as deterministic models) but also captures the most salient structural inhomogeneity in contact patterns in many applied contexts. Despite the progress that has been made in both the theory and application of such metapopulation models, we present here several major challenges that remain for future work, focusing on models that, in contrast to agent-based ones, are amenable to mathematical analysis. The challenges range from clarifying the usefulness of systems of weakly-coupled large sub-populations in modelling the spread of specific diseases to developing a theory for endemic models with household structure. They include also developing inferential methods for data on the emerging phase of epidemics, extending metapopulation models to more complex forms of human social structure, developing metapopulation models to reflect spatial population structure, developing computationally efficient methods for calculating key epidemiological model quantities, and integrating within- and between-host dynamics in models.

  • 255. Ball, Frank
    et al.
    Britton, Tom
    Stockholm University, Faculty of Science, Department of Mathematics.
    Sirl, David
    Household epidemic models with varying infection response2011In: Journal of Mathematical Biology, ISSN 0303-6812, E-ISSN 1432-1416, Vol. 63, no 2, p. 309-337Article in journal (Refereed)
    Abstract [en]

    This paper is concerned with SIR (susceptible -> infected -> removed) household epidemic models in which the infection response may be either mild or severe, with the type of response also affecting the infectiousness of an individual. Two different models are analysed. In the first model, the infection status of an individual is predetermined, perhaps due to partial immunity, and in the second, the infection status of an individual depends on the infection status of its infector and on whether the individual was infected by a within- or between-household contact. The first scenario may be modelled using a multitype household epidemic model, and the second scenario by a model we denote by the infector-dependent-severity household epidemic model. Large population results of the two models are derived, with the focus being on the distribution of the total numbers of mild and severe cases in a typical household, of any given size, in the event that the epidemic becomes established. The aim of the paper is to investigate whether it is possible to determine which of the two underlying explanations is causing the varying response when given final size household outbreak data containing mild and severe cases. We conduct numerical studies which show that, given data on sufficiently many households, it is generally possible to discriminate between the two models by comparing the Kullback-Leibler divergence for the two fitted models to these data.

  • 256. Balldin, Jan
    et al.
    Berglund, Kristina J.
    Berggren, Ulf
    Wennberg, Peter
    Stockholm University, Faculty of Social Sciences, Centre for Social Research on Alcohol and Drugs (SoRAD).
    Fahlke, Claudia
    TAQ1A1 Allele of the DRD2 Gene Region Contribute to Shorter Survival Time in Alcohol Dependent Individuals When Controlling for the Influence of Age and Gender. A Follow-up Study of 18 Years2018In: Alcohol and Alcoholism, ISSN 0735-0414, E-ISSN 1464-3502, Vol. 53, no 3, p. 216-220Article in journal (Refereed)
    Abstract [en]

    Aims: To investigate the influence of the A1 allele of the TAQ1A polymorphism in the dopamine D2 receptor (DRD2) gene region on mortality in adult individuals with alcohol dependence. Methods: The study sample consisted of 359 alcohol-dependent individuals treated for severe alcohol withdrawal symptoms in 1997. Years of survival was studied in an 18-year follow-up. In the analyses, gender and age were controlled for. Results: At the 18-year follow-up, 53% individuals had deceased. The analyses showed that older age (P < 0.001), male gender (P < 0.05) and carrying the A1 allele (P < 0.01) all significantly and independently contributed to shorten years of survival. Among the deceased individuals, the genotype A1+ was the only significant contributor to shorten years of survival. Conclusions: An important contribution of the present study is that in alcohol dependence the Taq1A1 allele of the DRD2 gene region is a risk factor for premature death of similar importance as the well-known risk factors of age and gender. Short Summary: We investigated the influence of A1 allele of the TAQ1A polymorphism in DRD2 receptor gene region on mortality in alcohol-dependent individuals in an 18-year follow-up. Age, gender and the A1 allele contributed to shorten years of survival. Among the deceased, the A1+ was the only contributor to shorten years of survival.

  • 257.
    Balogun, Halima A.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute .
    Immunological characteristics of recombinant fragments of the Plasmodium falciparum blood-stage antigen Pf3322011Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Effective malaria vaccine might help improve control strategies against malaria, but the complexity of interactions between the parasite and its hosts poses challenges. The asexual blood stage P. falciparum antigen Pf332 has potentials as one of the proteins in understanding the complex host-parasite interactions. The interest in Pf332 as a target for parasite neutralizing antibodies, evolved from previous studies demonstrating that Pf332-reactive antibodies inhibits parasite growth in vitro. The presence of natural P. falciparum infection also indicated that Pf332 has the ability to induce protective antibodies.

    In paper I, we identified and characterized the immunogenicity of a C-terminal region of Pf332. Immunological analyses carried out with this fragment revealed that rabbit anti-C231 antibodies possess parasite in vitro inhibitory capabilities. In paper II, the functional activity of C231 specific antibodies was confirmed with human-affinity purified antibodies, where the antibodies inhibited late stage parasite development, by the presence of abnormal parasites and disintegrated red cell membranes.

    Epidemiological data from malaria endemic area of Senegal (Paper III & IV), showed that antibodies were reactive with two different fragments of Pf332 (C231 and DBL). Distribution of anti-C231 antibodies in the IgG subclasses, gave similar levels of IgG2 and IgG3. The levels of anti-C231 antibodies were associated with protection from clinical malaria, but with DBL reactive antibodies IgG3 was associated with protection from clinical malaria.

    We hereby conclude that antigen Pf332 contains immunogenic epitopes, and is a potential target for parasite neutralizing antibodies. The Pf332 protein should thus be considered as a candidate antigen for inclusion in a subunit P. falciparum malaria vaccine.

  • 258.
    Balogun, Halima
    et al.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Awah, Nancy
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Farouk, S.
    Berzins, Klavs
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Pf332-C231- reactive antibodies affect growth and development of intraerythrocytic Plasmodium falciparum parasitesArticle in journal (Refereed)
  • 259.
    Balogun, Halima
    et al.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Awah, Nancy
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Nilsson, S.
    Rousillhon, C.
    Rogier, C.
    Trape, J. F.
    Chen, Q.
    Berzins, Klavs
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Pattern of antibodies to the Duffy binding-like domain of Plasmodium falciparum antigen Pf332 in Senegalese individualsManuscript (preprint) (Other academic)
  • 260. Bal-Price, Anna
    et al.
    Crofton, Kevin M.
    Sachana, Magdalini
    Shafer, Timothy J.
    Behl, Mamta
    Forsby, Anna
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Hargreaves, Alan
    Landesmann, Brigitte
    Lein, Pamela J.
    Louisse, Jochem
    Monnet-Tschudi, Florianne
    Paini, Alicia
    Rolaki, Alexandra
    Schrattenholz, Andre
    Sunol, Cristina
    van Thriel, Christoph
    Whelan, Maurice
    Fritsche, Ellen
    Putative adverse outcome pathways relevant to neurotoxicity2015In: Critical reviews in toxicology, ISSN 1040-8444, E-ISSN 1547-6898, Vol. 45, no 1, p. 83-91Article, review/survey (Refereed)
    Abstract [en]

    The Adverse Outcome Pathway (AOP) framework provides a template that facilitates understanding of complex biological systems and the pathways of toxicity that result in adverse outcomes (AOs). The AOP starts with an molecular initiating event (MIE) in which a chemical interacts with a biological target(s), followed by a sequential series of KEs, which are cellular, anatomical, and/or functional changes in biological processes, that ultimately result in an AO manifest in individual organisms and populations. It has been developed as a tool for a knowledge-based safety assessment that relies on understanding mechanisms of toxicity, rather than simply observing its adverse outcome. A large number of cellular and molecular processes are known to be crucial to proper development and function of the central (CNS) and peripheral nervous systems (PNS). However, there are relatively few examples of well-documented pathways that include causally linked MIEs and KEs that result in adverse outcomes in the CNS or PNS. As a first step in applying the AOP framework to adverse health outcomes associated with exposure to exogenous neurotoxic substances, the EU Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) organized a workshop (March 2013, Ispra, Italy) to identify potential AOPs relevant to neurotoxic and developmental neurotoxic outcomes. Although the AOPs outlined during the workshop are not fully described, they could serve as a basis for further, more detailed AOP development and evaluation that could be useful to support human health risk assessment in a variety of ways.

  • 261.
    Baltzer, Maria
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Westerlund, Hugo
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Backhans, Mona
    Melinder, Karin
    Involvement and structure: A qualitative study of organizational change and sickness absence among women in the public sector in Sweden2011In: BMC Public Health, ISSN 1471-2458, E-ISSN 1471-2458, Vol. 11, p. 318-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Organizational changes in modern corporate life have become increasingly common and there are indications that they often fail to achieve their ends. An earlier study of 24,036 employees showed that those who had repeatedly been exposed to large increases in staffing during 1991-1996 had an excess risk of both long-term sickness absence and hospital admission during 1997-1999, while moderate expansion appeared to be protective. The former was most salient among female public sector employees. We used qualitative interviews to explore work environment factors underlying the impact of organizational changes (moderate and large expansions in staffing) on sickness absence from an employee perspective. METHOD: We interviewed 21 strategically selected women from the earlier study using semi-structured telephone interviews focusing on working conditions during the organizational changes. We identified 22 themes which could explain the association between organizational changes and sickness absence. We then used Qualitative Comparative Analysis (QCA) to reduce the number of themes and discover patterns of possible causation. RESULTS: The themes that most readily explained the outcomes were Well Planned Process of Change (a clear structure for involvement of the employees in the changes), Agent of Change (an active role in the implementation of the changes), Unregulated Work (a lack of clear limits and guidelines regarding work tasks from the management and among the employees), and Humiliating Position (feelings of low status or of not being wanted at the workplace), which had been salient throughout the analytic process, in combination with Multiple Contexts (working in several teams in parallel) and Already Ill (having already had a debilitating illness at the beginning of 1991), which may indicate degree of individual exposure and vulnerability. Well Planned Process of Change, Agent of Change and Multiple Contexts are themes that were associated with low sickness absence. Unregulated Work, Humiliating Position and Already Ill were associated with high sickness absence. CONCLUSIONS: These findings suggest that promising areas for future research and improvement in change management could be the structured involvement of the employees in the planning of organizational changes, and the development of methods to avoid highly unregulated working conditions.

  • 262.
    Banerjee, Albert
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Social Work.
    James, Robert
    McGregor, Margaret
    Lexchin, Joel
    Nursing Home Physicians Discuss Caring for Elderly Residents: An Exploratory Study2018In: Canadian Journal on Aging, ISSN 0714-9808, E-ISSN 1710-1107, Vol. 37, no 2, p. 133-144Article in journal (Refereed)
    Abstract [en]

    Despite the increasing complexity of nursing home care, the role of physicians caring for residents is largely unexplored. This international, exploratory study sought to learn about physicians' roles, responsibilities, and tasks as well as investigate the unique qualities of medical practice in nursing homes. We conducted interviews with 18 physicians, who reported making important contributions to the quality of resident care, including clarifying the goals of care, working to reduce unnecessary medication and hospitalization, as well as contributing to staff education. Nursing home practice involved physicians in networks of relations that were instrumental to the quality of medical care and physicians' job satisfaction. The importance of these relationships disrupts the oft-drawn boundary between the medical and the social, suggesting that good medical practice depends on good social practice. Reflecting the exploratory nature of the study, we recommend research to better understand and support the relational dimensions of nursing home medicine.

  • 263. Bao, Cuiping
    et al.
    Pedersen, Nancy L.
    Yang, Rongrong
    Marseglia, Anna
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Xu, Weige
    Wang, Yaogang
    Qi, Xiuying
    Xu, Weili
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Tianjin Medical University, China..
    Diabetes in midlife and risk of cancer in late life: A nationwide Swedish twin study2018In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 143, no 4, p. 793-800Article in journal (Refereed)
    Abstract [en]

    The association between diabetes and cancer risk remains controversial. Hence, we examined whether midlife diabetes is related to the risk of cancer in late-life, and whether genetic and early-life environmental factors play a role in this association. This study included 25,154 twin individuals born in 1958 or earlier from the Swedish Twin Registry. Information on cancer diagnosis in late life (aged >= 65) during 1998-2014, was derived from the National Patient and Cancer Registries. Diabetes was ascertained based on self- or informant-reported history, patient registry and antidiabetic medication use. Midlife diabetes was defined when diabetes was diagnosed before 65 years. Data were analyzed following two strategies: (i) unmatched case-control analysis for all participants using generalized estimating equation (GEE) models, and (ii) co-twin control analysis for cancer-discordant twin pairs using conditional logistic regression. Overall, 1,766 (7.0%) had midlife diabetes and 5,293 (21.0%) had cancer in late-life. In multiadjusted GEE models, the odds ratios (95% CIs) of diabetes were 10.55 (2.95-37.67) for pharynx cancer, 5.78 (1.72-19.40) for small intestine cancer, 2.37 (1.14-4.91) for liver cancer and 0.48 (0.35-0.67) for prostate cancer. In people with diabetes, diabetes duration was dose-dependently associated with cancer risk. In conditional logistic regression analysis of 176 prostate cancer-discordant twin pairs, the association between midlife diabetes and prostate cancer in later life became stronger. Midlife diabetes increases the risk of pharynx, small intestine and liver cancers, but reduces prostate cancer risk in late life. Genetic and early-life environmental factors may partially contribute to the diabetes-prostate cancer association.

  • 264. Bao, Cuiping
    et al.
    Yang, Xilin
    Xu, Weili
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Tianjin Med Univ, Dept Epidemiol & Biostat, Sch Publ Hlth, Tianjin, Peoples R China.
    Luo, Hongbin
    Xu, Zhongliang
    Su, Cheng
    Qi, Xiuying
    Diabetes mellitus and incidence and mortality of kidney cancer: A meta-analysis2013In: Journal of diabetes and its complications, ISSN 1056-8727, E-ISSN 1873-460X, Vol. 27, no 4, p. 357-364Article in journal (Refereed)
    Abstract [en]

    Background: Diabetes is associated with increased risk of a spectrum of cancers, but there are few meta-analyses on the association between diabetes and kidney cancer. We performed a meta-analysis of case-control studies and cohort studies to address the incidence and mortality of kidney cancer in diabetes. Methods: Studies were identified by searching PubMed database and manual assessment of the cited references in the retrieved articles. Study-specific relative risks (RRs) and 95% confidence intervals (CIs) were estimated using a random-effect model. Study quality was assessed using the Newcastle-Ottawa scale. Results: A total of 24 studies were included. We found that diabetes was significantly associated with increased risk of kidney cancer (RR=1.40, 95% CI = 1.16 to 1.69), and the results were consistent between case-control and cohort studies. A slightly stronger positive relation was observed in women (RR = 1.47, 95% CI=1.18 to 1.83) than in men (RR=1.28, 95% CI=1.10 to 1.48). Additional analyses indicated that the increased risk of kidney cancer was independent of alcohol consumption, body mass index (BMI)/obesity and smoking. However, there was no association between diabetes and mortality of kidney cancer (RR=1.12, 95% CI=0.99 to 1.20), without heterogeneity (P = 0.419, I-2 = 1.8%). Conclusions: Diabetes mellitus may increase the risk of kidney cancer in both women and men.

  • 265. Barbeiro, A. R.
    et al.
    Ureba, Ana
    Stockholm University, Faculty of Science, Department of Physics. Universidad de Sevilla, Spain; Instituto de Biomedicina de Sevilla, IBIS, Spain; Karolinska Institutet, Sweden.
    Baeza, J. A.
    Linares, R.
    Perucha, M.
    Jimenez-Ortega, E.
    Velazquez, S.
    Mateos, J. C.
    Leal, A.
    3D VMAT Verification Based on Monte Carlo Log File Simulation with Experimental Feedback from Film Dosimetry2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 11, article id e0166767Article in journal (Refereed)
    Abstract [en]

    A model based on a specific phantom, called QuAArC, has been designed for the evaluation of planning and verification systems of complex radiotherapy treatments, such as volumetric modulated arc therapy (VMAT). This model uses the high accuracy provided by the Monte Carlo (MC) simulation of log files and allows the experimental feedback from the high spatial resolution of films hosted in QuAArC. This cylindrical phantom was specifically designed to host films rolled at different radial distances able to take into account the entrance fluence and the 3D dose distribution. Ionization chamber measurements are also included in the feedback process for absolute dose considerations. In this way, automated MC simulation of treatment log files is implemented to calculate the actual delivery geometries, while the monitor units are experimentally adjusted to reconstruct the dose-volume histogram (DVH) on the patient CT. Prostate and head and neck clinical cases, previously planned with Monaco and Pinnacle treatment planning systems and verified with two different commercial systems (Delta4 and COMPASS), were selected in order to test operational feasibility of the proposed model. The proper operation of the feedback procedure was proved through the achieved high agreement between reconstructed dose distributions and the film measurements (global gamma passing rates > 90% for the 2%/2 mm criteria). The necessary discretization level of the log file for dose calculation and the potential mismatching between calculated control points and detection grid in the verification process were discussed. Besides the effect of dose calculation accuracy of the analytic algorithm implemented in treatment planning systems for a dynamic technique, it was discussed the importance of the detection density level and its location in VMAT specific phantom to obtain a more reliable DVH in the patient CT. The proposed model also showed enough robustness and efficiency to be considered as a pre-treatment VMAT verification system.

  • 266. Barbera, Mariagnese
    et al.
    Mangialasche, Francesca
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Jongstra, Susan
    Guillemont, Juliette
    Ngandu, Tiia
    Beishuizen, Cathrien
    Coley, Nicola
    Brayne, Carol
    Andrieu, Sandrine
    Richard, Edo
    Soininen, Hilkka
    Kivipelto, Miia
    Designing an Internet-Based Multidomain Intervention for the Prevention of Cardiovascular Disease and Cognitive Impairment in Older Adults: The HATICE Trial2018In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 62, no 2, p. 649-663Article in journal (Refereed)
    Abstract [en]

    Background: Many dementia and cardiovascular disease (CVD) cases in older adults are attributable to modifiable vascular and lifestyle-related risk factors, providing opportunities for prevention. In the Healthy Aging Through Internet Counselling in the Elderly (HATICE) randomized controlled trial, an internet-based multidomain intervention is being tested to improve the cardiovascular risk (CVR) profile of older adults. Objective: To design a multidomain intervention to improve CVR, based on the guidelines for CVR management, and administered through a coach-supported, interactive, platform to over 2500 community-dwellers aged 65+ in three European countries. Methods: A comparative analysis of national and European guidelines for primary and secondary CVD prevention was performed. Results were used to define the content of the intervention. Results: The intervention design focused on promoting awareness and self-management of hypertension, dyslipidemia, diabetes mellitus, and overweight, and supporting smoking cessation, physical activity, and healthy diet. Overall, available guidelines lacked specific recommendations for CVR management in older adults. The comparative analysis of the guidelines showed general consistency for lifestyle-related recommendations. Key differences, identified mostly in methods used to assess the overall CVR, did not hamper the intervention design. Minor country-specific adaptations were implemented to maximize the intervention feasibility in each country. Conclusion: Despite differences inCVRmanagement within the countries considered, itwas possible to design and implement the HATICE multidomain intervention. The study can help define preventative strategies for dementia and CVD that are applicable internationally.

  • 267. Barbosa, Cristina
    et al.
    Feio, Paulo
    Fernandes, Ana
    Thorslund, Mats
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    GOVERNANCE STRATEGIES TO AN AGEING SOCIETY - LOCAL ROLL IN MULTI LEVEL PROCESSES2016In: Journal of Comparative Politics, ISSN 1337-7477, E-ISSN 1338-1385, Vol. 9, no 1, p. 4-18Article in journal (Refereed)
    Abstract [en]

    Demographic ageing marks strategic orientations and public policies. It's a challenge to societies, public and private institutions and Welfare State. The goal of this study is to understand the local governance strategies to an ageing population and the role of the local in multilevel governance processes. A qualitative methodology it was followed that supports analysis and understanding of both local ageing policies. The samples are case studies of two contexts, Portugal and Sweden, respectively city councils of Lisbon and Nacka, where stakeholders were interviewed. Different concepts and visions influence local ageing policies. Vertical coordination is easier to follow in Portugal, but without concrete laws, and in Sweden, horizontal coordination is emphasized between providers and municipalities. Local public intervention in ageing seeks renewed actions and this study allows to conclude that a perfect local policy doesn't exist. However in many aspects, can be complementary.

  • 268.
    Barclay, Kieron
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Sociology. London School of Economics and Political Science, UK; Max Planck Institute for Demographic Research, Germany.
    Myrskylä, Mikko
    Tynelius, Per
    Berglind, Daniel
    Rasmussen, Finn
    Birth order and hospitalization for alcohol and narcotics use in Sweden2016In: Drug And Alcohol Dependence, ISSN 0376-8716, E-ISSN 1879-0046, Vol. 167, p. 15-22Article in journal (Refereed)
    Abstract [en]

    Background: Previous studies have shown that birth order is an important predictor of later life health as well as socioeconomic attainment. In this study, we examine the relationship between birth order and hospitalization for alcohol and narcotics use in Sweden. Methods: We study the relationship between birth order and hospitalization related to alcohol and narcotics use before and after the age of 20 using Swedish register data for cohorts born 1987-1994. We apply Cox proportional hazard models and use sibling fixed effects, eliminating confounding by factors shared by the siblings. Results: Before age 20 we find that later born siblings are hospitalized for alcohol use at a higher rate than first-borns, and there is a monotonic increase in the hazard of hospitalization with increasing birth order. Second-borns are hospitalized at a rate 47% higher than first-borns, and third-borns at a rate 65% higher. Similar patterns are observed for hospitalization for narcotics use. After age 20 the pattern is similar, but the association is weaker. These patterns are consistent across various sibling group sizes. Conclusions: Later born siblings are more likely to be hospitalized for both alcohol and narcotics use in Sweden. These birth order effects are substantial in size, and larger than the estimated sex differences for the risk of hospitalization related to alcohol and drug use before age 20, and previous estimates for socioeconomic status differences in alcohol and drug abuse.

  • 269. Barghadouch, Amina
    et al.
    Kristiansen, Maria
    Smith Jervelund, Signe
    Hjern, Anders
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS). Karolinska Institutet, Sweden.
    Montgomery, Edith
    Norredam, Marie
    Refugee children have fewer contacts to psychiatric healthcare services: an analysis of a subset of refugee children compared to Danish-born peers2016In: Social Psychiatry and Psychiatric Epidemiology, ISSN 0933-7954, E-ISSN 1433-9285, Vol. 51, no 8, p. 1125-1136Article in journal (Refereed)
    Abstract [en]

    Studies show a high level of mental health problems among refugee children. This study examined whether a subset of refugee children living in Denmark accessed psychiatric healthcare services more than those born in the country. This study compared 24,427 refugee children from Asia, The Middle East, Sub-Saharan Africa and former Yugoslavia, who obtained residency in Denmark between 1 January 1993 and 31 December 2010 with 146,562 Danish-born children, matched 1:6 on age and sex. The study looked at contacts with psychiatric hospitals as well as psychologists and psychiatrists in private practice. Between 1 January 1996 and 30 June 2012, 3.5 % of the refugee children accessed psychiatric healthcare services compared to 7.7 % of the Danish-born children. The rate ratio of having any first-time psychiatric contact was 0.42 (95 % CI 0.40-0.45) among refugee boys and 0.35 (95 % CI 0.33-0.37) among refugee girls, compared to Danish-born children. Figures were similar for those accessing private psychologists or psychiatrists, emergency room, inpatient and outpatient services. Refugee children used fewer psychiatric healthcare services than Danish-born children. This may indicate that refugee children experience barriers in accessing psychiatric healthcare systems and do not receive adequate assessment of their mental health and subsequent referral to specialist services.

  • 270. Barisic, Ivan
    et al.
    Schoenthaler, Silvia
    Ke, Rongqin
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Nilsson, Mats
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Noehammer, Christa
    Wiesinger-Mayr, Herbert
    Multiplex detection of antibiotic resistance genes using padlock probes2013In: Diagnostic microbiology and infectious disease, ISSN 0732-8893, E-ISSN 1879-0070, Vol. 77, no 2, p. 118-125Article in journal (Refereed)
    Abstract [en]

    The elucidation of resistance mechanisms is of central importance to providing and maintaining efficient medical treatment. However, molecular detection methods covering the complete set of resistance genes with a single test are still missing. Here, we present a novel 100-plex assay based on padlock probes in combination with a microarray that allows the simultaneous large-scale identification of highly diverse beta-lactamases. The specificity of the assay was performed using 70 clinical bacterial isolates, recovering 98% of the beta-lactamase nucleotide sequences present. Additionally, the sensitivity was evaluated with PCR products and genomic bacterial DNA, revealing a detection limit of 10(4) DNA copies per reaction when using PCR products as the template. Pre-amplification of genomic DNA in a 25-multiplex PCR further facilitated the detection of beta-lactamase genes in dilutions of 10(7) cells/mL. In summary, we present an efficient, highly specific, and highly sensitive multiplex detection method for any gene.

  • 271. Barlind, Jonas G.
    et al.
    Buckett, Linda K.
    Crosby, Sharon G.
    Davidsson, Ojvind
    Emtenas, Hans
    Ertan, Anne
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Jurva, Ulrik
    Lemurell, Malin
    Gutierrez, Pablo Morentin
    Nilsson, Karolina
    O'Mahony, Gavin
    Petersson, Annika U.
    Redzic, Alma
    Wagberg, Fredrik
    Yuan, Zhong-Qing
    Identification and design of a novel series of MGAT2 inhibitors2013In: Bioorganic & Medicinal Chemistry Letters, ISSN 0960-894X, E-ISSN 1090-2120, Vol. 23, no 9, p. 2721-2726Article in journal (Refereed)
    Abstract [en]

    [Acyl CoA]monoacylglycerol acyltransferase 2 (MGAT2) is of interest as a target for therapeutic treatment of diabetes, obesity and other diseases which together constitute the metabolic syndrome. In this Letter we report our discovery and optimisation of a novel series of MGAT2 inhibitors. The development of the SAR of the series and a detailed discussion around some key parameters monitored and addressed during the lead generation phase will be given. The in vivo results from an oral lipid tolerance test (OLTT) using the MGAT2 inhibitor (S)-10, shows a significant reduction (68% inhibition relative to naive, p < 0.01) in plasma triacylglycerol (TAG) concentration.

  • 272. Barnevik Olsson, Martina
    et al.
    Holm, Anette
    Westerlund, Joakim
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Cognitive psychology. Gothenburg University, Sweden.
    Lundholm Hedvall, Åsa
    Gillberg, Christopher
    Fernell, Elisabeth
    Children with borderline intellectual functioning and autism spectrum disorder: developmental trajectories from 4 to 11 years of age2017In: Neuropsychiatric Disease and Treatment, ISSN 1176-6328, E-ISSN 1178-2021, Vol. 13, p. 2519-2526Article in journal (Refereed)
    Abstract [en]

    Background: Studies on autism have tended to focus either on those with intellectual disability (ie, those with intellectual quotient [IQ] under 70) or on the group that is referred to as high-functioning, that is, those with borderline, average or above average IQ. The literature on cognition and daily functioning in autism spectrum disorder combined specifically with borderline intellectual functioning (IQ 70-84) is limited. Methods: From a representative group of 208 preschool children diagnosed with autism spectrum disorder, those 50 children in the group with borderline intellectual functioning at ages 4.5-6.5 years were targeted for follow-up at a median age of 10 years. A new cognitive test was carried out in 30 children. Parents were interviewed with a semi-structured interview together with the Vineland Adaptive Behavior Scales (n=41) and the Autism-Tics, attention-deficit/hyperactivity disorder (AD/HD) and other comorbidities inventory (A-TAC) (n=36). Results: Most children of interviewed parents presented problems within several developmental areas. According to A-TAC and the clinical interview, there were high rates of attention deficits and difficulties with regulating activity level and impulsivity. Vineland Adaptive Behavior Scales composite scores showed that at school age, a majority of the children had declined since the previous assessment at ages between 4.5 and 6.5 years. Almost half the tested group had shifted in their IQ level, to below 70 or above 84. Conclusion: None of the children assessed was without developmental/neuropsychiatric problems at school-age follow-up. The results support the need for comprehensive follow-up of educational, medical and developmental/neuropsychiatric needs, including a retesting of cognitive functions. There is also a need for continuing parent/family follow-up and support.

  • 273. Barnevik Olsson, Martina
    et al.
    Westerlund, Joakim
    Stockholm University, Faculty of Social Sciences, Department of Psychology. Gothenburg University, Sweden.
    Lundstrom, Sebastian
    Giacobini, MaiBritt
    Fernell, Elisabeth
    Gillberg, Christopher
    Recovery from the diagnosis of autism - and then?2015In: Neuropsychiatric Disease and Treatment, ISSN 1176-6328, E-ISSN 1178-2021, Vol. 11, p. 999-1005Article in journal (Refereed)
    Abstract [en]

    Background: The aim of this study was to follow up the 17 children, from a total group of 208 children with autism spectrum disorder (ASD), who recovered from autism. They had been clinically diagnosed with ASD at or under the age of 4 years. For 2 years thereafter they received intervention based on applied behavior analysis. These 17 children were all of average or borderline intellectual functioning. On the 2-year follow-up assessment, they no longer met criteria for ASD. Methods: At about 10 years of age they were targeted for a new follow-up. Parents were given a semistructured interview regarding the child's daily functioning, school situation, and need of support, and were interviewed using the Vineland Adaptive Behavior Scales (VABS) and the Autism - Tics, Attention-deficit/hyperactivity disorder (AD/HD), and other Comorbidities (A-TAC) telephone interview. Results: The vast majority of the children had moderate-to-severe problems with attention/activity regulation, speech and language, behavior, and/or social interaction. A majority of the children had declined in their VABS scores. Most of the 14 children whose parents were A-TAC-interviewed had problems within many behavioral A-TAC domains, and four (29%) had symptom levels corresponding to a clinical diagnosis of ASD, AD/HD, or both. Another seven children (50%) had pronounced subthreshold indicators of ASD, AD/HD, or both. Conclusion: Children diagnosed at 2-4 years of age as suffering from ASD and who, after appropriate intervention for 2 years, no longer met diagnostic criteria for the disorder, clearly needed to be followed up longer. About 3-4 years later, they still had major problems diagnosable under the umbrella term of ESSENCE (Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations). They continued to be in need of support, educationally, from a neurodevelopmental and a medical point of view. According to parent interview data, a substantial minority of these children again met diagnostic criteria for ASD.

  • 274.
    Barragan, Antonio
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Karolinska Institutet, Sweden.
    Weidner, Jessica M.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Karolinska Institutet, Sweden.
    Jin, Z.
    Korpi, E. R.
    Birnir, B.
    GABAergic signalling in the immune system2015In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 213, no 4, p. 819-827Article, review/survey (Refereed)
    Abstract [en]

    The GABAergic system is the main inhibitory neurotransmitter system in the central nervous system (CNS) of vertebrates. Signalling of the transmitter c-aminobutyric acid (GABA) via GABA type A receptor channels or G-protein-coupled type B receptors is implicated in multiple CNS functions. Recent findings have implicated the GABAergic system in immune cell functions, inflammatory conditions and diseases in peripheral tissues. Interestingly, the specific effects may vary between immune cell types, with stage of activation and be altered by infectious agents. GABA/GABA-A receptor-mediated immunomodulatory functions have been unveiled in immune cells, being present in T lymphocytes and regulating the migration of Toxoplasma-infected dendritic cells. The GABAergic system may also play a role in the regulation of brain resident immune cells, the microglial cells. Activation of microglia appears to regulate the function of GABAergic neurotransmission in neighbouring neurones through changes induced by secretion of brain-derived neurotrophic factor. The neurotransmitter-driven immunomodulation is a new but rapidly growing field of science. Herein, we review the present knowledge of the GABA signalling in immune cells of the periphery and the CNS and raise questions for future research.

  • 275. Barregard, Lars
    et al.
    Haghdoost, Siamak
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Cooke, Marcus S.
    Human and Methodological Sources of Variability in the Measurement of Urinary 8-Oxo-7,8-dihydro-2 '-deoxyguanosine2013In: Antioxidants and Redox Signaling, ISSN 1523-0864, E-ISSN 1557-7716, Vol. 18, no 18, p. 2377-2391Article in journal (Refereed)
    Abstract [en]

    Aims: Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) is a widely used biomarker of oxidative stress. However, variability between chromatographic and ELISA methods hampers interpretation of data, and this variability may increase should urine composition differ between individuals, leading to assay interference. Furthermore, optimal urine sampling conditions are not well defined. We performed inter-laboratory comparisons of 8-oxodG measurement between mass spectrometric-, electrochemical- and ELISA-based methods, using common within-technique calibrants to analyze 8-oxodG-spiked phosphate-buffered saline and urine samples. We also investigated human subject- and sample collection-related variables, as potential sources of variability. Results: Chromatographic assays showed high agreement across urines from different subjects, whereas ELISAs showed far more inter-laboratory variation and generally overestimated levels, compared to the chromatographic assays. Excretion rates in timed 'spot' samples showed strong correlations with 24 h excretion (the 'gold' standard) of urinary 8-oxodG (r(p) 0.67-0.90), although the associations were weaker for 8-oxodG adjusted for creatinine or specific gravity (SG). The within-individual excretion of 8-oxodG varied only moderately between days (CV 17% for 24 h excretion and 20% for first void, creatinine-corrected samples). Innovation: This is the first comprehensive study of both human and methodological factors influencing 8-oxodG measurement, providing key information for future studies with this important biomarker. Conclusion: ELISA variability is greater than chromatographic assay variability, and cannot determine absolute levels of 8-oxodG. Use of standardized calibrants greatly improves intra-technique agreement and, for the chromatographic assays, importantly allows integration of results for pooled analyses. If 24 h samples are not feasible, creatinine- or SG-adjusted first morning samples are recommended.

  • 276.
    Barrett, Damon
    Stockholm University, Faculty of Law, Department of Law. University of Essex, UK.
    Re: ‘Access to treatment with controlled medicines: rationale and recommendations for neutral, precise, and respectful language’2018In: Public Health, ISSN 0033-3506, E-ISSN 1476-5616, Vol. 160, p. 156-156Article in journal (Other academic)
  • 277.
    Barrett, Damon
    Stockholm University, Faculty of Law, Department of Law. University of Essex, UK.
    The Child's Right to Protection from Drugs: Understanding History to Move Forward2017In: Health and Human Rights: An International Journal, ISSN 1079-0969, E-ISSN 2150-4113, Vol. 19, no 1, p. 263-268Article in journal (Refereed)
  • 278. Bartelink, Eric J.
    et al.
    Sholts, Sabrina B.
    Milligan, Colleen F.
    Van Deest, Traci L.
    Wärmländer, Sebastian K. T. S.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Linköping University, Sweden.
    A Case of Contested Cremains Analyzed Through Metric and Chemical Comparison2015In: Journal of Forensic Sciences, ISSN 0022-1198, E-ISSN 1556-4029, Vol. 60, no 4, p. 1068-1073Article in journal (Refereed)
    Abstract [en]

    Since the 1980s, cremation has become the fastest growing area of the U.S. funeral industry. At the same time, the number of litigations against funeral homes and cremation facilities has increased. Forensic anthropologists are often asked to determine whether the contents of an urn are actually cremated bone, and to address questions regarding the identity of the remains. This study uses both metric and chemical analyses for resolving a case of contested cremains. A cremains weight of 2021.8 g was predicted based on the decedent's reported stature and weight. However, the urn contents weighed 4173.5 g. The urn contents also contained material inconsistent with cremains (e.g., moist sediment, stones, ferrous metal). Analysis using XRD and SEM demonstrated that the urn contained thermally altered bone as well as inorganic material consistent with glass fiber cement. Although forensically challenging, cremains cases such as this one can be resolved using a multidisciplinary approach.

  • 279.
    Bartonek, Frida
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS).
    The role of self-esteem for the relation between school performance and psychosomatic health in adolescence: Sex differences and gender theoretical interpretations2012Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    While socioeconomic inequalities in health seem to level out during adolescence, circumstances related to school appears to have increased in importance. Such circumstances include, for example, school performance. The primary aim of this study is to examine the relationship between school performance and psychosomatic health. The moderating role of self-esteem and the presence of any sex differences will additionally be investigated. Data from the Stockholm School Survey in 2004, covering a total sample of 5 135 adolescents in 9th grade, were used. Based on linear regression, a significant association between school marks and psychosomatic health was found where higher school performance was linked to better health. Moreover, lower self-esteem was linked to more health complaints. Self-esteem moderated the association between school marks and psychosomatic health but only among boys, for whom the effect of having both high marks and high self-esteem was not as beneficial for health as expected. While differences by sex were found in the distribution of school marks, self-esteem and psychosomatic health, none were found in the associations between self-esteem and school performance and psychosomatic health (the only exception being the moderating role of self-esteem among boys).

  • 280.
    Basmarke-Wehelie, Rahma
    et al.
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Sjölinder, Hong
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Jurkowski, Wiktor
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Elofsson, Arne
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Arnqvist, Anna
    Umea Univ, Dept Med Biochem & Biophys, Sweden.
    Engstrand, Lars
    Karolinska Inst, Swedish Inst Infect Dis Control, Sweden.
    Hagner, Matthias
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Wallin, Elin
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Guan, Na
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Kuranasekera, Hasanthi
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Aro, Helena
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Jonsson, Ann-Beth
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    The complement regulator CD46 is bactericidal to Helicobacter pylori and blocks urease activity2011In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 141, no 3, p. 918-928Article in journal (Refereed)
    Abstract [en]

    BACKGROUND & AIMS: CD46 is a C3b/C4b binding complement regulator and a receptor for several human pathogens. We examined the interaction between CD46 and Helicobacter pylori (a bacterium that colonizes the human gastric mucosa and causes gastritis), peptic ulcers, and cancer.

    METHODS: Using gastric epithelial cells, we analyzed a set of H pylori strains and mutants for their ability to interact with CD46 and/or influence CD46 expression. Bacterial interaction with full-length CD46 and small CD46 peptides was evaluated by flow cytometry, fluorescence microscopy, enzyme-linked immunosorbent assay, and bacterial survival analyses.

    RESULTS: H pylori infection caused shedding of CD46 into the extracellular environment. A soluble form of CD46 bound to H pylori and inhibited growth, in a dose- and time-dependent manner, by interacting with urease and alkyl hydroperoxide reductase, which are essential bacterial pathogenicity-associated factors. Binding of CD46 or CD46-derived synthetic peptides blocked the urease activity and ability of bacteria to survive in acidic environments. Oral administration of one CD46 peptide eradicated H pylori from infected mice.

    CONCLUSIONS: CD46 is an antimicrobial agent that can eradicate H pylori. CD46 peptides might be developed to treat H pylori infection.

  • 281. Bassyouni, Fatma A.
    et al.
    Saleh, Tamer S.
    ElHefnawi, Mahmoud M.
    Abd El-Moez, Sherein I.
    El-Senousy, Waled M.
    Abdel-Rehim, Mohamed E.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Synthesis, pharmacological activity evaluation and molecular modeling of new polynuclear heterocyclic compounds containing benzimidazole derivatives2012In: Archives of pharmacal research, ISSN 0253-6269, E-ISSN 1976-3786, Vol. 35, no 12, p. 2063-2075Article in journal (Refereed)
    Abstract [en]

    Novel heterocyclic compounds containing benzimidazole derivatives were synthesized from 2-(1Hbenzimidazol-2-yl) acetonitrile (1) and arylhydrazononitrile derivative 2 was obtained via coupling of 1 with 4-methyl phenyldiazonium salt, which was then reacted with hydroxylamine hydrochloride to give amidooxime derivative 3. This product was cyclized into the corresponding oxadiazole derivative 4 upon reflux in acetic anhydride. Compound 4 was refluxed in DMF in the presence of triethylamine to give the corresponding 5-(1H-benzimidazol-2-yl)-2-p-tolyl-2H-1,2,3-triazol-4-amine 6. Treatment of compound 6 with ethyl chloroformate afforded 2,6-dihydro-2-(4-methylphenyl)-1,2,3-triazolo[4aEuro(3),5aEuro(3)-4',5']pyrimido[1,6-a]benzimidazole-5(4H)-one (8). 1,2-bis(2-cyanomethyl-1H-benzimidazol-1-yl)ethane-1,2-dione (10) was synthesized via the condensation reaction of 2-(1H-benzimidazol-2-yl) acetonitrile (1) and diethyloxalate. The reactivity of compound 10 towards some diamine reagents was studied. The in vitro antimicrobial activity of the synthesized compounds was investigated against several pathogenic bacterial strains such as Escherichia coli O157, Salmonella typhimurium, E. coli O119, S. paratyphi, Pseudomonas aeruginosa, Staphylococcus aureus, Listeria monocytogenes and Bacillus cereus. The results of MIC revealed that compounds 12a-c showed the most effective antimicrobial activity against tested strains. On the other hand, compounds 12a, b exhibited high activity against rotavirus Wa strain while compounds 12b, c exhibited high activity against adenovirus type 7. In silico target prediction, docking and validation of the compounds 12a-c were performed. The dialkylglycine decarboxylase bacterial enzyme was predicted as a potential bacterial target receptor using pharmacophorebased correspondence with previous leads; giving the highest normalized scores and a high correlation docking score with mean inhibition concentrations. A novel binding mechanism was predicted after docking using the MOE software and its validation.

  • 282. 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.

  • 283.
    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.

  • 284. 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.

  • 285.
    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.

  • 286. 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.

  • 287. Beaussant, Yvan
    et al.
    Daguindau, Etienne
    Chauchet, Adrien
    Rochigneux, Philippe
    Tournigand, Christophe
    Aubry, Régis
    Morin, Lucas
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Hospital end-of-life care in haematological malignancies2018In: BMJ Supportive & Palliative Care, ISSN 2045-435X, E-ISSN 2045-4368, Vol. 8, no 3, p. 314-324Article in journal (Refereed)
    Abstract [en]

    Objective To investigate patterns of care during the last months of life of hospitalised patients who died from different haematological malignancies.

    Methods Nationwide register-based study, including all hospitalised adults >= 20 years who died from haematological malignancies in France in 2010-2013. Outcomes included use of invasive cancer treatments and referral to palliative care. Percentages are adjusted for sex and age using direct standardisation.

    Results Of 46 629 inpatients who died with haematological malignancies, 24.5% received chemotherapy during the last month before death, 48.5% received blood transfusion, 12.3% were under invasive ventilation and 18.1% died in intensive care units. We found important variations between haematological malignancies. The use of chemotherapy during the last month of life varied from 8.6% among patients with chronic myeloid leukaemia up to 30.1% among those with non-Hodgkin's lymphoma (P<0.001). Invasive ventilation was used in 10.2% of patients with acute leukaemia but in 19.0% of patients with Hodgkin's lymphoma (P<0.001). Palliative status was reported 30 days before death in only 14.8% of patients, and at time of death in 46.9% of cases. Overall, 5.5% of haematology patients died in palliative care units.

    Conclusion A high proportion of patients who died from haematological malignancies receive specific treatments near the end of life. There is a need for a better and earlier integration of the palliative care approach in the standard practice of haematology. However, substantial variation according to the type of haematological malignancy suggests that the patients should not be considered as one homogeneous group. Implementation of palliative care should account for differences across haematological malignancies.

  • 288. 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.

  • 289. 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.

  • 290.
    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.

  • 291.
    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.

  • 292.
    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.

  • 293. 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)
  • 294.
    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 Offending2018In: JAMA pediatrics, ISSN 2168-6203, E-ISSN 2168-6211, Vol. 172, no 2, p. 166-173Article 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.

  • 295.
    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.

  • 296.
    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.

  • 297.
    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.

  • 298. 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.

  • 299. 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.

  • 300. 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.

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