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1.	Breznau, Nate, et al. (författare) Observing many researchers using the same data and hypothesis reveals a hidden universe of uncertainty 2022 Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:44 Tidskriftsartikel (refereegranskat)abstract This study explores how researchers analytical choices affect the reliability of scientific findings. Most discussions of reliability problems in science focus on systematic biases. We broaden the lens to emphasize the idiosyncrasy of conscious and unconscious decisions that researchers make during data analysis. We coordinated 161 researchers in 73 research teams and observed their research decisions as they used the same data to independently test the same prominent social science hypothesis: that greater immigration reduces support for social policies among the public. In this typical case of social science research, research teams reported both widely diverging numerical findings and substantive conclusions despite identical start conditions. Researchers expertise, prior beliefs, and expectations barely predict the wide variation in research outcomes. More than 95% of the total variance in numerical results remains unexplained even after qualitative coding of all identifiable decisions in each teams workflow. This reveals a universe of uncertainty that remains hidden when considering a single study in isolation. The idiosyncratic nature of how researchers results and conclusions varied is a previously underappreciated explanation for why many scientific hypotheses remain contested. These results call for greater epistemic humility and clarity in reporting scientific findings.
2.	Smith, Jennifer A, et al. (författare) Genome-wide association study identifies 74 loci associated with educational attainment 2016 Ingår i: Nature (London). - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 533:7604, s. 539-542 Tidskriftsartikel (refereegranskat)abstract Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.
3.	Hibar, Derrek P., et al. (författare) Novel genetic loci associated with hippocampal volume 2017 Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8 Tidskriftsartikel (refereegranskat)abstract The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
4.	Keller, Magdalena, et al. (författare) Inhibiting the glycerophosphodiesterase EDI3 in ER-HER2+breast cancer cells resistant to HER2-targeted therapy reduces viability and tumour growth 2023 Ingår i: Journal of Experimental & Clinical Cancer Research. - : BioMed Central (BMC). - 1756-9966. ; 42 Tidskriftsartikel (refereegranskat)abstract Background: Intrinsic or acquired resistance to HER2-targeted therapy is often a problem when small molecule tyrosine kinase inhibitors or antibodies are used to treat patients with HER2 positive breast cancer. Therefore, the identification of new targets and therapies for this patient group is warranted. Activated choline metabolism, characterized by elevated levels of choline-containing compounds, has been previously reported in breast cancer. The glycerophosphodiesterase EDI3 (GPCPD1), which hydrolyses glycerophosphocholine to choline and glycerol-3-phosphate, directly influences choline and phospholipid metabolism, and has been linked to cancer-relevant phenotypes in vitro. While the importance of choline metabolism has been addressed in breast cancer, the role of EDI3 in this cancer type has not been explored.Methods: EDI3 mRNA and protein expression in human breast cancer tissue were investigated using publicly-available Affymetrix gene expression microarray datasets (n = 540) and with immunohistochemistry on a tissue microarray (n = 265), respectively. A panel of breast cancer cell lines of different molecular subtypes were used to investigate expression and activity of EDI3 in vitro. To determine whether EDI3 expression is regulated by HER2 signalling, the effect of pharmacological inhibition and siRNA silencing of HER2, as well as the influence of inhibiting key components of signalling cascades downstream of HER2 were studied. Finally, the influence of silencing and pharmacologically inhibiting EDI3 on viability was investigated in vitro and on tumour growth in vivo.Results: In the present study, we show that EDI3 expression is highest in ER-HER2 + human breast tumours, and both expression and activity were also highest in ER-HER2 + breast cancer cell lines. Silencing HER2 using siRNA, as well as inhibiting HER2 signalling with lapatinib decreased EDI3 expression. Pathways downstream of PI3K/Akt/mTOR and GSK3 beta, and transcription factors, including HIF1 alpha, CREB and STAT3 were identified as relevant in regulating EDI3 expression. Silencing EDI3 preferentially decreased cell viability in the ER-HER2 + cells. Furthermore, silencing or pharmacologically inhibiting EDI3 using dipyridamole in ER-HER2 + cells resistant to HER2-targeted therapy decreased cell viability in vitro and tumour growth in vivo.Conclusions: Our results indicate that EDI3 may be a potential novel therapeutic target in patients with HER2-targeted therapy-resistant ER-HER2 + breast cancer that should be further explored.
5.	Mauritsen, Thorsten, et al. (författare) Developments in the MPI-M Earth System Model version 1.2 (MPI-ESM1.2) and Its Response to Increasing CO2 2019 Ingår i: Journal of Advances in Modeling Earth Systems. - 1942-2466. ; 11:4, s. 998-1038 Tidskriftsartikel (refereegranskat)abstract A new release of the Max Planck Institute for Meteorology Earth System Model version 1.2 (MPI-ESM1.2) is presented. The development focused on correcting errors in and improving the physical processes representation, as well as improving the computational performance, versatility, and overall user friendliness. In addition to new radiation and aerosol parameterizations of the atmosphere, several relatively large, but partly compensating, coding errors in the model's cloud, convection, and turbulence parameterizations were corrected. The representation of land processes was refined by introducing a multilayer soil hydrology scheme, extending the land biogeochemistry to include the nitrogen cycle, replacing the soil and litter decomposition model and improving the representation of wildfires. The ocean biogeochemistry now represents cyanobacteria prognostically in order to capture the response of nitrogen fixation to changing climate conditions and further includes improved detritus settling and numerous other refinements. As something new, in addition to limiting drift and minimizing certain biases, the instrumental record warming was explicitly taken into account during the tuning process. To this end, a very high climate sensitivity of around 7 K caused by low-level clouds in the tropics as found in an intermediate model version was addressed, as it was not deemed possible to match observed warming otherwise. As a result, the model has a climate sensitivity to a doubling of CO2 over preindustrial conditions of 2.77 K, maintaining the previously identified highly nonlinear global mean response to increasing CO2 forcing, which nonetheless can be represented by a simple two-layer model.
6.	Satizabal, Claudia L., et al. (författare) Genetic architecture of subcortical brain structures in 38,851 individuals 2019 Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:11, s. 1624- Tidskriftsartikel (refereegranskat)abstract Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
7.	Schijven, Dick, et al. (författare) Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium 2023 Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 120:14 Tidskriftsartikel (refereegranskat)abstract Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.
8.	Schumann, Gunter, et al. (författare) KLB is associated with alcohol drinking, and its gene product beta-Klotho is necessary for FGF21 regulation of alcohol preference 2016 Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 113:50, s. 14372-14377 Tidskriftsartikel (refereegranskat)abstract Excessive alcohol consumption is a major public health problem worldwide. Although drinking habits are known to be inherited, few genes have been identified that are robustly linked to alcohol drinking. We conducted a genome-wide association metaanalysis and replication study among >105,000 individuals of European ancestry and identified beta-Klotho (KLB) as a locus associated with alcohol consumption (rs11940694; P = 9.2 x 10(-12)). beta-Klotho is an obligate coreceptor for the hormone FGF21, which is secreted from the liver and implicated in macronutrient preference in humans. We show that brain-specific beta-Klotho KO mice have an increased alcohol preference and that FGF21 inhibits alcohol drinking by acting on the brain. These data suggest that a liver-brain endocrine axis may play an important role in the regulation of alcohol drinking behavior and provide a unique pharmacologic target for reducing alcohol consumption.
9.	Vogel, Katharina U, et al. (författare) Roquin paralogs 1 and 2 redundantly repress the Icos and Ox40 costimulator mRNAs and control follicular helper T cell differentiation 2013 Ingår i: Immunity. - Cambridge, USA : Cell Press. - 1074-7613 .- 1097-4180. ; 38:4, s. 655-68 Tidskriftsartikel (refereegranskat)abstract The Roquin-1 protein binds to messenger RNAs (mRNAs) and regulates gene expression posttranscriptionally. A single point mutation in Roquin-1, but not gene ablation, increases follicular helper T (Tfh) cell numbers and causes lupus-like autoimmune disease in mice. In T cells, we did not identify a unique role for the much lower expressed paralog Roquin-2. However, combined ablation of both genes induced accumulation of T cells with an effector and follicular helper phenotype. We showed that Roquin-1 and Roquin-2 proteins redundantly repressed the mRNA of inducible costimulator (Icos) and identified the Ox40 costimulatory receptor as another shared mRNA target. Combined acute deletion increased Ox40 signaling, as well as Irf4 expression, and imposed Tfh differentiation on CD4(+) T cells. These data imply that both proteins maintain tolerance by preventing inappropriate T cell activation and Tfh cell differentiation, and that Roquin-2 compensates in the absence of Roquin-1, but not in the presence of its mutated form.
10.	Bustin, Stephen A., et al. (författare) The need for transparency and good practices in the qPCR literature 2013 Ingår i: Nature Methods. - : Springer Science and Business Media LLC. - 1548-7091 .- 1548-7105. ; 10:11, s. 1063-1067 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract Two surveys of over 1,700 publications whose authors use quantitative real-time PCR (qPCR) reveal a lack of transparent and comprehensive reporting of essential technical information. Reporting standards are significantly improved in publications that cite the Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines, although such publications are still vastly outnumbered by those that do not.
11.	Dahlbäck, Katharina, 1957, et al. (författare) ”Jag vet att man inte kan förändra världen, men man kan ha ambitioner” – sociala hållbarhetsperspektiv på ett musik- och poesiprojekt 2021 Ingår i: Forskning om undervisning & lärande. - : Lärarstiftelsen. - 2001-6131 .- 2000-9674. ; 9:3, s. 89-113 Tidskriftsartikel (refereegranskat)abstract Att utforska olika problemställningar genom konst kan vara ett sätt att ge nya perspektiv på komplexa frågor i arbetet med att uppfylla målen i Agenda 2030. När samhället ska anpassas till ekologiska, ekonomiska och sociala förändringar kan estetiska uttryck spela en viktig roll för att hitta nya vägar till lösningar och visa olika möjligheter för hur vi kan leva våra liv. Denna artikel utgår från ett musik- och poesiprojekt som pågick under ett år. Syftet är att undersöka möjligheter och hinder för konstnärliga samverkansprojekt i skolan samt relationen mellan rumslig, social och didaktisk inkludering och betydelsen av dessa ur ett hållbarhetsperspektiv. Intervjuer har valts som metod, och Illeris teori, Art Education for Sustainable Development, används som teoretisk utgångspunkt. I resultatet synliggörs hur elever inkluderades såväl rumsligt och socialt som didaktiskt i en konstnärlig process. Projektet var en deltagarorienterad intervention och kan ses som ett exempel på hur olika former av inkludering är en förutsättning för ett socialt hållbart samhälle.
12.	Dahlbäck, Katharina, et al. (författare) Multiliteracies in a Swedish Poetry and Music Project : A!ordances and challenges in a diverse society 2021 Konferensbidrag (refereegranskat)abstract This paper draws on a poetry and music project initiated by a producer at the Gothenburg Symphony Orchestra. The project has been running for a year and has been carried out in cooperation with teachers and students from three public schools. The focus in this paper will be on the participating children in Grades 1 and 2 from one school, who have been encouraged and supported to write poetry in their classrooms. In January 2020, the children performed settings of their poems in collaboration with children from other schools as well as musicians from the Symphony Orchestra. We as researchers have followed this project from the start, and will present preliminary results in this paper. The aim is to investigate what it has meant for the participating teachers and their students to be involved in the project, and to find out about the multiliteracies that were used and performed during the processes in the classrooms and in the final performance. We ask:In what ways and through what kind of multiliteracies, including various modalities and languages, did the children express themselves?Which affordances and/or challenges emerged in relation to the teachers’ and the children’s perspectives, and why?
13.	Dahlbäck, Katharina, 1957, et al. (författare) Multiliteracies in a Swedish Poetry and Music Project: Affordances and Challenges in a Diverse Society 2021 Ingår i: ECER 2021: European Conference on Educational Research, 6-10 september 2021 Geneve. Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract Multiliteracies in a Swedish Poetry and Music Project: Affordances and Challenges in a Diverse Society This paper draws on a poetry and music project initiated by a producer at the Gothenburg Symphony Orchestra. The project has been running for a year and has been carried out in cooperation with teachers and students from three public schools. The focus in this paper will be on the participating children in Grades 1 and 2 from one school, who have been encouraged and supported to write poetry in their classrooms. In January 2020, the children performed settings of their poems in collaboration with children from other schools as well as musicians from the Symphony Orchestra. We as researchers have followed this project from the start, and will present preliminary results in this paper. The aim is to investigate what it has meant for the participating teachers and their students to be involved in the project, and to find out about the multiliteracies that were used and performed during the processes in the classrooms and in the final performance. We ask: •In what ways and through what kind of multiliteracies, including various modalities and languages, did the children express themselves? •Which affordances and/or challenges emerged in relation to the teachers’ and the children’s perspectives, and why? This study is motivated by an interest in democratic aspects of children’s participation and agency, and the crucial role which multifaceted literacy competences play in this. Over the last four decades, the definition and meaning of “literacy” has broadened and evolved. From entailing only the ability to read and write, literacy is now interpreted as using language in socially and culturally situated contexts (see e.g. Baynham & Prinsloo, 2009; Heath, 1983; Street, 1993). Further, multimodal forms of expressions impregnate Western societies of today, which has an impact on how children develop language and how they think about communication. Barton (1994) proposes that literacy, including different modes of text, takes place on different occasions in life. This multimodal perspective on literacy highlights how different modes and types of text, such as talk and gestures, are combined in communication. According to Kress and Van Leeuwen (2001), all communication is multimodal and includes several interacting semiotic systems. The New London Group (1996) has identified five comprehensive systems to define meaning making: written and linguistic (the use of vocabulary and grammar); visual (the use of, for example, colour, light and shadow); audial (the use of sound, music, noise and silence through pitch, volume and rhythm); gestural (the use of hands, facial expressions and body language through speed, stillness, and rhythm); and, finally, spatial (the use of proximity, direction and position). Multimodal texts that children encounter include texts in theatre, video games, movies and picture books. When children play, dramatize, draw, paint, write and compose stories, modalities are combined, such as gestures, sound, colour and script. Drawing on the plurality of texts and media in current societies, Luke and Freebody (1997) propose that effective literacy learning needs to integrate and balance practices of coding, functional use, meaning making and critical analysis of texts. Comber and Nixon (2004) describe this literacy approach as a focus “not only on what children read and view, but also on what they design, compose and produce across a wide range of genres, medias and modes” (p. 116). Further, aesthetic expressions can play significant roles in children’s identity building and meaning making and this might lead to transformative learning, i.e. when learning brings about changes in attitudes and thinking patterns, providing opportunities to act in new ways and changing identity formation (Bamford, 2017; Illeris, 2014), which could be considered useful for both themselves and for society (Dahlbäck et al, 2018; Hall, 1989). Methods The school in question is situated in an area characterized by socioeconomic inequality. A majority of the students speak a language other than Swedish in their homes. These students do not per se have lower cognitive and/or literacy abilities, but these conditions do affect teachers’ work in comparison to teachers’ work in schools in more affluent areas. Several methods were used for creating data: participant observations in classrooms, focus-group interviews with participating teachers, individual interviews with five children from two classrooms and teachers’ documentation from the process. On five daylong visits, we have observed poetry writing in the classes. Focus-group interviews were chosen as a methodological approach with the purpose of creating active and dynamic discussions, making it possible for several different views and experiences to be voiced among the teachers (Halkier, 2010). Five individual students, with various language backgrounds and attitudes regarding literacy were selected. Through individual interviews with these students we were able to capture the personal perspectives of these specific children. During the interviews, we used poems, pictures and music created by the students to stimulate reflections from their individual perspectives. All poems created by the focus students have been collected and documented. In this research project, we study events from the perspective of teachers and pupils based on the following empirical material: •Observations from poetry writing in the classrooms •Poems/pictures/music from 5 students and 10 transcribed interviews with these students. •Teacher documentation of the whole process. •One transcribed group interview with 5 participating teachers. The analysis of the created data material will be carried out in accordance with the aim and the research questions. The analysis of the classroom activities, together with the analysis of the focus-group interviews and the individual interviews, will enable us to develop further knowledge about conditions and possibilities for children’s participation, and development of literacy competences through the multiliteracies that they had access to via this project. Also, the analysis will shed light on challenges and affordances that came to light. The focus of the analysis will be on the meaning that is created and designed through various multiliteracies and aesthetics (Cummins, 2001; Comber & Nixon, 2004). Conclusions To participate in society, children depend on classroom practices that support them in developing complex multiliteracy competences, including basic reading and writing, but also expressing oneself and reflecting on and drawing conclusions from texts, as well as critically reviewing them (Comber & Nixon, 2004; Cummins, 2001; Schmidt, 2018). There is hence a need for many ways and multiple modalities for communicating and developing knowledge from, in particular together with children in diverse classrooms. The processes and performances in the poetry and music project meant a meeting between the students and teachers who participated, as well as a meeting between various musical genres and forms of expression. This study is a work in progress and the empirical data will be analysed the coming spring. We will therefore present preliminary results in line with the paper’s aim and research questions. Further, our ambition is to relate the analysed results to aspects of children’s opportunities for representation, drawing on Fraser’s (1997). There are, of course, several arguments for classroom work with poetry, including functional, emancipatory and literary ones. Through poetry, it may be possible for the children to discover the power of language (Heard, 1989). Poetic language reflects the variety of languages and poets could be said to work at the frontline linguistically (Hall, 1989). Children have the ‘right’ to use their imagination as well as practising their freedom of speech, in line with the United Nations Convention on the Rights of the Child (UNICEF, 2009). We will present what teachers and students learned from participating in this project where different modalities and languages interact. References Bamford, A. (2009). The Wow Factor Global research compendium on the impact of the arts in education. Münster: Waxmann. Barton, D. (1994) An introduction to the ecology of the written language. Oxford: Blackwell Publishing. Baynham, M. & Prinsloo, M. (2009) The future of literacy studies. New York: Palgrave Macmillan. Comber, B. & Nixon, H. (2004) Children reread and rewrite their local neighborhoods: Critical literacies and identity work. In J. Evans, ed: Literacy moves on. Using popular culture, new technologies and critical literacy in the primary classroom, p. 127–148. New York: David Fulton Publishers. Cummins, J. (2001). Negotiating Identities: Education for Empowerment in a Diverse Society. . 2nd ed. Los Angeles: California Association for Bilingual Education. Dahlbäck, K., Lyngfelt, A., & Bengtsdotter Katz, V. (2018). Views of poetry as a competence expressed by students in teacher education. Theoria et Historia Scientiarum, volym (XV), s.101-119. doi:http://dx.doi.org/10.12775/ths.2018.007 Fraser, N. 1997. Justice Interruptus: Critical Reflections on the “Postsocialist” Condition. New York: Routledge. Halkier, B. (2010). Focus groups as social enactments: integrating interaction and content in the analysis of focus group data. Qualitative Research, vol 10 (1), p. 71-89. Heath, B. S. 1983. Ways with Words. Language, Life and Work in Communities and Classrooms. Cambridge: Cambridge University Press. Heard, G. (1989). For the Good of the Earth and Sun: Teaching Poetry. Heinemann Educational Books. ISBN: 9780435084950. Hall, L. (1989). Poetry for life. A practical guide to teaching poetry in the primary school. London: Cassell. Illeris, K. (2014). Transformative Learnin
14.	Fischer, Benjamin, et al. (författare) A complete workflow for the differentiation and the dissociation of hiPSC-derived cardiospheres 2018 Ingår i: Stem Cell Research. - : Elsevier. - 1873-5061 .- 1876-7753. ; 32, s. 65-72 Tidskriftsartikel (refereegranskat)abstract Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) are an invaluable tool for both basic and translational cardiovascular research. The potential that these cells hold for therapy, disease modeling and drug discovery is hampered by several bottlenecks that currently limit both the yield and the efficiency of cardiac induction. Here, we present a complete workflow for the production of ready-to-use hiPSC-CMs in a dynamic suspension bioreactor. This includes the efficient and highly reproducible differentiation of hiPSCs into cardiospheres, which display enhanced physiological maturation compared to static 3D induction in hanging drops, and a novel papain-based dissociation method that offers higher yield and viability than the broadly used dissociation reagents TrypLE and Accutase. Molecular and functional analyses of the cardiomyocytes reseeded after dissociation confirmed both the identity and the functionality of the cells, which can be used in down-stream applications, either as monolayers or spheroids.
15.	Hess, Timo, et al. (författare) Dissecting the genetic heterogeneity of gastric cancer 2023 Ingår i: EBioMedicine. - : Elsevier. - 2352-3964. ; 92 Tidskriftsartikel (refereegranskat)abstract Background: Gastric cancer (GC) is clinically heterogenous according to location (cardia/non-cardia) and histopathology (diffuse/intestinal). We aimed to characterize the genetic risk architecture of GC according to its subtypes. Another aim was to examine whether cardia GC and oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett's oesophagus (BO), which are all located at the gastro-oesophageal junction (GOJ), share polygenic risk architecture.Methods: We did a meta-analysis of ten European genome-wide association studies (GWAS) of GC and its subtypes. All patients had a histopathologically confirmed diagnosis of gastric adenocarcinoma. For the identification of risk genes among GWAS loci we did a transcriptome-wide association study (TWAS) and expression quantitative trait locus (eQTL) study from gastric corpus and antrum mucosa. To test whether cardia GC and OAC/BO share genetic aetiology we also used a European GWAS sample with OAC/BO.Findings: Our GWAS consisting of 5816 patients and 10,999 controls highlights the genetic heterogeneity of GC according to its subtypes. We newly identified two and replicated five GC risk loci, all of them with subtype-specific association. The gastric transcriptome data consisting of 361 corpus and 342 antrum mucosa samples revealed that an upregulated expression of MUC1, ANKRD50, PTGER4, and PSCA are plausible GC-pathomechanisms at four GWAS loci. At another risk locus, we found that the blood-group 0 exerts protective effects for non-cardia and diffuse GC, while blood-group A increases risk for both GC subtypes. Furthermore, our GWAS on cardia GC and OAC/BO (10,279 patients, 16,527 controls) showed that both cancer entities share genetic aetiology at the polygenic level and identified two new risk loci on the single-marker level.Interpretation: Our findings show that the pathophysiology of GC is genetically heterogenous according to location and histopathology. Moreover, our findings point to common molecular mechanisms underlying cardia GC and OAC/BO.
16.	Jovanovic, Milena, et al. (författare) Perturbed bone composition and integrity with disorganized osteoblast function in zinc receptor/Gpr39-deficient mice 2018 Ingår i: FASEB Journal. - 0892-6638. ; 32:5, s. 2507-2518 Tidskriftsartikel (refereegranskat)abstract Changes in bone matrix composition are frequently found with bone diseases and may be associated with increased fracture risk. Bone is rich in the trace element zinc. Zinc was established to play a significant role in the growth, development, and maintenance of healthy bones; however, the mechanisms underlying zinc effects on the integrity of the skeleton are poorly understood. Here, we show that the zinc receptor (ZnR)/Gpr39 is required for normal bone matrix deposition by osteoblasts. Initial analysis showed that Gpr39-deficient (Gpr39-/-) mice had weaker bones as a result of altered bone composition. Fourier transform infrared spectroscopy analysis showed high mineral-to-matrix ratios in the bones of Gpr39-/- mice. Histologic analysis showed abnormally high numbers of active osteoblasts but normal osteoclast numbers on the surfaces of bones from Gpr39-/- mice. Furthermore, Gpr39-/- osteoblasts had disorganized matrix deposition in vitro with cultures exhibiting abnormally low collagen and high mineral contents, findings that demonstrateacell-intrinsic role for ZnR/Gpr39 in these cells. We show that both collagen synthesis and deposition by Gpr39-/- osteoblasts are perturbed. Finally, the expression of the zinc transporter Zip13 and a disintegrin and metalloproteinase with thrombospondin motifs family of zinc-dependent metalloproteases that regulate collagen processing was downregulated in Gpr39-/- osteoblasts. Altogether, our results suggest that zinc sensing by ZnR/Gpr39 affects the expression levels of zinc-dependent enzymes in osteo-blasts and regulates collagen processing and deposition.
17.	Jörger, Katharina, et al. (författare) MEIOZORES 2019 - EXPLORING THE MARINE MEIOFAUNA OF THE AZORES 2021 Ingår i: AÇOREANA. ; , s. 17-41 Tidskriftsartikel (refereegranskat)abstract In July 2019 an international team of 39 senior and junior researchers from ninecountries met at the University of the Azores in Ponta Delgada, São Miguel for a 10-daysworkshop/ summer school to explore the meiofaunal biodiversity in marine sediments of the Azores. In total, we sampled intertidal and subtidal sediments from 54 localities on 14 major sites around São Miguel and additionally explored eight freshwater and terrestrial sites for rotifers. We sorted and investigated more than 2000 living specimens in the field, yielding approximately 180 species of soft-bodied meiofauna, representing most major clades of meiofauna with a focus on nematodes, polychaete annelids, proseriate andrhabdocoel flatworms, gastrotrichs, acoelomorphs, nemerteans, molluscs and cnidarians. Most of the encountered diversity shows similarities to the North-East Atlantic continental meiofauna, but in-depth morphological and molecular analyses are still pending. About 60 of the 180 species could not be assigned a species-level identification in the field, and nearly 15% of the total diversity is expected to be new to science and is awaiting formal description. Herein, we present an overview of the results of the workshop, providing detailed information on the sampling sites, methodology and encountered diversity, and we offer a preliminary discussion on aspects of faunal elements shared with other biogeographic regions. We highlight the most common members of the marine meiofauna of the Azores, provide preliminary diversity estimates and suggest a roadmap for future research towards a better understanding of the meiofauna in this remote archipelago.
18.	Kattge, Jens, et al. (författare) TRY plant trait database - enhanced coverage and open access 2020 Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188 Tidskriftsartikel (refereegranskat)abstract Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
19.	Kessler, Henrik, et al. (författare) Visuospatial computer game play after memory reminder delivered three days after a traumatic film reduces the number of intrusive memories of the experimental trauma 2020 Ingår i: Journal of Behavior Therapy and Experimental Psychiatry. - : Elsevier. - 0005-7916 .- 1873-7943. ; 67 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: The experience of intrusive memories is a core clinical symptom of posttraumatic stress disorder (PTSD), and can be distressing in its own right. Notions of dual task interference and reconsolidation-update mechanisms suggest novel approaches to target intrusive memories. This study tested the hypothesis that a single-session cognitive intervention (memory reminder task plus Tetris gameplay) would reduce the occurrence of experimental trauma memories even when delivered 3 days post-trauma. Critically, this study tested effects against two control groups: Reminder-only, and reminder plus another computer game (a form of Quiz).METHODS: 86 healthy volunteers (59% female, age M = 24.35, SD = 4.59 years) watched a trauma film and then recorded their intrusive memories in a diary for 3 days (pre-intervention). They then returned to the lab. After presentation of visual reminder cues for the film plus a 10 min wait period (memory reminder task), participants were randomized into one of three task conditions (Tetris game play, Quiz game play, vs. reminder-only). They then kept the diary for a further 3 days (post-intervention).RESULTS: As predicted, after the experimental manipulation, the reminder + Tetris group experienced significantly fewer intrusions than the reminder-only group (d = 1.37). Further, the reminder + Tetris group also experienced significantly fewer intrusions than the reminder + Quiz (d = 0.65) group. Contrary to predictions, the reminder + Quiz group experienced significantly fewer intrusions than the reminder-only group (d = 0.69). Prior to the experimental manipulation, there was no significant difference between groups in number of intrusions. Recognition memory test scores for facts of the trauma film after 6 days were comparable between groups.CONCLUSIONS: We demonstrated that 3 days after experimental trauma (i.e. after memory consolidation) an intervention comprising a reminder task prior to a 15 min cognitive interference task (one of two computer games) led to a reduction in intrusion occurrence compared to reminder only. We interpret and discuss our findings within the framework of supposed reconsolidation-update mechanisms and competition for limited (visuospatial) working memory resources. Should these effects hold true in clinical populations, this type of simple intervention approach could help contribute to reducing intrusive memories of trauma.
20.	Klionsky, Daniel J, et al. (författare) Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). 2016 Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 12:1, s. 1-222 Tidskriftsartikel (refereegranskat)
21.	Krebs, Alice, et al. (författare) The EU-ToxRisk method documentation, data processing and chemical testing pipeline for the regulatory use of new approach methods 2020 Ingår i: Archives of Toxicology. - : Springer Science and Business Media LLC. - 0340-5761 .- 1432-0738. ; 94:7, s. 2435-2461 Tidskriftsartikel (refereegranskat)abstract Hazard assessment, based on new approach methods (NAM), requires the use of batteries of assays, where individual tests may be contributed by different laboratories. A unified strategy for such collaborative testing is presented. It details all procedures required to allow test information to be usable for integrated hazard assessment, strategic project decisions and/or for regulatory purposes. The EU-ToxRisk project developed a strategy to provide regulatorily valid data, and exemplified this using a panel of > 20 assays (with > 50 individual endpoints), each exposed to 19 well-known test compounds (e.g. rotenone, colchicine, mercury, paracetamol, rifampicine, paraquat, taxol). Examples of strategy implementation are provided for all aspects required to ensure data validity: (i) documentation of test methods in a publicly accessible database; (ii) deposition of standard operating procedures (SOP) at the European Union DB-ALM repository; (iii) test readiness scoring accoding to defined criteria; (iv) disclosure of the pipeline for data processing; (v) link of uncertainty measures and metadata to the data; (vi) definition of test chemicals, their handling and their behavior in test media; (vii) specification of the test purpose and overall evaluation plans. Moreover, data generation was exemplified by providing results from 25 reporter assays. A complete evaluation of the entire test battery will be described elsewhere. A major learning from the retrospective analysis of this large testing project was the need for thorough definitions of the above strategy aspects, ideally in form of a study pre-registration, to allow adequate interpretation of the data and to ensure overall scientific/toxicological validity.
22.	Ludwig, Sebastian, et al. (författare) Transcatheter Mitral Valve Replacement versus Medical Therapy for Secondary Mitral Regurgitation: A Propensity Score-Matched Comparison. 2023 Ingår i: Circulation. Cardiovascular interventions. - 1941-7632. ; 16:6 Tidskriftsartikel (refereegranskat)abstract Background: Transcatheter mitral valve replacement (TMVR) is an emerging therapeutic alternative for patients with secondary mitral regurgitation (MR). Outcomes of TMVR versus guideline-directed medical therapy (GDMT) have not been investigated for this population. This study aimed to compare clinical outcomes of patients with secondary MR undergoing TMVR versus GDMT alone. Methods: The CHOICE-MI registry included patients with MR undergoing TMVR using dedicated devices. Patients with MR etiologies other than secondary MR were excluded. Patients treated with GDMT alone were derived from the control arm of the COAPT trial. We compared outcomes between the TMVR and GDMT groups, using propensity score (PS)-matching to adjust for baseline differences. Results: After PS-matching, 97 patient pairs undergoing TMVR (72.9±8.7 years, 60.8% male, transapical access 91.8%) versus GDMT (73.1±11.0 years, 59.8% male) were compared. At 1 and 2 years, residual MR was ≤1+ in all patients of the TMVR group compared to 6.9% and 7.7%, respectively, in those receiving GDMT alone (both p<0.001). The 2-year rate of HF hospitalization was significantly lower in the TMVR group (32.8% vs. 54.4%, HR 0.59, 95% CI 0.35-0.99; p=0.04). Among survivors, a higher proportion of patients were in NYHA functional class I or II in the TMVR group at 1 year (78.2% vs. 59.7%, p=0.03) and at 2 years (77.8% vs. 53.2%, p=0.09). Two-year mortality was similar in the two groups (TMVR vs. GDMT, 36.8% vs. 40.8%, HR 1.01, 95% CI 0.62-1.64; p=0.98). Conclusions: In this observational comparison, over 2-year follow-up, TMVR using mostly transapical devices in patients with secondary MR was associated with significant reduction of MR, symptomatic improvement, less frequent hospitalizations for HF and similar mortality compared with GDMT.
23.	Ramirez Camargo, Luis, et al. (författare) Pathway to a land-neutral expansion of Brazilian renewable fuel production 2022 Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 13:1 Tidskriftsartikel (refereegranskat)abstract Biofuels are currently the only available bulk renewable fuel. They have, however, limited expansion potential due to high land requirements and associated risks for biodiversity, food security, and land conflicts. We therefore propose to increase output from ethanol refineries in a land-neutral methanol pathway: surplus CO2-streams from fermentation are combined with H2 from renewably powered electrolysis to synthesize methanol. We illustrate this pathway with the Brazilian sugarcane ethanol industry using a spatio-temporal model. The fuel output of existing ethanol generation facilities can be increased by 43%–49% or ~100 TWh without using additional land. This amount is sufficient to cover projected growth in Brazilian biofuel demand in 2030. We identify a trade-off between renewable energy generation technologies: wind power requires the least amount of land whereas a mix of wind and solar costs the least. In the cheapest scenario, green methanol is competitive to fossil methanol at an average carbon price of 95€ tCO2−1.
24.	Schmidt, Catarina, et al. (författare) Musik- och poesiprojekt 2020 Ingår i: SMDI 14, 18-19 november 2020, Malmö universitet. Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract Musik- och poesiprojekt Studien utgår från ett avslutat musik- och poesiprojekt på en lågstadieskola, initierat av en producent vid Göteborgs Konserthus. Vi har följt hela projektet under ett år, och presenterar preliminära resultat. Syftet är att bidra med kunskap om vilka former för deltagande och representation som möjliggjordes för de involverade eleverna från årskurs 1 och 2 i undervisningen i svenska och svenska som andraspråk, samt elevers och lärares perspektiv kring detta. I studien undersöks demokratiska aspekter kring elevers språk- och kunskapsutveckling och vilka möjligheter elever erbjuds för att representera sig själva (Fraser, 1997) genom olika uttrycksformer och modaliteter (Cummins, 2001; Illeris, 2014; Kress, 1997; Schmidt & Häggström, 2019). Skolan präglas i viss mån av socioekonomiska ojämlikheter. En majoritet av eleverna talar ett annat språk än svenska i sina hem. Det insamlade datamaterial som bidraget utgår från är: fältanteckningar från deltagande observationer i klassrum, transkriberade fokusgruppsintervjuer med elever respektive lärare samt dokumentation av musik- och poesiprojektets upplägg. Materialet kommer att analyseras under våren. Först görs en tematisk innehållsanalys (Hsieh & Shannon, 2005). Därefter analyseras vilka modaliteter och estetiska uttrycksformer som integreras samt elevernas möjligheter till representation. Det finns flera argument för elevers poesiskapande då det kan leda till att de blir varse språkets makt (Heard, 1989), får använda sin fantasi samt uttrycka tankar, känslor och åsikter (Wolf, 2004; UNICEF, 2009). Vi önskar i detta bidrag presentera och problematisera de möjligheter och utmaningar som framkommer i relation till det undervisningsinnehåll som skapades. Estetiska uttrycksformer; poesi; representation Referenser Cummins, J. (2001). Negotiating Identities: Education for Empowerment in a Diverse Society. . 2nd ed. Los Angeles: California Association for Bilingual Education. Fraser, N. 1997. Justice Interruptus: Critical Reflections on the “Postsocialist” Condition. New York: Routledge. Heard, G. (1989). For the Good of the Earth and Sun: Teaching Poetry. Heinemann Educational Books. ISBN: 9780435084950. Hsieh, H-F. & Shannon, S.E. (2005). Three approaches to Qualitative Content Analysis. Qualitative Health Research, 15 (9), 1277-1288. Illeris, K. (2014). Transformative Learning and Identity. New York: Routledge. Kress, G. (1997). Before writing. London: Routledge. Schmidt, C. & Häggström, M. (2019). Literacy and Multimodality in Swedish Teacher Education: Understanding and Bringing Together Theory and Practice. Utbildning & Lärande, 13 (1), 7-23. Wolf, L. (2004). Till dig en blå tussilago. Att läsa och skriva lyrik i skolan. Lund: Studentlitteratur.
25.	Schmidt, Catarina, et al. (författare) Musik- och poesiprojekt i skolan 2020 Ingår i: SMDI konferens 2020. Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract Studien utgår från ett avslutat musik- och poesiprojekt på en skola, initierat av en producent vid Göteborgs Konserthus. Vi har följt hela projektet under ett år, och presenterar preliminära resultat. Syftet är att bidra med kunskap om vilka former för deltagande och representation som möjliggjordes för de involverade eleverna från årskurs 1 och 2 i undervisningen i svenska och svenska som andraspråk, samt elevers och lärares perspektiv kring detta. I studien undersöks demokratiska aspekter kring elevers språk- och kunskapsutveckling och vilka möjligheter elever erbjuds för att representera sig själva (Fraser, 1997) genom olika uttrycksformer och modaliteter (Cummins, 2001; Illeris, 2014; Kress, 1997; Schmidt & Häggström, 2019). Skolan präglas i viss mån av socioekonomiska ojämlikheter. En majoritet av eleverna talar ett annat språk än svenska i sina hem. Det insamlade datamaterial som bidraget utgår från är: fältanteckningar från deltagande observationer i klassrum, transkriberade fokusgruppsintervjuer med elever respektive lärare samt dokumentation av musik- och poesiprojektets upplägg. Materialet kommer att analyseras under våren. Först görs en tematisk innehållsanalys (Hsieh & Shannon, 2005). Därefter analyseras vilka modaliteter och estetiska uttrycksformer som integreras samt elevernas möjligheter till representation. Det finns flera argument för elevers poesiskapande då det kan leda till att de blir varse språkets makt (Heard, 1989), får använda sin fantasi samt uttrycka tankar, känslor och åsikter (Wolf, 2004; UNICEF, 2009). Vi önskar i detta bidrag presentera och problematisera de möjligheter och utmaningar som framkommer i relation till det undervisningsinnehåll som skapades.
26.	Schmidt, Catarina, 1964-, et al. (författare) Musik- och poesiprojekt på Långmosseskolan 2020 Ingår i: SMDI 14 den 18-19 nov 2020, Didaktiska perspektiv på språk och litteratur i en globaliserad värld. Konferensbidrag (refereegranskat)abstract Studien utgår från ett avslutat musik- och poesiprojekt på Långmosseskolan, initierat av en producent vid Göteborgs Konserthus. Vi har följt hela projektet under ett år, och presenterar preliminära resultat. Syftet är att bidra med kunskap om vilka former för deltagande och representation som möjliggjordes för de involverade eleverna från årskurs 1 och 2 i undervisningen i svenska och svenska som andraspråk, samt elevers och lärares perspektiv kring detta.I studien undersöks demokratiska aspekter kring elevers språk- och kunskapsutveckling och vilka möjligheter elever erbjuds för att representera sig själva (Fraser, 1997) genom olika uttrycksformer och modaliteter (Cummins, 2001; Illeris, 2014; Kress, 1997; Schmidt & Häggström, 2019). Långmosseskolan präglas i viss mån av socioekonomiska ojämlikheter. En majoritet av eleverna talar ett annat språk än svenska i sina hem. Det insamlade datamaterial som bidraget utgår från är: fältanteckningar från deltagande observationer i klassrum, transkriberade fokusgruppsintervjuer med elever respektive lärare samt dokumentation av musik- och poesiprojektets upplägg.Materialet kommer att analyseras under våren. Först görs en tematisk innehållsanalys (Hsieh & Shannon, 2005). Därefter analyseras vilka modaliteter och estetiska uttrycksformer som integreras samt elevernas möjligheter till representation. Det finns flera argument för elevers poesiskapande då det kan leda till att de blir varse språkets makt (Heard, 1989), får använda sin fantasi samt uttrycka tankar, känslor och åsikter (Wolf, 2004; UNICEF, 2009). Vi önskar i detta bidrag presentera och problematisera de möjligheter och utmaningar som framkommer i relation till det undervisningsinnehåll som skapades.
27.	Schmidt, Johannes, et al. (författare) A new perspective on global renewable energy systems : why trade in energy carriers matters 2019 Ingår i: Energy & Environmental Science. - : Royal Society of Chemistry. - 1754-5692 .- 1754-5706. ; 12:7, s. 2022-2029 Tidskriftsartikel (refereegranskat)abstract Recent global modelling studies suggest a decline of long-distance trade in energy carriers in future global renewable energy systems, compared to today's fossil fuel based system. In contrast, we identify four drivers that facilitate trade of renewable energy carriers. These drivers may lead to trade volumes remaining at current levels or even to an increase during the transition to an energy system with very high shares of renewables. First, new land-efficient technologies for renewable fuel production become increasingly available and technically allow for long-distance trade in renewables. Second, regional differences in social acceptance and land availability for energy infrastructure support the development of renewable fuel import and export streams. Third, the economics of renewable energy systems, i.e. the different production conditions globally and the high costs of fully renewable regional electricity systems, will create opportunities for spatial arbitrage. Fourth, a reduction of stranded investments in the fossil fuel sector is possible by switching from fossil fuels to renewable fuel trade. The impact of these drivers on trade in renewable energy carriers is currently under-investigated by the global energy systems research community. The importance of the topic, in particular as trade can redistribute profits and losses of decarbonization and may hence support finding new partners in climate change mitigation negotiations, warrants further research efforts in this area therefore.
28.	Schmidt-Mende, Katharina, et al. (författare) Drug-disease interactions in Swedish senior primary care patients were dominated by non-steroid anti-inflammatory drugs and hypertension - a population-based registry study 2020 Ingår i: Scandinavian Journal of Primary Health Care. - : Informa UK Limited. - 0281-3432 .- 1502-7724. ; 38:3, s. 330-339 Tidskriftsartikel (refereegranskat)abstract Objective Drug-disease interactions (DDSIs) are present when a drug prescribed for one disease worsens a concomitant disease. The prevalence of DDSIs in older patients in primary care is largely unknown, as well as to what extent physicians individualize drug prescribing in relation to concomitant diseases. We therefore analysed the prevalence of DDSIs in older patients in primary care and explored to what extent physicians take possible DDSIs into account when prescribing. Design and Setting:Cross-sectional population-based register study in primary care in Region Stockholm, Sweden. Thirty-one DDSIs derived from Irish STOPP-START-Criteria were assessed. We derived data from a regional administrative healthcare database including information on all healthcare consultations and dispensed prescription drugs in the region. Data on demography, diagnoses, drug dispensations and healthcare consumption were extracted. Drugs were assessed during 2016. Subjects A total of 336,295 patients aged >= 65 registered with one of the 206 primary care practices in Region Stockholm. Main outcome measures Prevalence and prevalence differences for DDSIs. Results In 10.8% of older patients, at least one DDSI was observed. Non-steroidal anti-inflammatory drugs (NSAIDs) were implicated in more than 75% of cases. The most common DDSI was NSAID/hypertension (8.1%), followed by NSAID/cardiovascular disease and loop diuretics/urinary incontinence (both 0.7%). The use of NSAIDs among patients with heart failure or impaired renal function was 15% lower than among patients without these diseases. Conclusion DDSIs were present in every tenth older patient in primary care. Patients with cardiovascular disease receive NSAIDs to a lower extent, possibly indicating physician awareness of DDSI.
29.	Schmidt-Mende, Katharina (författare) Every coin has two sides : the challenge of addressing inappropriate prescribing in older patients in primary care 2019 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Background: Drug-related morbidity contributes to every tenth unplanned hospital admission in older patients. A way to address this problem is to identify and minimize potentially inappropriate prescribing (PIP). Two important types of PIP are the use of contraindicated or excessively dosed drugs in patients with renal impairment and drug-disease interactions, where a drug worsens a concomitant disease. It is largely unknown how commonly older patients (≥ 65) are exposed to these two types of PIP. Similarly, there is insufficient knowledge on how general practitioners (GPs) and nurses in primary care should address PIP in their older patients. One important step in understanding how to address PIP is to investigate GPs’ and nurses’ views on PIP and medication reviews. Aim: 1) To increase knowledge on how commonly older patients in primary care are exposed to PIP in relation to renal function and drug-disease interactions; 2) To examine if an intervention on medication reviews combining several evidencebased educational strategies is a valuable measure to address PIP in primary care; and 3) To understand GPs’ and nurses’ views on PIP and medication reviews. Material and methods: Two cross-sectional population-based studies (I+II) in patients aged ≥65 in primary care in Stockholm County were performed. Drug dispense was assessed during one year. PIP in relation to renal function was assessed in patients with chronic kidney disease stage 3 (n=30 372) or 4 (n=2161) according to CKD-EPI formula (I). Drug-disease interactions were analyzed among 336 295 patients. PIP was addressed in a cluster-randomized controlled trial including 69 primary care practices (III). The multifaceted educational intervention targeted GPs and nurses, with the aim to promote medication reviews in accordance with a new regulation, thus reduce PIP and unplanned healthcare use. Data (I-III) were derived from regional and national registers (diagnoses, drugs, healthcare use) and SCREAM database (creatinine). Qualitative data were collected after each educational session and explored with thematic analysis (IV). Results: I: Contraindicated medicines were used by 9% of patients with chronic kidney disease stage 3 compared to 38% with stage 4, and excessive dosing was present in 43% vs. 58%, respectively. II: Drug-disease interactions were found in 10.8 % of older adults, the most common was hypertension/NSAID. I+II: A limited number of potentially inappropriate medicines explained the majority of PIP, such as NSAIDs (I + II) and drugs acting on the renin-angiotensin-aldosterone system (I). III: Neither PIP nor unplanned healthcare decreased after a multifaceted educational intervention in primary care. IV: A possible explanation for this result is the complexity of prescribing in older patients, as expressed by GPs and nurses. Conclusions: In patients with impaired renal function, excessive dosing was more common than the use of contraindicated medicines. Drug-disease interactions were less common than PIP in relation to renal function. Both types of PIP seem manageable as only a few medicines are implicated. Medication reviews that address PIP in its entirety are difficult to implement in primary care and may not improve prescribing in older patients. According to GPs and nurses, the complexity of PIP is a major challenge. Their efforts to improve prescribing are undermined by this complexity. In view of the potential harm of PIP in older patients, it is crucial to continue research on how it may be decreased.
30.	Wachtler, Caroline, et al. (författare) “Returning to the core tasks”: a qualitative interview study about how general practitioners in home health care solved problems during the COVID-19 pandemic 2024 Ingår i: Scandinavian Journal of Primary Health Care. - 0281-3432 .- 1502-7724. ; 42:1, s. 91-100 Tidskriftsartikel (refereegranskat)abstract Objective: Optimizing care at home, or home health care (HHC), is necessary as the population of care-dependent older people receiving care at home steadily increases. The COVID-19 pandemic tested Swedish primary care professionals as they provided HHC for a population of very frail older homebound people, but a better understanding of what healthcare workers did to manage the crisis may be useful for the further development of HHC. In this study, we aimed to understand how HHC physicians solved the problems of providing home healthcare during the pandemic to learn lessons on how to improve future HHC. Methods: This is a qualitative study of individual interviews with 11 primary care physicians working in HHC (8 women) from 7 primary care practices in Region Stockholm, Sweden. Interviews were conducted between 1 December 2020, and 11 March 2021. The data were analyzed using inductive thematic analysis. Results: We generated an overarching theme in our analysis: Physicians focus on core tasks and professional values in response to crisis. This theme incorporated three underlying subthemes describing this response: physicians prioritize and resolve ethically challenging situations in new ways, cultivate the patient perspective, and build on existing teams. Conclusion: This study indicates that a healthcare system that gives HHC physicians agency to focus on core tasks and professional values could promote person-centered care.
31.	Watson, Hunna J., et al. (författare) Common Genetic Variation and Age of Onset of Anorexia Nervosa 2022 Ingår i: BIOLOGICAL PSYCHIATRY: GLOBAL OPEN SCIENCE. - : Elsevier BV. - 2667-1743. ; 2:4, s. 368-378 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Genetics and biology may influence the age of onset of anorexia nervosa (AN). The aims of this study were to determine whether common genetic variation contributes to age of onset of AN and to investigate the genetic associations between age of onset of AN and age at menarche.METHODS: A secondary analysis of the Psychiatric Genomics Consortium genome-wide association study (GWAS) of AN was performed, which included 9335 cases and 31,981 screened controls, all from European ancestries. We conducted GWASs of age of onset, early-onset AN (,13 years), and typical-onset AN, and genetic correlation, genetic risk score, and Mendelian randomization analyses.RESULTS: Two loci were genome-wide significant in the typical-onset AN GWAS. Heritability estimates (single nucleotide polymorphism-h2) were 0.01-0.04 for age of onset, 0.16-0.25 for early-onset AN, and 0.17-0.25 for typical-onset AN. Early-and typical-onset AN showed distinct genetic correlation patterns with putative risk factors for AN. Specifically, early-onset AN was significantly genetically correlated with younger age at menarche, and typical-onset AN was significantly negatively genetically correlated with anthropometric traits. Genetic risk scores for age of onset and early-onset AN estimated from independent GWASs significantly predicted age of onset. Mendelian randomization analysis suggested a causal link between younger age at menarche and early -onset AN.CONCLUSIONS: Our results provide evidence consistent with a common variant genetic basis for age of onset and implicate biological pathways regulating menarche and reproduction.
32.	Zhang, C., et al. (författare) LIPG-promoted lipid storage mediates adaptation to oxidative stress in breast cancer 2019 Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 145:4, s. 901-915 Tidskriftsartikel (refereegranskat)abstract Endothelial lipase (LIPG) is a cell surface associated lipase that displays phospholipase A1 activity towards phosphatidylcholine present in high‐density lipoproteins (HDL). LIPG was recently reported to be expressed in breast cancer and to support proliferation, tumourigenicity and metastasis. Here we show that severe oxidative stress leading to AMPK activation triggers LIPG upregulation, resulting in intracellular lipid droplet accumulation in breast cancer cells, which supports survival. Neutralizing oxidative stress abrogated LIPG upregulation and the concomitant lipid storage. In human breast cancer, high LIPG expression was observed in a limited subset of tumours and was significantly associated with shorter metastasis‐free survival in node‐negative, untreated patients. Moreover, expression of PLIN2 and TXNRD1 in these tumours indicated a link to lipid storage and oxidative stress. Altogether, our findings reveal a previously unrecognized role for LIPG in enabling oxidative stress‐induced lipid droplet accumulation in tumour cells that protects against oxidative stress, and thus supports tumour progression.

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