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  • Public defence: 2024-11-08 13:15 Örebro universitet, Gymnastik- och idrottshuset, Hörsal G, Örebro
    Jansson, Kalle
    Örebro University, School of Health Sciences.
    Gud vad jobbigt: Religion och etnicitet i ämnet idrott och hälsa2024Doctoral thesis, monograph (Other academic)
    Abstract [en]

    This thesis provides knowledge about how religion and ethnicity, in intersection with gender, become significant in physical education (PE). This is achieved through an empirical study at four different secondary schools which investigates (a) how tensions related to religion and ethnicity take shape and are managed in PE, (b) the didactic consequences of these managements, and (c) how religion, ethnicity, and gender intersect when the tensions take shape and are managed. The study is grounded in intersectionality and pragmatism, employing lesson observations and interviews with teachers and students. Unlike previous research, which often concentrates on specific minority groups, this dissertation investigates how religion, ethnicity and gender take shape as tensions and lead to didactic consequences for teachers, students and the subject content. The study highlights how tensions take shape and are managed in various ways and at different levels, with a range of didactic consequences. Furthermore, the study highlights a vast variation in individual attitudes and how religion, ethnicity and gender are not static but become more or less prominent in different contexts. Tensions generally take shape at the encounter between subject traditions and teaching contents in PE and students from religious and ethnic minority groups who are unable or unwilling to do what is expected. Tensions are rarely managed by schools but rather by teachers and students during PE lessons. The managements rarely involve changes in the subject content or the structure of the teaching. Instead, it is often the students who must adapt or change. Regardless of school, tensions often arise around similar issues and are managed in similar ways, yet significant contextual differences emerge depending on whether participants are in a setting where they are part of a minority or a majority. The thesis’ main scientific contribution lies within the field of sport didactics by providing knowledge about events that teachers and students encounter in their daily school life, which have so far not been investigated in a similar way.

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  • Public defence: 2024-11-14 09:00 Örebro universitet, Campus USÖ, Tidefeltsalen, Örebro
    Manjate, Alice
    Örebro University, School of Medical Sciences.
    Evaluation and improvements of current and future diagnostic strategies for STIs/HIV diagnosisin Mozambique2024Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Sexually transmitted infections (STIs), including HIV, are major global health concerns. Mozambique ranks eighth in the world for HIV prevalence (12.6% in the adult population). Proper diagnosis and treatment are important for prevention and control of the spread of STI/HIV. Untreated STIs are associated with numerous complications, and increased transmission and acquisition of HIV. This thesis aims to evaluate and improve methods of diagnosing STIs, including HIV, in Mozambique. In study I, the impact of vaccine-induced seroreactivity (VISR) on the accuracy of HIV diagnostic algorithms in Tanzania and Mozambique was assessed using stored serum/plasma samples from previous HIV vaccine trials. A substantial part of the samples was misclassified as HIV-infected using standard HIV diagnostic strategies based on antibody detection. In study II, the accuracy of a 4th generation rapid diagnostic test (RDT) in detecting acute and seroconverted HIV infection was evaluated in samples collected from sexually active women in Maputo, Mozambique, and in three commercial HIV-1 seroconversion panels. The antibody component of the 4th generation RDT performed comparably to the Mozambican 3rd generation HIV algorithm while the antigen component showed low sensitivity in detecting acute infection. In study III, vaginal/cervical samples collected from a cohort of sexually active women with urogenital complaints in Maputo were used to assess the accuracy of vaginal discharge syndromes in diagnosing four non-viral STIs. High prevalences of chlamydia, trichomoniasis and HIV-1/2 were recorded. Syndromic management of vaginal discharge revealed low specificity in detecting four non-viral STIs leading to misclassification and overtreatment of cases. In study IV, we determined the prevalence of bacterial vaginosis (BV) using a BV multiplex real-time PCR assay among women in Maputo. A very high prevalence of BV associated with certain sociodemographic and behavioural factors was recorded.

    List of papers
    1. Vaccine-Induced Seroreactivity Impacts the Accuracy of HIV Testing Algorithms in Sub-Saharan Africa: An Exploratory Study
    Open this publication in new window or tab >>Vaccine-Induced Seroreactivity Impacts the Accuracy of HIV Testing Algorithms in Sub-Saharan Africa: An Exploratory Study
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    2022 (English)In: Vaccines, E-ISSN 2076-393X, Vol. 10, no 7, article id 1062Article in journal (Refereed) Published
    Abstract [en]

    The detection of vaccine-induced HIV antibody responses by rapid diagnostic tests (RDTs) may confound the interpretation of HIV testing results. We assessed the impact of vaccine-induced seroreactivity (VISR) on the diagnosis of HIV in sub-Saharan Africa. Samples collected from healthy participants of HIVIS and TaMoVac HIV vaccine trials after the final vaccination were analyzed for VISR using HIV testing algorithms used in Mozambique and Tanzania that employ two sequential RDTs. The samples were also tested for VISR using Enzygnost HIV Integral 4 ELISA and HIV western blot assays. Antibody titers to subtype C gp140 were determined using an in-house enzyme-linked immunosorbent assay (ELISA). The frequency of VISR was 93.4% (128/137) by Enzygnost HIV Integral 4 ELISA, and 66.4% (91/137) by western blot assay (WHO interpretation). The proportion of vaccine recipients that would have been misdiagnosed as HIV-positive in Mozambique was half of that in Tanzania: 26.3% (36/137) and 54.0% (74/137), respectively, p < 0.0001. In conclusion, the HIV RDTs and algorithms assessed here will potentially misclassify a large proportion of the HIV vaccine recipients if no other test is used. Increased efforts are needed to develop differential serological or molecular tools for use at the point of care.

    Place, publisher, year, edition, pages
    MDPI, 2022
    Keywords
    HIV diagnostic algorithms, HIV misdiagnosis, vaccine-induced HIV antibodies, vaccine-induced seroreactivity
    National Category
    Infectious Medicine
    Identifiers
    urn:nbn:se:oru:diva-100615 (URN)10.3390/vaccines10071062 (DOI)000833204500001 ()35891226 (PubMedID)2-s2.0-8513454015 (Scopus ID)
    Funder
    Sida - Swedish International Development Cooperation Agency, 75000516; 51170072
    Available from: 2022-08-19 Created: 2022-08-19 Last updated: 2024-10-25Bibliographically approved
    2. Laboratory-based evaluation of the 4th-generation Alere™ HIV Combo rapid point-of-care test
    Open this publication in new window or tab >>Laboratory-based evaluation of the 4th-generation Alere™ HIV Combo rapid point-of-care test
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    2024 (English)In: PLOS ONE, E-ISSN 1932-6203, Vol. 19, no 2, article id e0298912Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: Mozambique is a high-prevalence country for HIV and early detection of new HIV infections is crucial for control of the epidemic. We aimed to evaluate the accuracy of the 4th-generation rapid diagnostic test (RDT) AlereTM HIV Combo in detecting acute and seroconverted HIV-infection, among sexually-active women attending three clinical health centers in Maputo, Mozambique.

    METHODS: Women aged 14-55 years (n = 920) seeking care at the Mavalane Health Area, Maputo (February 2018-January 2019) were included, and blood specimens sampled. Sociodemographic and sexual behavior data were collected. Point-of-care HIV testing was performed using Alere DetermineTM HIV-1/2 and Uni-GoldTM HIV-1/2. All samples were also tested using Enzygnost® HIV Integral 4 and Innotest® HIV Antigen mAb in laboratory. The 4th-generation RDT AlereTM HIV Combo was evaluated on serum samples in the laboratory. Finally, Innotest® HIV Antigen mAb, Enzygnost® HIV Integral 4 (Ag/Ab), and HIV RNA quantification acted as gold standard assays in the evaluation of AlereTM HIV Combo test for HIV antigen detection (in clinical samples and in three HIV-1 seroconversion panels).

    RESULTS: The antibody component of the 4th generation AlereTM HIV Combo RDT demonstrated a sensitivity and specificity of 100% examining clinical samples. However, the test did not detect HIV p24 antigen in any clinical samples, while Innotest® HIV Antigen mAb, verified by Enzygnost® HIV Integral 4 (Ag/Ab) and/or HIV RNA quantification, detected HIV antigen in six clinical samples. Furthermore, the AlereTM HIV Combo RDT had a low sensitivity in the detection of HIV p24 antigen in seroconversion panels. The HIV prevalence among the examined women was 17.8%.

    CONCLUSIONS: The 4th-generation RDT AlereTM HIV Combo showed similar sensitivity to the 3rd-generation RDTs to detect seroconverted HIV-infections. However, the sensitivity for detection of HIV p24 antigen and diagnosing acute HIV infections, before seroconversion, was low. There is an urgent need to develop and evaluate simple and affordable POC tests with high sensitivity and specificity for diagnosing individuals with acute HIV infection in resource-limited settings with high HIV prevalence.

    Place, publisher, year, edition, pages
    Public Library of Science (PLoS), 2024
    National Category
    Infectious Medicine
    Identifiers
    urn:nbn:se:oru:diva-111952 (URN)10.1371/journal.pone.0298912 (DOI)001174439300051 ()38394120 (PubMedID)2-s2.0-85185790146 (Scopus ID)
    Funder
    Sida - Swedish International Development Cooperation Agency
    Available from: 2024-02-26 Created: 2024-02-26 Last updated: 2024-10-16Bibliographically approved
    3. Prevalence of sexually transmitted infections (STIs), associations with sociodemographic and behavioural factors, and assessment of the syndromic management of vaginal discharge in women with urogenital complaints in Mozambique
    Open this publication in new window or tab >>Prevalence of sexually transmitted infections (STIs), associations with sociodemographic and behavioural factors, and assessment of the syndromic management of vaginal discharge in women with urogenital complaints in Mozambique
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    2024 (English)In: Frontiers in reproductive health, E-ISSN 2673-3153, Vol. 6, article id 1323926Article in journal (Refereed) Published
    Abstract [en]

    In Mozambique, sexually transmitted infections (STIs) are estimated to be prevalent, but diagnosis and treatment of curable STIs rely only on syndromic management. We examined the prevalence of four non-viral STIs and HIV-1/2, based on etiological diagnosis, associations with sociodemographic and behavioural factors, and the STI diagnostic accuracy of the vaginal discharge syndromic management in women with urogenital complaints in Maputo, Mozambique. A cross-sectional study was performed in Maputo, Mozambique, February 2018-January 2019, enrolling 924 women of reproductive age with urogenital complaints. Endocervical/vaginal swabs were sampled and chlamydia, gonorrhoea, trichomoniasis and Mycoplasma genitalium infections were diagnosed using a multiplex real-time PCR (AmpliSens; InterLabServices). Serological testing was performed for HIV-1/2. A structured questionnaire collected metadata. All data were analyzed in STATA/IC 12.1 using descriptive statistics, chi-square tests and logistic regression model. About 40% of the women were less than 24 years old, 50.8% were single, 62.1% had their sexual debut between 12 and 17 years of age, and the main complaint was vaginal discharge syndrome (85%). The prevalence of chlamydia was 15.5%, trichomoniasis 12.1%, gonorrhoea 4.0%, M. genitalium 2.1%, and HIV-1/2 22.3%. The vaginal discharge syndrome flowchart had a sensitivity of 73.0%-82.5% and a specificity of 14%-15% for the detection of any individual non-viral STI in women with urogenital complaints. In total, 19.2% of the symptomatic women with chlamydia, trichomoniasis or gonorrhoea would not be detected and accordingly treated using the vaginal discharge syndromic management (missed treatment) and 70.0% of the women would be treated despite not being infected with any of these three STIs (overtreatment). In conclusion, a high prevalence of especially chlamydia, trichomoniasis, and HIV-1/2 was found in women of childbearing age with urogenital complaints in Maputo, Mozambique. Syndromic management of vaginal discharge revealed low accuracy in the detection of STIs in symptomatic women, especially low specificity, which resulted in under-treatment of STI-positive cases and incorrect or over-treatment of women with urogenital complaints, many of whom were negative for all the non-viral STIs. Etiological diagnosis is imperative for effective management of STIs in symptomatic and asymptomatic women.

    Place, publisher, year, edition, pages
    Frontiers Media S.A., 2024
    Keywords
    Mozambique, prevalence, sexually transmitted infections, syndromic management, vaginal discharge
    National Category
    Infectious Medicine
    Identifiers
    urn:nbn:se:oru:diva-113566 (URN)10.3389/frph.2024.1323926 (DOI)001211024800001 ()38706519 (PubMedID)2-s2.0-85191779455 (Scopus ID)
    Funder
    Sida - Swedish International Development Cooperation AgencyRegion Örebro County
    Note

    The present study was supported by grants from the SIDA (Swedish International Development Cooperation Agency), EDCTP programs (European and Developing Countries Clinical Trials Partnership), Örebro County Council Research Committee, and the Foundation for Medical Research at Örebro University Hospital, Sweden.

    Available from: 2024-05-08 Created: 2024-05-08 Last updated: 2024-10-16Bibliographically approved
    4. Diagnosis of bacterial vaginosis using a real-time PCR assay among non-pregnant, sexually-active women with urogenital complaints in Maputo, Mozambique
    Open this publication in new window or tab >>Diagnosis of bacterial vaginosis using a real-time PCR assay among non-pregnant, sexually-active women with urogenital complaints in Maputo, Mozambique
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    (English)Manuscript (preprint) (Other academic)
    National Category
    General Practice
    Identifiers
    urn:nbn:se:oru:diva-116780 (URN)
    Available from: 2024-10-16 Created: 2024-10-16 Last updated: 2024-10-16Bibliographically approved
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  • Public defence: 2024-11-15 10:15 Örebro universitet, Forumhuset, Hörsal F, Örebro
    Sjöström, Ylva
    Örebro University, School of Science and Technology.
    Children’s exposure to flame retardants and plasticizers in preschools and homes: a chemical and bioanalytical approach2024Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Chemicals with plasticizing and flame-retardant properties have widespread usage in materials and products designed and produced for everyday life, therefore present in various indoor environments. Their associations with endocrine-disrupting potentials and related health concerns, particularly for children, motivated exploring children's exposure through their everyday indoor environments, which is the main objective of this thesis. Therefore, a suit of chemicals including 50 halogenated flame retardants (HFRs) and organophosphate esters (OPEs) were measured in preschool and home indoor dust (Paper I) and in children’s handwipes (Paper II), along with 14 urinary plasticizer metabolites (Paper III). In addition, the endocrine activity of home and preschool dust was assessed employing cell-based bioassays (Paper IV) and compared to the results in Paper I-III. HFRs and/or OPEs were detected in all handwipe samples with higher levels related to more electronic devices and plastic toys in the premises. For most compounds the levels differed statistically significantly between municipalities, and several correlated with indoor dust levels. Hand-to-mouth dust ingestion was the predominate exposure route. However, no established reference doses (RfD) were exceeded, except for one OPE in a worst-case scenario. Urinary metabolite levels of strictly regulated plasticizers were higher if attending an older preschool. However, the levels were higher after the weekend than after a preschool day, suggesting higher exposure to banned chemicals in environments other than preschools, with human biomonitoring guidance values (HBM-GV) exceeded in three samples. Endocrine activity was detected in both home and preschool dust, which further emphasizes exposure to EDCs through the indoor environment, promoting a focus on indoor spaces to reduce children’s exposure.

    List of papers
    1. Organohalogenated flame retardants and organophosphate esters from home and preschool dust in Sweden: Pollution characteristics, indoor sources and intake assessment
    Open this publication in new window or tab >>Organohalogenated flame retardants and organophosphate esters from home and preschool dust in Sweden: Pollution characteristics, indoor sources and intake assessment
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    2023 (English)In: Science of the Total Environment, ISSN 0048-9697, E-ISSN 1879-1026, Vol. 896, article id 165198Article in journal (Refereed) Published
    Abstract [en]

    This study analysed settled dust samples in Sweden to assess children's combined exposure to 39 organohalogenated flame retardants (HFRs) and 11 organophosphate esters (OPEs) from homes and preschools. >94 % of the targeted compounds were present in dust, indicating widespread use of HFRs and OPEs in Swedish homes and preschools. Dust ingestion was the primary exposure pathway for most analytes, except BDE-209 and DBDPE, where dermal contact was predominant. Children's estimated intakes of ∑emerging HFRs and ∑legacy HFRs from homes were 1-4 times higher than from preschools, highlighting higher exposure risk for HFRs in homes compared to preschools. In a worst-case scenario, intakes of tris(2-butoxyethyl) phosphate (TBOEP) were 6 and 94 times lower than the reference dose for children in Sweden, indicating a potential concern if exposure from other routes like inhalation and diet is as high. The study also found significant positive correlations between dust concentrations of some PBDEs and emerging HFRs and the total number of foam mattresses and beds/m2, the number of foam-containing sofas/m2, and the number of TVs/m2 in the microenvironment, indicating these products as the main source of those compounds. Additionally, younger preschool building ages were found to be linked to higher ΣOPE concentrations in preschool dust, suggesting higher ΣOPE exposure. The comparison with earlier Swedish studies indicates decreasing dust concentrations for some banned and restricted legacy HFRs and OPEs but increasing trends for several emerging HFRs and several unrestricted OPEs. Therefore, the study concludes that emerging HFRs and OPEs are replacing legacy HFRs in products and building materials in homes and preschools, possibly leading to increased exposure of children.

    Place, publisher, year, edition, pages
    Elsevier, 2023
    Keywords
    Dermal contact, Dust ingestion, Estimated intake, Organohalogenated flame retardants, Organophosphate esters, Site characteristics
    National Category
    Occupational Health and Environmental Health
    Identifiers
    urn:nbn:se:oru:diva-106754 (URN)10.1016/j.scitotenv.2023.165198 (DOI)001037732900001 ()37391153 (PubMedID)2-s2.0-85163844513 (Scopus ID)
    Funder
    Region Sörmland
    Note

    Funding agencies:

    National Natural Science Foundation of China (NSFC) 22006144

    European Chemical Industry Council (CEFIC) LRI-B17-SHINE

     

    Available from: 2023-07-03 Created: 2023-07-03 Last updated: 2024-10-24Bibliographically approved
    2. Children's exposure to halogenated flame retardants and organophosphate esters through dermal absorption and hand-to-mouth ingestion in Swedish preschools
    Open this publication in new window or tab >>Children's exposure to halogenated flame retardants and organophosphate esters through dermal absorption and hand-to-mouth ingestion in Swedish preschools
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    2024 (English)In: Science of the Total Environment, ISSN 0048-9697, E-ISSN 1879-1026, Vol. 943, article id 173635Article in journal (Refereed) Published
    Abstract [en]

    Children are exposed to endocrine disrupting chemicals (EDCs) through inhalation and ingestion, as well as through dermal contact in their everyday indoor environments. The dermal loadings of EDCs may contribute significantly to children's total EDC exposure due to dermal absorption as well as hand-to-mouth behaviors. The aim of this study was to measure potential EDCs, specifically halogenated flame retardants (HFRs) and organophosphate esters (OPEs), on children's hands during preschool attendance and to assess possible determinants of exposure in preschool indoor environments in Sweden. For this, 115 handwipe samples were collected in winter and spring from 60 participating children (arithmetic mean age 4.5 years, standard deviation 1.0) and analyzed for 50 compounds. Out of these, 31 compounds were identified in the majority of samples. Levels were generally several orders of magnitude higher for OPEs than HFRs, and 2-ethylhexyl diphenyl phosphate (EHDPP) and tris(2-butoxyethyl) phosphate (TBOEP) were detected in the highest median masses, 61 and 56 ng/wipe, respectively. Of the HFRs, bis(2-ethyl-1-hexyl)-2,3,4,5-tetrabromobenzoate (BEH-TEBP) and 2,2',3,3',4,4',5,5',6,6'-decabromodiphenyl ether (BDE-209) were detected in the highest median masses, 2.8 and 1.8 ng/wipe, respectively. HFR and/or OPE levels were found to be affected by the number of plastic toys, and electrical and electronic devices, season, municipality, as well as building and/or renovation before/after 2004. Yet, the calculated health risks for single compounds were below available reference dose values for exposure through dermal uptake as well as for ingestion using mean hand-to-mouth contact rate. However, assuming a high hand-to-mouth contact rate, at the 95th percentile, the calculated hazard quotient was above 1 for the maximum handwipe mass of TBOEP found in this study, suggesting a risk of negative health effects. Furthermore, considering additive effects from similar compounds, the results of this study indicate potential concern if additional exposure from other routes is as high.

    Place, publisher, year, edition, pages
    Elsevier, 2024
    Keywords
    Children, Exposure, Hand-to-mouth, Handwipe, Indoor environment, Preschool
    National Category
    Environmental Sciences
    Identifiers
    urn:nbn:se:oru:diva-114003 (URN)10.1016/j.scitotenv.2024.173635 (DOI)001253789900001 ()38821289 (PubMedID)2-s2.0-85195817562 (Scopus ID)
    Funder
    Region Sörmland
    Note

    The county of Sörmland (Region Sörmland); the National Natural Science Foundation of China (No. 22006144); and the European Chemical Industry Council (CEFIC) (LRI-B17-SHINE) supported this project.

    Available from: 2024-06-03 Created: 2024-06-03 Last updated: 2024-10-24Bibliographically approved
    3. Exposure to phthalates and DiNCH among preschool children in Sweden: Urinary metabolite concentrations and predictors of exposure
    Open this publication in new window or tab >>Exposure to phthalates and DiNCH among preschool children in Sweden: Urinary metabolite concentrations and predictors of exposure
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    2023 (English)In: International journal of hygiene and environmental health, ISSN 1438-4639, E-ISSN 1618-131X, Vol. 250, article id 114161Article in journal (Refereed) Published
    Abstract [en]

    Several plasticizing chemicals induce endocrine disrupting effects in humans, and the indoor environment is suggested to be a source of exposure. As children are particularly vulnerable to the effects from exposure to endocrine disrupting chemicals (EDCs), it is essential to monitor exposure to EDCs such as phthalates and non-phthalate plasticizers in indoor environments intended for use by children. The aim of this study was to assess everyday plasticizer exposure among preschool-aged children in Sweden by measuring urinary plasticizer metabolite concentrations. In addition, it was investigated whether the concentrations would be altered as a result of the children spending part of the day at preschool, in comparison with weekend exposure, when they may spend more time in home environments or engage in various weekend and leisure activities. For this purpose, fourteen metabolites from eight phthalates (di-ethylhexyl phthalate, DEHP; di-n-butyl phthalate, DnBP; di-isobutyl phthalate, DiBP; butyl-benzyl phthalate, BBzP; di-iso-nonyl phthalate, DiNP; di-propylheptyl phthalate, DPHP; di-iso-decyl phthalate, DiDP; and di-ethyl phthalate, DEP) and one non-phthalate plasticizer (di-isononyl cyclohexane 1,2-dicarboxylate, DiNCH) were measured in 206 urine samples collected at four occasions, i.e. twice during the winter and twice during the spring from 54 children (mean 5.1 years, SD 0.94) enrolled at eight preschools in Sweden. A detection frequency (DF) of 99.9% for the 14 metabolites indicates a widespread exposure to plasticizers among children in Sweden. Compared to previous Swedish and international studies performed during approximately the same time period, high urinary concentrations of monobenzyl phthalate (MBzP), a metabolite from the strictly regulated BBzP, were measured in this study (median 17 ng/mL). Overall, high urinary phthalate metabolite concentrations were observed in this study compared to the US CDC-NHANES from the same time period and similar age-group. Compared to European studies, however, similar concentrations were observed for most metabolites and the urinary concentrations from few participating children exceeded the human biomonitoring guidance values (HBM-GV) for children. After days with preschool attendance, lower urinary concentrations of metabolites originating from DEP and phthalates that are strictly regulated within the EU REACH legislation (DEHP, DnBP, and DiBP) and higher concentrations of metabolites originating from DiNP, DPHP, and DiDP, i.e. less or non-regulated phthalates were found compared the urinary concentrations of these metabolites in weekends. This may indicate that factors in the indoor environment itself are important for the extent of the plasticizer exposure. All the analyzed metabolites were measured in lower concentrations in urine collected from children attending preschools built or renovated after the year 2000, while no seasonal differences were observed in this study.

    Place, publisher, year, edition, pages
    Urban & Fischer, 2023
    Keywords
    Biomonitoring, Children, Home, Indoor, Plasticizer, Preschool
    National Category
    Occupational Health and Environmental Health
    Identifiers
    urn:nbn:se:oru:diva-105267 (URN)10.1016/j.ijheh.2023.114161 (DOI)000967035600001 ()36990000 (PubMedID)2-s2.0-85150789784 (Scopus ID)
    Funder
    Region SörmlandRegion Örebro CountyÖrebro University
    Available from: 2023-03-30 Created: 2023-03-30 Last updated: 2024-10-24Bibliographically approved
    4. Endocrine activities of dust in children's indoor environments: Associations with multiple chemicals from various compound classes across exposure matrices used for health risk assessment
    Open this publication in new window or tab >>Endocrine activities of dust in children's indoor environments: Associations with multiple chemicals from various compound classes across exposure matrices used for health risk assessment
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    (English)Manuscript (preprint) (Other academic)
    National Category
    Other Chemistry Topics
    Identifiers
    urn:nbn:se:oru:diva-116975 (URN)
    Available from: 2024-10-24 Created: 2024-10-24 Last updated: 2024-10-24Bibliographically approved
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  • Public defence: 2024-11-15 13:00 Måltidens Hus, Gastronomiska Teatern, Grythyttan
    Hult, Kajsa
    Örebro University, School of Hospitality, Culinary Arts & Meal Science.
    Hipster Hospitality and Beyond: Exploring dining room professionals in contemporary restaurants2024Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In recent years, the line between high and low culinary standards has become blurred, leading to a transformative shift in restaurant culture. While considerable attention has been paid to consumption, there is a notable research gap concerning the production side within restaurant dining rooms. This thesis explores the meaning and practice of dining room professionals’ work in restaurants and expands the interpretation of hospitality as a dynamic and multifaceted practice within the restaurant. Drawing on interviews, observations, and autoethnography in contemporary casual restaurants and critically examining the portrayal of the dining room professional as communicated through recruitment, this thesis illustrates how dining room professionals incorporate personal values and self-fulfillment into their professional roles and abstract from traditional hospitality traits. The findings indicate that these professionals are not primarily driven by an ambition to advance their careers in traditional fine dining settings. Instead, they are seeking workplaces that foster the growth of their culinary skills and personal interests in collaboration with like-minded individuals, including guests as well as colleagues. This shift marks a departure from conventional hospitality norms, as these professionals express a desire for more autonomy and flexibility in their work, as well as enacting a shift away from the predictability of service manuals, the constraints of scripted interactions, and the limited opportunities for self-expression within the meal experience. Seen in a time of changes within the culinary field, this thesis contributes to the restaurant industry by showing how contemporary dining room professionals experience liberation when guided by personal beliefs, social tastes and identities, rather than guest demands or business directives, allowing them freedom to provide the work. In turn, this impacts their motivations for being in, and navigating through the restaurant industry.

    List of papers
    1. Constructing the hospitality superstar in restaurant dining rooms
    Open this publication in new window or tab >>Constructing the hospitality superstar in restaurant dining rooms
    2023 (English)In: Scandinavian Journal of Hospitality and Tourism, ISSN 1502-2250, E-ISSN 1502-2269, Vol. 23, no 2-3, p. 264-281Article in journal (Refereed) Published
    Abstract [en]

    The need for competent hospitality workers is significant for the sustainable development of the restaurant industry. However, with the recurring challenges of recruiting and retaining a competent workforce, there is a need to understand how employers portray and communicate hospitality work in the recruitment process. Therefore, this study examines how employers construct the image of the hospitality worker, by analyzing what job advertisements signal and communicate to the applicants. Through thematic analysis of 100 job advertisements in Sweden, we found that the ideal hospitality worker is an individualized team player with occupational passion. This means that social capacities and commitment to hospitality and gastronomy, factors that are difficult to measure, are of relevance to gaining employment. Additionally, by asking for social capacities, the distance between work and leisure is diminished and the employee is constructed as a commodity for the purpose of improving service. In contrast to the common image that hospitality work is work that anyone could do, we conclude that the qualifications for becoming a hospitality worker in the restaurant industry are fairly complex.

    Place, publisher, year, edition, pages
    Oslo: Taylor & Francis, 2023
    Keywords
    recruitment, job advertisement, restaurant work
    National Category
    Social Sciences Interdisciplinary
    Research subject
    Culinary Arts and Meal Science
    Identifiers
    urn:nbn:se:oru:diva-109448 (URN)10.1080/15022250.2023.2272167 (DOI)001085784300001 ()2-s2.0-85174264941 (Scopus ID)
    Available from: 2023-10-30 Created: 2023-10-30 Last updated: 2024-10-22Bibliographically approved
    2. Contemporary dining room professionals: towards a “hip” style of hospitality identity
    Open this publication in new window or tab >>Contemporary dining room professionals: towards a “hip” style of hospitality identity
    2023 (English)In: Research in Hospitality Management, ISSN 2224-3534, Vol. 13, no 1, p. 11-21Article in journal (Refereed) Published
    Abstract [en]

    Interest in having an occupation that connects with consumption practices of taste has increased in the contemporary creative economy. In addition, the restaurant scene in Sweden as well as globally has recently been moving towards a casualisation of high-quality restaurants, which presents new questions about how to understand and practise the work in restaurant dining rooms. The study focuses on dining room professionals working in an evolving culinary restaurant scene, with the purpose of investigating them and their search for sense in contemporary restaurant venues. We use identity perspectives and hospitality as concepts to understand how the professionals create meaning in their work through interviews with professionals working in a subset of restaurants in Sweden. With such an emphasis, this study identifies a certain culinary hospitality identity that needs creative spaces, social exchanges and the idea of authentic materiality to make sense of the restaurant work. In contrast to the way dining room work has traditionally been pictured, this article shows that the industry needs to understand hospitality professionals who put their own authenticity in the foreground, which also guides their choices about where to work and how to perform in these contexts. This also helps the industry to become more attractive, as it is in a vulnerable position after the coronavirus pandemic.

    Place, publisher, year, edition, pages
    Taylor & Francis Group, 2023
    Keywords
    authenticity, creative economy, culinary identity, restaurant work, service work, taste
    National Category
    Social Sciences Interdisciplinary
    Research subject
    Culinary Arts and Meal Science
    Identifiers
    urn:nbn:se:oru:diva-109093 (URN)10.1080/22243534.2023.2239573 (DOI)
    Available from: 2023-10-19 Created: 2023-10-19 Last updated: 2024-10-22Bibliographically approved
    3. Hipster Hospitality: Blurred Boundaries in Restaurants
    Open this publication in new window or tab >>Hipster Hospitality: Blurred Boundaries in Restaurants
    2024 (English)In: Journal of Gastronomy and Tourism, ISSN 2169-2971, E-ISSN 2169-298X, Vol. 8, no 2, p. 65-82Article in journal (Refereed) Published
    Abstract [en]

    The restaurant industry is currently experiencing a shift in taste judgements. Practices and discourses on taste are communicated and expressed in contexts where food enthusiasts meet, resulting in a complex debate about the production and consumption of “good and bad” taste. This study aims to explore the intricate dynamics that shape the performances of dining room professionals in contemporary restaurants. Based on autoethnographic fieldwork at two restaurants in Sweden, this study uses cultural taste and dramaturgical theory to understand the social processes in restaurant culture. The results demonstrate how dining room work is organized within an unstructured environment through organic service, aesthetical framing, and self-representation. Based on these findings, the article argues that the interplay between the restaurant’s ambiance and the self holds value in shaping specific hipster hospitality. For instance, this is achieved through the blurred line between frontstage and backstage. This study contributes to the understanding of the changing role of work in contemporary restaurant culture, in which a less pronounced distinction between private and public, and between formal and informal service are some of the elements.

    Place, publisher, year, edition, pages
    Cognizant Communication Corporation, 2024
    Keywords
    restaurant professionals, service, hospitality, cultural taste, autoethnography
    National Category
    Social Sciences Interdisciplinary
    Research subject
    Culinary Arts and Meal Science
    Identifiers
    urn:nbn:se:oru:diva-113114 (URN)10.3727/216929722X16354101932474 (DOI)
    Available from: 2024-04-15 Created: 2024-04-15 Last updated: 2024-10-22Bibliographically approved
    4. Autoethnography from the restaurant floor: Exploring the embodied experience of dining room professionals
    Open this publication in new window or tab >>Autoethnography from the restaurant floor: Exploring the embodied experience of dining room professionals
    (English)Manuscript (preprint) (Other academic)
    National Category
    Social Sciences Interdisciplinary
    Identifiers
    urn:nbn:se:oru:diva-116950 (URN)
    Available from: 2024-10-22 Created: 2024-10-22 Last updated: 2024-10-22Bibliographically approved
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    Hipster Hospitality and Beyond: Exploring dining room professionals in contemporary restaurants
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  • Public defence: 2024-11-19 09:00 Örebro universitet, Campus USÖ, hörsal X1, Örebro
    Lovane Matias, Lucília Trindade
    Örebro University, School of Medical Sciences.
    Human papillomavirus in cervical carcinoma in an HIV endemic milieu, Moçambique2024Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Cervical cancer (CC) is the fourth most frequent cancer and cause of death related to cancer in women worldwide. CC is mainly caused by a persistent infection with human papillomaviruses (HPV). Mozambique is one of the African countries with high prevalence of HPV and HIV. The development of CC may be different in HIV immuno-compromised patients. In this thesis we investigated both the pathogenetic perspective of HPV, and the expression of immunotherapeutic target concerning the possible impacts in an HIV endemic milieu. In paper I, virtual tissue microarrays (TMA) were used to validate the representativity to study biomarkers in CC compared to whole slide images. Our study presents an approach to address TMA sampling that could be generalized to TMA-based research. In paper II, the immunoregulatory programmed deathligand 1 (PD-L1) was immunohistochemically assessed in cervical squamous carcinomas (SCC) in TMA. 575 cases of SCC were included, HIV status was available in 46% cases. Our findings indicated that the immunotherapeutic target of PD-L1 is not influenced by HIV status. In paper III, 40 cases of endocervical adenocarcinomas (ECA) were included. HIV status was established, and HPV was detected in all cases. In paper IV, 260 cases of SCC with known HIV status, were assessed concerning HPV genotype differences between HIV positive and negative cases. With a combination of HPV detection methods, almost all cases of our series were HPV positive. Our results in paper III and IV indicate that the newly established vaccination scheme in Mozambique, using quadrivalent vaccine would have the same potential to prevent morbidity and reduce mortality of CC regardless of a concomitant HIV infection or not.

    List of papers
    1. Tissue microarray validation in cervical carcinoma studies: A methodological approach
    Open this publication in new window or tab >>Tissue microarray validation in cervical carcinoma studies: A methodological approach
    2024 (English)In: Histology and Histopathology, ISSN 0213-3911, E-ISSN 1699-5848, article id 18796Article in journal (Refereed) Epub ahead of print
    Abstract [en]

    Tissue microarrays (TMAs) are a cost-effective tool to study biomarkers in clinical research. Cervical cancer (CC) is one of the most prevalent in women worldwide, with the highest prevalence in low-middle-income countries due to a lack of organized screening. CC is associated with persistent high-risk human papillomavirus infection. Several biomarkers have been studied for diagnostic, therapeutic, and prognostic purposes. We aimed to evaluate and validate the effectiveness of TMA in CC compared to whole slide images (WSs). We selected and anonymized twenty cases of CC. P16, cytokeratin 5 (CK5), cytokeratin 7 (CK7), programmed death-ligand 1 (PD-L1), and CD8 expression were immunohistochemically investigated. All WS were scanned and 10 representative virtual TMA cores with 0.6 mm diameter per sample were selected. Ten random combinations of 1-5 cylinders per case were assessed for each biomarker. The agreement of scoring between TMA and WS was evaluated by kappa statistics. We found that three cores of 0.6 mm on TMA can accurately represent WS in our setting. The Kappa value between TMA and WS varied from 1 for p16 to 0.61 for PD-L1. Our study presents an approach to address TMA sampling that could be generalized to TMA-based research, regardless of the tissue and biomarkers of interest.

    Place, publisher, year, edition, pages
    University of Murcia, Murcia, Spain, 2024
    Keywords
    Cervical cancer, Tissue microarray, Immunohistochemistry, Heterogeneity, Validation
    National Category
    Cancer and Oncology
    Identifiers
    urn:nbn:se:oru:diva-115391 (URN)10.14670/HH-18-796 (DOI)39086316 (PubMedID)
    Available from: 2024-08-15 Created: 2024-08-15 Last updated: 2024-10-25Bibliographically approved
    2. PD-L1 expression in squamous cervical carcinomas of Mozambican women living with or without HIV
    Open this publication in new window or tab >>PD-L1 expression in squamous cervical carcinomas of Mozambican women living with or without HIV
    2024 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 14, no 1, article id 12974Article in journal (Refereed) Published
    Abstract [en]

    Programmed death-ligand 1 (PD-L1) is overexpressed in squamous cervical cancer (SCC) and can be used for targeted immunotherapy. The highest mortality rates of SCC are reported in sub-Saharan Africa, where Human immunodeficiency virus (HIV) prevalence is high. In Mozambique most SCC patients present at advanced stages. Thus, there is a need to introduce new treatment options. However, immunocompromised patients were frequently excluded in previous clinical trials. Our aim was to determine if PD-L1 expression in SCC is as prevalent among women living with HIV (WLWH) as among other patients. 575 SCC from Maputo Central Hospital were included. HIV status was available in 266 (46%) cases PD-L1 expression was scored through tumour proportion score (TPS) and combined positive score (CPS). PD-L1 was positive in 20.1% of the cases (n = 110), TPS (score ≥ 25%) and in 26.3% (n = 144), CPS (score ≥ 1). Stratifying according to the HIV status, WLWH were TPS positive in 16.7%, compared to 20.9%, p = 0.43, and concerning CPS 21.1% versus 28.7%, p = 0.19, respectively. PD-L1 status was not influenced by stage, Ki-67 or p16, CD8 expression influenced only CPS status. Our data indicates that the documented effect of PD-L1 therapy on SCC should be confirmed in randomized clinical trials in an HIV endemic milieu.

    Place, publisher, year, edition, pages
    Nature Publishing Group, 2024
    National Category
    Cancer and Oncology
    Identifiers
    urn:nbn:se:oru:diva-114103 (URN)10.1038/s41598-024-63595-7 (DOI)001244399200099 ()38839923 (PubMedID)2-s2.0-85195341528 (Scopus ID)
    Funder
    Sida - Swedish International Development Cooperation Agency
    Available from: 2024-06-07 Created: 2024-06-07 Last updated: 2024-10-25Bibliographically approved
    3. Endocervical adenocarcinomas and HPV genotyping in an HIV endemic milieu: a retrospective study
    Open this publication in new window or tab >>Endocervical adenocarcinomas and HPV genotyping in an HIV endemic milieu: a retrospective study
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    (English)Manuscript (preprint) (Other academic)
    National Category
    Other Health Sciences
    Identifiers
    urn:nbn:se:oru:diva-116949 (URN)
    Available from: 2024-10-22 Created: 2024-10-22 Last updated: 2024-10-22Bibliographically approved
    4. HPV genotypes in cervical squamous cell carcinoma in an HIV endemic milieu: Mozambique
    Open this publication in new window or tab >>HPV genotypes in cervical squamous cell carcinoma in an HIV endemic milieu: Mozambique
    Show others...
    (English)Manuscript (preprint) (Other academic)
    National Category
    Other Health Sciences
    Identifiers
    urn:nbn:se:oru:diva-116952 (URN)
    Available from: 2024-10-22 Created: 2024-10-22 Last updated: 2024-10-22Bibliographically approved
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  • Public defence: 2024-11-22 13:15 Örebro universitet, Långhuset, Hörsal L2, Örebro
    Owiredua, Christiana
    Örebro University, School of Behavioural, Social and Legal Sciences.
    Understanding Chronic Pain from a Life Course Perspective: An exploration of the psychosocial predictors, correlates, and consequences of pain onset early in Life2024Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Chronic pain conditions can debut at any point in a person’s lifespan, although prevalence estimates peak in late adulthood. However, many adults report living with chronic pain for several decades, with some tracing this back to the early years of life. Given its impact, early life exposure to pain may be a risk factor for further health comorbid-ities and socioeconomic disadvantages. The studies in this dissertation examined differences in psychosocial outcomes between persons with early and later chronic pain onset. They also explored school absen-teeism due to pain in adolescents with recurrent pain as a pathway to accumulating risk over time. Data were gathered from a registry data-base and longitudinal surveys.

    Study I (a retrospective design) found that those with an early life pain onset had a higher burden in terms of overall pain characteris-tics and psychosocial outcomes. Studies II and III (prospective longi-tudinal designs) showed that having at least one absenteeism due to pain was quite common (64%) among adolescents with recurrent pain, while about a quarter reported a more frequent rate. The risk factors for school absenteeism due to pain were sociodemographic factors, pain characteristics, stressors in the school context, and a his-tory of absenteeism due to pain at baseline (Study II). Further, about 1 in 5 adolescents with recurrent pain had persistently high absentee-ism due to pain throughout their high school education, and these in-dividuals perceived a poorer future work ability and overall future ex-pectancy compared to those with low to no absenteeism trajectory over time (Study III). These findings indicate that individuals with early life onset pain have a higher psychosocial burden of pain, with risk accumulation already noted in the early years of life.

    List of papers
    1. The Context Matters: A Retrospective Analysis of Life Stage at Chronic Pain Onset in Relation to Pain Characteristics and Psychosocial Outcomes
    Open this publication in new window or tab >>The Context Matters: A Retrospective Analysis of Life Stage at Chronic Pain Onset in Relation to Pain Characteristics and Psychosocial Outcomes
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    2020 (English)In: Journal of Pain Research, E-ISSN 1178-7090, Vol. 13, p. 2685-2695Article in journal (Refereed) Published
    Abstract [en]

    Background: Developmental life stage at chronic pain onset differs among chronic pain patients. Although pain affects multiple life domains, it is unknown whether the timing of chronic pain onset relates to pain characteristics and psychosocial outcomes. The purpose of this retrospective study was to investigate differences in pain characteristics and psychosocial outcomes in patients at different developmental life stages at chronic pain onset.

    Methods: Cross-sectional baseline data from the Swedish Quality Registry for Pain Rehabilitation (2009 to 2016) were used, selecting the middle-aged patients (45-65 years, n=6225) reporting chronic nonmalignant pain. Patients were categorized into three groups, depending on their developmental life stage at chronic pain onset: early onset (age ≤30 years), intermediate onset (age 31-45 years), and late onset (age ≥46 years). Pain characteristics and psychosocial outcomes were assessed with validated self-reported measures.

    Results: One-way MANCOVA indicated differences in number of pain locations and psychosocial outcomes among the groups. Post hoc analysis showed differences in the trends for how groups differed on outcome domains. Overall, patients with earlier chronic pain onset showed significantly poorer psychosocial outcomes and more spreading of pain.

    Conclusion: Developmental life stage at chronic pain onset is associated with different pain outcomes. Pain onset early in life is linked to worse outcomes in multiple domains, pointing to a need for identifying these patients early.

    Place, publisher, year, edition, pages
    Dove Medical Press Ltd., 2020
    Keywords
    Aging, chronic pain, developmental stage of onset, life course, outcomes, psychosocial outcomes
    National Category
    Physiotherapy
    Identifiers
    urn:nbn:se:oru:diva-87088 (URN)000582327100001 ()33122938 (PubMedID)2-s2.0-85094138871 (Scopus ID)
    Note

    Funding Agency:

    European Union (EU) 754285

    DOI https://doi.org/10.2147/JPR.S263035 fungerar ej som länk

    Available from: 2020-11-02 Created: 2020-11-02 Last updated: 2024-10-23Bibliographically approved
    2. Prevalence and risk factors for pain-specific school absenteeism in adolescents with recurrent pain: A prospective population-based design
    Open this publication in new window or tab >>Prevalence and risk factors for pain-specific school absenteeism in adolescents with recurrent pain: A prospective population-based design
    2023 (English)In: European Journal of Pain, ISSN 1090-3801, E-ISSN 1532-2149, Vol. 27, no 3, p. 390-400Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: Adolescents with recurrent pain miss out from school more often than pain-free peers. Research has so far used cross-sectional designs, focusing on non-specific absenteeism in clinical samples. Hence, it is unknown whether estimates of absenteeism are specifically linked to the pain itself or reflects the characteristics of clinical samples. This study aimed to prospectively explore pain-related school absenteeism in a non-clinical sample, its variance and potential risk factors.

    METHODS: This prospective study followed a cohort of 1300 Sweden-based adolescents (mean age =16.9; 17.2% immigrants; 62.7% girls) with recurrent pain (headache, abdominal and/or musculoskeletal pain) through self-reports at two assessment points 12 months apart. RESULTS: Overall, 64.2% reported any absenteeism at follow-up and about half of these (26.2%) reported frequent absenteeism. Adolescents who indicated missing school were more often girls, slightly older, and had a higher overall pain burden and stressor levels. Yet, after adjusting for previous absenteeism, independent predictors were age, pain intensity, medication use, and stress associated with school attendance. Further to this, immigrant status predicted frequent absenteeism.

    CONCLUSIONS: Many adolescents with pain frequently miss out from school due to pain. Identified risk factors points at pain characteristics and coping, stressors associated with participation and advancing age. Taken together, the burden of pain and its correlates emerge earlier and escalate with increasing age hence, early interventions targeting broader domains are needed.

    Place, publisher, year, edition, pages
    John Wiley & Sons, 2023
    National Category
    Public Health, Global Health, Social Medicine and Epidemiology
    Identifiers
    urn:nbn:se:oru:diva-102656 (URN)10.1002/ejp.2065 (DOI)000898707600001 ()36478020 (PubMedID)2-s2.0-85144193898 (Scopus ID)
    Available from: 2022-12-12 Created: 2022-12-12 Last updated: 2024-10-23Bibliographically approved
    3. Trajectories of school absenteeism in adolescents with recurrent pain: Predictors and distal outcomes
    Open this publication in new window or tab >>Trajectories of school absenteeism in adolescents with recurrent pain: Predictors and distal outcomes
    (English)Manuscript (preprint) (Other academic)
    National Category
    Psychology (excluding Applied Psychology)
    Identifiers
    urn:nbn:se:oru:diva-116970 (URN)
    Available from: 2024-10-23 Created: 2024-10-23 Last updated: 2024-10-23Bibliographically approved
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    Understanding Chronic Pain from a Life Course Perspective: An exploration of the psychosocial predictors, correlates, and consequences of pain onset early in Life
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  • Public defence: 2024-11-22 13:15 Örebro universitet, Forumhuset, Hörsal F, Örebro
    Gonçalves de Sousa, Ricardo
    Örebro University, School of Humanities, Education and Social Sciences.
    Fysisk beröring som pedagogisk handling i förskolan: Beröringens funktioner och villkor i mötet mellan manliga förskollärare och barn2024Doctoral thesis, monograph (Other academic)
    Abstract [en]

    This thesis focuses on physical touch as a pedagogical action in the interplay between male preschool teachers and children in preschool. Previous research shows preschool teachers consider touch an essential resource when supporting children’s care, learning, and development. Touch has also been subject to surveillance due to a discourse on children’s protection and the adoption of policies towards children’s rights to bodily integrity. Men, as a minority group working in a female-dominated preschool, express that they are extra careful when involved in touch situations with children to avoid possible suspicions that may arise. Against this background, the thesis aims to gain knowledge about touch as a pedagogical action for male preschool teachers and children, focusing on its functions, usage, and contextual conditions.

    The study draws upon John Dewey’s pragmatism from a transactional perspective by examining different types of touch as pedagogical action. Fieldwork with participant observation has been conducted in three Swedish preschool classes with 45 children and three male preschool teachers. The findings present five types of touch as pedagogical action according to their functions: focus-oriented action, guiding action, assisting action, affectionate action, and playful action. Touch is used in different forms and is shaped by contextual conditions such as pedagogical situations, unexpected events, male preschool teachers’ and children’s initiative, children’s communication needs, and children’s age. These findings suggest that touch can support children’s meaning-making, participation, and caring relations with their teachers during several situations. Touch, understood as a pedagogical action, also contributes to strengthening male preschool teachers’ professional practice.

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    Fysisk beröring som pedagogisk handling i förskolan: Beröringens funktioner och villkor i mötet mellan manliga förskollärare och barn
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  • Public defence: 2024-11-27 13:00 Örebro universitet, Campus USÖ, Tidefeltsalen, Örebro
    Hayderi, Assim
    Örebro University, School of Medical Sciences.
    Impact of interferon-regulated genes on vascular cells and their implications for atherosclerosis2024Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Interferon gamma (IFN-γ) regulates the expression of numerous genes, many with known immunomodulatory, angiostatic, and antiviral functions. However, the functions of many of these genes in vascular cells and their implications for atherosclerosis remain to be fully understood.

    In this thesis, we investigate the functions of IFN-γ-regulated genes in vascular cells to understand their implications for atherosclerosis. In Paper I, we demonstrate RSAD2, a gene strongly induced by IFN-γ, to regulate the expression of CXCR3 chemokines in vascular smooth muscle cells (VSMCs), which are crucial for monocyte migration in vitro. Both VSMCs and macrophages express RSAD2 within human carotid atherosclerotic lesions where RSAD2 also correlates with CXCL10 and CXCL11. In Paper II, we generated a mousemodel of atherosclerosis lacking one or both alleles for RSAD2 and report that RSAD2-deficient mice exhibit reduced body weight without significant differences in plaque size. In Paper III, we observed tumour necrosis factor alpha (TNF-α) to upregulate the expression of genes encoding laminin-332 (LN332). These genes are downregulated by IFN-γ (unpublished results included in this thesis). Endothelial cells, when cultured on LN332, acquire an atherogenic phenotype and the levels of two of the genes encoding LN332 are elevated in human carotid atherosclerotic lesions where they also correlate with TNF-α. In Paper IV we demonstrate IFN-γ to alter the expression of genes involved in glutamine metabolism in VSMCs. Among these, a significant downregulation is observed for the enzyme, glutaminase, which converts glutamine to glutamate, a precursor required for de novo glutathione synthesis, a molecule that counters oxidative damage. Notably, glutaminase expression is significantly reduced in human carotid atherosclerotic lesions. Furthermore, the expression pattern of genes associated with glutamine metabolism in IFN-γ-stimulated VSMCs closely resembles that observed in human carotid lesions. In summary, this thesis investigates the effects of IFN-γ-regulated genes on vascular cells and demonstrates that IFN-γ may exert both pro- and anti-atherogenic effects in vascular cells.

    List of papers
    1. RSAD2 is abundant in atherosclerotic plaques and promotes interferon-induced CXCR3-chemokines in human smooth muscle cells
    Open this publication in new window or tab >>RSAD2 is abundant in atherosclerotic plaques and promotes interferon-induced CXCR3-chemokines in human smooth muscle cells
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    2024 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 14, no 1, article id 8196Article in journal (Refereed) Published
    Abstract [en]

    In atherosclerotic lesions, monocyte-derived macrophages are major source of interferon gamma (IFN-γ), a pleotropic cytokine known to regulate the expression of numerous genes, including the antiviral gene RSAD2. While RSAD2 was reported to be expressed in endothelial cells of human carotid lesions, its significance for the development of atherosclerosis remains utterly unknown. Here, we harnessed publicly available human carotid atherosclerotic data to explore RSAD2 in lesions and employed siRNA-mediated gene-knockdown to investigate its function in IFN-γ-stimulated human aortic smooth muscle cells (hAoSMCs). Silencing RSAD2 in IFN-γ-stimulated hAoSMCs resulted in reduced expression and secretion of key CXCR3-chemokines, CXCL9, CXCL10, and CXCL11. Conditioned medium from RSAD2-deficient hAoSMCs exhibited diminished monocyte attraction in vitro compared to conditioned medium from control cells. Furthermore, RSAD2 transcript was elevated in carotid lesions where it was expressed by several different cell types, including endothelial cells, macrophages and smooth muscle cells. Interestingly, RSAD2 displayed significant correlations with CXCL10 (r =  0.45, p = 0.010) and CXCL11 (r = 0.53, p = 0.002) in human carotid lesions. Combining our findings, we uncover a novel role for RSAD2 in hAoSMCs, which could potentially contribute to monocyte recruitment in the context of atherosclerosis.

    Place, publisher, year, edition, pages
    Nature Publishing Group, 2024
    National Category
    Cardiac and Cardiovascular Systems
    Identifiers
    urn:nbn:se:oru:diva-113037 (URN)10.1038/s41598-024-58592-9 (DOI)001198838600052 ()38589444 (PubMedID)2-s2.0-85189798266 (Scopus ID)
    Funder
    Örebro UniversityKnowledge Foundation, 20180035Stiftelsen Gamla Tjänarinnor, 2020-01074; 2021-01198Stiftelsen Sigurd och Elsa Goljes minne, LA2020-0196Sjukvårdsregionala forskningsrådet Mellansverige, RFR-750481; RFR-940393
    Available from: 2024-04-09 Created: 2024-04-09 Last updated: 2024-11-04Bibliographically approved
    2. Impact of RSAD2 deficiency on atherosclerosisdevelopment in ApoE-/- mice
    Open this publication in new window or tab >>Impact of RSAD2 deficiency on atherosclerosisdevelopment in ApoE-/- mice
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    (English)Manuscript (preprint) (Other academic)
    National Category
    Other Basic Medicine
    Identifiers
    urn:nbn:se:oru:diva-117172 (URN)
    Available from: 2024-11-04 Created: 2024-11-04 Last updated: 2024-11-04Bibliographically approved
    3. TNF Induces Laminin-332-Encoding Genes in Endothelial Cells and Laminin-332 Promotes an Atherogenic Endothelial Phenotype
    Open this publication in new window or tab >>TNF Induces Laminin-332-Encoding Genes in Endothelial Cells and Laminin-332 Promotes an Atherogenic Endothelial Phenotype
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    2024 (English)In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 25, no 16, article id 8699Article in journal (Refereed) Published
    Abstract [en]

    Laminins are essential components of the basement membranes, expressed in a tissue- and cell-specific manner under physiological conditions. During inflammatory circumstances, such as atherosclerosis, alterations in laminin composition within vessels have been observed. Our study aimed to assess the influence of tumor necrosis factor-alpha (TNF), a proinflammatory cytokine abundantly found in atherosclerotic lesions, on endothelial laminin gene expression and the effects of laminin-332 (LN332) on endothelial cells' behavior. We also evaluated the expression of LN332-encoding genes in human carotid atherosclerotic plaques. Our findings demonstrate that TNF induces upregulation of LAMB3 and LAMC2, which, along with LAMA3, encode the LN332 isoform. Endothelial cells cultured on recombinant LN332 exhibit decreased claudin-5 expression and display a loosely connected phenotype, with an elevated expression of chemokines and leukocyte adhesion molecules, enhancing their attractiveness and adhesion to leukocytes in vitro. Furthermore, LAMB3 and LAMC2 are upregulated in human carotid plaques and show a positive correlation with TNF expression. In summary, TNF stimulates the expression of LN332-encoding genes in human endothelial cells and LN332 promotes an endothelial phenotype characterized by compromised junctional integrity and increased leukocyte interaction. These findings highlight the importance of basement membrane proteins for endothelial integrity and the potential role of LN332 in atherosclerosis.

    Place, publisher, year, edition, pages
    MDPI, 2024
    Keywords
    ECM, activated endothelial cells, atherosclerosis, laminin-5, monocytes migration
    National Category
    Cell and Molecular Biology
    Identifiers
    urn:nbn:se:oru:diva-115699 (URN)10.3390/ijms25168699 (DOI)001305177900001 ()39201392 (PubMedID)2-s2.0-85202650459 (Scopus ID)
    Funder
    Knowledge Foundation, 2018-0035; 2018-0139Stiftelsen Gamla Tjänarinnor, 2020-01074; 2021-01198Stiftelsen Sigurd och Elsa Goljes minne, LA2020-0196
    Available from: 2024-09-02 Created: 2024-09-02 Last updated: 2024-11-04Bibliographically approved
    4. Interferon gamma induces perturbation in glutamine metabolism: insights from human smooth muscle cells and atherosclerotic lesions
    Open this publication in new window or tab >>Interferon gamma induces perturbation in glutamine metabolism: insights from human smooth muscle cells and atherosclerotic lesions
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    (English)Manuscript (preprint) (Other academic)
    National Category
    Other Basic Medicine
    Identifiers
    urn:nbn:se:oru:diva-117173 (URN)
    Available from: 2024-11-04 Created: 2024-11-04 Last updated: 2024-11-04Bibliographically approved
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  • Public defence: 2024-11-29 09:00 Örebro universitet, Campus USÖ, hörsal X1, Örebro
    Heidenreich, Kaja
    Örebro University, School of Medical Sciences.
    Making ethics visible: Doctors´moral reasoning in patient care2024Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Healthcare is infused with values concerning what is important to patients and healthcare professionals and, thereby, ethics might seem to be inherent and self-evident. However, in clinical practice, ethics is elusive and difficult to articulate, and a gap persists between theory and practice. Thus, the overall aim of this thesis was to generate understandings about ethics close to practice by exploring doctors’ moral reasoning when caring for the patient.

    The research design was qualitative and explorative. The phenomenon of‘moral reasoning’ was explored in 22 audio recorded ethical reflection groups (Moral case deliberation) (I), 27 interviews with UK consultants about their experiences of the complex decision-making process of initiating intensive care (II), 19 Swedish vascular surgeons in the outpatient setting (III), and observation and audio recording of 7 team conferences accompanied by 23 follow-up interviews with vascular surgeons (VI). The data were analysed by using content analysis, employing a phenomenological-hermeneutical method, and systematic text condensation.

    A composite result of the four studies revealed moral reasoning as a proces sof balancing between promoting the patient’s best interests and the patients’ preferences, deliberating one’s moral responsibility in the patient’s care, and expanding understandings of complex situations through multiple perspectives. Moral reasoning is embedded in the clinical language, and the patient encounter emerges as the hub for these reasonings. As such, the patient encounter signifies carefully exploring the clinical details of the case to weigh conflicting values, to expand one’s understanding of the patient’s health and life beyond the diseases, and to explore the patient’s wishes for care. Meetings between doctors to discuss the patient’s care entailed learning by broadening their understanding of complex situations as well as balancing different perceptions to reach reasonable decisions. The doctors’ own security instanding in complex decision-making and critical situations can be facilitated through discussions with colleagues as well as meetings by expanding perspectives and generating new understanding of what is important in a clinical situation. The clinical implications of this knowledge are that ethics is a tangible part of doctors’ care of patients that needs continuous exploration and verbalizing as a means of maintaining quality of care, which is a moral obligation in itself.

    List of papers
    1. Relational autonomy in the care of the vulnerable: health care professionals' reasoning in Moral Case Deliberation (MCD)
    Open this publication in new window or tab >>Relational autonomy in the care of the vulnerable: health care professionals' reasoning in Moral Case Deliberation (MCD)
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    2018 (English)In: Medicine, Health care and Philosophy, ISSN 1386-7423, E-ISSN 1572-8633, Vol. 21, no 4, p. 467-477Article in journal (Refereed) Published
    Abstract [en]

    In Moral Case Deliberation (MCD), healthcare professionals discuss ethically difficult patient situations in their daily practice. There is a lack of knowledge regarding the content of MCD and there is a need to shed light on this ethical reflection in the midst of clinical practice. Thus, the aim of the study was to describe the content of healthcare professionals' moral reasoning during MCD. The design was qualitative and descriptive, and data consisted of 22 audio-recorded inter-professional MCDs, analysed with content analysis. The moral reasoning centred on how to strike the balance between personal convictions about what constitutes good care, and the perceived dissonant care preferences held by the patient. The healthcare professionals deliberated about good care in relation to demands considered to be unrealistic, justifications for influencing the patient, the incapacitated patient's nebulous interests, and coping with the conflict between using coercion to achieve good while protecting human dignity. Furthermore, as a basis for the reasoning, the healthcare professionals reflected on how to establish a responsible relationship with the vulnerable person. This comprised acknowledging the patient as a susceptible human being, protecting dignity and integrity, defining their own moral responsibility, and having patience to give the patient and family time to come to terms with illness and declining health. The profound struggle to respect the patient's autonomy in clinical practice can be understood through the concept of relational autonomy, to try to secure both patients' influence and at the same time take responsibility for their needs as vulnerable humans.

    Place, publisher, year, edition, pages
    Dordrecht, Netherlands: Springer Netherlands, 2018
    Keywords
    Clinical ethics, ethics consultation, health care professionals, moral case deliberation, ualitative research
    National Category
    Medical Ethics
    Identifiers
    urn:nbn:se:oru:diva-63400 (URN)10.1007/s11019-017-9818-6 (DOI)000451022600004 ()29243015 (PubMedID)2-s2.0-85038102190 (Scopus ID)
    Available from: 2018-01-08 Created: 2018-01-08 Last updated: 2024-11-05Bibliographically approved
    2. UK consultants' experiences of the decision-making process around referral to intensive care: an interview study
    Open this publication in new window or tab >>UK consultants' experiences of the decision-making process around referral to intensive care: an interview study
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    2021 (English)In: BMJ Open, E-ISSN 2044-6055, Vol. 11, no 3, article id e044752Article in journal (Refereed) Published
    Abstract [en]

    OBJECTIVE: The decision whether to initiate intensive care for the critically ill patient involves ethical questions regarding what is good and right for the patient. It is not clear how referring doctors negotiate these issues in practice. The aim of this study was to describe and understand consultants' experiences of the decision-making process around referral to intensive care.

    DESIGN: Qualitative interviews were analysed according to a phenomenological hermeneutical method.

    SETTING AND PARTICIPANTS: Consultant doctors (n=27) from departments regularly referring patients to intensive care in six UK hospitals.

    RESULTS: In the precarious and uncertain situation of critical illness, trust in the decision-making process is needed and can be enhanced through the way in which the process unfolds. When there are no obvious right or wrong answers as to what ought to be done, how the decision is made and how the process unfolds is morally important. Through acknowledging the burdensome doubts in the process, contributing to an emerging, joint understanding of the patient's situation, and responding to mutual moral duties of the doctors involved, trust in the decision-making process can be enhanced and a shared moral responsibility between the stake holding doctors can be assumed.

    CONCLUSION: The findings highlight the importance of trust in the decision-making process and how the relationships between the stakeholding doctors are crucial to support their moral responsibility for the patient. Poor interpersonal relationships can damage trust and negatively impact decisions made on behalf of a critically ill patient. For this reason, active attempts must be made to foster good relationships between doctors. This is not only important to create a positive working environment, but a mechanism to improve patient outcomes.

    Place, publisher, year, edition, pages
    BMJ Publishing Group Ltd, 2021
    Keywords
    Adult intensive & critical care, medical ethics, qualitative research
    National Category
    Medical Ethics
    Identifiers
    urn:nbn:se:oru:diva-90758 (URN)10.1136/bmjopen-2020-044752 (DOI)000634886700021 ()33762241 (PubMedID)2-s2.0-85103265918 (Scopus ID)
    Note

    Funding Agency:

    National Institute for Health Research under the Health Services and Delivery Research programme 13/10/14

    Available from: 2021-03-26 Created: 2021-03-26 Last updated: 2024-11-05Bibliographically approved
    3. Exploring what is reasonable: uncovering moral reasoning of vascular surgeons in daily practice
    Open this publication in new window or tab >>Exploring what is reasonable: uncovering moral reasoning of vascular surgeons in daily practice
    2023 (English)In: BMC Medical Ethics, E-ISSN 1472-6939, Vol. 24, no 1Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: Vascular surgery offers a range of treatments to relieve pain and ulcerations, and to prevent sudden death by rupture of blood vessels. The surgical procedures involve risk of injury and harm, which increases with age and frailty leading to complex decision-making processes that raise ethical questions. However, how vascular surgeons negotiate these questions is scarcely studied. The aim was therefore to explore vascular surgeons' moral reasoning of what ought to be done for the patient.

    METHODS: Qualitative, semi-structured interviews were conducted with 19 vascular surgeons working at three Swedish university hospitals. Data were analysed according to systematic text condensation.

    RESULTS: The surgeons' moral reasoning about what ought to be done comprised a quest to relieve suffering and avoid harm by exploring what is reasonable to do for the patient. Exploring reasonableness included to shift one´s perspective from the vessels to the whole person, to balance patient's conflicting needs and to place responsibility for right decision on one´s shoulders. The shift from blood vessels to the whole person implied gaining holistic knowledge in pondering of what is best, struggling with one´s authority for surgery through dialogue, and building relationship for mutual security. To balance patient's conflicting needs implied weighing the patient's independence and a sense of being whole against ease of suffering, respecting the patient's will against protecting life and well-being, and weighing longer life against protecting the present well-being. Finally, to place responsibility on one´s shoulders was conveyed as an urge to remind oneself of the risk of complications, withholding one's power of proficiency, and managing time during the illness course.

    CONCLUSIONS: This study contributes to uncovering how moral reasoning is embodied in the vascular surgeons' everyday clinical discourse as a tangible part of their patient care. The results underpin the significance of moral considerations in the assemblage of medical knowledge and technical skills to further understand vascular surgeons' clinical practice. The clinical application of these results is the need of forums with sufficient possibilities for articulating these important moral considerations in everyday care.

    Place, publisher, year, edition, pages
    BioMed Central (BMC), 2023
    Keywords
    Decision-making, Medical ethics, Physicians, Qualitative research, Surgeons
    National Category
    Surgery Health Care Service and Management, Health Policy and Services and Health Economy Medical Ethics
    Identifiers
    urn:nbn:se:oru:diva-103153 (URN)10.1186/s12910-022-00881-x (DOI)000911437200001 ()36624427 (PubMedID)2-s2.0-85145956386 (Scopus ID)
    Funder
    Örebro UniversityRegion Örebro County
    Note

    Funding agency:

    Swedish government under the ALF agreement

    Available from: 2023-01-19 Created: 2023-01-19 Last updated: 2024-11-05Bibliographically approved
    4. Moral reasoning during vascular surgeons' team conferences: finding the balance of risk and benefit by exploring the clinical details
    Open this publication in new window or tab >>Moral reasoning during vascular surgeons' team conferences: finding the balance of risk and benefit by exploring the clinical details
    (English)Manuscript (preprint) (Other academic)
    National Category
    General Practice Medical Ethics
    Identifiers
    urn:nbn:se:oru:diva-117213 (URN)
    Available from: 2024-11-05 Created: 2024-11-05 Last updated: 2024-11-05Bibliographically approved
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  • Public defence: 2024-11-29 09:00 Örebro universitet, Campus USÖ, Tidefeltsalen, Örebro
    Qvick, Alvida
    Örebro University, School of Medical Sciences.
    Achieving Precision Diagnostics for Cancer using Circulating Biomarkers2024Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Each year, nearly 20 million people are diagnosed with cancer worldwide,and over 9.7 million die of the disease. Tumor tissue sampling is essential for diagnosis and treatment, but it poses risks and may not fully represent the tumor due to heterogeneity. Additionally, limited sample sizes can hinder comprehensive testing, affecting precision diagnostics.

    Circulating biomarkers offer a non-invasive alternative, as they are easily obtained from body fluids, and reflect tumor activity. These biomarkers include DNA, RNA, vesicles, proteins, metabolites, and whole tumor cells. They hold potential for screening, diagnosis, treatment selection, monitoring, and prognosis. Currently, circulating cell-free DNA (cfDNA) is the only clinically used biomarker for treatment selection and monitoring in cases without available tumor tissue.

    The main aim of this thesis was to explore the clinical use of circulating biomarkers in cancer care. Paper I investigated liquid biopsy for variant analysis in lung cancer, finding that plasma cfDNA could predict overall survival and reliably detect variants in advanced cases. Paper II explored glycosaminoglycans (GAGs) as biomarkers for lung cancer, revealing that combining cfDNA and GAG profiles improved diagnostic sensitivity. Paper III developed sensitive assays to detect HPV in plasma, correlating ctHPV-DNA levels with tumor characteristics in oropharyngeal cancer. Paper IV examined methylation patterns in cfDNA, identifying regions that could distinguish cancer from other diseases using machine learning.

    Overall, this thesis demonstrates the clinical potential of circulating biomarkers for cancer diagnosis, prognosis, and monitoring, emphasizing the value of multimodal approaches in enhancing detection accuracy.

    List of papers
    1. Liquid biopsy as an option for predictive testing and prognosis in patients with lung cancer
    Open this publication in new window or tab >>Liquid biopsy as an option for predictive testing and prognosis in patients with lung cancer
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    2021 (English)In: Molecular Medicine, ISSN 1076-1551, E-ISSN 1528-3658, Vol. 27, no 1, article id 68Article in journal (Refereed) Published
    Abstract [en]

    Background: The aim of this study was to investigate the clinical value of liquid biopsy as a primary source for variant analysis in lung cancer. In addition, we sought to characterize liquid biopsy variants and to correlate mutational load to clinical data.

    Methods: Circulating cell-free DNA was extracted from plasma from patients with lung cancer (n = 60) and controls with benign lung disease (n = 16). Variant analysis was performed using the AVENIO ctDNA Surveillance kit and the results were correlated to clinical and variant analysis data from tumor tissue or cytology retrieved from clinical routine diagnostics.

    Results: There were significantly more variants detected in lung cancer cases compared to controls (p = 0.011), but no difference between the histological subgroups of lung cancer was found (p = 0.465). Furthermore, significantly more variants were detected in patients with stage IIIb-IV disease compared to patients with stage I-IIIa (median 7 vs 4, p = 0.017). Plasma cfDNA mutational load was significantly associated with overall survival (p = 0.010). The association persisted when adjusted for stage and ECOG performance status (HR: 3.64, 95% CI 1.37-9.67, p = 0.009). Agreement between tumor and plasma samples significantly differed with stage; patients with stage IIIb-IV disease showed agreement in 88.2% of the cases with clinically relevant variants, compared to zero cases in stage I-IIIa (p = 0.004). Furthermore, one variant in EGFR, two in KRAS, and one in BRAF were detected in plasma but not in tumor samples.

    Conclusion: This study concludes that in the vast majority of advanced NSCLC patients a reliable variant analysis can be performed using liquid biopsy from plasma. Furthermore, we found that the number of variants in plasma is associated with prognosis, possibly indicating a strategy for closer follow up on this crucial patient group.

    Place, publisher, year, edition, pages
    Springer, 2021
    National Category
    Cancer and Oncology
    Identifiers
    urn:nbn:se:oru:diva-93189 (URN)10.1186/s10020-021-00331-1 (DOI)000669300200001 ()34217228 (PubMedID)2-s2.0-85110796418 (Scopus ID)
    Note

    Funding Agencies:

    Örebro County Council Research committee  

    Lions fund for cancer research Uppsala-Örebro  

    Nyckelfonden-Örebro University Hospital Research Foundation  

    Uppsala-Örebro Regional research council 

    Available from: 2021-07-30 Created: 2021-07-30 Last updated: 2024-11-06Bibliographically approved
    2. Discriminating Benign from Malignant Lung Diseases Using Plasma Glycosaminoglycans and Cell-Free DNA
    Open this publication in new window or tab >>Discriminating Benign from Malignant Lung Diseases Using Plasma Glycosaminoglycans and Cell-Free DNA
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    2024 (English)In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 25, no 18, article id 9777Article in journal (Refereed) Published
    Abstract [en]

    We aimed to investigate the use of free glycosaminoglycan profiles (GAGomes) and cfDNA in plasma to differentiate between lung cancer and benign lung disease, in a cohort of 113 patients initially suspected of lung cancer. GAGomes were analyzed in all samples using the MIRAM® Free Glycosaminoglycan Kit with ultra-high-performance liquid chromatography and electrospray ionization triple quadrupole mass spectrometry. In a subset of samples, cfDNA concentration and NGS-data was available. We detected two GAGome features, 0S chondroitin sulfate (CS), and 4S CS, with cancer-specific changes. Based on the observed GAGome changes, we devised a model to predict lung cancer. The model, named the GAGome score, could detect lung cancer with 41.2% sensitivity (95% CI: 9.2-54.2%) at 96.4% specificity (95% CI: 95.2-100.0%, n = 113). When we combined the GAGome score with a cfDNA-based model, the sensitivity increased from 42.6% (95% CI: 31.7-60.6%, cfDNA alone) to 70.5% (95% CI: 57.4-81.5%) at 95% specificity (95% CI: 75.1-100%, n = 74). Notably, the combined GAGome and cfDNA testing improved the sensitivity, compared to cfDNA alone, especially in ASCL stage I (55.6% vs 11.1%). Our findings show that plasma GAGome profiles can enhance cfDNA testing performance, highlighting the applicability of a multiomics approach in lung cancer diagnostics.

    Place, publisher, year, edition, pages
    MDPI, 2024
    Keywords
    GAGome, cfDNA, glycosaminoglycans, lung cancer, multiomics
    National Category
    Cancer and Oncology
    Identifiers
    urn:nbn:se:oru:diva-116392 (URN)10.3390/ijms25189777 (DOI)001323972500001 ()39337265 (PubMedID)2-s2.0-85205260687 (Scopus ID)
    Funder
    NyckelfondenInsamlingsstiftelsen Lions Cancerforskningsfond Mellansverige Uppsala-Örebro
    Note

    Funding: This work was funded by the Nyckelfonden-Örebro University Hospital Research Foundation, the Lions Fund for Cancer Research Uppsala-Örebro, and the Uppsala-Örebro Regional Research Council.

    Available from: 2024-09-30 Created: 2024-09-30 Last updated: 2024-11-06Bibliographically approved
    3. Sensitive and Specific Droplet Digital PCR Assays for Circulating Tumor HPV DNA: Development, Validation, and Clinical Application in HPV-Associated Cancers
    Open this publication in new window or tab >>Sensitive and Specific Droplet Digital PCR Assays for Circulating Tumor HPV DNA: Development, Validation, and Clinical Application in HPV-Associated Cancers
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    2024 (English)In: Molecular Diagnosis & Therapy, ISSN 1177-1062, E-ISSN 1179-2000Article in journal (Refereed) Epub ahead of print
    Abstract [en]

    BACKGROUND: Human papillomavirus (HPV) has emerged as a significant contributor to cancer incidence globally, particularly in the context of oropharyngeal squamous cell carcinoma (OPSCC) and cancer of unknown primary (HNCUP). This study aimed to develop and validate droplet digital PCR (ddPCR) assays for the detection of circulating tumor HPV DNA (ctHPV-DNA) in plasma, focusing on high-risk HPV genotypes associated with these cancers.

    METHODS: ddPCR assays for HPV16, 18, 33, 35, 56, and 59 were developed and tested using gBlocks, HPV cell-free DNA, fragmented tumor HPV+ DNA, and plasma samples from patients with HPV+ OPSCC (n = 110) and HNCUP (n = 9).

    RESULTS: Assays demonstrated robust technical sensitivity across all tested HPV genotypes. Clinical application of the assays on a cohort of patients with HPV+ OPSCC and HNCUP revealed high sensitivity (91.6%) and wide variability in ctHPV-DNA levels. Analyses revealed correlations between ctHPV-DNA levels and TNM stage and tumor viral load. The association between ctHPV-DNA and tumor viral load persisted even after adjusting for TNM stage. At posttreatment, 72.5% of samples had reached undetectable ctHPV-DNA levels. Having detectable ctHPV-DNA posttreatment was associated with a higher ctHPV-DNA level at diagnosis and higher viral load at diagnosis.

    CONCLUSION: The findings underscore the potential of ctHPV-DNA as a biomarker for monitoring HPV+ cancers and offer insights into tumor dynamics. Implementation of these assays in clinical practice could enhance no-invasive treatment monitoring and recurrence detection in HPV-associated cancers.

    CLINICAL TRIALS: NCT05904327.

    Place, publisher, year, edition, pages
    Adis International Ltd., 2024
    National Category
    Cancer and Oncology
    Identifiers
    urn:nbn:se:oru:diva-116394 (URN)10.1007/s40291-024-00743-9 (DOI)001321547500001 ()39325260 (PubMedID)
    Funder
    Örebro UniversityRegion Örebro CountyInsamlingsstiftelsen Lions Cancerforskningsfond Mellansverige Uppsala-Örebro
    Note

    Funding: Open access funding provided by Örebro University. This work was funded by the Örebro County Council Research committee, Nyckelfonden-Örebro University Hospital Research Foundation, Lions fund for cancer research Uppsala-Örebro, and Uppsala-Örebro Regional research council.

    Available from: 2024-09-30 Created: 2024-09-30 Last updated: 2024-11-06Bibliographically approved
    4. Methylation patterns in cell-free DNA for pan-cancer detection
    Open this publication in new window or tab >>Methylation patterns in cell-free DNA for pan-cancer detection
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    (English)Manuscript (preprint) (Other academic)
    National Category
    Other Basic Medicine
    Identifiers
    urn:nbn:se:oru:diva-117226 (URN)
    Available from: 2024-11-06 Created: 2024-11-06 Last updated: 2024-11-06Bibliographically approved
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  • Public defence: 2024-12-02 09:00 Örebro universitet, Campus USÖ, hörsal X3, Örebro
    Kapetanaki, Stefania
    Örebro University, School of Medical Sciences.
    The role of TMAO in renal interstitium and chronic kidney disease2024Doctoral thesis, comprehensive summary (Other academic)
  • Public defence: 2024-12-12 09:15 Örebro universitet, Campus USÖ, Tidefeltsalen, Örebro
    Visuri, Isabella
    Örebro University, School of Medical Sciences.
    Biological treatment in inflammatory bowel disease: clinical and therapeutic aspects2024Doctoral thesis, comprehensive summary (Other academic)
  • Public defence: 2024-12-13 09:00 Örebro universitet, Campus USÖ, hörsal X1, Örebro
    Ferrari, Gabriele
    Örebro University, School of Medical Sciences.
    Percutaneous coronary intervention in no-touch vein grafts: Clinical and angiographic results2024Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Coronary artery disease is one of the biggest health issues worldwide; it is estimated that cardiovascular diseases cause around 45% of all deaths in Sweden and in the Western world. In a large proportion of cases, the treatment involves a coronary artery bypass grafting (CABG) operation. One of the most commonly-used grafts is the saphenous vein from the leg, but this has the disadvantage of a predisposition to early obstruction, with inter-national literature showing occlusion rates of 15% in the first year and 40% after 10 years.

    At the Department of Cardiothoracic and Vascular Surgery at Örebro University Hospital, a method was developed for harvesting the saphenous vein together with the surrounding fat tissue. This technique, called the no-touch technique (NT), has the advantage of reducing damage to the vein during the harvesting, and carries a substantially reduced risk of future occlusion (5% after 18 months and 10% after 8.5 years).

    The aim of this dissertation was to evaluate the results of the no-touch technique in comparison to the conventional (C) technique for venous graft harvesting, focusing on patients who received a percutaneous coronary intervention (PCI) in their NT or C ve-nous graft. This study is the first to examine the long-term results of the no-touch tech-nique after stenting of the venous graft.

    Paper I was a systematic review and meta-analysis of the international literature re-garding PCI in vein grafts. It included 36 articles covering nearly 15 000 patients in total. Paper II was a retrospective clinical cohort study including 346 patients (67 NT, 279 C) who underwent PCI in a stenosed vein graft, with a mean follow-up time of 6.4 ± 3.7 years. The primary endpoint was in-stent restenosis, and secondary endpoints were major adverse cardiovascular events (MACE) and 1-year re-hospitalization rate. Paper III was a retrospective cohort study analysing all individuals who required clinically-driven coro-nary angiography after CABG. It included 1520 patients (618 NT, 825 C, 77 arterial graft) with a mean follow-up time of 8.4 ± 5.5 years. The patency rate of the vein grafts was compared between the two techniques as primary outcome. Paper IV was a retro-spective cohort study in which individuals who received a PCI in their vein graft (NT or C) were asked to estimate their quality of life using the RAND-36 survey, which consists of eight domains. A total of 165 patients answered the questionnaire (48 NT, 117 C).

    The results showed that in comparison to C grafts, NT vein grafts displayed a statisti-cally significantly higher patency rate and statistically significantly lower rates of long-term in-stent restenoses and MACE. Among patients who later required a PCI in the vein graft, those who received a primary NT graft estimated their quality of life as better than those who received a primary C graft. The NT vein graft results in this dissertation were significantly better than results in the international literature, suggesting that use of this technique will have both clinical and economic benefits at both the individual and the community level. Clinical benefits consist of fewer recurrences of angina and myocardial infarction, less risk of needing a new interventional procedure, and improved quality of life. These in turn will create health-economic benefits for the healthcare system.

    List of papers
    1. Percutaneous coronary intervention in saphenous vein grafts after coronary artery bypass grafting: a systematic review and meta-analysis
    Open this publication in new window or tab >>Percutaneous coronary intervention in saphenous vein grafts after coronary artery bypass grafting: a systematic review and meta-analysis
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    2021 (English)In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 55, no 4, p. 245-253Article, review/survey (Refereed) Published
    Abstract [en]

    To investigate the results of percutaneous coronary intervention (PCI) in saphenous vein grafts after coronary artery bypass grafting (CABG). Design. MEDLINE, Embase, and the Cochrane library were searched for relevant articles published between 1 January 2000 and 29 February 2020. The PICO (population, intervention, comparison, outcome) model was applied in constructing the clinical question. Two independent researchers performed the literature search. Thirty-six articles were identified and subjected to a quality assessment. The primary outcomes of the meta-analysis were long-term in-stent restenosis and long-term major adverse cardiac events (MACE). Results. In-stent restenosis was 9.4% (95% CI: 4.2-14.7%) and MACE was 35.3% (95% CI: 27-43.7%) at mean time 2.7 ± 1.0 years. The secondary outcomes were the unsuccessful PCI rate (7.7%; 95% CI: 2.9-12.5%), 30-day MACE (4.3%; 95% CI: 2.5-6.1%), and 1-year MACE (15.5%; 95% CI: 11.7-19.3%). The use of drug-eluting stents resulted in better outcomes at least in term of in-stent restenosis, while the benefit of using embolic protection devices was questionable. Conclusions. PCI of a stenosed or occluded saphenous vein graft is a challenge for interventional cardiologists, and is still associated with relatively high rates of restenosis, MACE, and procedural failure. All efforts to enhance the results are warranted, including improved quality of the venous grafts used during CABG. 

    Place, publisher, year, edition, pages
    Taylor & Francis, 2021
    Keywords
    Coronary artery bypass graft, MACE, meta-analysis, percutaneous coronary intervention, saphenous vein
    National Category
    Cardiac and Cardiovascular Systems
    Identifiers
    urn:nbn:se:oru:diva-90623 (URN)10.1080/14017431.2021.1900598 (DOI)000630402400001 ()33733984 (PubMedID)2-s2.0-85103018461 (Scopus ID)
    Note

    Funding Agency:

    Region Örebro County through the regional research board OLL-812871

    Available from: 2021-03-22 Created: 2021-03-22 Last updated: 2024-11-05Bibliographically approved
    2. Long-term results of percutaneous coronary intervention in no-touch vein grafts are significantly better than in conventional vein grafts
    Open this publication in new window or tab >>Long-term results of percutaneous coronary intervention in no-touch vein grafts are significantly better than in conventional vein grafts
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    2024 (English)In: Perfusion, ISSN 0267-6591, E-ISSN 1477-111X, article id 2676591241230012Article in journal (Refereed) Epub ahead of print
    Abstract [en]

    INTRODUCTION: Conventional vein grafts have a high risk of thrombosis and early atherosclerosis. Percutaneous coronary intervention (PCI) in conventional vein grafts is associated with a higher incidence of late adverse cardiac events. The aim of this study was to evaluate the long-term results after PCI in saphenous vein grafts (SVG) harvested with the no-touch technique compared to the conventional technique.

    METHODS: This was a single-center, retrospective, cohort study, based on data from the Swedeheart register. The inclusion criterion was individuals who underwent CABG using different vein graft techniques between January 1992 and July 2020, and who required a PCI in SVGs between January 2006 and July 2020. The primary end point was long-term in-stent restenosis. The secondary endpoints were long-term major adverse cardiac events (MACE) and 1-year re-hospitalization rates. The associations between the graft types and the endpoints were evaluated using the Fine and Gray competing-risk regression analysis.

    RESULTS: The study included 346 individuals (67 no-touch, 279 conventional). The mean clinical follow-up time was 6.4 years with a standard deviation of 3.7 years. The long-term in-stent restenosis rate for the no-touch grafts was 3.2% compared to 18.7% for the conventional grafts (p < .01), with a subdistribution hazard ratio (SHR) of 0.16 (p = .010). The long-term MACE rate was 27.0% in the no-touch group and 48.3% in the conventional group (p < .01) with a SHR of 0.53 (p = .017). The short-term results were similar in both groups.

    CONCLUSIONS: Percutaneous coronary intervention in a no-touch vein graft was associated with statistically significantly fewer in-stent restenoses and MACE at long-term follow-up compared to a conventional SVG.

    Place, publisher, year, edition, pages
    Sage Publications, 2024
    Keywords
    coronary artery bypass graft, major adverse cardiac events, no-touch, percutaneous coronary intervention, saphenous vein, stent
    National Category
    Cardiac and Cardiovascular Systems
    Identifiers
    urn:nbn:se:oru:diva-111036 (URN)10.1177/02676591241230012 (DOI)001147222400001 ()38253348 (PubMedID)2-s2.0-85182996475 (Scopus ID)
    Funder
    Region Örebro County, OLL-935188Region Uppsala, RFR-55691
    Available from: 2024-01-30 Created: 2024-01-30 Last updated: 2024-11-05Bibliographically approved
    3. Superior long-term patency of no-touch vein graft compared to conventional vein grafts in over 1500 consecutive patients
    Open this publication in new window or tab >>Superior long-term patency of no-touch vein graft compared to conventional vein grafts in over 1500 consecutive patients
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    2024 (English)In: Journal of Cardiothoracic Surgery, E-ISSN 1749-8090, Vol. 19, no 1, article id 570Article in journal (Refereed) Published
    Abstract [en]

    OBJECTIVES: To evaluate the long-term angiographic patency of saphenous vein grafts (SVG) harvested using the no-touch technique compared to the conventional technique.

    METHODS: This was a single-center, retrospective, cohort study. The inclusion criteria were individuals who underwent a CABG (coronary artery bypass grafting) between January 1995 and July 2020, and who successively needed a clinically-driven angiography. The primary endpoint was long-term patency. The secondary endpoints were differences in patency based on sub-group analysis (single vs. sequential graft, divided by target vessel).

    RESULTS: The study included 1520 individuals (618 no-touch, 825 conventional and 77 arterial grafts). The mean clinical follow-up time was 8.4 years ± 5.5 years. The patency per patient was 70.7% in the no-touch grafts vs. 46.7% in the conventional grafts (p < 0.001, OR = 2.8). The graft patency was 75.9% in the no-touch grafts vs. 62.8% in the conventional grafts (p < 0.001, OR = 1.8). CONCLUSIONS: The no-touch vein grafts were associated with statistically significantly higher patency at long-term compared to the conventional grafts.

    CLINICAL TRIAL REGISTRATION: NCT04656366, 7 December 2020.

    Place, publisher, year, edition, pages
    BioMed Central (BMC), 2024
    Keywords
    Coronary artery bypass graft, major adverse cardiac events, no-touch, patency, saphenous vein, stent
    National Category
    Cardiac and Cardiovascular Systems
    Identifiers
    urn:nbn:se:oru:diva-116473 (URN)10.1186/s13019-024-03057-3 (DOI)001326765400001 ()39354611 (PubMedID)2-s2.0-85205528212 (Scopus ID)
    Funder
    Örebro UniversityRegion Örebro County, OLL-935188
    Available from: 2024-10-03 Created: 2024-10-03 Last updated: 2024-11-05Bibliographically approved
    4. Quality of Life After Percutaneous Coronary Intervention in No-Touch Saphenous Vein Grafts is Significantly Better Than in Conventional Vein Grafts
    Open this publication in new window or tab >>Quality of Life After Percutaneous Coronary Intervention in No-Touch Saphenous Vein Grafts is Significantly Better Than in Conventional Vein Grafts
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    2022 (English)In: Brazilian Journal of Cardiovascular Surgery, ISSN 0102-7638, E-ISSN 1678-9741, Vol. 37, no 4, p. 430-438Article in journal (Refereed) Published
    Abstract [en]

    OBJECTIVE: To compare health-related quality of life (HRQoL) of patients primarily treated with a no-touch saphenous vein graft with that of patients who received a conventional graft.

    METHODS: The study included all individuals treated with a percutaneous coronary intervention (PCI) on a saphenous vein graft (SVG) between January 2006 and June 2020. The RAND-36 health survey was used to assess HRQoL. The Mann-Whitney U test was used to test differences in HRQoL between the two groups. Effect size was estimated via Cohen's d. The average treatment effect between the groups was tested by propensity score matching (PSM).

    RESULTS: Of the 346 patients treated with a PCI in a stenosed or occluded SVG, 165 responded to RAND-36 (no-touch: n=48; conventional: n=117). Patients with a no-touch graft reported better mean values on seven of the eight health survey domains. Statistically significant differences were observed for four of the domains, all in favour of the no-touch group. The effect size estimates indicated a small difference for five domains, with the highest values (>0.40) seen for the general health and energy/fatigue domains. PSM confirmed a statistically significant difference for the physical functioning and general health domains.

    CONCLUSION: At a mean follow-up of 5.4 years, patients who received a PCI in no-touch vein grafts showed significantly better HRQoL than those who received a PCI in conventional vein grafts.

    Place, publisher, year, edition, pages
    Sociedade Brasileira de Cirurgia Cardiovascular, 2022
    Keywords
    Coronary Artery Bypass, Fatigue, Percutaneous Coronary Intervention, Propensity Score., Quality of Life, Saphenous Vein
    National Category
    Surgery
    Identifiers
    urn:nbn:se:oru:diva-100713 (URN)10.21470/1678-9741-2021-0576 (DOI)000862466400001 ()35976202 (PubMedID)2-s2.0-85136216148 (Scopus ID)
    Funder
    Region Örebro County, OLL-935188
    Available from: 2022-08-18 Created: 2022-08-18 Last updated: 2024-11-05Bibliographically approved
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