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1.	Blokland, G. A. M., et al. (author) Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders 2022 In: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 91:1, s. 102-117 Journal article (peer-reviewed)abstract Background: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. Methods: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. Results: Across disorders, genome-wide significant single nucleotide polymorphism–by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10−8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10−6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10−7; rs73033497, p = 8.8 × 10−7; rs7914279, p = 6.4 × 10−7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10−7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10−7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10−7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). Conclusions: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels. © 2021 Society of Biological Psychiatry
2.	Mullins, N., et al. (author) Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology 2021 In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 53, s. 817-829 Journal article (peer-reviewed)abstract Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies. Genome-wide association analyses of 41,917 bipolar disorder cases and 371,549 controls of European ancestry provide new insights into the etiology of this disorder and identify novel therapeutic leads and potential opportunities for drug repurposing.
3.	Jonsson, Lina, 1982, et al. (author) Characterisation of age and polarity at onset in bipolar disorder 2021 In: British Journal of Psychiatry. - : Royal College of Psychiatrists. - 0007-1250 .- 1472-1465. ; 219:6, s. 659-669 Journal article (peer-reviewed)abstract Background Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools. Aims To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics. Method Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts. Results Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (beta = -0.34 years, s.e. = 0.08), major depression (beta = -0.34 years, s.e. = 0.08), schizophrenia (beta = -0.39 years, s.e. = 0.08), and educational attainment (beta = -0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO. Conclusions AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
4.	Jia, X. M., et al. (author) Investigating rare pathogenic/likely pathogenic exonic variation in bipolar disorder 2021 In: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 26:9, s. 5239-5250 Journal article (peer-reviewed)abstract Bipolar disorder (BD) is a serious mental illness with substantial common variant heritability. However, the role of rare coding variation in BD is not well established. We examined the protein-coding (exonic) sequences of 3,987 unrelated individuals with BD and 5,322 controls of predominantly European ancestry across four cohorts from the Bipolar Sequencing Consortium (BSC). We assessed the burden of rare, protein-altering, single nucleotide variants classified as pathogenic or likely pathogenic (P-LP) both exome-wide and within several groups of genes with phenotypic or biologic plausibility in BD. While we observed an increased burden of rare coding P-LP variants within 165 genes identified as BD GWAS regions in 3,987 BD cases (meta-analysis OR = 1.9, 95% CI = 1.3-2.8, one-sided p = 6.0 x 10(-4)), this enrichment did not replicate in an additional 9,929 BD cases and 14,018 controls (OR = 0.9, one-side p = 0.70). Although BD shares common variant heritability with schizophrenia, in the BSC sample we did not observe a significant enrichment of P-LP variants in SCZ GWAS genes, in two classes of neuronal synaptic genes (RBFOX2 and FMRP) associated with SCZ or in loss-of-function intolerant genes. In this study, the largest analysis of exonic variation in BD, individuals with BD do not carry a replicable enrichment of rare P-LP variants across the exome or in any of several groups of genes with biologic plausibility. Moreover, despite a strong shared susceptibility between BD and SCZ through common genetic variation, we do not observe an association between BD risk and rare P-LP coding variants in genes known to modulate risk for SCZ.
5.	Kattge, Jens, et al. (author) TRY plant trait database - enhanced coverage and open access 2020 In: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188 Journal article (peer-reviewed)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.
6.	Mullins, Niamh, et al. (author) Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors 2022 In: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 91:3, s. 313-327 Journal article (peer-reviewed)abstract BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders.METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors.RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged.CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.
7.	Docherty, Anna R, et al. (author) GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors. 2023 In: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 180:10, s. 723-738 Journal article (peer-reviewed)abstract Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures.This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses.Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors.This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.
8.	Azevedo, Flavio, et al. (author) Social and moral psychology of COVID-19 across 69 countries 2023 In: Scientific Data. - : NATURE PORTFOLIO. - 2052-4463. ; 10:1 Journal article (peer-reviewed)abstract The COVID-19 pandemic has affected all domains of human life, including the economic and social fabric of societies. One of the central strategies for managing public health throughout the pandemic has been through persuasive messaging and collective behaviour change. To help scholars better understand the social and moral psychology behind public health behaviour, we present a dataset comprising of 51,404 individuals from 69 countries. This dataset was collected for the International Collaboration on Social & Moral Psychology of COVID-19 project (ICSMP COVID-19). This social science survey invited participants around the world to complete a series of moral and psychological measures and public health attitudes about COVID-19 during an early phase of the COVID-19 pandemic (between April and June 2020). The survey included seven broad categories of questions: COVID-19 beliefs and compliance behaviours; identity and social attitudes; ideology; health and well-being; moral beliefs and motivation; personality traits; and demographic variables. We report both raw and cleaned data, along with all survey materials, data visualisations, and psychometric evaluations of key variables.
9.	Maron, David J., et al. (author) Initial Invasive or Conservative Strategy for Stable Coronary Disease 2020 In: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 382:15, s. 1395-1407 Journal article (peer-reviewed)abstract Background: Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain.Methods: We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction.Results: Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32).Conclusions: Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, .) Patients with stable coronary disease were randomly assigned to an initial invasive strategy with angiography and revascularization if appropriate or to medical therapy alone. At 3.2 years, there was no significant difference between the groups with respect to the estimated rate of ischemic events. The findings were sensitive to the definition of myocardial infarction.
10.	Van Bavel, Jay J., et al. (author) National identity predicts public health support during a global pandemic 2022 In: Nature Communications. - : Nature Portfolio. - 2041-1723. ; 13:1 Journal article (peer-reviewed)abstract Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic. Changing collective behaviour and supporting non-pharmaceutical interventions is an important component in mitigating virus transmission during a pandemic. In a large international collaboration (Study 1, N = 49,968 across 67 countries), we investigated self-reported factors associated with public health behaviours (e.g., spatial distancing and stricter hygiene) and endorsed public policy interventions (e.g., closing bars and restaurants) during the early stage of the COVID-19 pandemic (April-May 2020). Respondents who reported identifying more strongly with their nation consistently reported greater engagement in public health behaviours and support for public health policies. Results were similar for representative and non-representative national samples. Study 2 (N = 42 countries) conceptually replicated the central finding using aggregate indices of national identity (obtained using the World Values Survey) and a measure of actual behaviour change during the pandemic (obtained from Google mobility reports). Higher levels of national identification prior to the pandemic predicted lower mobility during the early stage of the pandemic (r = -0.40). We discuss the potential implications of links between national identity, leadership, and public health for managing COVID-19 and future pandemics.
11.	Palmer, Duncan S., et al. (author) Exome sequencing in bipolar disorder identifies AKAP11 as a risk gene shared with schizophrenia 2022 In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 54:5, s. 541-547 Journal article (peer-reviewed)abstract We report results from the Bipolar Exome (BipEx) collaboration analysis of whole-exome sequencing of 13,933 patients with bipolar disorder (BD) matched with 14,422 controls. We find an excess of ultra-rare protein-truncating variants (PTVs) in patients with BD among genes under strong evolutionary constraint in both major BD subtypes. We find enrichment of ultra-rare PTVs within genes implicated from a recent schizophrenia exome meta-analysis (SCHEMA; 24,248 cases and 97,322 controls) and among binding targets of CHD8. Genes implicated from genome-wide association studies (GWASs) of BD, however, are not significantly enriched for ultra-rare PTVs. Combining gene-level results with SCHEMA, AKAP11 emerges as a definitive risk gene (odds ratio (OR) = 7.06, P = 2.83 × 10−9). At the protein level, AKAP-11 interacts with GSK3B, the hypothesized target of lithium, a primary treatment for BD. Our results lend support to BD’s polygenicity, demonstrating a role for rare coding variation as a significant risk factor in BD etiology.
12.	Sánchez Van Kammen, Mayte, et al. (author) Characteristics and Outcomes of Patients with Cerebral Venous Sinus Thrombosis in SARS-CoV-2 Vaccine-Induced Immune Thrombotic Thrombocytopenia 2021 In: JAMA Neurology. - : American Medical Association. - 2168-6149 .- 2168-6157. ; 78:11, s. 1314-1323 Journal article (peer-reviewed)abstract Importance: Thrombosis with thrombocytopenia syndrome (TTS) has been reported after vaccination with the SARS-CoV-2 vaccines ChAdOx1 nCov-19 (Oxford-AstraZeneca) and Ad26.COV2.S (Janssen/Johnson & Johnson).Objective: To describe the clinical characteristics and outcome of patients with cerebral venous sinus thrombosis (CVST) after SARS-CoV-2 vaccination with and without TTS.Design, Setting, and Participants: This cohort study used data from an international registry of consecutive patients with CVST within 28 days of SARS-CoV-2 vaccination included between March 29 and June 18, 2021, from 81 hospitals in 19 countries. For reference, data from patients with CVST between 2015 and 2018 were derived from an existing international registry. Clinical characteristics and mortality rate were described for adults with (1) CVST in the setting of SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia, (2) CVST after SARS-CoV-2 vaccination not fulling criteria for TTS, and (3) CVST unrelated to SARS-CoV-2 vaccination.Exposures: Patients were classified as having TTS if they had new-onset thrombocytopenia without recent exposure to heparin, in accordance with the Brighton Collaboration interim criteria.Main Outcomes and Measures: Clinical characteristics and mortality rate.Results: Of 116 patients with postvaccination CVST, 78 (67.2%) had TTS, of whom 76 had been vaccinated with ChAdOx1 nCov-19; 38 (32.8%) had no indication of TTS. The control group included 207 patients with CVST before the COVID-19 pandemic. A total of 63 of 78 (81%), 30 of 38 (79%), and 145 of 207 (70.0%) patients, respectively, were female, and the mean (SD) age was 45 (14), 55 (20), and 42 (16) years, respectively. Concomitant thromboembolism occurred in 25 of 70 patients (36%) in the TTS group, 2 of 35 (6%) in the no TTS group, and 10 of 206 (4.9%) in the control group, and in-hospital mortality rates were 47% (36 of 76; 95% CI, 37-58), 5% (2 of 37; 95% CI, 1-18), and 3.9% (8 of 207; 95% CI, 2.0-7.4), respectively. The mortality rate was 61% (14 of 23) among patients in the TTS group diagnosed before the condition garnered attention in the scientific community and 42% (22 of 53) among patients diagnosed later.Conclusions and Relevance: In this cohort study of patients with CVST, a distinct clinical profile and high mortality rate was observed in patients meeting criteria for TTS after SARS-CoV-2 vaccination..
13.	Scutelnic, Adrian, et al. (author) Management of Cerebral Venous Thrombosis Due to Adenoviral COVID-19 Vaccination. 2022 In: Annals of neurology. - : Wiley. - 1531-8249 .- 0364-5134. ; 92:4, s. 562-573 Journal article (peer-reviewed)abstract Cerebral venous thrombosis (CVT) caused by vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare adverse effect of adenovirus-based severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) vaccines. In March 2021, after autoimmune pathogenesis of VITT was discovered, treatment recommendations were developed. These comprised immunomodulation, non-heparin anticoagulants, and avoidance of platelet transfusion. The aim of this study was to evaluate adherence to these recommendations and its association with mortality.We used data from an international prospective registry of patients with CVT after the adenovirus-based SARS-CoV-2 vaccination. We analyzed possible, probable, or definite VITT-CVT cases included until January 18, 2022. Immunomodulation entailed administration of intravenous immunoglobulins and/or plasmapheresis.Ninety-nine patients with VITT-CVT from 71 hospitals in 17 countries were analyzed. Five of 38 (13%), 11 of 24 (46%), and 28 of 37 (76%) of the patients diagnosed in March, April, and from May onward, respectively, were treated in-line with VITT recommendations (p<0.001). Overall, treatment according to recommendations had no statistically significant influence on mortality (14/44 [32%] vs 29/55 [52%], adjusted odds ratio [OR]=0.43, 95% confidence interval [CI]=0.16-1.19). However, patients who received immunomodulation had lower mortality (19/65 [29%] vs 24/34 [70%], adjusted OR=0.19, 95% CI=0.06-0.58). Treatment with non-heparin anticoagulants instead of heparins was not associated with lower mortality (17/51 [33%] vs 13/35 [37%], adjusted OR=0.70, 95% CI=0.24-2.04). Mortality was also not significantly influenced by platelet transfusion (17/27 [63%] vs 26/72 [36%], adjusted OR=2.19, 95% CI=0.74-6.54).In patients with VITT-CVT, adherence to VITT treatment recommendations improved over time. Immunomodulation seems crucial for reducing mortality of VITT-CVT. ANN NEUROL 2022;92:562-573.
14.	Yaakub, S. N., et al. (author) On brain atlas choice and automatic segmentation methods: a comparison of MAPER & FreeSurfer using three atlas databases 2020 In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1 Journal article (peer-reviewed)abstract Several automatic image segmentation methods and few atlas databases exist for analysing structural T1-weighted magnetic resonance brain images. The impact of choosing a combination has not hitherto been described but may bias comparisons across studies. We evaluated two segmentation methods (MAPER and FreeSurfer), using three publicly available atlas databases (Hammers_mith, Desikan-Killiany-Tourville, and MICCAI 2012 Grand Challenge). For each combination of atlas and method, we conducted a leave-one-out cross-comparison to estimate the segmentation accuracy of FreeSurfer and MAPER. We also used each possible combination to segment two datasets of patients with known structural abnormalities (Alzheimer’s disease (AD) and mesial temporal lobe epilepsy with hippocampal sclerosis (HS)) and their matched healthy controls. MAPER was better than FreeSurfer at modelling manual segmentations in the healthy control leave-one-out analyses in two of the three atlas databases, and the Hammers_mith atlas database transferred to new datasets best regardless of segmentation method. Both segmentation methods reliably identified known abnormalities in each patient group. Better separation was seen for FreeSurfer in the AD and left-HS datasets, and for MAPER in the right-HS dataset. We provide detailed quantitative comparisons for multiple anatomical regions, thus enabling researchers to make evidence-based decisions on their choice of atlas and segmentation method. © 2020, The Author(s).
15.	Chakroborty, Anand, et al. (author) Modified Hederagenin Derivatives Demonstrate Ex Vivo Anthelmintic Activity against Fasciola hepatica 2023 In: Pharmaceutics. - : MDPI AG. - 1999-4923. ; 15:7 Journal article (peer-reviewed)abstract Infection with Fasciola hepatica (liver fluke) causes fasciolosis (or fascioliasis) and poses a considerable economic as well as welfare burden to both the agricultural and animal health sectors. Here, we explore the ex vivo anthelmintic potential of synthetic derivatives of hederagenin, isolated in bulk from Hedera helix. Thirty-six compounds were initially screened against F. hepatica newly excysted juveniles (NEJs) of the Italian strain. Eleven of these compounds were active against NEJs and were selected for further study, using adult F. hepatica derived from a local abattoir (provenance unknown). From these eleven compounds, six demonstrated activity and were further assessed against immature liver flukes of the Italian strain. Subsequently, the most active compounds (n = 5) were further evaluated in ex vivo dose response experiments against adult Italian strain liver flukes. Overall, MC042 was identified as the most active molecule and the EC50 obtained from immature and adult liver fluke assays (at 24 h post co-culture) are estimated as 1.07 & mu;M and 13.02 & mu;M, respectively. When compared to the in vitro cytotoxicity of MDBK bovine cell line, MC042 demonstrated the highest anthelmintic selectivity (44.37 for immature and 3.64 for adult flukes). These data indicate that modified hederagenins display properties suitable for further investigations as candidate flukicides.
16.	Fjermestad, Krister W., et al. (author) Therapist Alliance-Building Behaviors, Alliance, and Outcomes in Cognitive Behavioral Treatment for Youth Anxiety Disorders 2021 In: Journal of clinical child and adolescent psychology (Print). - : Informa UK Limited. - 1537-4416 .- 1537-4424. ; 50:2, s. 229-242 Journal article (peer-reviewed)abstract Objective: The alliance influences outcomes in CBT for youth anxiety disorders. Thus, knowledge about how therapists can enhance the alliance is needed.Method: Seventy-three youth with anxiety diagnoses (M age = 11.5 years, SD = 2.2; range 8 to 15 years; 47.9% boys; 90.4% white-European) participated in 10-session cognitive behavioral therapy in community clinics. Therapist alliance-building behaviors in session 2 was reliably coded with the observer-rated Adolescent Alliance-Building Behavior Scale (Revised) (AABS(R)). Alliance was measured as youth- and therapist-rated alliance, and youth-therapist alliance discrepancy in session 3. Outcomes were diagnostic recovery and anxiety symptom reduction at post-treatment and one-year follow-up, and treatment dropout. We examined the direct effects of alliance-building on alliance, alliance on outcomes, and alliance-building on outcomes in multilevel mediation models, and between- versus within-therapist variance across these effects.Results: The alliance-building behaviors collaborate, present treatment model, and explore motivation positively predicted alliance, whereas actively structuring the session (i.e., dominating) negatively predicted alliance. The alliance-building behaviors attend to experience, collaborate, explore motivation, praise, and support positively predicted outcomes. The alliance-building behaviors present treatment model, express positive expectations, explore cognitions, and support negatively predicted outcomes. The effect of collaborate on symptom reduction was mediated by youth-therapist alliance discrepancy. There was almost zero between-therapist variance in alliance-building, and considerable within-therapist variance.Conclusion: Therapist alliance-building behaviors were directly (positively and negatively) associated with alliance and/or outcomes, with only one effect mediated by alliance. Alliance-building behaviors varied far more within therapists (i.e., across clients) than between therapists.
17.	Humbert, Marc, et al. (author) 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension 2023 In: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 61:1 Journal article (peer-reviewed)
18.	Kuhrmann, Marco, et al. (author) What Makes Agile Software Development Agile 2022 In: IEEE Transactions on Software Engineering. - 0098-5589 .- 1939-3520. ; 48:9, s. 3523-3539 Journal article (peer-reviewed)abstract Together with many success stories, promises such as the increase in production speed and the improvement in stakeholders' collaboration have contributed to making agile a transformation in the software industry in which many companies want to take part. However, driven either by a natural and expected evolution or by contextual factors that challenge the adoption of agile methods as prescribed by their creator(s), software processes in practice mutate into hybrids over time. Are these still agile In this article, we investigate the question: what makes a software development method agile We present an empirical study grounded in a large-scale international survey that aims to identify software development methods and practices that improve or tame agility. Based on 556 data points, we analyze the perceived degree of agility in the implementation of standard project disciplines and its relation to used development methods and practices. Our findings suggest that only a small number of participants operate their projects in a purely traditional or agile manner (under 15%). That said, most project disciplines and most practices show a clear trend towards increasing degrees of agility. Compared to the methods used to develop software, the selection of practices has a stronger effect on the degree of agility of a given discipline. Finally, there are no methods or practices that explicitly guarantee or prevent agility. We conclude that agility cannot be defined solely at the process level. Additional factors need to be taken into account when trying to implement or improve agility in a software company. Finally, we discuss the field of software process-related research in the light of our findings and present a roadmap for future research.
19.	McCloy, John S., et al. (author) Reproduction of melting behavior for vitrified hillforts based on amphibolite, granite, and basalt lithologies 2021 In: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11 Journal article (peer-reviewed)abstract European Bronze and Iron Age vitrified hillforts have been known since the 1700s, but archaeological interpretations regarding their function and use are still debated. We carried out a series of experiments to constrain conditions that led to the vitrification of the inner wall rocks in the hillfort at Broborg, Sweden. Potential source rocks were collected locally and heat treated in the laboratory, varying maximum temperature, cooling rate, and starting particle size. Crystalline and amorphous phases were quantified using X-ray diffraction both in situ, during heating and cooling, and ex situ, after heating and quenching. Textures, phases, and glass compositions obtained were compared with those for rock samples from the vitrified part of the wall, as well as with equilibrium crystallization calculations. ‘Dark glass’ and its associated minerals formed from amphibolite or dolerite rocks melted at 1000–1200 °C under reducing atmosphere then slow cooled. ‘Clear glass’ formed from non-equilibrium partial melting of feldspar in granitoid rocks. This study aids archaeological forensic investigation of vitrified hillforts and interpretation of source rock material by mapping mineralogical changes and glass production under various heating conditions.
20.	Nava-Farias, Lorena, et al. (author) Applying laboratory methods for durability assessment of vitrified material to archaeological samples 2021 In: npj Materials Degradation. - : Springer Nature. - 2397-2106. ; 5:1 Journal article (peer-reviewed)abstract Laboratory testing used to assess the long-term chemical durability of nuclear waste forms may not be applicable to disposal because the accelerated conditions may not represent disposal conditions. To address this, we examine the corrosion of vitrified archeological materials excavated from the near surface of a ~1500-year old Iron Age Swedish hillfort, Broborg, as an analog for the disposal of vitrified nuclear waste. We compare characterized site samples with corrosion characteristics generated by standard laboratory durability test methods including the product consistency test (PCT), the vapor hydration test (VHT), and the EPA Method 1313 test. Results show that the surficial layer of the Broborg samples resulting from VHT displays some similarities to the morphology of the surficial layer formed over longer timescales in the environment. This work provides improved understanding of long-term glass corrosion behavior in terms of the thickness, morphology, and chemistry of the surficial features that are formed.
21.	Pilla, Rachel M., et al. (author) Global data set of long-term summertime vertical temperature profiles in 153 lakes 2021 In: Scientific Data. - : Springer Nature. - 2052-4463. ; 8:1 Journal article (peer-reviewed)abstract Climate change and other anthropogenic stressors have led to long-term changes in the thermal structure, including surface temperatures, deepwater temperatures, and vertical thermal gradients, in many lakes around the world. Though many studies highlight warming of surface water temperatures in lakes worldwide, less is known about long-term trends in full vertical thermal structure and deepwater temperatures, which have been changing less consistently in both direction and magnitude. Here, we present a globally-expansive data set of summertime in-situ vertical temperature profiles from 153 lakes, with one time series beginning as early as 1894. We also compiled lake geographic, morphometric, and water quality variables that can influence vertical thermal structure through a variety of potential mechanisms in these lakes. These long-term time series of vertical temperature profiles and corresponding lake characteristics serve as valuable data to help understand changes and drivers of lake thermal structure in a time of rapid global and ecological change.
22.	Rauhala, A S, et al. (author) Which factors are associated with COVID-19 infection incidence in care services for older people in Nordic countries? : A cross-sectional survey 2022 In: Scandinavian Journal of Public Health. - : SAGE Publications. - 1403-4948 .- 1651-1905. Journal article (peer-reviewed)abstract Aims: To investigate the differences between Sweden, Denmark, Finland and Norway regarding residential/home care units' and frontline managers' background factors, the resources allocated and measures taken during the initial phases of the COVID-19 pandemic, and whether and how these differences were associated with COVID-19 among older people in residential/home units.Methods: Register- and survey-based data. Responses from managers in municipal and private residential/home units. Number of municipal COVID-19 cases from national registries. Multilevel logistic multivariate regression analysis with presence of COVID-19 among older people in residential/home units as the outcome variable.Results: The proportions of residential/home units with client COVID-19 cases, mid-March-April 2020 were Denmark 22.7%, Finland 9.0%, Norway 9.7% and Sweden 38.8%, most cases found in clusters. The proportions were similar among employees. Client likelihood of having COVID-19 was six-fold higher if the employees had COVID-19. Mean client cases per residential/home unit were Denmark 0.78, Finland 0.46, Norway 0.22 and Sweden 1.23. For the same municipal infection incidence class, Sweden's mean client infection levels were three-fold those of other countries. The regression analysis variables country, municipal COVID-19 incidence proportion, and care type were associated with client cases at p <= .001. Compared with Denmark, the odds ratios (ORs) for Sweden, Norway and Finland were 1.86, 0.41 and 0.35 respectively. The variable difficulties in preventive testing had an OR of 1.56, p <= .05.Conclusions: Municipal COVID-19 incidence, employee cases, and the lack of testing resources somewhat explained the confirmed COVID-19 cases among older people in residential/home units. A two- to five-fold unexplained inter-country difference in ORs in the multivariate analyses was notable. The level of protection of vulnerable older clients in municipal and private residential/home units differed between the included countries.
23.	Saba, Luca, et al. (author) Carotid plaque-RADS : a novel stroke risk classification system 2024 In: JACC Cardiovascular Imaging. - : Elsevier. - 1936-878X .- 1876-7591. ; 17:1, s. 62-75 Journal article (peer-reviewed)abstract Background: Carotid artery atherosclerosis is highly prevalent in the general population and is a well-established risk factor for acute ischemic stroke. Although the morphological characteristics of vulnerable plaques are well recognized, there is a lack of consensus in reporting and interpreting carotid plaque features.Objectives: The aim of this document is to establish a consistent and comprehensive approach for imaging and reporting carotid plaque by introducing the Plaque–Reporting and Data System (RADS) score.Methods: A panel of experts recognized the necessity to develop a classification system for carotid plaque and its defining characteristics. Using a multimodality analysis approach, the Plaque-RADS categories were established through consensus, drawing on existing published reports.Results: The authors present a universal classification that is applicable to both researchers and clinicians. The Plaque-RADS score offers a morphological assessment in addition to the prevailing quantitative parameter of “stenosis.” The Plaque-RADS score spans from grade 1 (indicating complete absence of plaque) to grade 4 (representing complicated plaque). Accompanying visual examples are included to facilitate a clear understanding of the Plaque-RADS categories.Conclusions: Plaque-RADS is a standardized and reliable system of reporting carotid plaque composition and morphology via different imaging modalities, such as ultrasound, computed tomography, and magnetic resonance imaging. This scoring system has the potential to help in the precise identification of patients who may benefit from exclusive medical intervention and those who require alternative treatments, thereby enhancing patient care. A standardized lexicon and structured reporting promise to enhance communication between radiologists, referring clinicians, and scientists.
24.	Srikrishna, Meera, et al. (author) CT-based volumetric measures obtained through deep learning: Association with biomarkers of neurodegeneration 2024 In: Alzheimers & Dementia. - 1552-5260. ; 20:1, s. 629-640 Journal article (peer-reviewed)abstract INTRODUCTIONCranial computed tomography (CT) is an affordable and widely available imaging modality that is used to assess structural abnormalities, but not to quantify neurodegeneration. Previously we developed a deep-learning-based model that produced accurate and robust cranial CT tissue classification.MATERIALS AND METHODSWe analyzed 917 CT and 744 magnetic resonance (MR) scans from the Gothenburg H70 Birth Cohort, and 204 CT and 241 MR scans from participants of the Memory Clinic Cohort, Singapore. We tested associations between six CT-based volumetric measures (CTVMs) and existing clinical diagnoses, fluid and imaging biomarkers, and measures of cognition.RESULTSCTVMs differentiated cognitively healthy individuals from dementia and prodromal dementia patients with high accuracy levels comparable to MR-based measures. CTVMs were significantly associated with measures of cognition and biochemical markers of neurodegeneration.DISCUSSIONThese findings suggest the potential future use of CT-based volumetric measures as an informative first-line examination tool for neurodegenerative disease diagnostics after further validation.HIGHLIGHTSComputed tomography (CT)-based volumetric measures can distinguish between patients with neurodegenerative disease and healthy controls, as well as between patients with prodromal dementia and controls.CT-based volumetric measures associate well with relevant cognitive, biochemical, and neuroimaging markers of neurodegenerative diseases.Model performance, in terms of brain tissue classification, was consistent across two cohorts of diverse nature.Intermodality agreement between our automated CT-based and established magnetic resonance (MR)-based image segmentations was stronger than the agreement between visual CT and MR imaging assessment.
25.	Steinbart, David, et al. (author) Automatic and manual segmentation of the piriform cortex: Method development and validation in patients with temporal lobe epilepsy and Alzheimer's disease. 2023 In: Human brain mapping. - 1065-9471 .- 1097-0193. ; 44:8, s. 3196-3209 Journal article (peer-reviewed)abstract The piriform cortex (PC) is located at the junction of the temporal and frontal lobes. It is involved physiologically in olfaction as well as memory and plays an important role in epilepsy. Its study at scale is held back by the absence of automatic segmentation methods on MRI. We devised a manual segmentation protocol for PC volumes, integrated those manually derived images into the Hammers Atlas Database (n=30) and used an extensively validated method (multi-atlas propagation with enhanced registration, MAPER) for automatic PC segmentation. We applied automated PC volumetry to patients with unilateral temporal lobe epilepsy with hippocampal sclerosis (TLE; n=174 including n=58 controls) and to the Alzheimer's Disease Neuroimaging Initiative cohort (ADNI; n=151, of whom with mild cognitive impairment (MCI), n=71; Alzheimer's disease (AD), n=33; controls, n=47). In controls, mean PC volume was 485mm3 on the right and 461mm3 on the left. Automatic and manual segmentations overlapped with a Jaccard coefficient (intersection/union) of ~0.5 and a mean absolute volume difference of ~22mm3 in healthy controls, ~0.40/ ~28mm3 in patients with TLE, and~0.34/~29mm3 in patients with AD. In patients with TLE, PC atrophy lateralised to the side of hippocampal sclerosis (p<.001). In patients with MCI and AD, PC volumes were lower than those of controls bilaterally (p<.001). Overall, we have validated automatic PC volumetry in healthy controls and two types of pathology. The novel finding of early atrophy of PC at the stage of MCI possibly adds a novel biomarker. PC volumetry can now be applied at scale.
26.	Treydte, Kerstin, et al. (author) Recent human-induced atmospheric drying across Europe unprecedented in the last 400 years 2024 In: NATURE GEOSCIENCE. - 1752-0894 .- 1752-0908. ; 17, s. 58-65 Journal article (peer-reviewed)abstract The vapor pressure deficit reflects the difference between how much moisture the atmosphere could and actually does hold, a factor that fundamentally affects evapotranspiration, ecosystem functioning, and vegetation carbon uptake. Its spatial variability and long-term trends under natural versus human-influenced climate are poorly known despite being essential for predicting future effects on natural ecosystems and human societies such as crop yield, wildfires, and health. Here we combine regionally distinct reconstructions of pre-industrial summer vapor pressure deficit variability from Europe's largest oxygen-isotope network of tree-ring cellulose with observational records and Earth system model simulations with and without human forcing included. We demonstrate that an intensification of atmospheric drying during the recent decades across different European target regions is unprecedented in a pre-industrial context and that it is attributed to human influence with more than 98% probability. The magnitude of this trend is largest in Western and Central Europe, the Alps and Pyrenees region, and the smallest in southern Fennoscandia. In view of the extreme drought and compound events of the recent years, further atmospheric drying poses an enhanced risk to vegetation, specifically in the densely populated areas of the European temperate lowlands. The atmosphere has dried across most regions of Europe in recent decades, a trend that can be attributed primarily to human impacts, according to tree ring records spanning 400 years and Earth system model simulations.
27.	Windhorst, Rogier A., et al. (author) JWST PEARLS. Prime extragalactic areas for reionization and lensing science : project overview and first results 2023 In: Astronomical Journal. - : Institute of Physics (IOP). - 0004-6256 .- 1538-3881. ; 165:1 Journal article (peer-reviewed)abstract We give an overview and describe the rationale, methods, and first results from NIRCam images of the JWST “Prime Extragalactic Areas for Reionization and Lensing Science” (PEARLS) project. PEARLS uses up to eight NIRCam filters to survey several prime extragalactic survey areas: two fields at the North Ecliptic Pole (NEP); seven gravitationally lensing clusters; two high redshift protoclusters; and the iconic backlit VV 191 galaxy system to map its dust attenuation. PEARLS also includes NIRISS spectra for one of the NEP fields and NIRSpec spectra of two high-redshift quasars. The main goal of PEARLS is to study the epoch of galaxy assembly, active galactic nucleus (AGN) growth, and First Light. Five fields—the JWST NEP Time-Domain Field (TDF), IRAC Dark Field, and three lensing clusters—will be observed in up to four epochs over a year. The cadence and sensitivity of the imaging data are ideally suited to find faint variable objects such as weak AGN, high-redshift supernovae, and cluster caustic transits. Both NEP fields have sightlines through our Galaxy, providing significant numbers of very faint brown dwarfs whose proper motions can be studied. Observations from the first spoke in the NEP TDF are public. This paper presents our first PEARLS observations, their NIRCam data reduction and analysis, our first object catalogs, the 0.9–4.5 μm galaxy counts and Integrated Galaxy Light. We assess the JWST sky brightness in 13 NIRCam filters, yielding our first constraints to diffuse light at 0.9–4.5 μm. PEARLS is designed to be of lasting benefit to the community.
28.	Allesøe, Rosa Lundbye, et al. (author) Discovery of drug–omics associations in type 2 diabetes with generative deep-learning models 2023 In: Nature Biotechnology. - : Springer Nature. - 1087-0156 .- 1546-1696. ; 41:3, s. 399-408 Journal article (peer-reviewed)abstract The application of multiple omics technologies in biomedical cohorts has the potential to reveal patient-level disease characteristics and individualized response to treatment. However, the scale and heterogeneous nature of multi-modal data makes integration and inference a non-trivial task. We developed a deep-learning-based framework, multi-omics variational autoencoders (MOVE), to integrate such data and applied it to a cohort of 789 people with newly diagnosed type 2 diabetes with deep multi-omics phenotyping from the DIRECT consortium. Using in silico perturbations, we identified drug–omics associations across the multi-modal datasets for the 20 most prevalent drugs given to people with type 2 diabetes with substantially higher sensitivity than univariate statistical tests. From these, we among others, identified novel associations between metformin and the gut microbiota as well as opposite molecular responses for the two statins, simvastatin and atorvastatin. We used the associations to quantify drug–drug similarities, assess the degree of polypharmacy and conclude that drug effects are distributed across the multi-omics modalities.
29.	Andersson, Claes, et al. (author) Mebendazole is unique among tubulin-active drugs in activating the MEK-ERK pathway 2020 In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1 Journal article (peer-reviewed)abstract We recently showed that the anti-helminthic compound mebendazole (MBZ) has immunomodulating activity in monocyte/macrophage models and induces ERK signalling. In the present study we investigated whether MBZ induced ERK activation is shared by other tubulin binding agents (TBAs) and if it is observable also in other human cell types. Curated gene signatures for a panel of TBAs in the LINCS Connectivity Map (CMap) database showed a unique strong negative correlation of MBZ with MEK/ERK inhibitors indicating ERK activation also in non-haematological cell lines. L1000 gene expression signatures for MBZ treated THP-1 monocytes also connected negatively to MEK inhibitors. MEK/ERK phosphoprotein activity testing of a number of TBAs showed that only MBZ increased the activity in both THP-1 monocytes and PMA differentiated macrophages. Distal effects on ERK phosphorylation of the substrate P90RSK and release of IL1B followed the same pattern. The effect of MBZ on MEK/ERK phosphorylation was inhibited by RAF/MEK/ERK inhibitors in THP-1 models, CD3/IL2 stimulated PBMCs and a MAPK reporter HEK-293 cell line. MBZ was also shown to increase ERK activity in CD4+ T-cells from lupus patients with known defective ERK signalling. Given these mechanistic features MBZ is suggested suitable for treatment of diseases characterized by defective ERK signalling, notably difficult to treat autoimmune diseases.
30.	Cavallaro, Sara, et al. (author) Multiplexed electrokinetic sensor for detection and therapy monitoring of extracellular vesicles from liquid biopsies of non-small-cell lung cancer patients 2021 In: Biosensors & bioelectronics. - : Elsevier. - 0956-5663 .- 1873-4235. ; 193 Journal article (peer-reviewed)abstract Liquid biopsies based on extracellular vesicles (EVs) represent a promising tool for treatment monitoring of tumors, including non-small-cell lung cancers (NSCLC). In this study, we report on a multiplexed electrokinetic sensor for surface protein profiling of EVs from clinical samples. The method detects the difference in the streaming current generated by EV binding to the surface of a functionalized microcapillary, thereby estimating the expression level of a marker. Using multiple microchannels functionalized with different antibodies in a parallel fluidic connection, we first demonstrate the capacity for simultaneous detection of multiple surface markers in small EVs (sEVs) from NSCLC cells. To investigate the prospects of liquid biopsies based on EVs, we then apply the method to profile sEVs isolated from the pleural effusion (PE) fluids of five NSCLC patients with different genomic alterations (ALK, KRAS or EGFR) and applied treatments (chemotherapy, EGFR- or ALKtyrosine kinase inhibitors). The vesicles were targeted against CD9, as well as EGFR and PD-L1, two treatment targets in NSCLC. The electrokinetic signals show detection of these markers on sEVs, highlighting distinct interpatient differences, e.g., increased EGFR levels in sEVs from a patient with EGFR mutation as compared to an ALK-fusion one. The sensors also detect differences in PD-L1 expressions. The analysis of sEVs from a patient prior and post ALK-TKI crizotinib treatment reveals significant increases in the expressions of some markers (EGFR and PD-L1). These results hold promise for the application of the method for tumor treatment monitoring based on sEVs from patient liquid biopsies.
31.	Chen, Kaixuan, et al. (author) Optimisation of deformation properties in as-cast copper by microstructural engineering. Part II. Mechanical properties 2020 In: Journal of Alloys and Compounds. - : Elsevier Ltd. - 0925-8388 .- 1873-4669. ; 812 Journal article (peer-reviewed)abstract The microstructure evolution in the as-cast pure Cu and Cu-(1.0–3.0)Fe-0.5Co and Cu-1.5Fe-0.1Sn (wt. %) alloys was characterised in the previous work. Herein, the plastic deformation characteristics were examined by uniaxial tensile tests at room temperature. Along with the microstructure evolution, the yield strength increased with increasing Fe content and reached a peak value at 1.5 wt % Fe, but thereafter decreased with the further addition of Fe in the Cu–Fe–Co alloys. Nevertheless, the tensile strength and elongation synchronously improve with increasing Fe content. In particular, the Cu-1.5Fe-0.1Sn alloy achieved the optimal strength–ductility combination. In terms of the strengthening mechanism, the (Fe, Co)- or (Fe, Sn)-doped copper encouraged impediment, trapping, and storage of dislocations by the iron-rich nanoparticles and grain boundaries, which enhanced the strength and sustained the work hardening and elongation. The evolution of mechanical properties under an alloying effect was quantitatively described by the strengthening models. The results indicate that the optimum balance between strength and ductility was achieved by designing a microstructure containing fine grains, intragranular smaller spherical nanoparticles, and a minor solute element with higher misfit and higher growth restriction effect. The necessities for engineering a microstructure to achieve simultaneously strong and ductile bulk metals were discussed.
32.	Eichenlaub, Manuel, et al. (author) Comparator Data Characteristics and Testing Procedures for the Clinical Performance Evaluation of Continuous Glucose Monitoring Systems 2024 In: Diabetes Technology & Therapeutics. - : Mary Ann Liebert. - 1520-9156 .- 1557-8593. ; 26:4, s. 263-275 Journal article (peer-reviewed)abstract Comparing the performance of different continuous glucose monitoring (CGM) systems is challenging due to the lack of comprehensive guidelines for clinical study design. In particular, the absence of concise requirements for the distribution of comparator (reference) blood glucose (BG) concentrations and their rate of change (RoC), that are used to evaluate CGM performance, impairs comparability. For this article, several experts in the field of CGM performance testing have collaborated to propose characteristics of the distribution of comparator measurements that should be collected during CGM performance testing. Specifically, it is proposed that at least 7.5% of comparator BG concentrations are <70 mg/dL (3.9 mmol/L) and >300 mg/dL (16.7 mmol/L), respectively and that at least 7.5% of BG-RoC combinations indicate fast BG changes with impending hypo- or hyperglycemia, respectively. These proposed characteristics of the comparator data can facilitate the harmonization of testing conditions across different studies and CGM systems and ensure that the most relevant scenarios representing real-life situations are established during performance testing. In addition, a study protocol and testing procedure for the manipulation of glucose levels is suggested that enables the collection of comparator data with these characteristics. This work is an important step towards establishing a future standard for the performance evaluation of CGM systems.
33.	Gerdtsson, Axel, et al. (author) Initial surveillance in men with marker negative clinical stage IIA non-seminomatous germ cell tumours 2024 In: BJU INTERNATIONAL. - : John Wiley & Sons. - 1464-4096 .- 1464-410X. Journal article (peer-reviewed)abstract Objectives To assess whether extended surveillance with repeated computed tomography (CT) scans for patients with clinical stage IIA (CS IIA; <2 cm abdominal node involvement) and negative markers (Mk-) non-seminomatous germ cell tumours (NSGCTs) can identify those with true CS I. To assess the rate of benign lymph nodes, teratoma, and viable cancer in retroperitoneal lymph node dissection (RPLND) histopathology for patients with CS IIA Mk- NSGCT. Patients and methods Observational prospective population-based study of patients diagnosed 2008-2019 with CS IIA Mk- NSGCT in the Swedish and Norwegian Testicular Cancer Group (SWENOTECA) registry. Patients were managed with surveillance, with CT scans, and tumour markers every sixth week for a maximum of 18 weeks. Patients with radiological regression were treated as CS I, if progression with chemotherapy, and remaining CS IIA Mk- disease with RPLND. The end-point was the number and percentage of patients down-staged to CS I on surveillance and rate of RPLND histopathology presented as benign, teratoma, or viable cancer. Results Overall, 126 patients with CS IIA Mk- NSGCT were included but 41 received therapy upfront. After surveillance for a median (range) of 6 (6-18) weeks, 23/85 (27%) patients were in true CS I and four (5%) progressed. Of the remaining 58 patients with lasting CS IIA Mk- NSGCT, 16 received chemotherapy and 42 underwent RPLND. The RPLND histopathology revealed benign lymph nodes in 11 (26%), teratoma in two (6%), and viable cancer in 29 (70%) patients. Conclusions Surveillance with repeated CT scans can identify patients in true CS I, thus avoiding overtreatment. The RPLND histopathology in patients with CS IIA Mk- NSGCT had a high rate of cancer and a low rate of teratoma.
34.	Gerdtsson, Axel, et al. (author) Surgical Complications in Postchemotherapy Retroperitoneal Lymph Node Dissection for Nonseminoma Germ Cell Tumour : A Population-based Study from the Swedish Norwegian Testicular Cancer Group 2020 In: European Urology Oncology. - : Elsevier BV. - 2588-9311. ; 3:3, s. 382-389 Journal article (peer-reviewed)abstract BACKGROUND: Reports on perioperative complications after postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) for nonseminoma germ cell tumour (NSGCT) are from experienced single centres, with a lack of population-based studies. OBJECTIVE: To assess the complications of bilateral and unilateral PC-RPLND. DESIGN, SETTING, AND PARTICIPANTS: A prospective, population-based, observational multicentre study included all patients with NSGCT who underwent PC-RPLND in Norway and Sweden during 2007-2014. Of a total of 318 patients, 87 underwent bilateral PC-RPLND and 231 underwent unilateral PC-RPLND. The median follow-up was 6 yr. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Bilateral and unilateral PC-RPLND were compared for the outcomes of intra- and postoperative complications (graded by Clavien-Dindo) and retrograde ejaculation (with or without nerve-sparing surgery). Complications were reported as absolute counts and percentages. The χ2 test was used for comparisons. RESULTS AND LIMITATIONS: The incidence of intraoperative complications was higher for bilateral PC-RPLND than for unilateral PC-RPLND (14% vs 4.3%, p = 0.003), with ureteral injury as the most frequent reported complication (2% of the patients). Postoperative complications were more common after bilateral than after unilateral PC-RPLND (45% vs 25%, p = 0.001) with Clavien ≥3b reported in 8.3% and 2.2%, respectively (p = 0.009). Lymphatic leakage was the most common complication occurring in 11% of the patients. Retrograde ejaculation occurred more frequently after bilateral than after unilateral surgery (59% vs 32%, p < 0.001). Limitations of the study include reporting of retrograde ejaculation, which was based on a chart review. CONCLUSIONS: Intra- and postoperative complications including retrograde ejaculation are more frequent after bilateral PC-RPLND than after unilateral PC-RPLND. PATIENT SUMMARY: Lymph node dissection in patients with testicular cancer puts them at risk of complications. In this study, we present the complications after lymph node dissection.
35.	Gerdtsson, Axel, et al. (author) Unilateral or Bilateral Retroperitoneal Lymph Node Dissection in Nonseminoma Patients with Postchemotherapy Residual Tumour? Results from RETROP, a Population-based Mapping Study by the Swedish Norwegian Testicular Cancer Group 2022 In: European Urology Oncology. - : Elsevier BV. - 2588-9311. ; 5:2, s. 235-243 Journal article (peer-reviewed)abstract BACKGROUND: The distribution of retroperitoneal lymph node metastases for patients with nonseminoma and a residual tumour of 10-49 mm in a population-based setting is unknown. This information is needed to justify selection of patients for a unilateral template resection. OBJECTIVE: To describe the location of retroperitoneal metastases and recurrences in patients with nonseminoma germ cell tumour (NSGCT) with a residual tumour of 10-49 mm. DESIGN, SETTING, AND PARTICIPANTS: RETROP is a population-based prospective observational mapping study of 213 patients in Sweden and Norway with a retroperitoneal residual tumour of 10-49 mm who underwent postchemotherapy retroperitoneal lymph node dissection for metastatic NSGCT during 2007-2014 with median follow-up of 100 mo. Patients were classified according to the testis primary tumour and the distribution of unilateral or bilateral lymph node metastases (with reference to the aorta) present on pre- and/or postchemotherapy computed tomography (CT) scans. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The distribution and rate of teratoma or cancer in unilateral or bilateral retroperitoneal fields and the location and rate of retroperitoneal recurrence were measured. RESULTS AND LIMITATIONS: In total, 65% of the patients had unilateral retroperitoneal lymph node metastases (RLNMs) on CT scans. Patients with unilateral RLNMs had a low risk of contralateral teratoma or cancer (1.6% for right- and 2.6% for left-sided NSGCT) or retroperitoneal recurrence (0% for right- and 4% for left-sided NSGCT). A weakness of the study is that the pathology specimen could not be fully designated to one specific area for some of the patients. CONCLUSIONS: Men with postchemotherapy residual disease of 10-49 mm and unilateral metastases on pre- and postchemotherapy CT scans have a low risk of contralateral disease and should be considered for a unilateral template resection. PATIENT SUMMARY: The surgeon can use computed tomography (CT) scans in deciding on the extent of lymph node dissection in patients with testicular cancer.
36.	Haug, Joachim T., et al. (author) Comment on the letter of the Society of Vertebrate Paleontology (SVP) dated April 21, 2020 regarding “Fossils from conflict zones and reproducibility of fossil‑based scientific data”: Myanmar amber 2020 In: Paläontologische Zeitschrift. - : Springer Science and Business Media LLC. - 0031-0220. ; 94, s. 431-437 Journal article (pop. science, debate, etc.)
37.	Jia, Xiaoming, et al. (author) Correction: Investigating rare pathogenic/likely pathogenic exonic variation in bipolar disorder. 2021 In: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 26:9 Journal article (peer-reviewed)
38.	Jones, Geraint H., et al. (author) The Comet Interceptor Mission 2024 In: Space Science Reviews. - : Springer Nature. - 0038-6308 .- 1572-9672. ; 220:1 Journal article (peer-reviewed)abstract Here we describe the novel, multi-point Comet Interceptor mission. It is dedicated to the exploration of a little-processed long-period comet, possibly entering the inner Solar System for the first time, or to encounter an interstellar object originating at another star. The objectives of the mission are to address the following questions: What are the surface composition, shape, morphology, and structure of the target object? What is the composition of the gas and dust in the coma, its connection to the nucleus, and the nature of its interaction with the solar wind? The mission was proposed to the European Space Agency in 2018, and formally adopted by the agency in June 2022, for launch in 2029 together with the Ariel mission. Comet Interceptor will take advantage of the opportunity presented by ESA’s F-Class call for fast, flexible, low-cost missions to which it was proposed. The call required a launch to a halo orbit around the Sun-Earth L2 point. The mission can take advantage of this placement to wait for the discovery of a suitable comet reachable with its minimum Δ V capability of 600 ms − 1 . Comet Interceptor will be unique in encountering and studying, at a nominal closest approach distance of 1000 km, a comet that represents a near-pristine sample of material from the formation of the Solar System. It will also add a capability that no previous cometary mission has had, which is to deploy two sub-probes – B1, provided by the Japanese space agency, JAXA, and B2 – that will follow different trajectories through the coma. While the main probe passes at a nominal 1000 km distance, probes B1 and B2 will follow different chords through the coma at distances of 850 km and 400 km, respectively. The result will be unique, simultaneous, spatially resolved information of the 3-dimensional properties of the target comet and its interaction with the space environment. We present the mission’s science background leading to these objectives, as well as an overview of the scientific instruments, mission design, and schedule.
39.	Kalarus, Zbigniew, et al. (author) Searching for atrial fibrillation : looking harder, looking longer, and in increasingly sophisticated ways. An EHRA position paper' 2023 In: Europace. - : Oxford University Press. - 1099-5129 .- 1532-2092. ; 25:1, s. 185-198 Research review (peer-reviewed)
40.	Knief, Ulrich, et al. (author) Highly pathogenic avian influenza causes mass mortality in Sandwich Tern Thalasseus sandvicensis breeding colonies across north-western Europe 2024 In: Bird conservation international. - : Cambridge University Press. - 0959-2709 .- 1474-0001. ; 34 Journal article (peer-reviewed)abstract In 2022, highly pathogenic avian influenza (HPAI) A(H5N1) virus clade 2.3.4.4b became enzootic and caused mass mortality in Sandwich TernThalasseus sandvicensis and other seabird species across north-western Europe. We present data on the characteristics of the spread of the virus between and within breeding colonies and the number of dead adult Sandwich Terns recorded at breeding sites throughout north-western Europe. Within two months of the first reported mortalities, 20,531 adult Sandwich Terns were found dead, which is >17% of the total north-western European breeding population. This is probably an under-representation of total mortality, as many carcasses are likely to have gone unnoticed and unreported. Within affected colonies, almost all chicks died. After the peak of the outbreak, in a colony established by late breeders, 25.7% of tested adults showed immunity to HPAI subtype H5. Removal of carcasses was associated with lower levels of mortality at affected colonies. More research on the sources and modes of transmission, incubation times, effective containment, and immunity is urgently needed to combat this major threat for colonial seabirds.
41.	Korwisi, Beatrice, et al. (author) Classification algorithm for the International Classification of Diseases-11 chronic pain classification : development and results from a preliminary pilot evaluation 2021 In: Pain. - : Lippincott Williams & Wilkins. - 0304-3959 .- 1872-6623. ; 162:7, s. 2087-2096 Journal article (peer-reviewed)abstract ABSTRACT: The International Classification of Diseases-11 (ICD-11) chronic pain classification includes about 100 chronic pain diagnoses on different diagnostic levels. Each of these diagnoses requires specific operationalized diagnostic criteria to be present. The classification comprises more than 200 diagnostic criteria. The aim of the Classification Algorithm for Chronic Pain in ICD-11 (CAL-CP) is to facilitate the use of the classification by guiding users through these diagnostic criteria. The diagnostic criteria were ordered hierarchically and visualized in accordance with the standards defined by the Society for Medical Decision Making Committee on Standardization of Clinical Algorithms. The resulting linear decision tree underwent several rounds of iterative checks and feedback by its developers, as well as other pain experts. A preliminary pilot evaluation was conducted in the context of an ecological implementation field study of the classification itself. The resulting algorithm consists of a linear decision tree, an introduction form, and an appendix. The initial decision trunk can be used as a standalone algorithm in primary care. Each diagnostic criterion is represented in a decision box. The user needs to decide for each criterion whether it is present or not, and then follow the respective yes or no arrows to arrive at the corresponding ICD-11 diagnosis. The results of the pilot evaluation showed good clinical utility of the algorithm. The CAL-CP can contribute to reliable diagnoses by structuring a way through the classification and by increasing adherence to the criteria. Future studies need to evaluate its utility further and analyze its impact on the accuracy of the assigned diagnoses.
42.	Labarque, Veerle, et al. (author) F8/F9 variants in the population-based PedNet Registry cohort compared with locus-specific genetic databases of the European Association for Haemophilia and Allied Disorders and the Centers for Disease Control and Prevention Hemophilia A or Hemophilia B Mutation Project. 2023 In: Research and practice in thrombosis and haemostasis. - : Elsevier BV. - 2475-0379. ; 7:1 Journal article (peer-reviewed)abstract BACKGROUND: Hemophilia A and B are caused by variants in the factor (F) VIII or FIX gene. Selective reporting may influence the distribution of variants reported in genetic databases.OBJECTIVES: To compare the spectrum of F8 and F9 variants in an international population-based pediatric cohort (PedNet Registry) with the spectrum found in the European Association for Haemophilia and Allied Disorders (EAHAD) and the Centers for Disease Control and Prevention Hemophilia A or Hemophilia B Mutation Project (CHAMP/CHBMP) databases. METHODS: All patients registered in the PedNet Registry on January 1, 2021 were included in this study. As comparators, data from patients with severe hemophilia included in the CHAMP/CHBMP registry (US center data) and EAHAD were used.RESULTS: Genetic information was available for 1941 patients. Intron 22 inversion was present in 52% of patients with severe hemophilia A; frameshift (36%), missense (28%), and nonsense (20%) were the most frequent variants in patients with severe hemophilia A who were inversion-negative. The most frequent variants in severe hemophilia B were missense (48%). In nonsevere disease, most variants were missense variants (moderate hemophilia A: 91%; mild hemophilia A: 95%, moderate and mild hemophilia B: 86% each). Comparison with the databases demonstrated a higher proportion of missense variants associated with severe hemophilia B in EAHAD (68%) than in PedNet (48%) and CHBMP (46%).CONCLUSION: The PedNet population-based cohort provides an alternative to the established databases, which collect data by selective reporting, as it is a well-maintained database covering the full spectrum of pathogenic F8 and F9 variants, and indicates the number of patients affected by each particular variant.
43.	Lundin, Björn, et al. (author) International Prophylaxis Study Group (IPSG) haemophilia joint MRI scale version 2.0 2024 In: Haemophilia. - 1351-8216. ; 30:3, s. 862-864 Journal article (peer-reviewed)
44.	Madani, Nima, et al. (author) Below-surface water mediates the response of African forests to reduced rainfall 2020 In: Environmental Research Letters. - : IOP Publishing. - 1748-9318 .- 1748-9326. ; 15:3 Journal article (peer-reviewed)abstract Terrestrial ecosystem gross primary productivity (GPP) is the largest land-atmosphere carbon flux and the primary mechanism of photosynthetic fixation of atmospheric CO2 into plant biomass. Anomalous rainfall events have been shown to have a great impact on the global carbon cycle. However, less is known about the impact of these events on GPP, especially in Africa, where in situ observations are sparse. Here, we use a suite of satellite and other geospatial data to examine the responses of major ecosystems in Africa to anomalous rainfall events from 2003 to 2017. Our results reveal that higher-than-average groundwater storage in tropical ecosystems offsets the rainfall deficit during the dry years. While the inter-annual variations in GPP in semi-arid ecosystems are controlled by near surface soil water, deeper soil moisture and groundwater control the inter-annual variability of the GPP in dense tropical forests. Our study highlights the critical role of groundwater in buffering rainfall shortages and continued availability of near-surface water to plants through dry spells.
45.	Madani, Nima, et al. (author) The Impacts of Climate and Wildfire on Ecosystem Gross Primary Productivity in Alaska 2021 In: Journal of Geophysical Research: Biogeosciences. - 2169-8953. ; 126:6 Journal article (peer-reviewed)abstract The increase in wildfire occurrence and severity seen over the past decades in the boreal and Arctic biomes is expected to continue in the future in response to rapid climate change in this region. Recent studies documented positive trends in gross primary productivity (GPP) for Arctic boreal biomes driven by warming, but it is unclear how GPP trends are affected by wildfires. Here, we used satellite vegetation observations and environmental data with a diagnostic GPP model to analyze recovery from large fires in Alaska over the period 2000–2019. We confirmed earlier findings that warmer-than-average years provide favorable climate conditions for vegetation growth, leading to a GPP increase of 1 Tg C yr−1, contributed mainly from enhanced productivity in the early growing season. However, higher temperatures increase the risk of wildfire occurrence leading to direct carbon loss over a period of 1–3 years. While mortality related to severe wildfires reduce ecosystem productivity, post-fire productivity in moderately burned areas shows a significant positive trend. The rapid GPP recovery following fires reported here might be favorable for maintaining the region's net carbon sink, but wildfires can indirectly promote the release of long-term stored carbon in the permafrost. With the projected increase in severity and frequency of wildfires in the future, we expect a reduction of GPP and therefore amplification of climate warming in this region.
46.	Malmi, Teemu, et al. (author) The use of management controls in different cultural regions : an empirical study of Anglo-Saxon, Germanic and Nordic practices 2022 In: Journal of Management Control. - : Springer Science and Business Media LLC. - 2191-4761 .- 2191-477X. ; 33:3, s. 273-334 Journal article (peer-reviewed)abstract Most cross-cultural studies on management control have compared Anglo-Saxon firms to Asian firms, leaving us with limited understanding of potential variations between developed Western societies. This study addresses differences and similarities in a wide variety of management control practices in Anglo-Saxon (Australia, English Canada), Germanic (Austria, non-Walloon Belgium, Germany) and Nordic firms (Denmark, Finland, Norway, Sweden). Unique data is collected through structured interviews from 584 strategic business units (SBUs). We find that management control structures in Anglo-Saxon SBUs, relative to those from Germanic and Nordic regions, are more decentralized and participative and place greater emphasis on performance-based pay. Comparing Germanic SBUs to Nordic ones, we find Germanic SBUs to rely more on individual behaviour in performance evaluation, whereas Nordic SBUs rely more on quantitative measures and value alignment in employee selection. We also observe numerous similarities in MC practices between the three cultural regions. The implications of these findings for theory development are outlined.
47.	Marker, Jeffery (author) Forests, Functions, and Food Webs : Riparian processes through an ecological and molecular lens 2023 Doctoral thesis (other academic/artistic)abstract Riparian systems are critical ecological interfaces that have a significant impact on the surrounding aquatic and terrestrial ecosystems. The riparian and surrounding systems have significant roles in regulating energy flow, providing essential nutrients, and supporting unique species, making them important for ecosystem function. Both the aquatic and terrestrial ecosystems are reliant on the reciprocal exchange of energy subsides to maintain productive and stable food webs. Retention of forested buffers along streams during tree felling operations is a common management technique used to protect aquatic resources and conserve the surrounding ecosystem processes. Measuring the effects of forestry practices on the function and food webs of riparian predators is vital to making forest management decisions that strengthen and protect these fundamental services. Insight into predator function and predator-prey interactions using powerful molecular techniques can further the understanding of these complex systems and help to mitigate the effects of forestry practices.This thesis explores the functional diversity, food webs, and predator-prey interactions in riparian systems impacted by forestry felling practices. I have studied the effects of clear-cutting and forested buffer zones on riparian functional diversity through the assessment of functional richness and redundancy of spider and plant communities. In addition, I have both validated and used stable isotope analysis and DNA metabarcoding to investigate the primary food sources and prey choices of riparian predators. Riparian buffer size had no direct effect on the functional richness or redundancy of riparian spiders and vascular plants. However, riparian buffer variables such as canopy closure, buffer density, and vegetation coverage did have direct impacts on both spider and plant function. Most riparian spiders and brown trout received a significant majority of their food source from the terrestrial environment and the presence or absence of a riparian buffer did not effect this outcome. However, web-weaving spiders in unbuffered systems were more likely to exploit aquatic resources as a primary food source. Overall, the responses of predator function and food webs to forestry practice are site-specific.
48.	Marzano, Luca, 1995-, et al. (author) A novel analytical framework for risk stratification of real‐world data using machine learning: A small cell lung cancer study 2022 In: Clinical and Translational Science. - : Wiley. - 1752-8054 .- 1752-8062. ; 15:10, s. 2437-2447 Journal article (peer-reviewed)abstract In recent studies, small cell lung cancer (SCLC) treatment guidelines based on Veterans’ Administration Lung Study Group limited/extensive disease staging and resulted in broad and inseparable prognostic subgroups. Evidence suggests that the eight versions of tumor, node, and metastasis (TNM) staging can play an important role to address this issue. The aim of the present study was to improve the detection of prognostic subgroups from a real-word data (RWD) cohort of patients and analyze their patterns using a development pipeline with thoracic oncologists and machine learning methods. The method detected subgroups of patients informing unsupervised learning (partition around medoids) including the impact of covariates on prognosis (Cox regression and random survival forest). An analysis was carried out using patients with SCLC (n = 636) with stage IIIA–IVB according to TNM classification. The analysis yielded k = 7 compacted and well-separated clusters of patients. Performance status (Eastern Cooperative Oncology Group-Performance Status), lactate dehydrogenase, spreading of metastasis, cancer stage, and CRP were the baselines that characterized the subgroups. The selected clustering method outperformed standard clustering techniques, which were not capable of detecting meaningful subgroups. From the analysis of cluster treatment decisions, we showed the potential of future RWD applications to understand disease, develop individualized therapies, and improve healthcare decision making.
49.	Marzano, Luca, 1995-, et al. (author) Application of Process Mining for Modelling Small Cell Lung Cancer Prognosis 2023 In: Studies in Health Technology and Informatics. - : IOS Press. - 0926-9630 .- 1879-8365. ; 302, s. 18-22 Journal article (peer-reviewed)abstract Process mining is a relatively new method that connects data science and process modelling. In the past years a series of applications with health care production data have been presented in process discovery, conformance check and system enhancement. In this paper we apply process mining on clinical oncological data with the purpose of studying survival outcomes and chemotherapy treatment decision in a real-world cohort of small cell lung cancer patients treated at Karolinska University Hospital (Stockholm, Sweden). The results highlighted the potential role of process mining in oncology to study prognosis and survival outcomes with longitudinal models directly extracted from clinical data derived from healthcare.
50.	Matthews, Bethany E., et al. (author) Micro- and Nanoscale Surface Analysis of Late Iron Age Glass from Broborg, a Vitrified Swedish Hillfort 2023 In: Microscopy and Microanalysis. - : Oxford University Press. - 1431-9276 .- 1435-8115. ; 29:1, s. 50-68 Journal article (peer-reviewed)abstract Archaeological glasses with prolonged exposure to biogeochemical processes in the environment can be used to understand glass alteration, which is important for the safe disposal of vitrified nuclear waste. Samples of mafic and felsic glasses with different chemistries, formed from melting amphibolitic and granitoid rocks, were obtained from Broborg, a Swedish Iron Age hillfort. Glasses were excavated from the top of the hillfort wall and from the wall interior. A detailed microscopic, spectroscopic, and diffraction study of surficial textures and chemistries were conducted on these glasses. Felsic glass chemistry was uniform, with a smooth surface showing limited chemical alteration (<150 nm), irrespective of the position in the wall. Mafic glass was heterogeneous, with pyroxene, spinel, feldspar, and quartz crystals in the glassy matrix. Mafic glass surfaces in contact with topsoil were rougher than those within the wall and had carbon-rich material consistent with microbial colonization. Limited evidence for chemical or physical alteration of mafic glass was found; the thin melt film that coated all exposed surfaces remained intact, despite exposure to hydraulically unsaturated conditions, topsoil, and associated microbiome for over 1,500 years. This supports the assumption that aluminosilicate nuclear waste glasses will have a high chemical durability in near-surface disposal facilities.

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