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1.	Klionsky, Daniel J., et al. (författare) Guidelines for the use and interpretation of assays for monitoring autophagy 2012 Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544 Forskningsöversikt (refereegranskat)abstract In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
2.	Leo, P. J., et al. (författare) Defining the genetic susceptibility to cervical neoplasia-A genome-wide association study 2017 Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 13:8 Tidskriftsartikel (refereegranskat)abstract A small percentage of women with cervical HPV infection progress to cervical neoplasia, and the risk factors determining progression are incompletely understood. We sought to define the genetic loci involved in cervical neoplasia and to assess its heritability using unbiased unrelated case/control statistical approaches. We demonstrated strong association of cervical neoplasia with risk and protective HLA haplotypes that are determined by the amino-acids carried at positions 13 and 71 in pocket 4 of HLA-DRB1 and position 156 in HLA-B. Furthermore, 36% (standard error 2.4%) of liability of HPV-associated cervical pre-cancer and cancer is determined by common genetic variants. Women in the highest 10% of genetic risk scores have approximately > 7.1% risk, and those in the highest 5% have approximately > 21.6% risk, of developing cervical neoplasia. Future studies should examine genetic risk prediction in assessing the risk of cervical neoplasia further, in combination with other screening methods.
3.	Tajkumar, T, et al. (författare) Cervical carcinoma and sexual behavior: collaborative reanalysis of individual data on 15,461 women with cervical carcinoma and 29,164 women without cervical carcinoma from 21 epidemiological studies 2009 Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755. ; 18:4, s. 1060-1069 Tidskriftsartikel (refereegranskat)abstract High-risk human papillomavirus (HPV) types cause most cervical carcinomas and are sexually transmitted. Sexual behavior therefore affects HPV exposure and its cancer sequelae. The International Collaboration of Epidemiological Studies of Cervical Cancer has combined data on lifetime number of sexual partners and age at first sexual intercourse from 21 studies, or groups of studies, including 10,773 women with invasive cervical carcinoma, 4,688 women with cervical intraepithelial neoplasia grade 3 (CIN3)/carcinoma in situ, and 29,164 women without cervical carcinoma. Relative risks for invasive cancer and CIN3 were estimated by conditional logistic regression. Risk of invasive cervical carcinoma increased with lifetime number of sexual partners (P for linear trend <0.001). The relative risk for > or =6 versus 1 partner, conditioned on age, study, and age at first intercourse, was 2.27 [95% confidence interval (95% CI), 1.98-2.61] and increased to 2.78 (95% CI, 2.22-3.47) after additional conditioning on reproductive factors. The risk of invasive cervical carcinoma increased with earlier age at first intercourse (P for linear trend <0.001). The relative risk for age at first intercourse < or =14 versus > or =25 years, conditioned on age, study, and lifetime number of sexual partners was 3.52 (95% CI, 3.04-4.08), which decreased to 2.05 (95% CI, 1.54-2.73) after additional conditioning on reproductive factors. CIN3/carcinoma in situ showed a similar association with lifetime number of sexual partners; however, the association with age at first intercourse was weaker than for invasive carcinoma. Results should be interpreted with caution given the strong correlation between sexual and reproductive factors and the limited information on HPV status.
4.	Parsons, Sam, et al. (författare) A community-sourced glossary of open scholarship terms 2022 Ingår i: Nature Human Behaviour. - : Springer Science and Business Media LLC. - 2397-3374. ; 6:3, s. 312-318 Tidskriftsartikel (refereegranskat)
5.	Martrat, Griselda, et al. (författare) Exploring the link between MORF4L1 and risk of breast cancer 2011 Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 13:2 Tidskriftsartikel (refereegranskat)abstract Introduction: Proteins encoded by Fanconi anemia (FA) and/or breast cancer (BrCa) susceptibility genes cooperate in a common DNA damage repair signaling pathway. To gain deeper insight into this pathway and its influence on cancer risk, we searched for novel components through protein physical interaction screens. Methods: Protein physical interactions were screened using the yeast two-hybrid system. Co-affinity purifications and endogenous co-immunoprecipitation assays were performed to corroborate interactions. Biochemical and functional assays in human, mouse and Caenorhabditis elegans models were carried out to characterize pathway components. Thirteen FANCD2-monoubiquitinylation-positive FA cell lines excluded for genetic defects in the downstream pathway components and 300 familial BrCa patients negative for BRCA1/2 mutations were analyzed for genetic mutations. Common genetic variants were genotyped in 9,573 BRCA1/2 mutation carriers for associations with BrCa risk. Results: A previously identified co-purifying protein with PALB2 was identified, MRG15 (MORF4L1 gene). Results in human, mouse and C. elegans models delineate molecular and functional relationships with BRCA2, PALB2, RAD51 and RPA1 that suggest a role for MRG15 in the repair of DNA double-strand breaks. Mrg15-deficient murine embryonic fibroblasts showed moderate sensitivity to g-irradiation relative to controls and reduced formation of Rad51 nuclear foci. Examination of mutants of MRG15 and BRCA2 C. elegans orthologs revealed phenocopy by accumulation of RPA-1 (human RPA1) nuclear foci and aberrant chromosomal compactions in meiotic cells. However, no alterations or mutations were identified for MRG15/MORF4L1 in unclassified FA patients and BrCa familial cases. Finally, no significant associations between common MORF4L1 variants and BrCa risk for BRCA1 or BRCA2 mutation carriers were identified: rs7164529, P-trend = 0.45 and 0.05, P-2df = 0.51 and 0.14, respectively; and rs10519219, P-trend = 0.92 and 0.72, P-2df = 0.76 and 0.07, respectively. Conclusions: While the present study expands on the role of MRG15 in the control of genomic stability, weak associations cannot be ruled out for potential low-penetrance variants at MORF4L1 and BrCa risk among BRCA2 mutation carriers.
6.	Rajkumar, T, et al. (författare) Carcinoma of the cervix and tobacco smoking: Collaborative reanalysis of individual data on 13,541 women with carcinoma of the cervix and 23,017 women without carcinoma of the cervix from 23 epidemiological studies - International collaboration of epidemiological studies of cervical cancer 2006 Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 118:6, s. 1481-1495 Tidskriftsartikel (refereegranskat)abstract Tobacco smoking has been classified as a cause of cervical cancer, but the effect of different patterns of smoking on risk is unclear. The International Collaboration of Epidemiological Studies of Cervical Cancer has brought together and combined individual data on 13,541 women with and 23,017 women without cervical carcinoma, from 23 epidemiological studies. Relative risks (RRs) and 95% confidence intervals (CIs) of carcinoma of the cervix in relation to tobacco smoking were calculated with stratification by study, age, sexual partners, age at first intercourse, oral contraceptive use and parity. Current smokers had a significantly increased risk of squamous cell carcinoma of the cervix compared to never smokers (RR = 1.60 (95% CI: 1.48-1.73), p < 0.001). There was increased risk for past smokers also, though to a lesser extent (RR = 1.12 (1.01-1.25)), and there was no clear trend with time since stopping smoking (p-trend = 0.6). There was no association between smoking and adenocarcinoma of the cervix (RR = 0.89 (0.74-1.06) and 0.89 (0.72-1.10) for current and past smokers respectively), and the differences between the RRs for smoking and squamous cell and adenocarcinoma were statistically significant (current smoking p < 0.001 and past smoking p = 0.01). In current smokers, the RR of squamous cell carcinoma increased with increasing number of cigarettes smoked per day and also with younger age at starting smoking (p < 0.001 for each trend), but not with duration of smoking (p-trend = 0.3). Eight of the studies had tested women for cervical HPV-DNA, and in analyses restricted to women who tested positive, there was a significantly increased risk in current compared to never smokers for squamous cell carcinoma (RR = 1.95 (1.43-2.65)), but not for adenocarcinoma (RR = 1.06 (0.14-7.96)). In summary, smokers are at an increased risk of squamous cell but not of adenocarcinoma of the cervix. The risk of squamous cell carcinoma increases in current smokers with the number of cigarettes smoked per day and with younger age at starting smoking.
7.	Hasselhorn, H M, et al. (författare) Nurses' health, age and the wish to leave the profession--findings from the European NEXT-Study. 2006 Ingår i: Med Lav: Nurses' health, age and the wish to leave the profession--findings from the European NEXT-Study.. - 0025-7818. ; 97:2, s. 207-14 Tidskriftsartikel (refereegranskat)
8.	Klug, Stefanie J, et al. (författare) TP53 codon 72 polymorphism and cervical cancer : a pooled analysis of individual data from 49 studies 2009 Ingår i: The Lancet Oncology. - 1470-2045 .- 1474-5488. ; 10:8, s. 772-784 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Cervical cancer is caused primarily by human papillomaviruses (HPV). The polymorphism rs1042522 at codon 72 of the TP53 tumour-suppressor gene has been investigated as a genetic cofactor. More than 80 studies were done between 1998 and 2006, after it was initially reported that women who are homozygous for the arginine allele had a risk for cervical cancer seven times higher than women who were heterozygous for the allele. However, results have been inconsistent. Here we analyse pooled data from 49 studies to determine whether there is an association between TP53 codon 72 polymorphism and cervical cancer. METHODS: Individual data on 7946 cases and 7888 controls from 49 different studies worldwide were reanalysed. Odds ratios (OR) were estimated using logistic regression, stratifying by study and ethnic origin. Subgroup analyses were done for infection with HPV, ethnic origin, Hardy-Weinberg equilibrium, study quality, and the material used to determine TP53 genotype. FINDINGS: The pooled estimates (OR) for invasive cervical cancer were 1.22 (95% CI 1.08-1.39) for arginine homozygotes compared with heterozygotes, and 1.13 (0.94-1.35) for arginine homozygotes versus proline homozygotes. Subgroup analyses showed significant excess risks only in studies where controls were not in Hardy-Weinberg equilibrium (1.71 [1.21-2.42] for arginine homozygotes compared with heterozygotes), in non-epidemiological studies (1.35 [1.15-1.58] for arginine homozygotes compared with heterozygotes), and in studies where TP53 genotype was determined from tumour tissue (1.39 [1.13-1.73] for arginine homozygotes compared with heterozygotes). Null results were noted in studies with sound epidemiological design and conduct (1.06 [0.87-1.29] for arginine homozygotes compared with heterozygotes), and studies in which TP53 genotype was determined from white blood cells (1.06 [0.87-1.29] for arginine homozygotes compared with heterozygotes). INTERPRETATION: Subgroup analyses indicated that excess risks were most likely not due to clinical or biological factors, but to errors in study methods. No association was found between cervical cancer and TP53 codon 72 polymorphism when the analysis was restricted to methodologically sound studies.
9.	Nakamoto, T, et al. (författare) Dental panoramic radiograph as a tool to detect postmenopausal women with low bone mineral density : untrained general dental practitioners’ diagnostic performance 2003 Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 14:8, s. 659-664 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract The detection of postmenopausal women with low bone mineral density (BMD) is an important strategy to reduce the incidence of osteoporotic fracture. Recent studies suggested that incidental findings on dental panoramic radiographs may be used as a tool to detect women with low BMD. However, little is known whether this finding is sufficiently assessed by untrained general dental practitioners (GDPs). The purpose of this study was to investigate: (1) the observer agreement and (2) the diagnostic efficacy in detecting women with low BMD, when untrained GDPs assess the appearance (normal or eroded) of the mandibular inferior cortex on dental panoramic radiographs of postmenopausal women. Twenty-seven GDPs were asked to classify the appearance of the mandibular inferior cortex on dental panoramic radiographs of 100 postmenopausal women who had completed BMD assessments of the lumbar spine and of the femoral neck. Intra- and inter-observer agreements were analyzed with kappa statistics. The diagnostic efficacy (sensitivity, specificity and predictive values) was analyzed by comparing two groups classified by the mandibular inferior cortex (women with normal and women with eroded mandibular inferior cortex) with those classified by BMD (women with normal BMD and women with osteopenia or osteoporosis). The mean sensitivity and specificity were 77 % and 40 %, respectively, when BMD of the lumbar spine was used as standard and 75 % and 39 %, respectively, when BMD of the femoral neck comprised the standard. Nineteen untrained GDPs (70 %) presented a moderate to almost perfect intra-observer agreement. We conclude that dental panoramic radiograph may be used in clinical dental practice to identify postmenopausal women who have undetected low BMD and should undergo further testing with bone densitometry.
10.	Patterson, Nick, et al. (författare) Large-scale migration into Britain during the Middle to Late Bronze Age 2022 Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; , s. 588-594 Tidskriftsartikel (refereegranskat)abstract Present-day people from England and Wales harbour more ancestry derived from Early European Farmers (EEF) than people of the Early Bronze Age1. To understand this, we generated genome-wide data from 793 individuals, increasing data from the Middle to Late Bronze and Iron Age in Britain by 12-fold, and Western and Central Europe by 3.5-fold. Between 1000 and 875 BC, EEF ancestry increased in southern Britain (England and Wales) but not northern Britain (Scotland) due to incorporation of migrants who arrived at this time and over previous centuries, and who were genetically most similar to ancient individuals from France. These migrants contributed about half the ancestry of Iron Age people of England and Wales, thereby creating a plausible vector for the spread of early Celtic languages into Britain. These patterns are part of a broader trend of EEF ancestry becoming more similar across central and western Europe in the Middle to Late Bronze Age, coincident with archaeological evidence of intensified cultural exchange2-6. There was comparatively less gene flow from continental Europe during the Iron Age, and Britain's independent genetic trajectory is also reflected in the rise of the allele conferring lactase persistence to ~50% by this time compared to ~7% in central Europe where it rose rapidly in frequency only a millennium later. This suggests that dairy products were used in qualitatively different ways in Britain and in central Europe over this period.
11.	Johansson, Peter A., et al. (författare) Evaluation of the contribution of germline variants in BRCA1 and BRCA2 to uveal and cutaneous melanoma 2019 Ingår i: Melanoma Research. - 0960-8931 .- 1473-5636. ; 29:5, s. 483-490 Tidskriftsartikel (refereegranskat)abstract Germline mutations of BRCA1 and BRCA2 predispose individuals to a high risk of breast and ovarian cancer, and elevated risk of other cancers, including those of the pancreas and prostate. BRCA2 mutation carriers may have increased risk of uveal melanoma (UM) and cutaneous melanoma (CM), but associations with these cancers in BRCA1 mutation carriers have been mixed. Here, we further assessed whether UM and CM are associated with BRCA1 or BRCA2 by assessing the presence, segregation and reported/predicted pathogenicity of rare germline mutations (variant allele frequency < 0.01) in families with multiple members affected by these cancers. Whole-genome or exome sequencing was performed on 160 CM and/or UM families from Australia, the Netherlands, Denmark and Sweden. Between one and five cases were sequenced from each family, totalling 307 individuals. Sanger sequencing was performed to validate BRCA1 and BRCA2 germline variants and to assess carrier status in other available family members. A nonsense and a frameshift mutation were identified in BRCA1, both resulting in premature truncation of the protein (the first at p.Q516 and the second at codon 91, after the introduction of seven amino acids due to a frameshift deletion). These variants co-segregated with CM in individuals who consented for testing and were present in individuals with pancreatic, prostate and breast cancer in the respective families. In addition, 33 rare missense mutations (variant allele frequency ranging from 0.00782 to 0.000001 in the aggregated ExAC data) were identified in 34 families. Examining the previously reported evidence of functional consequence of these variants revealed all had been classified as either benign or of unknown consequence. Seeking further evidence of an association between BRCA1 variants and melanoma, we examined two whole-genome/exome sequenced collections of sporadic CM patients (total N = 763). We identified one individual with a deleterious BRCA1 variant, however, this allele was lost (with the wild-type allele remaining) in the corresponding CM, indicating that defective BRCA1 was not a driver of tumorigenesis in this instance. Although this is the first time that deleterious BRCA1 mutations have been described in high-density CM families, we conclude that there is an insufficient burden of evidence to state that the increased familial CM or UM susceptibility is because of these variants. In addition, in conjunction with other studies, we conclude that the previously described association between BRCA2 mutations and UM susceptibility represents a rare source of increased risk.
12.	Pettersson-Kymmer, Ulrika, et al. (författare) HLA and KIR Associations of Cervical Neoplasia 2018 Ingår i: Journal of Infectious Diseases. - : Oxford University Press. - 0022-1899 .- 1537-6613. ; 218:12, s. 2006-2015 Tidskriftsartikel (refereegranskat)abstract Background: Cervical cancer is the fourth most common cancer in women, and we recently reported human leukocyte antigen (HLA) alleles showing strong associations with cervical neoplasia risk and protection. HLA ligands are recognised by killer immunoglobulin-like receptors (KIRs) expressed on a range of immune cell subsets, governing their proinflammatory activity. We hypothesized that the inheritance of particular HLA-KIR combinations would increase cervical neoplasia risk.Methods: Here, we used HLA and KIR dosages imputed from SNP genotype data from 2,143 cervical neoplasia cases and 13,858 healthy controls of European decent.Results: Four novel HLA alleles were identified in association with cervical neoplasia: HLA-DRB39901 (OR=1.24, P=2.49×10-9), HLA-DRB50101 (OR=1.29, P=2.26×10-8), HLA-DRB59901 (OR=0.77, P=1.90×10-9) and HLA-DRB30301 (OR=0.63, P=4.06×10-5), due to their linkage disequilibrium with known cervical neoplasia-associated HLA-DRB1 alleles. We also found homozygosity of HLA-C1 group alleles is a protective factor for HPV16-related cervical neoplasia (C1/C1, OR=0.79, P=0.005). This protective association was restricted to carriers of either KIR2DL2 (OR=0.67, P=0.00045) or KIR2DS2 (OR=0.69, P=0.0006).Conclusions: Our findings suggest that HLA-C1 group alleles play a role in protecting against HPV16-related cervical neoplasia, mainly through a KIR-mediated mechanism.
13.	Rydberg Sterner, Therese, et al. (författare) The Gothenburg H70 Birth cohort study 2014-16: design, methods and study population. 2019 Ingår i: European journal of epidemiology. - : Springer Science and Business Media LLC. - 1573-7284 .- 0393-2990. ; 34:2, s. 191-209 Tidskriftsartikel (refereegranskat)abstract To improve health care for older persons, we need to learn more about ageing, e.g. identify protective factors and early markers for diseases. The Gothenburg H70 Birth Cohort Studies (the H70 studies) are multidisciplinary epidemiological studies examining representative birth cohorts of older populations in Gothenburg, Sweden. So far, six birth cohorts of 70-year-olds have been examined over time, and examinations have been virtually identical between studies. This paper describes the study procedures for the baseline examination of the Birth cohort 1944, conducted in 2014-16. In this study, all men and women born 1944 on specific dates, and registered as residents in Gothenburg, were eligible for participation (n=1839). A total of 1203 (response rate 72.2%; 559 men and 644 women; mean age 70.5years) agreed to participate in the study. The study comprised sampling of blood and cerebrospinal fluid, psychiatric, cognitive, and physical health examinations, examinations of genetics and family history, use of medications, social factors, functional ability and disability, physical fitness and activity, body composition, lung function, audiological and ophthalmological examinations, diet, brain imaging, as well as a close informant interview, and qualitative studies. As in previous examinations, data collection serves as a basis for future longitudinal follow-up examinations. The research gained from the H70 studies has clinical relevance in relation to prevention, early diagnosis, clinical course, experience of illness, understanding pathogenesis and prognosis. Results will increase our understanding of ageing and inform service development, which may lead to enhanced quality of care for older persons.
14.	Sharma, T., et al. (författare) Development of Hillchol (R), a low-cost inactivated single strain Hikojima oral cholera vaccine 2020 Ingår i: Vaccine. - : Elsevier BV. - 0264-410X. ; 38:50, s. 7998-8009 Tidskriftsartikel (refereegranskat)abstract Cholera remains an important global health problem with up to 4 million cases and 140,000 deaths annually. Oral cholera vaccines (OCVs) are now a cornerstone of the WHOs "Ending Cholera - A Global Roadmap to 2030" global program for the eventual elimination of cholera. There are currently three WHO prequalified OCVs available, Dukoral (R), Shanchol (R) and Euvichol-Plus (R). These vaccines are effective but due to a multiple strain composition and two different methods of inactivation, are complex and costly to manufacture. We describe here the characterization and industrial scale development of Hillchol (R); a novel, likely affordable single-component OCV for low and middle-income countries. Hillchol (R) consists of formalin-inactivated bacteria of a stable recombinant Vibrio cholerae O1 El Tor Hikojima serotype strain expressing approximately 50% each of Ogawa and Inaba O1 LPS antigens. The novel OCV can be manufactured on an industrial scale at a low cost. Hillchol (R) was well tolerated in animal toxicology studies and shown to have non-inferior oral immunogenicity in mice for both intestinalmucosal and serological immune responses when compared with a WHO-prequalified OCV. The optimized production of this single component OCV will reduce cost of OCV production and thus substantially increase vaccine availability. Based on these results, Hillchol (R) has been produced at a GMP facility and used successfully for clinical phase I/II studies. (C) 2020 MSD Wellcome Trust Hilleman Laboratories Pvt Ltd. Published by Elsevier Ltd.
15.	Subramanian, M. L., et al. (författare) Neurofilament light chain in the vitreous humor of the eye 2020 Ingår i: Alzheimer's Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 12:1 Tidskriftsartikel (refereegranskat)abstract Background Neurofilament light chain (NfL) is a promising biomarker of neurodegeneration in the cerebrospinal fluid and blood. This study investigated the presence of NfL in the vitreous humor and its associations with amyloid beta, tau, inflammatory cytokines and vascular proteins, apolipoprotein E (APOE) genotypes, Mini-Mental State Examination (MMSE) scores, systemic disease, and ophthalmic diseases. Methods This is a single-site, prospective, cross-sectional cohort study. Undiluted vitreous fluid (0.5-1.0 mL) was aspirated during vitrectomy, and whole blood was drawn for APOE genotyping. NfL, amyloid beta (A beta), total Tau (t-Tau), phosphorylated Tau (p-Tau181), inflammatory cytokines, chemokines, and vascular proteins in the vitreous were quantitatively measured by immunoassay. The main outcome measures were the detection of NfL levels in the vitreous humor and its associations with the aforementioned proteins. Linear regression was used to test the associations of NfL with other proteins,APOEgenotypes, MMSE scores, and ophthalmic and systemic diseases after adjustment for age, sex, education level, and other eye diseases. Results NfL was detected in all 77 vitreous samples. NfL was not found to be associated with ophthalmic conditions, APOE genotypes, MMSE scores, or systemic disease (p > 0.05). NfL levels were positively associated with increased vitreous levels of A beta(40)(p = 7.7 x 10(-5)), A beta(42)(p = 2.8 x 10(-4)), and t-tau (p = 5.5 x 10(-7)), but not with p-tau181 (p = 0.53). NfL also had significant associations with inflammatory cytokines such as interleukin-15 (IL-15,p = 5.3 x 10(-4)), IL-16 (p = 2.2 x 10(-4)), monocyte chemoattractant protein-1 (MCP1,p = 4.1 x 10(-4)), and vascular proteins such as vascular endothelial growth factor receptor-1 (VEGFR1,p = 2.9 x 10(-6)), Vegf-C (p = 8.6 x 10(-6)), vascular cell adhesion molecule-1 (VCAM-1,p = 5.0 x 10(-4)), Tie-2 (p = 6.3 x 10(-4)), and intracellular adhesion molecular-1 (ICAM-1,p = 1.6 x 10(-4)). Conclusion NfL is detectable in the vitreous humor of the eye and significantly associated with amyloid beta, t-tau, and select inflammatory and vascular proteins in the vitreous. Additionally, NfL was not associated with patients' clinical eye condition. Our results serve as a foundation for further investigation of NfL in the ocular fluids to inform us about the potential utility of its presence in the eye.
16.	Anderson, N. John, et al. (författare) The Arctic in the Twenty-First Century : Changing Biogeochemical Linkages across a Paraglacial Landscape of Greenland 2017 Ingår i: BioScience. - : Oxford University Press. - 0006-3568 .- 1525-3244. ; 67:2, s. 118-133 Tidskriftsartikel (refereegranskat)abstract The Kangerlussuaq area of southwest Greenland encompasses diverse ecological, geomorphic, and climate gradients that function over a range of spatial and temporal scales. Ecosystems range from the microbial communities on the ice sheet and moisture-stressed terrestrial vegetation (and their associated herbivores) to freshwater and oligosaline lakes. These ecosystems are linked by a dynamic glacio-fluvial-aeolian geomorphic system that transports water, geological material, organic carbon and nutrients from the glacier surface to adjacent terrestrial and aquatic systems. This paraglacial system is now subject to substantial change because of rapid regional warming since 2000. Here, we describe changes in the eco-and geomorphic systems at a range of timescales and explore rapid future change in the links that integrate these systems. We highlight the importance of cross-system subsidies at the landscape scale and, importantly, how these might change in the near future as the Arctic is expected to continue to warm.
17.	Bock, B.B., et al. (författare) Farmers' Relationship with Different Animals: The Importance of Getting Close to the Animals - Case Studies of French, Swedish and Dutch Cattle, Pig and Poultry Farmers. 2007 Ingår i: International Journal of Sociology of Agriculture and Food.. - 0798-1759. ; 15:3, s. 108-125 Tidskriftsartikel (refereegranskat)abstract The article analyses how cattle and poultry farmers in the Netherlands described their relationship with their farm animals and explores the factors that influence their level of attachment to them. The analysis draws upon Willkie’s (2005) framework of farmer-animal relationship, which distinguishes between different levels of attachment and detachment. This framework was useful for explaining why farmers developed different levels of attachment to animals, with the species, farm sector and housing system all playing roles in influencing this. Farmers tended to be more attached to cows than to chickens and felt more attachment towards breeding, as opposed to fattening, animals. Breeding, especially of cows, linked the animal to the personal histories of farmers, since their ancestors had often established the bloodlines of dairy cows. Farmers’ relationships with their animals were also influenced by the organization of production at the farm: the number of animals, their length of stay on the farm and the housing system. These factors all influenced the visibility of the animal as an individual and as a ‘real’ animal and not a living tool of production. The species and function of an animal and the organization of production largely defined the frequency, intensity and intimacy of farmers’ contact with individual animals. Practically all farmers (across sectors) perceived taking good care of animals and avoidance of suffering as a core element of their job and caring about animals as central to their definition of a ‘good farmer’. Beyond this, different groups of farmers showed clear differences in their level of attachment to their animals. In general dairy farmers felt more strongly attached to their dairy cows than farmers to their beef cattle or veal, whereas most poultry farmers felt rather detached from their chicken, and tended to perceive them as part of a flock and ‘living production tools’. These animals were not only de-individualized; at times and when seen solely as part of a meat and egg production system they were almost de-animalized.
18.	Davidson, Thomas, et al. (författare) Reimbursement systems influence prosthodontic treatment of adult patients 2015 Ingår i: Acta Odontologica Scandinavica. - : Informa UK Limited. - 0001-6357 .- 1502-3850. ; 73:6, s. 414-420 Tidskriftsartikel (refereegranskat)abstract Objective. To evaluate the influence of reimbursement system and organizational structure on oral rehabilitation of adult patients with tooth loss. Materials and methods. Patient data were retrieved from the databases of the Swedish Social Insurance Agency. The data consisted of treatment records of patients aged 19 years and above claiming reimbursement for dental care from July 1, 2007 until June 30, 2009. Before July 1, 2008, a proportionately higher level of subsidy was available for dental care in patients 65 years and above, but thereafter the system was changed, so that the subsidy was the same, regardless of the patient's age. Prosthodontic treatment in patients 65 years and above was compared with that in younger patients before and after the change of the reimbursement system. Prosthodontic treatment carried out in the Public Dental Health Service and the private sector was also analyzed. Results. Data were retrieved for 722,842 adult patients, covering a total of 1,339,915 reimbursed treatment items. After the change of the reimbursement system, there was a decrease in the proportion of items in patients 65 years and above in relation to those under 65. Overall, there was a minimal change in the proportion of treatment items provided by the private sector compared to the public sector following the change of the reimbursement system. Conclusions. Irrespective of service provider, private or public, financial incentive such as the reimbursement system may influence the provision of prosthodontic treatment, in terms of volume of treatment.
19.	Efferth, Thomas, et al. (författare) Biopiracy versus One-World Medicine-From colonial relicts to global collaborative concepts 2019 Ingår i: Phytomedicine. - : Elsevier. - 0944-7113 .- 1618-095X. ; 53, s. 319-331 Forskningsöversikt (refereegranskat)abstract Background: Practices of biopiracy to use genetic resources and indigenous knowledge by Western companies without benefit-sharing of those, who generated the traditional knowledge, can be understood as form of neo-colonialism. Hypothesis: The One-World Medicine concept attempts to merge the best of traditional medicine from developing countries and conventional Western medicine for the sake of patients around the globe. Study design: Based on literature searches in several databases, a concept paper has been written. Legislative initiatives of the United Nations culminated in the Nagoya protocol aim to protect traditional knowledge and regulate benefit-sharing with indigenous communities. The European community adopted the Nagoya protocol, and the corresponding regulations will be implemented into national legislation among the member states. Despite pleasing progress, infrastructural problems of the health care systems in developing countries still remain. Current approaches to secure primary health care offer only fragmentary solutions at best. Conventional medicine from industrialized countries cannot be afforded by the impoverished population in the Third World. Confronted with exploding costs, even health systems in Western countries are endangered to burst. Complementary and alternative medicine (CAM) is popular among the general public in industrialized countries, although the efficacy is not sufficiently proven according to the standards of evidence-based medicine. CAM is often available without prescription as over-the-counter products with non-calculated risks concerning erroneous self-medication and safety/toxicity issues. The concept of integrative medicine attempts to combine holistic CAM approaches with evidence-based principles of conventional medicine. Conclusion: To realize the concept of One-World Medicine, a number of standards have to be set to assure safety, efficacy and applicability of traditional medicine, e.g. sustainable production and quality control of herbal products, performance of placebo-controlled, double-blind, randomized clinical trials, phytovigilance, as well as education of health professionals and patients.
20.	Garnier, P., et al. (författare) The detection of energetic electrons with the Cassini Langmuir probe at Saturn 2012 Ingår i: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 117, s. A10202- Tidskriftsartikel (refereegranskat)abstract The Cassini Langmuir probe, part of the Radio and Plasma Wave Science (RPWS) instrument, has provided a wealth of information about the cold and dense plasma in the Saturnian system. The analysis of the ion side current (current for negative potentials) measured by the probe from 2005 to 2008 reveals also a strong sensitivity to energetic electrons (250-450 eV). These electrons impact the surface of the probe, and generate a detectable current of secondary electrons. A broad secondary electrons current region is inferred from the observations in the dipole L Shell range of similar to 6-10, with a peak full width at half maximum (FWHM) at L = 6.4-9.4 (near the Dione and Rhea magnetic dipole L Shell values). This magnetospheric flux tube region, which displays a large day/night asymmetry, is related to the similar structure in the energetic electron fluxes as the one measured by the onboard Electron Spectrometer (ELS) of the Cassini Plasma Spectrometer (CAPS). It corresponds spatially to both the outer electron radiation belt observed by the Magnetosphere Imaging Instrument (MIMI) at high energies and to the low-energy peak which has been observed since the Voyager era. Finally, a case study suggests that the mapping of the current measured by the Langmuir probe for negative potentials can allow to identify the plasmapause-like boundary recently identified at Saturn, and thus potentially identify the separation between the closed and open magnetic field lines regions.
21.	Holmberg, Madeleine K. G., et al. (författare) Ion densities and velocities in the inner plasma torus of Saturn 2012 Ingår i: Planetary and Space Science. - : Elsevier. - 0032-0633 .- 1873-5088. ; 73:1, s. 151-160 Tidskriftsartikel (refereegranskat)abstract We present plasma data from the Cassini Radio and Plasma Wave Science (RPWS) Langmuir probe (LP), mapping the ion density and velocity of Saturn's inner plasma torus. Data from 129 orbits, recorded during the period from the 1st of February 2005 to the 27th of June 2010, are used to map the extension of the inner plasma torus. The dominant part of the plasma torus is shown to be located in between 2.5 and 8 Saturn radii (1 RS=60,268 km) from the planet, with a north-southward extension of ±2RS. The plasma disk ion density shows a broad maximum in between the orbits of Enceladus and Tethys. Ion density values vary between 20 and 125 cm-3 at the location of the density maximum, indicating considerable dynamics of the plasma disk. The equatorial density structure, \|z\|<0.5RS, shows a slower decrease away from the planet than towards. The outward decrease, from 5 R S, is well described by the relation neq=2.2×10 4(1/R)3.63. The plume of the moon Enceladus is clearly visible as an ion density maximum of 105 cm-3, only present at the south side of the ring plane. A less prominent density peak, of 115 cm-3, is also detected at the orbit of Tethys, at ∼4.9 RS. No density peaks are recorded at the orbits of the moons Mimas, Dione, and Rhea. The presented ion velocity vi,θ shows a clear general trend in the region between 3 and 7 RS, described by vi, θ=1.5R2-8.7R+39. The average vi,θ starts to deviate from corotation at around 3 RS, reaching ∼68% of corotation close to 5 RS.
22.	Huik, van, M. M., et al. (författare) Attitudes of cattle, pig and pultry farmers in France, the Netherlands and Sweden towards animal welfare 2007 Ingår i: XII congress ESRS (European Society for Rural Sociology), Wageningen, The Netherlands. Konferensbidrag (refereegranskat)
23.	Kabosova, Andrea, et al. (författare) Compositional differences between infant and adult human corneal basement membranes 2007 Ingår i: Investigative Ophthalmology & Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 1552-5783. ; 48:11, s. 4989-4999 Tidskriftsartikel (refereegranskat)abstract PURPOSE. Adult human corneal epithelial basement membrane ( EBM) and Descemet's membrane ( DM) components exhibit heterogeneous distribution. The purpose of the study was to identify changes of these components during postnatal corneal development. METHODS. Thirty healthy adult corneas and 10 corneas from 12-day- to 3-year-old children were studied by immunofluorescence with antibodies against BM components. RESULTS. Type IV collagen composition of infant corneal central EBM over Bowman's layer changed from alpha 1-alpha 2 to alpha 3-alpha 4 chains after 3 years of life; in the adult, alpha 1-alpha 2 chains were retained only in the limbal BM. Laminin alpha 2 and beta 2 chains were present in the adult limbal BM where epithelial stem cells are located. By 3 years of age, beta 2 chain appeared in the limbal BM. In all corneas, limbal BM contained laminin gamma 3 chain. In the infant DM, type IV collagen alpha 1-alpha 6 chains, perlecan, nidogen-1, nidogen-2, and netrin-4 were found on both faces, but they remained only on the endothelial face of the adult DM. The stromal face of the infant but not the adult DM was positive for tenascin-C, fibrillin-1, SPARC, and laminin-332. Type VIII collagen shifted from the endothelial face of infant DM to its stromal face in the adult. Matrilin-4 largely disappeared after the age of 3 years. CONCLUSIONS. The distribution of laminin gamma 3 chain, nidogen-2, netrin-4, matrilin-2, and matrilin-4 is described in the cornea for the first time. The observed differences between adult and infant corneal BMs may relate to changes in their mechanical strength, corneal cell adhesion and differentiation in the process of postnatal corneal maturation.
24.	Kemaladewi, Dwi U, et al. (författare) A mutation-independent approach for muscular dystrophy via upregulation of a modifier gene 2019 Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 572:7767, s. 125-130 Tidskriftsartikel (refereegranskat)abstract Neuromuscular disorders are often caused by heterogeneous mutations in large, structurally complex genes. Targeting compensatory modifier genes could be beneficial to improve disease phenotypes. Here we report a mutation-independent strategy to upregulate the expression of a disease-modifying gene associated with congenital muscular dystrophy type 1A (MDC1A) using the CRISPR activation system in mice. MDC1A is caused by mutations in LAMA2 that lead to nonfunctional laminin-α2, which compromises the stability of muscle fibres and the myelination of peripheral nerves. Transgenic overexpression of Lama1, which encodes a structurally similar protein called laminin-α1, ameliorates muscle wasting and paralysis in mouse models of MDC1A, demonstrating its importance as a compensatory modifier of the disease1. However, postnatal upregulation of Lama1 is hampered by its large size, which exceeds the packaging capacity of vehicles that are clinically relevant for gene therapy. We modulate expression of Lama1 in the dy2j/dy2j mouse model of MDC1A using an adeno-associated virus (AAV9) carrying a catalytically inactive Cas9 (dCas9), VP64 transactivators and single-guide RNAs that target the Lama1 promoter. When pre-symptomatic mice were treated, Lama1 was upregulated in skeletal muscles and peripheral nerves, which prevented muscle fibrosis and paralysis. However, for many disorders it is important to investigate the therapeutic window and reversibility of symptoms. In muscular dystrophies, it has been hypothesized that fibrotic changes in skeletal muscle are irreversible. However, we show that dystrophic features and disease progression were improved and reversed when the treatment was initiated in symptomatic dy2j/dy2j mice with apparent hindlimb paralysis and muscle fibrosis. Collectively, our data demonstrate the feasibility and therapeutic benefit of CRISPR-dCas9-mediated upregulation of Lama1, which may enable mutation-independent treatment for all patients with MDC1A. This approach has a broad applicability to a variety of disease-modifying genes and could serve as a therapeutic strategy for many inherited and acquired diseases.
25.	Leo, Paul J, et al. (författare) Correction: Defining the genetic susceptibility to cervical neoplasia-A genome-wide association study. 2018 Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 14:3 Tidskriftsartikel (refereegranskat)abstract [This corrects the article DOI: 10.1371/journal.pgen.1006866.].
26.	Litjens, Carlijn H. C., et al. (författare) Protein binding of rifampicin is not saturated when using high-dose rifampicin 2019 Ingår i: Journal of Antimicrobial Chemotherapy. - : OXFORD UNIV PRESS. - 0305-7453 .- 1460-2091. ; 74:4, s. 986-990 Tidskriftsartikel (refereegranskat)abstract Background Higher doses of rifampicin are being investigated as a means to optimize response to this pivotal TB drug. It is unknown whether high-dose rifampicin results in saturation of plasma protein binding and a relative increase in protein-unbound (active) drug concentrations. Objectives To assess the free fraction of rifampicin based on an in vitro experiment and data from a clinical trial on high-dose rifampicin. Methods Protein-unbound rifampicin concentrations were measured in human serum spiked with increasing total concentrations (up to 64mg/L) of rifampicin and in samples obtained by intensive pharmacokinetic sampling of patients who used standard (10mg/kg daily) or high-dose (35mg/kg) rifampicin up to steady-state. The performance of total AUC(0-24) to predict unbound AUC(0-24) was evaluated. Results The in vitro free fraction of rifampicin remained unaltered (approximate to 9%) up to 21mg/L and increased up to 13% at 41mg/L and 17% at 64mg/L rifampicin. The highest (peak) concentration in vivo was 39.1mg/L (high-dose group). The arithmetic mean percentage unbound to total AUC(0-24)in vivo was 13.3% (range=8.1%-24.9%) and 11.1% (range=8.6%-13.6%) for the standard group and the high-dose group, respectively (P=0.214). Prediction of unbound AUC(0-24) based on total AUC(0-24) resulted in a bias of -0.05% and an imprecision of 13.2%. Conclusions Plasma protein binding of rifampicin can become saturated, but exposures after high-dose rifampicin are not high enough to increase the free fraction in TB patients with normal albumin values. Unbound rifampicin exposures can be predicted from total exposures, even in the higher dose range.
27.	McCrae, Cristopher, et al. (författare) Lanosterol Synthase Regulates Human Rhinovirus Replication in Human Bronchial Epithelial Cells 2018 Ingår i: American Journal of Respiratory Cell and Molecular Biology. - 1044-1549. ; 59:6, s. 713-722 Tidskriftsartikel (refereegranskat)abstract Human rhinovirus (RV) infections are a significant risk factor for exacerbations of asthma and chronic obstructive pulmonary disease. Thus, approaches to prevent RV infection in such patients would give significant benefit. Through RNA interference library screening, we identified lanosterol synthase (LSS), a component of the cholesterol biosynthetic pathway, as a novel regulator of RV replication in primary normal human bronchial epithelial cells. Selective knock down of LSS mRNA with short interfering RNA inhibited RV2 replication in normal human bronchial epithelial cells. Small molecule inhibitors of LSS mimicked the effect of LSS mRNA knockdown in a concentration-dependent manner. We further demonstrated that the antiviral effect is not dependent on a reduction in total cellular cholesterol but requires a 24-hour preincubation with the LSS inhibitor. The rank order of antiviral potency of the LSS inhibitors used was consistent with LSS inhibition potency; however, all compounds showed remarkably higher potency against RV compared with the LSS enzyme potency. We showed that LSS inhibition led to an induction of 24(S),25 epoxycholesterol, an important regulator of the sterol pathway. We also demonstrated that LSS inhibition led to a profound increase in expression of the innate antiviral defense protein, IFN-beta. We found LSS to be a novel regulator of RV replication and innate antiviral immunity and identified a potential molecular mechanism for this effect, via induction of 24(S),25 epoxycholesterol. Inhibition of LSS could therefore be a novel therapeutic target for prevention of RV-induced exacerbations.
28.	Mellqvist Fässberg, Madeleine, et al. (författare) Functional disability and death wishes in older Europeans: results from the EURODEP concerted action. 2014 Ingår i: Social psychiatry and psychiatric epidemiology. - : Springer Science and Business Media LLC. - 1433-9285 .- 0933-7954. ; 49:9, s. 1475-1482 Tidskriftsartikel (refereegranskat)abstract Physical illness has been shown to be a risk factor for suicidal behaviour in older adults. The association between functional disability and suicidal behaviour in older adults is less clear. The aim of this study was to examine the relationship between functional disability and death wishes in late life.
29.	Morooka, Michiko W., et al. (författare) Dusty plasma in the vicinity of Enceladus 2011 Ingår i: Journal of Geophysical Research. - : American Geophysical Union (AGU). - 0148-0227 .- 2156-2202. ; 116 Tidskriftsartikel (refereegranskat)abstract We present in situ Cassini Radio Plasma Wave Science observations in the vicinity of Enceladus and in the E ring of Saturn that indicate the presence of dusty plasma. The four flybys of Enceladus in 2008 revealed the following cold plasma characteristics: (1) there is a large plasma density (both ions and electrons) within the Enceladus plume region, (2) no plasma wake effect behind Enceladus was detected, (3) electron densities are generally much lower than the ion densities in the E ring (n(e)/n(i) < 0.5) as well as in the plume (n(e)/n(i) < 0.01), and (4) the average bulk ion drift speed is significantly less than the corotation speed and is instead close to the Keplerian speed. These signatures result from half or more of the electrons being attached to dust grains and by the interaction between the surrounding cold plasma and the predominantly negatively charged submicrometer-sized dust grains. The dust and plasma properties estimated from the observations clearly show that the dust-plasma interaction is collective. This strong dust-plasma coupling appears not only in the Enceladus plume but also in the Enceladus torus, typically from about 20 R(E) (similar to 5000 km) north and about 60 R(E) (similar to 15,000 km) south of Enceladus. We also suggest that the dust-plasma interaction in the E ring is the cause of the planetary spin-modulated dynamics of Saturn's magnetosphere at large.
30.	Nathan, Vaishnavi, et al. (författare) Germline variants in oculocutaneous albinism genes and predisposition to familial cutaneous melanoma 2019 Ingår i: Pigment Cell and Melanoma Research. - : Wiley. - 1755-1471 .- 1755-148X. ; 32:6, s. 854-863 Tidskriftsartikel (refereegranskat)abstract Approximately 1%–2% of cutaneous melanoma (CM) is classified as strongly familial. We sought to investigate unexplained CM predisposition in families negative for the known susceptibility genes using next-generation sequencing of affected individuals. Segregation of germline variants of interest within families was assessed by Sanger sequencing. Several heterozygous variants in oculocutaneous albinism (OCA) genes: TYR, OCA2, TYRP1 and SLC45A2, were present in our CM cohort. OCA is a group of autosomal recessive genetic disorders, resulting in pigmentation defects of the eyes, hair and skin. Missense variants classified as pathogenic for OCA were present in multiple families and some fully segregated with CM. The functionally compromised TYR p.T373K variant was present in three unrelated families. In OCA2, known pathogenic variants: p.V443I and p.N489D, were present in three families and one family, respectively. We identified a likely pathogenic SLC45A2 frameshift variant that fully segregated with CM in a family of four cases. Another four-case family harboured cosegregating variants (p.A24T and p.R153C) of uncertain functional significance in TYRP1. We conclude that rare, heterozygous variants in OCA genes confer moderate risk for CM.
31.	Qadri, F., et al. (författare) Safety and immunogenicity of the oral, inactivated, enterotoxigenic Escherichia coli vaccine ETVAX in Bangladeshi children and infants: a double-blind, randomised, placebo-controlled phase 1/2 trial 2020 Ingår i: Lancet Infectious Diseases. - : Elsevier BV. - 1473-3099. ; 20:2, s. 208-219 Tidskriftsartikel (refereegranskat)abstract Background Enterotoxigenic Escherichia coil causes diarrhoea, leading to substantial mortality and morbidity in children, but no specific vaccine exists. This trial tested an oral, inactivated, enterotoxigenic E coli vaccine (ETVAX), which has been previously shown to be safe and highly immuongenic in Swedish and Bangladeshi adults. We tested the safety and immunogenicity of ETVAX, consisting of four E coli strains overexpressing the most prevalent colonisation factors (CFA/I, CS3, CSS, and CS6) and a toxoid (LCTBA) administered with or without a double-mutant heat-labile enterotoxin (dmLT) as an adjuvant, in Bangladeshi children. Methods We did a randomised, double-blind, placebo-controlled, dose-escalation, age-descending, phase 1/2 trial in Dhaka, Bangladesh. Healthy children in one of three age groups (24-59 months, 12-23 months, and 6-11 months) were eligible. Children were randomly assigned with block randomisation to receive either ETVAX, with or without dmLT, or placebo. ETVAX (half [5.5 x 10(10) cells], quarter [2.5 x 10(10) cells], or eighth [1.25 x 10(10) cells] adult dose), with or without dmLT adjuvant (2.5 mu g, 5.0 mu g, or 10.0 mu g), or placebo were administered orally in two doses 2 weeks apart. Investigators and participants were masked to treatment allocation. The primary endpoint was safety and tolerability, assessed in all children who received at least one dose of vaccine. Antibody responses to vaccine antigens, defined as at least a two-times increase in antibody levels between baseline and post-immunisation, were assessed as secondary endpoints. This trial is registered with ClinicalTrials.gov , NCT02531802. Findings Between Dec 7, 2015, and Jan 10, 2017, we screened 1500 children across the three age groups, of whom 430 were enrolled and randomly assigned to the different treatment groups (130 aged 24-59 months, 100 aged 12-23 months, and 200 aged 6-11 months). All participants received at least one dose of vaccine. No solicited adverse events occurred that were greater than moderate in severity, and most were mild. The most common solicited event was vomiting (ten [8%] of 130 patients aged 24-59 months, 13 [13%] of 100 aged 12-23 months, and 29 115%1 of 200 aged 6-11 months; mostly of mild severity), which appeared related to dose and age. The addition of dmLT did not modify the safety profile. Three serious adverse events occurred but they were not considered related to the study drug. Mucosal IgA antibody responses in lymphocyte secretions were detected against all primary vaccine antigens (CFA/I, CS3, CSS, CS6, and the LCTBA toxoid) in most participants in the two older age groups, whereas such responses to four of the five antigens were less frequent and of lower magnitude in infants aged 6-11 months than in older children. Faecal secretory IgA immune responses were recorded against all vaccine antigens in infants aged 6-11 months. 78 (56%) of 139 infants aged 6-11 months who were vaccinated developed mucosal responses against at least three of the vaccine antigens versus 14 (29%) of 49 of the infants given placebo. Addition of the adjuvant dmLT enhanced the magnitude, breadth, and kinetics (based on number of responders after the first dose of vaccine) of immune responses in infants. Interpretation The encouraging safety and immunogenicity of ETVAX and benefit of dmLT adjuvant in young children support its further assessment for protective efficacy in children in enterotoxigenic E coli-endemic areas. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd.
32.	Roussos, E., et al. (författare) Energetic electron observations of Rhea's magnetospheric interaction 2012 Ingår i: Icarus. - : Elsevier BV. - 0019-1035 .- 1090-2643. ; 221:1, s. 116-134 Tidskriftsartikel (refereegranskat)abstract Saturn's moon Rhea is thought to be a simple plasma absorber, however, energetic particle observations in its vicinity show a variety of unexpected and complex interaction features that do not conform with our current understanding about plasma absorbing interactions. Energetic electron data are especially interesting, as they contain a series of broad and narrow flux depletions on either side of the moon's wake. The association of these dropouts with absorption by dust and boulders orbiting within Rhea's Hill sphere was suggested but subsequently not confirmed, so in this study we review data from all four Cassini flybys of Rhea to date seeking evidence for alternative processes operating within the moon's interaction region. We focus on energetic electron observations, which we put in context with magnetometer, cold plasma density and energetic ion data. All flybys have unique features, but here we only focus on several structures that are consistently observed. The most interesting common feature is that of narrow dropouts in energetic electron fluxes, visible near the wake flanks. These are typically seen together with narrow flux enhancements inside the wake. A phase-space-density analysis for these structures from the first Rhea flyby (R1) shows that Liouville's theorem holds, suggesting that they may be forming due to rapid transport of energetic electrons from the magnetosphere to the wake, through narrow channels. A series of possibilities are considered to explain this transport process. We examined whether complex energetic electron drifts in the interaction region of a plasma absorbing moon (modeled through a hybrid simulation code) may allow such a transport. With the exception of several features (e.g. broadening of the central wake with increasing electron energy), most of the commonly observed interaction signatures in energetic electrons (including the narrow structures) were not reproduced. Additional dynamical processes, not simulated by the hybrid code, should be considered in order to explain the data. For the small scale features, the possibility that a flute (interchange) instability acts on the electrons is discussed. This instability is probably driven by strong gradients in the plasma pressure and the magnetic field magnitude: magnetometer observations show clearly signatures consistent with the (expected) plasma pressure loss due to ion absorption at Rhea. Another potential driver of the instability could have been gradients in the cold plasma density, which are, however, surprisingly absent from most crossings of Rhea's plasma wake. The lack of a density depletion in Rhea's wake suggests the presence of a local cold plasma source region. Hybrid plasma simulations show that this source cannot be the ionized component of Rhea's weak exosphere. It is probably related to accelerated photoelectrons from the moon's negatively charged surface, indicating that surface charging may play a very important role in shaping Rhea's magnetospheric interaction region. (C) 2012 Elsevier Inc. All rights reserved.
33.	Rådinger, Madeleine, 1967, et al. (författare) Assay of mast cell mediators. 2015 Ingår i: Methods in molecular biology (Clifton, N.J.). - New York, NY : Springer New York. - 1940-6029. ; 1220, s. 307-23 Tidskriftsartikel (refereegranskat)abstract Mediator release from activated mast cells is a major initiator of the symptomology associated with allergic disorders such as anaphylaxis and asthma. Thus, methods to monitor the generation and release of such mediators have widespread applicability in studies designed to understand the processes regulating mast cell activation and for the identification of therapeutic approaches to block mast cell-driven disease. In this chapter, we discuss approaches used for the determination of mast cell degranulation, lipid-derived inflammatory mediator production, and cytokine/chemokine gene expression as well as cytokine release.
34.	Samitas, Konstantinos, 1977, et al. (författare) Precursor B Cells Increase in the Lung during Airway Allergic Inflammation: A Role for B Cell-Activating Factor 2016 Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 11:8 Tidskriftsartikel (refereegranskat)abstract Background B cells, key cells in allergic inflammation, differentiate in the bone marrow and their precursors include pro-B, pre-B and immature B cells. Eosinophil progenitor cells increase in the lung after allergen exposure. However, the existence and possible role of B cell precursors in the lung during allergic inflammation remains elusive. A BALB/c mouse model of allergic airway inflammation was utilized to perform phenotypic and quantification analyses of pro-B and pre-B cells in the lung by flow cytometry. B cell maturation factors IL-7 and B cell-activating factor (BAFF) and their receptors (CD127 and BAFFR, BCMA, TACI, respectively) were also evaluated in the lung and serum. The effect of anti-BAFF treatment was investigated both in vivo (i.p. administration of BAFF-R-Ig fusion protein) and in vitro (colony forming cell assay). Finally, BAFF levels were examined in the bronchoalveolar lavage (BAL) of asthmatic patients and healthy controls. Precursor pro and pre-B cells increase in the lung after allergen exposure, proliferate in the lung tissue in vivo, express markers of chemotaxis (CCR10 and CXCR4) and co-stimulation (CD40, CD86) and are resistant to apoptosis (Bax). Precursor B cells express receptors for BAFF at baseline, while after allergen challenge both their ligand BAFF and the BCMA receptor expression increases in B cell precursors. Blocking BAFFR in the lung in vivo decreases eosinophils and proliferating precursor B cells. Blocking BAFFR in bone marrow cultures in vitro reduces pre-B colony formation units. BAFF is increased in the BAL of severe asthmatics. Our data support the concept of a BAFF-mediated role for B cell precursors in allergic airway inflammation.
35.	Vickers, Madeleine L., et al. (författare) The ikaite to calcite transformation : Implications for palaeoclimate studies 2022 Ingår i: Geochimica et Cosmochimica Acta. - : Elsevier BV. - 0016-7037. ; 334, s. 201-216 Tidskriftsartikel (refereegranskat)abstract Marine sedimentary ikaite is the parent mineral to glendonite, stellate pseudomorphs found throughout the geological record which are most usually composed of calcite. Ikaite is known to be metastable at earth surface temperatures and pressures, readily breaking down to more stable carbonate polymorphs when exposed to warm (ambient) conditions. Yet the process of transformation of ikaite to calcite is not well understood, and there is an ongoing debate as to the palaeoclimatic significance of glendonites in the geological record. This study uses a combination of techniques to examine the breakdown of ikaite to calcite, outside of the ikaite growth medium, and to assess the palaeoclimatic and palaeoenvironmental significance of stable and clumped isotope compositions of ikaite-derived calcite. Powder X-ray diffraction shows that ikaite undergoes a quasi- solid-state transformation to calcite during heating of samples in air, yet when ikaite transforms under a high temperature differential, minor dissolution-recrystallisation may also occur with the ikaite structural waters. No significant isotopic equilibration to transformation temperature is observed in the resulting calcite. Therefore, in cases of transformation of ikaite in air, clumped and stable isotope thermometry can be used to reconstruct ikaite growth temperatures. In the case of ancient glendonites, where transformation of the ikaite occurred in contact with the interstitial waters of the host sediments over unknown timescales, it is uncertain whether the reconstructed clumped isotope temperatures reflect ikaite crystallisation or its transformation temperatures. Yet clumped and stable isotope thermometry may still be used conservatively to estimate an upper limit for bottom water temperatures. Furthermore, stable isotope along with element/Ca ratios shed light on the chemical environment of ikaite growth. Our data indicate that a range of (bio)geochemical processes may act to promote ikaite formation at different marine sedimentary sites, including bacterial sulphate reduction and anaerobic oxidation of methane. The colours of the ikaites, from light brown to dark brown, indicate a high organic matter content, favouring high rates of bacterial sulphate reduction as the main driver of ikaite precipitation. Highest Mg/Ca ratios are found in the most unstable ikaites, indicating that Mg acts to destabilise ikaite structure.
36.	Abrandt Dahlgren, Madeleine, 1956-, et al. (författare) Freshmen Students on Education and Work 2002 Rapport (övrigt vetenskapligt/konstnärligt)
37.	Adelöf, Julia, 1990, et al. (författare) Conclusions from a behavioral aging study on male and female F2 hybrid mice on age-related behavior, buoyancy in water-based tests, and an ethical method to assess lifespan. 2019 Ingår i: Aging. - : Impact Journals, LLC. - 1945-4589. ; 11:17, s. 7150-7168 Tidskriftsartikel (refereegranskat)abstract Due to strain-specific behavioral idiosyncrasies, inbred mouse strains are suboptimal research models for behavioral aging studies. The aim of this study is to determine age-related behavioral changes of F2 hybrid C57BL/6NxBALB/c male and female mice. Lifespan was followed (nmales=48, nfemales=51) and cohorts of mature adult (7 months), middle-aged (15 months), and old mice (22 months of age; n=7-12 per group) were assessed regarding open-field activity, exploration, passive avoidance learning/memory, and depressive-like behavior. We found that both males and females demonstrated decreased exploratory behavior with age, while memory and depressive-like behavior were maintained. Females exhibited enhanced depressive-like behavior compared to males; however, a correlation between fat mass and swimming activity in the test directly accounted for 30-46% of this behavioral sex difference. In addition, we suggest a method to qualitatively estimate natural lifespan from survival analyses in which animals with signs of pain or severe disease are euthanized. This is, to our knowledge, the first behavioral study to consider both sex and aging in hybrid mice. We here define decreased exploratory behavior as a conserved hallmark of aging independent of sex, highlight the effect of buoyancy in water tests, and provide a method to assay lifespan with reduced animal suffering.
38.	Adelöf, Julia, 1990, et al. (författare) Survival-Span Method: How to Qualitatively Estimate Lifespan to Improve the Study of Aging, and not Disease, in Aging Studies 2021 Ingår i: Frontiers in Aging. - : Frontiers Media SA. - 1663-4365 .- 2673-6217. ; 2 Tidskriftsartikel (refereegranskat)abstract Lifespan analyses are important for advancing our understanding of the aging process. There are two major issues in performing lifespan studies: 1) late-stage animal lifespan analysis may include animals with non-terminal, yet advanced illnesses, which can pronounce indirect processes of aging rather than the aging process per se and 2) they often involves challenging welfare considerations. Herein, we present an option to the traditional way of performing lifespan studies by using a novel method that generates high-quality data and allows for the inclusion of excluded animals, even animals removed at early signs of disease. This Survival-span method is designed to be feasibly done with simple means by any researcher and strives to improve the quality of aging studies and increase animal welfare.
39.	Anderson, Madeleine, et al. (författare) An investigation of the associations between stigma, self-compassion, and pain outcomes during treatment based on Acceptance and Commitment Therapy for chronic pain 2024 Ingår i: Frontiers in Psychology. - : Frontiers Media S.A.. - 1664-1078. ; 15 Tidskriftsartikel (refereegranskat)abstract Introduction: Stigma adversely affects people with chronic pain. The qualities within self-compassion may be particularly useful for buffering the impact of stigma on people with pain. In the context of an Acceptance and Commitment Therapy-based (ACT) treatment for chronic pain, this study investigated the association between changes in stigma and self-compassion and pain outcomes, and the potential moderating role of self-compassion on the association between stigma and pain outcomes.Materials and methods: Five-hundred and nineteen patients completed standardized self-report questionnaires of stigma, self-compassion, psychological flexibility, pain intensity and interference, work and social adjustment, and depression symptoms at the start of an interdisciplinary ACT-based treatment for chronic pain. The same measures were completed at post-treatment (n = 431).Results: The results indicated that key pain outcomes and self-compassion significantly improved during treatment, but stigma did not. Changes in stigma and self-compassion were significantly negatively correlated and changes in these variables were associated with improvements in treatment outcomes. There were significant main effects of stigma and self-compassion for many of the pre- and post-treatment regression models when psychological flexibility was not controlled for, but self-compassion did not moderate the association between stigma and pain outcomes. Stigma remained significant when psychological flexibility variables were controlled for, while self-compassion did not.Discussion: The findings add to our conceptual understanding of the inter-relationships between stigma, self-compassion, and psychological flexibility and can contribute to treatment advancements to optimally target these variables.
40.	Aria, S., et al. (författare) GLINT Gravitational-wave laser INterferometry triangle 2017 Ingår i: Experimental Astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 44:2, s. 181-208 Tidskriftsartikel (refereegranskat)abstract When the universe was roughly one billion years old, supermassive black holes (10(3)-10(6) solar masses) already existed. The occurrence of supermassive black holes on such short time scales are poorly understood in terms of their physical or evolutionary processes. Our current understanding is limited by the lack of observational data due the limits of electromagnetic radiation. Gravitational waves as predicted by the theory of general relativity have provided us with the means to probe deeper into the history of the universe. During the ESA Alpach Summer School of 2015, a group of science and engineering students devised GLINT (Gravitational-wave Laser INterferometry Triangle), a space mission concept capable of measuring gravitational waves emitted by black holes that have formed at the early periods after the big bang. Morespecifically at redshifts of 15
41.	Barrett, Aidan, et al. (författare) Physiological estrogen levels are dispensable for the sex difference in immune responses during allergen-induced airway inflammation 2023 Ingår i: Immunobiology. - : Elsevier BV. - 0171-2985. ; 228:3 Tidskriftsartikel (refereegranskat)abstract Women show an increased prevalence of adult-onset asthma compared to men and previous studies have shown that testosterone inhibits while estrogen worsens allergen-induced airway inflammation. However, detailed knowledge about the aggravating effects of estrogen on immune responses remain unclear. Defining the effects of physiological levels of estrogen on immune responses in asthma would aid in the development of improved treatment strategies.In this study, the importance of estrogen for the sex difference in asthma was determined using a murine model of house dust mite (HDM)-induced airway inflammation on intact female and male mice, as well as on ovariectomized (OVX) female mice treated with a physiological dose of 17 beta-estradiol (E2). Innate and adaptive immune responses were defined in bronchoalveolar lavage fluid, mediastinal lymph node (mLN) and lung tissue.The results reveal increased numbers of lung eosinophils, macrophages, and dendritic cells in female but not in male mice after HDM challenge. Females also exhibit higher numbers of Th17 cells in both mLN and lung in response to HDM. However, treatment of OVX mice with physiological levels of E2 does not influence any of the analyzed cell populations.Together, this study confirms the previously reported sex difference in allergen-induced airway inflammation and show that female mice mount stronger innate and adaptive immune responses to HDM challenge, but these effects are not mediated by physiological levels of E2.
42.	Beckman, M, et al. (författare) Degradation of GFP-labelled POM121, a non-invasive sensor of nuclear apoptosis, precedes clustering of nuclear pores and externalisation of phosphatidylserine 2004 Ingår i: Apoptosis (London). - 1360-8185 .- 1573-675X. ; 9:3, s. 363-368 Tidskriftsartikel (refereegranskat)abstract The nuclear pore membrane protein POM121 is specifically degraded during apoptosis by a caspase-3-dependent process enabling early detection of apoptosis in living cells expressing POM121-GFP. Here we further investigated temporal aspects of apoptotic degradation of POM121-GFP. We demonstrate that decreased POM121-GFP fluorescence precedes annexin V-labelling of apoptotic cells. This indicates that degradation of the nuclear pore complex starts prior to redistribution of plasma membrane phosphatidylserine, which serves as a signal for phagocytotic elimination of apoptotic cells. Furthermore, a caspase-resistant GFP-labelled mutant of POM121 resisted degradation even in late apoptosis and was detected in clustered nuclear pores. Thus, it can be concluded that loss of POM121-GFP is a specific sensor of the activation of caspase-3-dependent proteolysis at the nuclear pores.
43.	Bergqvist, Madeleine M D H, 1980, et al. (författare) A TECHNO-ECONOMIC ASSESSMENT OF RICE HUSK BASED HEAT AND POWER GENERATION IN THE MEKONG RIVER DELTA OF VIETNAM 2007 Ingår i: Proceedings of the IGEC-III international green energy conference, June 17-21, 2007, Västerås, Sweden. Konferensbidrag (refereegranskat)
44.	Bergqvist, Madeleine M D H, 1980, et al. (författare) A techno-economic assessment of rice husk-based power generation in the Mekong River Delta of Vietnam 2008 Ingår i: INTERNATIONAL JOURNAL OF ENERGY RESEARCH. ; 32, s. 1136-1150 Tidskriftsartikel (refereegranskat)abstract Rice husk is a residue from rice, which is grown in large quantities in Vietnam. By using rice husk as a fuel for heat andpower production, dual environmental benefits can be achieved. Since it is a carbon neutral fuel, it can be a way ofoffsetting carbon dioxide emissions from energy supply systems. The use of rice husk for energy purposes can also helpsolve disposal problems at locations where husk is dumped in rivers or burnt in open piles. The aim of this study is toinvestigate whether rice husk can be used in an economical way to meet the energy demand within the rice millingindustry, mainly electricity, and/or to produce electricity for sales to the national grid. Different energy conversiontechnologies are considered for three sizes of power plants, suitable to meet different demand categories, and their respective lifetime costs of generation are calculated. The impacts on project economy of the Clean Development Mechanism, rice husk ash sales and cogeneration of heat are also investigated. The lifetime costs of generation of the different power plants are compared with the electricity price in Vietnam. The results show that the profitability is influenced by whether the electricity is sold directly to rice mills or to the national grid. For large plants, economic viability can be reached without revenues from ash sales or the CDM. For smaller plants either of them is required.
45.	Bhat, Harshitha K., et al. (författare) Influence of Jets on [O iii] Extensions in Green Pea/Bean Galaxies 2024 Ingår i: Astrophysical Journal. - 1538-4357 .- 0004-637X. ; 960:2 Tidskriftsartikel (refereegranskat)abstract We present a study investigating the influence of jets on galaxies exhibiting strong [O iii]λ5007 emission, known as Green Peas and Green Beans. Our sample comprised 12 nearby sources (z ∼ 0.04-0.1, six with jets and six without jets) with high [O iii] luminosity (L ∼ 1040 erg s−1), selected from a radio-selected galaxy sample observed with the Sloan Digital Sky Survey and Radio Sky at Twenty-centimeters survey. We perform Large Binocular Telescope-Multi-Object Double Spectrograph long-slit spectroscopy at two position angles for each galaxy: one aligned with the jet direction and another perpendicular to it. By tracing the [O iii] emission along these slits, we aimed to assess the extension of the narrow line region and examine the impact of jets. Surprisingly, our analysis revealed no preferred direction for the extension of the [O iii] emission, indicating that jets have a limited influence on the extended emission line regions (EELRs). This also suggests the possibility of missed detection of conical-shaped EELRs aligned with the jets, attributable to our slit orientations. Furthermore, we compared the extension of [O ii] emission, which traces star-forming regions, with that of [O iii]. We observed a significant difference, with [O ii] exhibiting a considerably greater extension along the galactic plane. This suggests a stronger association of [O ii] emission with stellar processes.
46.	Bjarnsholt, T., et al. (författare) Biofilm formation – what we can learn from recent developments 2018 Ingår i: Journal of Internal Medicine. - : Wiley-Blackwell. - 0954-6820 .- 1365-2796. ; 284:4, s. 332-345 Tidskriftsartikel (refereegranskat)abstract Although biofilms have been observed early in the history of microbial research, their impact has only recently been fully recognized. Biofilm infections, which contribute to up to 80% of human microbial infections, are associated with common human disorders, such as diabetes mellitus and poor dental hygiene, but also with medical implants. The associated chronic infections such as wound infections, dental caries and periodontitis significantly enhance morbidity, affect quality of life and can aid development of follow-up diseases such as cancer. Biofilm infections remain challenging to treat and antibiotic monotherapy is often insufficient, although some rediscovered traditional compounds have shown surprising efficiency. Innovative anti-biofilm strategies include application of anti-biofilm small molecules, intrinsic or external stimulation of production of reactive molecules, utilization of materials with antimicrobial properties and dispersion of biofilms by digestion of the extracellular matrix, also in combination with physical biofilm breakdown. Although basic principles of biofilm formation have been deciphered, the molecular understanding of the formation and structural organization of various types of biofilms has just begun to emerge. Basic studies of biofilm physiology have also resulted in an unexpected discovery of cyclic dinucleotide second messengers that are involved in interkingdom crosstalk via specific mammalian receptors. These findings even open up new venues for exploring novel anti-biofilm strategies.
47.	Bond-Taylor, M., et al. (författare) Posterior vitreous detachment - prevalence of and risk factors for retinal tears 2017 Ingår i: Clinical Ophthalmology. - : Informa UK Limited. - 1177-5483. ; 11, s. 1689-1695 Tidskriftsartikel (refereegranskat)abstract Purpose: The present study aimed to describe clinical characteristics of patients with posterior vitreous detachment (PVD), to determine the prevalence of retinal tears in PVD patients, and to find predictors for retinal tears in this patient group. Methods: Retrospective analysis of medical records on patients diagnosed with PVD, retinal tears, or vitreous hemorrhage at the Department of Ophthalmology at Sahlgrenska University Hospital, a tertiary eye center. Results: Between February and July 2009, 365 patients consulted the Department of Ophthalmology for PVD-related symptoms. The incidence of retinal tears was 14.5% (n = 53) and that of vitreous and/or retinal hemorrhage was 22.7% (n= 83). For analysis of possible predictors for complications to PVD, patients diagnosed with retinal tears or vitreous hemorrhage between May and July 2009 were also included in the study, resulting in a total of 426 patients. Predictors of a retinal tear were symptoms of visual impairment (P = 0.024), the presence of vitreous or retinal hemorrhage at examination (P = 0.001), and a duration of symptoms for <24 hours (P = 0.004). Symptoms of flashes did not constitute an extra risk of retinal tears (P = 0.135). Subsequent retinal pathology (follow-up time 4.5 years), including vitreous detachment/hemorrhage or retinal tears/detachment, occurred more often in patients presenting with a retinal tear. For patients with a retinal tear, the relative risk of having a retinal detachment in the same eye during the follow-up time was 17.7 when compared to patients without a retinal tear (risk ratio 17.7, 95% confidence interval 2.2-145). Conclusion: Patients seeking care on the first day have a higher risk of retinal tears. Also, symptoms of visual loss or a history of previous PVD-related pathology and vitreous/retinal hemorrhage at examination indicate a substantially higher risk of retinal complications. These findings may lead to better management and order of priority among these patients.
48.	Brunet-Ratnasingham, Elsa, et al. (författare) Sustained IFN signaling is associated with delayed development of SARS-CoV-2-specific immunity 2023 Annan publikation (övrigt vetenskapligt/konstnärligt)abstract Plasma RNAemia, delayed antibody responses and inflammation predict COVID-19 outcomes, but the mechanisms underlying these immunovirological patterns are poorly understood. We profile 782 longitudinal plasma samples from 318 hospitalized COVID-19 patients. Integrated analysis using k-means reveal four patient clusters in a discovery cohort: mechanically ventilated critically-ill cases are subdivided into good prognosis and high-fatality clusters (reproduced in a validation cohort), while non-critical survivors are delineated by high and low antibody responses. Only the high-fatality cluster is enriched for transcriptomic signatures associated with COVID-19 severity, and each cluster has distinct RBD-specific antibody elicitation kinetics. Both critical and non-critical clusters with delayed antibody responses exhibit sustained IFN signatures, which negatively correlate with contemporaneous RBD-specific IgG levels and absolute SARS-CoV-2-specific B and CD4+ T cell frequencies. These data suggest that the “Interferon paradox” previously described in murine LCMV models is operative in COVID-19, with excessive IFN signaling delaying development of adaptive virus-specific immunity.
49.	Brunet-Ratnasingham, Elsa, et al. (författare) Sustained IFN signaling is associated with delayed development of SARS-CoV-2-specific immunity. 2024 Ingår i: Nature Communications. - 2041-1723. ; 15:1, s. 4177- Tidskriftsartikel (refereegranskat)abstract Plasma RNAemia, delayed antibody responses and inflammation predict COVID-19 outcomes, but the mechanisms underlying these immunovirological patterns are poorly understood. We profile 782 longitudinal plasma samples from 318 hospitalized patients with COVID-19. Integrated analysis using k-means reveals four patient clusters in a discovery cohort: mechanically ventilated critically-ill cases are subdivided into good prognosis and high-fatality clusters (reproduced in a validation cohort), while non-critical survivors segregate into high and low early antibody responders. Only the high-fatality cluster is enriched for transcriptomic signatures associated with COVID-19 severity, and each cluster has distinct RBD-specific antibody elicitation kinetics. Both critical and non-critical clusters with delayed antibody responses exhibit sustained IFN signatures, which negatively correlate with contemporaneous RBD-specific IgG levels and absolute SARS-CoV-2-specific B and CD4+ T cell frequencies. These data suggest that the "Interferon paradox" previously described in murine LCMV models is operative in COVID-19, with excessive IFN signaling delaying development of adaptive virus-specific immunity.
50.	Campbell, Rachel, et al. (författare) Measure of Ovarian Symptoms and Treatment concerns (MOST) indexes and their associations with health-related quality of life in recurrent ovarian cancer 2022 Ingår i: Gynecologic Oncology. - : ACADEMIC PRESS INC ELSEVIER SCIENCE. - 0090-8258 .- 1095-6859. ; 166:2, s. 254-262 Tidskriftsartikel (refereegranskat)abstract Purpose. The Measure of Ovarian Symptoms and Treatment (MOST) concerns is a validated patient-reported symptom assessment tool for assessing symptom benefit and adverse effects of palliative chemotherapy in women with recurrent ovarian cancer (ROC). We aimed to examine (i) how symptoms within MOST symptom indexes track together (i.e. co-occur) and (ii) the association between MOST symptom indexes and key aspects of health-related quality of life (HRQL). Method. A prospective cohort of women with ROC completed the MOST-T35, EORTC QLQ-C30 and EORTC QLQ-OV28 at baseline and before each cycle of chemotherapy. Analyses were conducted on baseline and end -of-treatment data. Exploratory factor analysis and hierarchical cluster analysis identified groups of co-occurring symptoms. Path models examined associations between MOST symptom indexes and HRQL. Results. Data from 762 women at baseline and 681 at treatment-end who completed all 22 symptom-specific MOST items and at least one HRQL measure were analysed. Four symptom clusters emerged at baseline and treatment-end: abdominal symptoms, symptoms associated with peripheral neuropathy, nausea and vomiting, and psychological symptoms. Psychological symptoms (MOST-Psych) and symptoms due to disease (ovarian cancer) or treatment (MOST-DorT) were associated with poorer scores on QLQ-C30 and OV28 functioning do-mains and worse overall health at both time points. Conclusion. Four MOST symptom clusters were consistent across statistical methods and time points. These findings suggest that routine standardized assessment of psychological and physical symptoms in clinical prac-tice with MOST plus appropriate symptom management referral pathways is an intervention for improving HRQL that warrants further research. (c) 2022 Elsevier Inc. All rights reserved.

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