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1.
  • Berndt, Sonja I., et al. (författare)
  • Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
  • 2013
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
  • Tidskriftsartikel (refereegranskat)abstract
    • Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
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2.
  • Locke, Adam E, et al. (författare)
  • Genetic studies of body mass index yield new insights for obesity biology.
  • 2015
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
  • Tidskriftsartikel (refereegranskat)abstract
    • Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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3.
  • Sarkadi, Anna, Professor, 1974-, et al. (författare)
  • An Integrated Care Strategy for Pre-schoolers with Suspected Developmental Disorders : The Optimus Co-design Project that has Made it to Regular Care
  • 2021
  • Ingår i: International Journal of Integrated Care. - : Ubiquity Press. - 1568-4156. ; 21:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Multiple neurodevelopmental problems affect 7-8% of children and require evaluation by more than one profession, posing a challenge to care systems.Description: The local problem comprised distressed parents, diagnostic processes averaging 36 months and 28 visits with 42% of children >4 years at referral to adequate services, and no routines for patient involvement. The co-design project was developed through a series of workshops using standard quality improvement methodology, where representatives of all services, as well as parents participated. The resulting integrated care model comprises a team of professionals who evaluate the child during an average of 5.4 appointments (N = 95), taking 4.8 weeks. Parents were satisfied with the holistic service model and 70% of children were under 4 at referral (p < 0.05). While 75% of children were referred, 25% required further follow-up by the team.Discussion: The Optimus model has elements of vertical, clinical and service integration. Reasons for success included leadership support, buy-in from the different organisations, careful process management, a team co-ordinator, and insistent user involvement.Conclusion: Evaluating multiple neurodevelopmental problems in children requires an integrated care approach. The Optimus care model is a relevant showcase for how people-initiated integrated care reforms can make it into usual care.
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4.
  • Arborelius, Lotta, et al. (författare)
  • A new interactive computer simulation system for violence risk assessment of mentally disordered violent offenders
  • 2013
  • Ingår i: CBMH. Criminal behaviour and mental health. - : Wiley. - 0957-9664 .- 1471-2857. ; 23:1, s. 30-40
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Assessment of risk of future violence has developed from reliance on static indicators towards a more dynamic approach. In the latter context, however, the offender is seldom confronted with real life situations. Aims The aim of this study is to evaluate a computer-based system Reactions on Display, which presents human interactions based on real-life situations for its effectiveness in distinguishing between potentially violent offenders with mental disorder and a healthy comparison group. Methods Male offenders with autism spectrum disorders or psychosis were recruited from specialist forensic psychiatric units in Sweden and healthy participants from the local communities. Each consenting participant was presented with film clips of a man in neutral and violent situations, which at critical moments stopped the story to ask him to predict the thoughts, feelings and actions of the actor. Results Offender patients, irrespective of diagnosis, detected fewer emotional reactions in the actor in the non-violent sequence compared with controls. When asked to choose one of four violent actions, the offender patients chose more violent actions than did the controls. They also reported fewer physical reactions in the actors when actors were being violent. There were also some examples of incongruent or deviant responses by some individual patients. Conclusions and implications for practice The use of interactive computer simulation techniques is not only generally acceptable to offender patients, but it also helps to differentiate their current response style to particular circumstances from that of healthy controls in a way that does not rely on their verbal abilities and may tap more effectively into their emotional reactions than standard verbal questions and answer approaches. This may pave the way for Reactions on Display providing a useful complement to traditional risk assessment, and a training route with respect to learning more empathic responding, thus having a role in aiding risk management.
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5.
  • Arvidsson, Yvonne, 1960, et al. (författare)
  • miRNA profiling of small intestinal neuroendocrine tumors defines novel molecular subtypes and identifies miR-375 as a biomarker of patient survival
  • 2018
  • Ingår i: Modern Pathology. - : Elsevier BV. - 0893-3952 .- 1530-0285. ; 31, s. 1302-1317
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2018, United States & Canadian Academy of Pathology. The aim of this study was to define the miRNA profile of small intestinal neuroendocrine tumors and to search for novel molecular subgroups and prognostic biomarkers. miRNA profiling was conducted on 42 tumors from 37 patients who underwent surgery for small intestinal neuroendocrine tumors. Unsupervised hierarchical clustering analysis of miRNA profiles identified two groups of tumor metastases, denoted cluster M1 and M2. The smaller cluster M1 was associated with shorter overall survival and contained tumors with higher grade (WHO grade G2/3) and multiple chromosomal gains including gain of chromosome 14. Tumors of cluster M1 had elevated expression of miR-1246 and miR-663a, and reduced levels of miR-488-3p. Pathway analysis predicted Wnt signaling to be the most significantly altered signaling pathway between clusters M1 and M2. Analysis of miRNA expression in relation to tumor proliferation rate showed significant alterations including downregulation of miR-137 and miR-204-5p in tumors with Ki67 index above 3%. Similarly, tumor progression was associated with significant alterations in miRNA expression, e.g. higher expression of miR-95 and miR-210, and lower expression of miR-378a-3p in metastases. Pathway analysis predicted Wnt signaling to be altered during tumor progression, which was supported by decreased nuclear translocation of β-catenin in metastases. Survival analysis revealed that downregulation of miR-375 was associated with shorter overall survival. We performed in situ hybridization on biopsies from an independent cohort of small intestinal neuroendocrine tumors using tissue microarrays. Expression of miR-375 was found in 578/635 (91%) biopsies and survival analysis confirmed that there was a correlation between downregulation of miR-375 in tumor metastases and shorter patient survival. We conclude that miRNA profiling defines novel molecular subgroups of metastatic small intestinal neuroendocrine tumors and identifies miRNAs associated with tumor proliferation rate and progression. miR-375 is highly expressed in small intestinal neuroendocrine tumors and may be used as a prognostic biomarker.
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6.
  • Axelson, Karin, 1977-, et al. (författare)
  • Resultat från nationella provet i matematik kurs 1a och 1b vårterminen 2022 : Delrapport 2
  • 2022
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • De nationella proven i matematik 1a och 1b konstrueras och utvecklas, på uppdrag av Skolverket, av PRIM-gruppen vid Stockholms universitet. I denna rapport presenteras en sammanställning och diskussion av resultaten för de nationella proven i matematik 1a och 1b som gavs vårterminen 2022.Det huvudsakliga syftet med rapporten är att redovisa och diskutera resultaten från genomförandet av dessa prov utifrån den revidering av ämnesplanen som genomförts. Resultatredovisningen från vårterminens nationella prov i matematik 1a och 1b kommer från PRIM-gruppens urvalsinsamling och bestod av lärarenkäter och inrapporterade resultat på uppgiftsnivå från ett slumpmässigt urval elever. PRIM-gruppens urvalsinsamling för matematik 1a omfattade vårterminen 2022 elever från olika yrkesprogram och för matematik 1b elever från samhällsvetenskapsprogrammet, ekonomiprogrammet, estetiska programmet och humanistiska programmet.Skolverket genomför enbart insamling av provbetyg på nationella prov för elevers avslutande matematikkurs i gymnasieskolan det vill säga för elever från de olika yrkesprogrammen som slutfört matematik 1a och för elever från estetiska och humanistiska programmet som slutfört matematik 1b. Resultaten från lärarenkäterna och elevresultaten på uppgiftsnivå är viktiga källor för analys och utvecklingen av de nationella proven. För matematik 1a bestod insamlingen från vårterminen 2022 av resultat från ca 600 lärare och ca 4 000 elever (ca 1 600 flickor respektive ca 2 400 pojkar) och för matematik 1b ca 550 lärare och ca 4 300 elever (ca 2 600 flickor respektive ca 1 700 pojkar).Resultatrapporten är uppdelad i två delrapporter. Detta är den andra delrapporten och den består av analyser av elevers prestationer på ett urval av uppgifter utifrån ett antal elevarbeten. Den första delrapporten innehåller resultat från prov och lärarenkäter. 
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7.
  • Bengtsson-Palme, Johan, 1985, et al. (författare)
  • Improved software detection and extraction of ITS1 and ITS2 from ribosomal ITS sequences of fungi and other eukaryotes for analysis of environmental sequencing data
  • 2013
  • Ingår i: Methods in Ecology and Evolution. - 2041-210X. ; 4:10, s. 914-919
  • Tidskriftsartikel (refereegranskat)abstract
    • The nuclear ribosomal internal transcribed spacer (ITS) region is the primary choice for molecular identification of fungi. Its two highly variable spacers (ITS1 and ITS2) are usually species specific, whereas the intercalary 5.8S gene is highly conserved. For sequence clustering and blast searches, it is often advantageous to rely on either one of the variable spacers but not the conserved 5.8S gene. To identify and extract ITS1 and ITS2 from large taxonomic and environmental data sets is, however, often difficult, and many ITS sequences are incorrectly delimited in the public sequence databases. We introduce ITSx, a Perl-based software tool to extract ITS1, 5.8S and ITS2 – as well as full-length ITS sequences – from both Sanger and high-throughput sequencing data sets. ITSx uses hidden Markov models computed from large alignments of a total of 20 groups of eukaryotes, including fungi, metazoans and plants, and the sequence extraction is based on the predicted positions of the ribosomal genes in the sequences. ITSx has a very high proportion of true-positive extractions and a low proportion of false-positive extractions. Additionally, process parallelization permits expedient analyses of very large data sets, such as a one million sequence amplicon pyrosequencing data set. ITSx is rich in features and written to be easily incorporated into automated sequence analysis pipelines. ITSx paves the way for more sensitive blast searches and sequence clustering operations for the ITS region in eukaryotes. The software also permits elimination of non-ITS sequences from any data set. This is particularly useful for amplicon-based next-generation sequencing data sets, where insidious non-target sequences are often found among the target sequences. Such non-target sequences are difficult to find by other means and would contribute noise to diversity estimates if left in the data set.
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8.
  • Bennet, Tova, et al. (författare)
  • Den rättspsykiatriska vården är inte rättssäker – agera nu
  • 2020
  • Ingår i: Göteborgs-Posten. - Göteborg : Göteborgposten. - 1103-9345. ; :Oktober 19
  • Tidskriftsartikel (populärvet., debatt m.m.)abstract
    • Det svenska rättssystemet som tillåter att vi dömer psykiskt sjuka för brott och att personer som saknar vårdbehov kan hållas frihetsberövade inom rättspsykiatrin under mycket lång tid med oklart vårdinnehåll, är unikt och har fått rättmätig kritik under lång tid. Ändå händer ingenting. 
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9.
  • Berglund, Fanny, et al. (författare)
  • An updated phylogeny of the metallo-β-lactamases.
  • 2021
  • Ingår i: The Journal of antimicrobial chemotherapy. - : Oxford University Press (OUP). - 1460-2091 .- 0305-7453. ; 76:1, s. 117-123
  • Tidskriftsartikel (refereegranskat)abstract
    • Metallo-β-lactamases (MBLs) are enzymes that use zinc-dependent hydrolysis to confer resistance to almost all available β-lactam antibiotics. They are hypothesized to originate from commensal and environmental bacteria, from where some have mobilized and transferred horizontally to pathogens. The current phylogeny of MBLs, however, is biased as it is founded largely on genes encountered in pathogenic bacteria. This incompleteness is emphasized by recent findings of environmental MBLs with new forms of zinc binding sites and atypical functional profiles.To expand the phylogeny of MBLs to provide a more accurate view of their evolutionary history.We searched more than 16 terabases of genomic and metagenomic data for MBLs of the three subclasses B1, B2 and B3 using the validated fARGene method. Predicted genes, together with the previously known ones, were used to infer phylogenetic trees.We identified 2290 unique MBL genes forming 817 gene families, of which 741 were previously uncharacterized. MBLs from subclasses B1 and B3 separated into distinct monophyletic groups, in agreement with their taxonomic and functional properties. We present evidence that clinically associated MBLs were mobilized from Proteobacteria. Additionally, we identified three new variants of the zinc binding sites, indicating that the functional repertoire is broader than previously reported.Based on our results, we recommend that the nomenclature of MBLs is refined into the phylogenetic groups B1.1-B1.5 and B3.1-B3.4 that more accurately describe their molecular and functional characteristics. Our results will also facilitate the annotation of novel MBLs, reflecting their taxonomic organization and evolutionary origin.
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10.
  • Berglund, Fanny, et al. (författare)
  • Comprehensive screening of genomic and metagenomic data reveals a large diversity of tetracycline resistance genes
  • 2020
  • Ingår i: Microbial genomics. - : Microbiology Society. - 2057-5858. ; 6:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Tetracyclines are broad-spectrum antibiotics used to prevent or treat a variety of bacterial infections. Resistance is often mediated through mobile resistance genes, which encode one of the three main mechanisms: active efflux, ribosomal target protection or enzymatic degradation. In the last few decades, a large number of new tetracycline-resistance genes have been discovered in clinical settings. These genes are hypothesized to originate from environmental and commensal bacteria, but the diversity of tetracycline-resistance determinants that have not yet been mobilized into pathogens is unknown. In this study, we aimed to characterize the potential tetracycline resistome by screening genomic and metagenomic data for novel resistance genes. By using probabilistic models, we predicted 1254 unique putative tetracycline resistance genes, representing 195 gene families (<70% amino acid sequence identity), whereof 164 families had not been described previously. Out of 17 predicted genes selected for experimental verification, 7 induced a resistance phenotype in an Escherichia coli host. Several of the predicted genes were located on mobile genetic elements or in regions that indicated mobility, suggesting that they easily can be shared between bacteria. Furthermore, phylogenetic analysis indicated several events of horizontal gene transfer between bacterial phyla. Our results also suggested that acquired efflux pumps originate from proteobacterial species, while ribosomal protection genes have been mobilized from Firmicutes and Actinobacteria. This study significantly expands the knowledge of known and putatively novel tetracycline resistance genes, their mobility and evolutionary history. The study also provides insights into the unknown resistome and genes that may be encountered in clinical settings in the future.
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11.
  • Berglund Kristiansson, Elisabeth, et al. (författare)
  • A qualitative study of older persons’ experiences of getting individual support with digital needs in the context of home ID 281
  • 2024
  • Ingår i: The first Global Conference on Person-Centred Care. - : University of Gothenburg Centre for Person-Centred Care. - 9789153106708 ; , s. 216-216
  • Konferensbidrag (refereegranskat)abstract
    • Background: Digitalization is seen as a necessity to manage the increasing burden on the health care system and is accordingly considered an important tool in the transformation to integrated care (Swedish Nära vård). However, when health care is digitalized older persons are at increased risk of being marginalized and dependent on others due to their generally lower digital competence. To address this, several Swedish municipalities offer individual support to older persons in their own home, a service called Digital Coach (DC). As this service is new, the aim is to describe older persons’ experiences of getting individual support with digital needs in the context of home. Method: Semi-structured interviews (n=14) were conducted with older persons who have had DC support in their home. The focus was on older persons’ experiences of the support. Data was analyzed with qualitative content analysis. Results, preliminary: The overall theme, to be a valued person in the digital society, represents a feeling of being taken seriously and worth investing resources in to gain access to society. Three categories emerged: (1) The need to keep up with the times which means to understand and navigate the new digital landscape with the opportunity for independence and participation, (2) Support and respect in the learning situation, is crucial for feeling comfortable to expose insufficient knowledge, and (3) Increased digital competence empowers autonomy and is manifested as the ability to handle the digital tools and services by your own creates a feeling of joy and satisfaction and increases the opportunity to participate in both social and community activities. Conclusion: The result shows that individual support with digital needs in the context of home increase digital competence in older persons and create feelings of being valued and included in the digital society, which can extend to integrated person-centered care.
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12.
  • Bjursell, Cecilia, 1971, et al. (författare)
  • PMM2 mutation spectrum, including 10 novel mutations, in a large CDG type 1A family material with a focus on Scandinavian families.
  • 2000
  • Ingår i: Human mutation. - 1098-1004 .- 1059-7794. ; 16:5, s. 395-400
  • Tidskriftsartikel (refereegranskat)abstract
    • Carbohydrate-deficient glycoprotein syndrome type IA (CDG IA) is an autosomal recessive disease characterized clinically by severe involvement of the central and peripheral nervous system, and biochemically by complex defects in carbohydrate residues in a number of serum glycoproteins. CDG IA is caused by mutations in the PMM2 gene located in chromosome region 16p13. In this study, 61 CDG type IA patients (122 chromosomes) were screened for mutations in the PMM2 gene using a combination of SSCP and sequence analysis. More than 95% of the mutations could be detected. All of them were missense mutations. Mutations 422G>A and 357C>A were strikingly more common in the material and comprised 58% of mutations detected. Of the 20 mutations found, 10 were not reported previously. Seven mutations, e.g. 26G>A (five alleles) and 548T>C (seven alleles), were found only in Scandinavian families. The most common genotype was 357C>A/422G>A (36%). Three patients were homozygous, 357C>A/357C>A (two cases), and 548T>C/548T>C (one case). No patients homozygous for the most common mutation 422G>A were detected. The different mutations were clustered e.g., in that most were located in exon 5 (five) and exon 8 (six), while no mutation was detected in exon 2. When the frequencies of each mutation were included, exon 5 comprised 61% (65 chromosomes) of the mutations; in Scandinavian patients the frequency of these mutations was 72%. Thus, analysis of exon five in these patients enables both reliable and time-saving first screening in prenatal diagnostic cases. This could be followed by a second step of additional strategies for the detection of other mutations.
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13.
  • Boulund, Fredrik, 1985, et al. (författare)
  • A novel method to discover fluoroquinolone antibiotic resistance (qnr) genes in fragmented nucleotide sequences
  • 2012
  • Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Broad-spectrum fluoroquinolone antibiotics are central in modern health care and are used to treat and prevent a wide range of bacterial infections. The recently discovered qnr genes provide a mechanism of resistance with the potential to rapidly spread between bacteria using horizontal gene transfer. As for many antibiotic resistance genes present in pathogens today, qnr genes are hypothesized to originate from environmental bacteria. The vast amount of data generated by shotgun metagenomics can therefore be used to explore the diversity of qnr genes in more detail. RESULTS: In this paper we describe a new method to identify qnr genes in nucleotide sequence data. We show, using cross-validation, that the method has a high statistical power of correctly classifying sequences from novel classes of qnr genes, even for fragments as short as 100 nucleotides. Based on sequences from public repositories, the method was able to identify all previously reported plasmid-mediated qnr genes. In addition, several fragments from novel putative qnr genes were identified in metagenomes. The method was also able to annotate 39 chromosomal variants of which 11 have previously not been reported in literature. CONCLUSIONS: The method described in this paper significantly improves the sensitivity and specificity of identification and annotation of qnr genes in nucleotide sequence data. The predicted novel putative qnr genes in the metagenomic data support the hypothesis of a large and uncharacterized diversity within this family of resistance genes in environmental bacterial communities. An implementation of the method is freely available at http://bioinformatics.math.chalmers.se/qnr/.
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14.
  • Boulund, Fredrik, 1985, et al. (författare)
  • Typing and Characterization of Bacteria Using Bottom-up Tandem Mass Spectrometry Proteomics
  • 2017
  • Ingår i: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 16:6, s. 1052-1063
  • Tidskriftsartikel (refereegranskat)abstract
    • Methods for rapid and reliable microbial identification are essential in modern healthcare. The ability to detect and correctly identify pathogenic species and their resistance phenotype is necessary for accurate diagnosis and efficient treatment of infectious diseases. Bottom-up tandem mass spectrometry (MS) proteomics enables rapid characterization of large parts of the expressed genes of microorganisms. However, the generated data are highly fragmented, making downstream analyses complex. Here we present TCUP, a new computational method for typing and characterizing bacteria using proteomics data from bottom-up tandem MS. TCUP compares the generated protein sequence data to reference databases and automatically finds peptides suitable for characterization of taxonomic composition and identification of expressed antimicrobial resistance genes. TCUP was evaluated using several clinically relevant bacterial species (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae), using both simulated data generated by in silico peptide digestion and experimental proteomics data generated by liquid chromatography-tandem mass spectrometry (MS/MS). The results showed that TCUP performs correct peptide classifications at rates between 90.3 and 98.5% at the species level. The method was also able to estimate the relative abundances of individual species in mixed cultures. Furthermore, TCUP could identify expressed beta-lactamases in an extended spectrum beta-lactamase-producing (ESBL) E.coli strain, even when the strain was cultivated in the absence of antibiotics. Finally, TCUP is computationally efficient, easy to integrate in existing bioinformatics workflows, and freely available under an open source license for both Windows and Linux environments.
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15.
  • Drevin, Jennifer, et al. (författare)
  • Adverse childhood experiences influence development of pain during pregnancy.
  • 2015
  • Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 94:8, s. 840-846
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To investigate the association between adverse childhood experiences (ACE) and pain with onset during pregnancy.DESIGN: Cross-sectional study.SETTING: Eighteen antenatal clinics in southern Mid-Sweden.SAMPLE: Of 293 women invited to participate, 232 (79%) women agreed to participate in early pregnancy and were assessed in late pregnancy.METHODS: Questionnaires were distributed in early and late pregnancy. The questionnaires sought information on socio-demography, ACE, pain location by pain drawing and pain intensity by visual analogue scales. Distribution of pain was coded in 41 predetermined areas.MAIN OUTCOME MEASURES: Pain in third trimester with onset during present pregnancy: intensity, location and number of pain locations.RESULTS: In late pregnancy, 62% of the women reported any ACE and 72% reported any pain location with onset during the present pregnancy. Among women reporting any ACE the median pain intensity was higher compared with women without such an experience (p = 0.01). The accumulated ACE displayed a positive association with the number of reported pain locations in late pregnancy (rs  = 0.19, p = 0.02). This association remained significant after adjusting for background factors in multiple regression analysis (p = 0.01). When ACE was dichotomized the prevalence of pain did not differ between women with and without ACE. The subgroup of women reporting physical abuse as a child reported a higher prevalence of sacral and pelvic pain (p = 0.0003 and p = 0.02, respectively).CONCLUSIONS: Adverse childhood experiences were associated with higher pain intensities and larger pain distributions in late pregnancy, which are risk factors for transition to chronic pain postpartum.
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16.
  • Dåderman, Anna Maria, 1953-, et al. (författare)
  • Degree of psychopathy : implications for treatment in male juvenile delinquents
  • 2003
  • Ingår i: International Journal of Law and Psychiatry. - Oxford : Pergamon Press. - 0160-2527 .- 1873-6386. ; 26:3, s. 301-315
  • Tidskriftsartikel (refereegranskat)abstract
    • Longitudinal studies have consistently shown that psychopathy in adulthood has its roots in childhood. The psychopathy concept described by Cleckley (1976) involves interpersonal, affective, and behavioral aspects. Moreover, children who show low levels of anxiety respond more poorly to treatment. The aim of the present study was to assess psychopathy in 56 male juvenile delinquents with conduct disorder, treated in youth correctional institutions for severe offenders. We used a modified Psychopathy Checklist-Revised (PCL-R) that has been used for young people (Forth et al., 1990). Each participant received PCL-R assessments from one rater, based on the file information and an extensive interview. Twenty-eight participants (50%) were rated by the second rater. Both the ICC and Cohens’s kappa revealed that the PCL-R ratings were reliable: the ICC(2,1) of the PCL-R total scores was 0.90, F(27, 28) = 11.70, P < .0001; Cohen’s kappa = 0.64, P < .001. The final scores on the PCL-R showed that the base rate for psychopathy (defined as a score of 30 or more) in the sample was 59% (33 of 56 juvenile delinquents). The mean PCL-R total score for all 56 participants was 29.3 (S.D. = 7.8), and ranged between 12 and 40. The high rates of psychopathy found in juvenile delinquents with conduct disorder should alert clinicians to the necessity of psychopathy scoring, and shows that high-quality treatment programs are needed. Psychopathy is not currently considered when assessing and treating young people in state-administered observational and correctional institutions for juvenile delinquents in Sweden.
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17.
  • Dåderman, Anna Maria, 1953-, et al. (författare)
  • Degree of psychopathy and patterns of personality traits : implications for treatment in male juvenile delinquents
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • We have assessed psychopathy in male juvenile delinquents, and examined the relationships between patterns of psychopathy-related personality traits and psychopathy (PCL-R). Our results are complemented by data regarding previous treatment occasions and reoffending, with the aim of discussing treatment strategies.We studied 56 male juvenile delinquents whose ages ranged from 14 to 20 years, with a mean of 17 years (SD = 1.2) from four youth correctional institutions in Sweden. All of the young people had shown early onset of conduct disorder. The modified version of the Hare Psychopathy Checklist – Revised (PCL-R), designed to be used with young people (Forth, Hart, & Hare, 1990), was used to assess psychopathy. Personality traits were measured along five dimensions: impulsiveness, monotony avoidance, socialization, verbal aggression, and somatic anxiety; scales were taken from the Karolinska Scales of Personality.The mean PCL-R score was 29.3 in this sample (SD = 7.8), and 73% had scores between 27 and 40, indicating high degree of psychopathy; 59% of the participants had scores above 30, and, according to the manual, were classified as psychopaths. No significant correlations were found between the personality scale scores and the PCL-R scores. We discovered seven clusters; three of these were multi-psychopathological clusters (the members of these clusters had all traits deviant from what is normal), three of these consisted of participants for who the majority of traits were deviant (only one or two traits were within the normal range), and one of these consisted of participants for who all traits were within the normal range. We suggest that the classification will be helpful in managing therapeutic efforts.The results indicate that psychopathy is common in male juvenile delinquents, and that personality profile may have implications for early intervention strategies in male adolescents with conduct disorder.
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18.
  • Dåderman, Anna Maria, 1953- (författare)
  • “Dr Jekyll and Mr Hyde?” : Abuse of potent benzodiazepines, exemplified by flunitrazepam, in mentally disordered male offenders
  • 2005
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Flunitrazepam (FZ) is an example of a sedative-hypnotic benzodiazepine whose pharmacokinetic properties include a rapid onset of action and an intermediate duration of action. It has a high affinity to central benzodiazepine receptors and affects them profoundly. These properties, and its profile of activity, increase the probability of abuse by those who have access to it. Known side effects of FZ are abuse and amnesia. FZ is widely abused and it has become a drug of choice among opioid abusers, as a club drug, and as a classic “date-rape” drug. FZ is often involved in fatal intoxication. It is therefore expected that FZ abuse is common in serious offenders. I have studied the reasons for FZ abuse and mapped the prevalence of the abuse, with the objective of studying the personalities and the background factors of the abusers, and of drawing some conclusions about assessment procedures of FZ abuse and the position of FZ in society.The participants in the studies summarised here were fifty-six juvenile delinquents from Swedish youth correctional institutions, aged 14-20 years, and sixty non-psychotic male offenders referred for a forensic psychiatric evaluation (FPE), aged 16-35 years. The participants answered questions regarding their abuse, and this enabled us to understand why they abused just FZ (and not another substance). The participants also completed a number of self-reported inventories, which enabled us to obtain measures of personality traits. They were also rated for psychopathy. Five forensic psychiatric cases of FZ abusers were studied in more detail. Furthermore, the forensic psychiatric participants’ psychiatric diagnoses, and both groups’ crime-related measures, were obtained from their files.About 40% of the juvenile delinquents and 30% of the offenders referred for a forensic psychiatric evaluation abused FZ. The main reason for the FZ abuse was to change a perception of reality and to obtain an increased feeling of power and self-esteem, a feeling that everything was possible. Both samples of offenders differed from the normal population in many personality traits, suggesting that the participants possessed a high level of vulnerability for developing mental disorders, but only a few differences in personality traits were found between FZ abusers and non-FZ abusers. The juvenile delinquent FZ abusers had higher scores than non-FZ abusers in the verbal aggression and sensation-seeking boredom susceptibility scales. In the juvenile sample, FZ abuse was associated with the abuse of amphetamines and/or cocaine, cannabis, and opiates, and with childhood psychological/psychiatrical contact, with living in a metropolitan housing area, and with recidivism into crimes leading to care in a juvenile correctional institution. In this sample, FZ abuse was also associated with weapons offences and narcotics-related crimes. In the forensic psychiatric sample, FZ abuse was significantly associated with previous admission to an FPE, and convictions for robbery, for weapons-related offences, for narcotics-related offences and for theft. The results show that FZ is more common in offenders who score high on Facet 4 (Antisocial) in the Hare psychopathy model, and that FZ abuse has high correlation with Item 20 (Criminal versatility). All of the FZ abusers reported side effects from FZ that resulted in the brutality of their violent acts and anterograde amnesia. FZ abusers, when intoxicated with FZ, had a reduced capacity for both empathy and anticipatory anxiety, in contrast to their “daily” behaviour and “ordinary” (i.e., without the influence of the FZ) personality characteristics. They were not characterised by classic characteristics of psychopathy, such as lack of empathy. This may indicate that FZ induces psychopathic-like state-dependant (FZ intoxication) traits, and temporary dissociate states (“Dr Jekyll and Mr Hyde”?).In conclusion, FZ abuse is common in the population of young offenders with mental disorders, and FZ is often used for nonmedical purposes. The practical implications of these conclusions are that clinicians and those who develop or manage therapeutic programs should be aware of FZ abuse when choosing the most effective treatment for male offenders. General practitioners who prescribe potent sedative compounds should be aware of their possible adverse effects. The availability of FZ should be limited further, because FZ is frequently abused in vulnerable male offenders, and because FZ has serious adverse mental health-related effects and is related to robbery and weapons‑related crimes.
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19.
  • Dåderman, Anna Maria, 1953-, et al. (författare)
  • Flunitrazepam intake in male offenders
  • 2012
  • Ingår i: Nordic Journal of Psychiatry. - : Informa Healthcare. - 0803-9488 .- 1502-4725. ; 66:2, s. 131-140
  • Tidskriftsartikel (refereegranskat)abstract
    • The abuse of flunitrazepam (FZ) compounds is worldwide, and several studies have reflected on the consequences with regard to violence, aggression and criminal lifestyle of FZ users. Criminals take high doses of FZ or some other benzodiazepines to "calm down" before the planned crime. There is support from earlier studies that most likely, all benzodiazepines may increase aggression in vulnerable males. Chronic intake of high doses of FZ increases aggression in male rats. Because psychopathy involves aggression, we have examined whether psychopathy as well as any of the four facets of the Psychopathy Checklist-Revised (PCL-R) (Interpersonal, Affective, Lifestyle and Antisocial) are related to different substance use disorders, with the focus on FZ. We have also examined the relationship between each PCL-R item and FZ use. Participants were 114 male offenders aged 14-35 years, all of whom were convicted for severe, predominantly violent, offences. Substance use, including FZ, was not more common in those who scored high in psychopathy. Use of FZ was more common in offenders who scored high in Facet 4 (Antisocial) of the PCL-R (odds ratio = 4.30, 95% CI 1.86-9.94). Only one of the PCL-R items, "Criminal versatility", was significantly associated with FZ use (odds ratio = 3.7). It may be concluded that intake of FZ has a specific relationship to only one of the facets and not to psychopathy per se. ; The findings have also important theoretical implications because Facet 4 is not a key factor of the construct of psychopathy. Clinical implications of the article: We have used the new two-factor and four-facet theoretical model of psychopathy in the young offender population, many of them with one or more substance use disorders. The present results suggest that antisocial behavior defined by Facet 4 (poor behavioral control, early behavior problems, juvenile delinquency, revocation of conditional release and criminal versatility) in the studied subjects is more typical for FZ users than it is for non-FZ users. This may have implications for assessment and treatment. Clinicians should be aware that criminals with high scores on Facet 4 have a more than fourfold odds of being a FZ user. This conclusion has an important clinical implication because FZ abuse is very common and is not always the focus of a forensic psychiatric assessment. ;
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20.
  • Dåderman, Anna Maria, 1953-, et al. (författare)
  • Psychopathic traits and lifestyle in flunitrazepam abusers
  • 2005
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • The abuse of flunitrazepam (FZ) compounds is world-wide. We have examined whether any of the four facets of the Psychopathy Checklist-Revised (PCL-R) (Interpersonal, Affective, Lifestyle, and Antisocial) (Hare, 2003) is related to different substance use disorders, with the focus on FZ abuse. Participants were 114 male offenders aged 14-35 years, all of whom were convicted for severe, predominantly violent, offences. Abuse of FZ was more common in offenders who scored high in Facet 4 (Antisocial) of the PCL-R (odds ratio = 4.30, 95% C.I. 1.86 - 9.94). Using all 20 PCL‑R items as individual predictors of being an FZ abuser, only one of the items, Item 20) (Criminal versatility) was significantly associated with FZ abuse (odds ratio = 3.72, 95% C.I. 1.85 - 7.50). We suggest that abuse of FZ is more common in offenders who score high in Facet 4, and that FZ abuse is significantly associated with Item 20. Our results show that clinicians and those who develop or manage therapeutic programs should be aware of FZ abuse when choosing the most effective treatment for young mentally disordered severe offenders.
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21.
  • Dåderman, Anna Maria, 1953-, et al. (författare)
  • Psychopathy-related personality traits in male juvenile delinquents : an application of a person-oriented approach
  • 2004
  • Ingår i: International Journal of Law and Psychiatry. - Göttingen : Elsevier. - 0160-2527 .- 1873-6386. ; 27:1, s. 45-64
  • Tidskriftsartikel (refereegranskat)abstract
    • Some personality characteristics, such as impulsiveness, thrill seeking, and the need for change, are clearly relevant when studying psychopathy. Psychopaths are certainly avid sensation seekers. The primary aim of the present study was to identify common patterns with respect to psychopathy-related personality traits in a sample of 56 juveniles from four Swedish national correctional institutions for juvenile delinquents. Karolinska Scales of Personality (KSP), the Impulsiveness scale from the Impulsiveness–Venturesomeness–Empathy (IVE) inventory and the Total Sensation-Seeking scale from the SSS-V were used to determine personality traits. Cluster analysis was performed with SLEIPNER. Ward’s hierarchical minimum variance clustering method was used. We discovered seven clusters of participants. The mean T scores of the profiles of personality traits in the clusters (the cluster centroids) have been used to describe the clusters. Three multideviant clusters emerged, into which 31 (63%) of the classified participants could be placed. To describe the clusters, the prevalence of participants with a high degree of psychopathy (cutoff PCL-R score 27or above) was computed for each cluster and was complemented with data on previous treatment occasions and reoffending. The results indicated that psychopaths may develop different personality pattern; each cluster contained participants with high values of the PCL-R. Deviant personality is not currently considered when assessing and treating people in state administered observational and correctional institutions for juvenile delinquents in Sweden. The present results suggest that young people with psychopathy are not a homogenous group but may develop various personality traits. This should have implications for risk assessment and treatment.
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22.
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23.
  • Dåderman, Anna Maria, 1953-, et al. (författare)
  • Violent behavior, impulsive decision-making, and anterograde amnesia while intoxicated with Flunitrazepam and alcohol or other drugs : A case study in forensic psychiatric patients
  • 2002
  • Ingår i: The journal of the American Academy of Psychiatry and the Law. - Bloomfield, CT, USA. - 1093-6793 .- 1943-3662. ; 30:2, s. 238-251
  • Tidskriftsartikel (refereegranskat)abstract
    • It is known that many male juvenile delinquents commit violent crimes while intoxicated with flunitrazepam (FZ), often in combination with alcohol or other drugs. We have also noted the combined abuse of FZ with, for example, alcohol in male forensic psychiatric patients. Our objective was to study violent behavior, impulsive decision making, and amnesia in male forensic psychiatric patients who were intoxicated predominantly with FZ, to increase knowledge of the abuse of FZ in vulnerable subjects. We studied five forensic psychiatric patients, all of whom were assessed in 1998. All of the subjects reported earlier reactions to FZ, including hostility and anterograde amnesia. At the time of their crimes they were all intoxicated with FZ, often in combination with alcohol or other drugs, such as amphetamine or cannabis. In contrast to their behavior based on their ordinary psychological characteristics, their crimes were extremely violent, and the subjects lacked both the ability to think clearly and to have empathy with their victims. Our observations support the view that FZ abuse can lead to serious violent behavior in subjects characterized by vulnerable personality traits, and that this effect is confounded by the concurrent use of alcohol or other drugs. It is evident that FZ causes anterograde amnesia. Previous research and the results presented herein allow us to draw the following conclusion: on the basis of the neuropsychopharmacologic properties of FZ, legal decisions, such as declaring FZ an illegal drug, are needed in countries where it is now legal.
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24.
  • Evangelou, Evangelos, et al. (författare)
  • Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.
  • 2018
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:10, s. 1412-1425
  • Tidskriftsartikel (refereegranskat)abstract
    • High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.
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25.
  • Fall, Tove, et al. (författare)
  • The Role of Adiposity in Cardiometabolic Traits : A Mendelian Randomization Analysis
  • 2013
  • Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 10:6, s. e1001474-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The association between adiposity and cardiometabolic traits is well known from epidemiological studies. Whilst the causal relationship is clear for some of these traits, for others it is not. We aimed to determine whether adiposity is causally related to various cardiometabolic traits using the Mendelian randomization approach. Methods and Findings: We used the adiposity-associated variant rs9939609 at the FTO locus as an instrumental variable (IV) for body mass index (BMI) in a Mendelian randomization design. Thirty-six population-based studies of individuals of European descent contributed to the analyses. Age-and sex-adjusted regression models were fitted to test for association between (i) rs9939609 and BMI (n = 198,502), (ii) rs9939609 and 24 traits, and (iii) BMI and 24 traits. The causal effect of BMI on the outcome measures was quantified by IV estimators. The estimators were compared to the BMI-trait associations derived from the same individuals. In the IV analysis, we demonstrated novel evidence for a causal relationship between adiposity and incident heart failure (hazard ratio, 1.19 per BMI-unit increase; 95% CI, 1.03-1.39) and replicated earlier reports of a causal association with type 2 diabetes, metabolic syndrome, dyslipidemia, and hypertension (odds ratio for IV estimator, 1.1-1.4; all p<0.05). For quantitative traits, our results provide novel evidence for a causal effect of adiposity on the liver enzymes alanine aminotransferase and gamma-glutamyl transferase and confirm previous reports of a causal effect of adiposity on systolic and diastolic blood pressure, fasting insulin, 2-h post-load glucose from the oral glucose tolerance test, C-reactive protein, triglycerides, and high-density lipoprotein cholesterol levels (all p<0.05). The estimated causal effects were in agreement with traditional observational measures in all instances except for type 2 diabetes, where the causal estimate was larger than the observational estimate (p = 0.001). Conclusions: We provide novel evidence for a causal relationship between adiposity and heart failure as well as between adiposity and increased liver enzymes.
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26.
  • Flach, Carl-Fredrik, 1977, et al. (författare)
  • Isolation of novel IncA/C and IncN fluoroquinolone resistance plasmids from an antibiotic-polluted lake
  • 2015
  • Ingår i: Journal of Antimicrobial Chemotherapy. - : Oxford University Press (OUP). - 0305-7453 .- 1460-2091. ; 70:10, s. 2709-2717
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives Antibiotic-polluted environments may function as reservoirs for novel resistance plasmids not yet encountered in pathogens. The aims of this study were to assess the potential of resistance transfer between bacteria from such environments and Escherichia coli, and to characterize the conjugative elements involved. Methods Sediment samples from Kazipally lake and Asanikunta tank, two Indian lakes with a history of severe pollution with fluoroquinolones, were investigated. Proportions of resistant bacteria were determined by selective cultivation, while horizontal gene transfer was studied using a GFP-tagged E. coli as recipient. Retrieved transconjugants were tested for susceptibility by Etest® and captured conjugative resistance elements were characterized by WGS. Results The polluted lakes harboured considerably higher proportions of ciprofloxacin-resistant and sulfamethoxazole-resistant bacteria than did other Indian and Swedish lakes included for comparison (52% versus 2% and 60% versus 7%, respectively). Resistance plasmids were captured from Kazipally lake, but not from any of the other lakes; in the case of Asanikunta tank because of high sediment toxicity. Eight unique IncA/C and IncN resistance plasmids were identified among 11 sequenced transconjugants. Five plasmids were fully assembled, and four of these carried the quinolone resistance gene qnrVC1, which has previously only been found on chromosomes. Acquired resistance genes, in the majority of cases associated with class 1 integrons, could be linked to decreased susceptibility to several different classes of antibiotics. Conclusions Our study shows that environments heavily polluted with antibiotics contain novel multiresistance plasmids transferrable to E. coli.
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27.
  • Gustavsson, Johan, 1974, et al. (författare)
  • High-speed 850-nm VCSELs for 40 Gb/s transmission
  • 2010
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • We have explored the possibility to extend the data transmission rate for standard 850-nm GaAs-based VCSELs beyond the 10 Gbit/s limit of today's commercially available directly-modulated devices. By sophisticated tailoring of the design for high-speed performance we demonstrate that 10 Gb/s is far from the upper limit. For example, the thermal conductivity of the bottom mirror is improved by the use of binary compounds, and the electrical parasitics are kept at a minimum by incorporating a large diameter double layered oxide aperture in the design. We also show that the intrinsic high speed performance is significantly improved by replacing the traditional GaAs QWs with strained InGaAs QWs in the active region. The best overall performance is achieved for a device with a 9 μm diameter oxide aperture, having in a threshold current of 0.6 mA, a maximum output power of 9 mW, a thermal resistance of 1.9 °C/mW, and a differential resistance of 80 Ω. The measured 3dB bandwidth exceeds 20 GHz, and we experimentally demonstrate that the device is capable of error-free transmission (BER
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28.
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29.
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30.
  • Hofving, Tobias, 1989, et al. (författare)
  • 177 Lu-octreotate therapy for neuroendocrine tumours is enhanced by Hsp90 inhibition
  • 2019
  • Ingår i: Endocrine-Related Cancer. - 1479-6821 .- 1351-0088. ; 26:4, s. 437-449
  • Tidskriftsartikel (refereegranskat)abstract
    • Lu-177-octreotate is an FDA-approved radionuclide therapy for patients with gastroenteropancreatic neuroendocrine tumours (NETs) expressing somatostatin receptors. The Lu-177-octreotate therapy has shown promising results in clinical trials by prolonging progression-free survival, but complete responses are still uncommon. The aim of this study was to improve the Lu-177-octreotate therapy by means of combination therapy. To identify radiosensitising inhibitors, two cell lines, GOT1 and P-STS, derived from small intestinal neuroendocrine tumours (SINETs), were screened with 1224 inhibitors alone or in combination with external radiation. The screening revealed that inhibitors of Hsp90 can potentiate the tumour cell-killing effect of radiation in a synergistic fashion (GOT1; false discovery rate < 3.2 x 10(-11)). The potential for Hsp90 inhibitor ganetespib to enhance the anti-tumour effect of Lu-177-octreotate in an in vivo setting was studied in the somatostatin receptor-expressing GOT1 xenograft model. The combination led to a larger decrease in tumour volume relative to monotherapies and the tumour-reducing effect was shown to be synergistic. Using patient-derived tumour cells from eight metastatic SINETs, we could show that ganetespib enhanced the effect of Lu-177-octreotate therapy for all investigated patient tumours. Levels of Hsp90 protein expression were evaluated in 767 SINETs from 379 patients. We found that Hsp90 expression was upregulated in tumour cells relative to tumour stroma in the vast majority of SINETs. We conclude that Hsp90 inhibitors enhance the tumour-killing effect of Lu-177-octreotate therapy synergistically in SINET tumour models and suggest that this potentially promising combination should be further evaluated.
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31.
  • Hofving, Tobias, 1989, et al. (författare)
  • SMAD4 haploinsufficiency in small intestinal neuroendocrine tumors
  • 2021
  • Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 21:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Patients with small intestinal neuroendocrine tumors (SINETs) frequently present with lymph node and liver metastases at the time of diagnosis, but the molecular changes that lead to the progression of these tumors are largely unknown. Sequencing studies have only identified recurrent point mutations at low frequencies with CDKN1B being the most common harboring heterozygous mutations in less than 10% of all tumors. Although SINETs are genetically stable tumors with a low frequency of point mutations and indels, they often harbor recurrent hemizygous copy number alterations (CNAs) yet the functional implications of these CNA are unclear. Methods: Utilizing comparative genomic hybridization (CGH) arrays we analyzed the CNA profile of 131 SINETs from 117 patients. Two tumor suppressor genes and corresponding proteins i.e. SMAD4, and CDKN1B, were further characterized using a tissue microarray (TMA) with 846 SINETs. Immunohistochemistry (IHC) was used to quantify protein expression in TMA samples and this was correlated with chromosome number evaluated with fluorescent in-situ hybridization (FISH). Intestinal tissue from a Smad4+/− mouse model was used to detect entero-endocrine cell hyperplasia with IHC. Results: Analyzing the CGH arrays we found loss of chromosome 18q and SMAD4 in 71% of SINETs and that focal loss of chromosome 12 affecting the CDKN1B was present in 9.4% of SINETs. No homozygous loss of chromosome 18 was detected. Hemizygous loss of SMAD4, but not CDKN1B, significantly correlated with reduced protein levels but hemizygous loss of SMAD4 did not induce entero-endocrine cell hyperplasia in the Smad4+/− mouse model. In addition, patients with low SMAD4 protein expression in primary tumors more often presented with metastatic disease. Conclusions: Hemizygous loss of chromosome 18q and the SMAD4 gene is the most common genetic event in SINETs and our results suggests that this could influence SMAD4 protein expression and spread of metastases. Although SMAD4 haploinsufficiency alone did not induce tumor initiation, loss of chromosome 18 could represent an evolutionary advantage in SINETs explaining the high prevalence of this aberration. Functional consequences of reduced SMAD4 protein levels could hypothetically be a potential mechanism as to why loss of chromosome 18 appears to be clonally selected in SINETs.
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32.
  • Inda Diaz, Juan Salvador, 1984, et al. (författare)
  • Latent antibiotic resistance genes are abundant, diverse, and mobile in human, animal, and environmental microbiomes
  • 2023
  • Ingår i: Microbiome. - : Springer Science and Business Media LLC. - 2049-2618. ; 11:1, s. 44-
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Bacterial communities in humans, animals, and the external environment maintain a large collection of antibiotic resistance genes (ARGs). However, few of these ARGs are well-characterized and thus established in existing resistance gene databases. In contrast, the remaining latent ARGs are typically unknown and overlooked in most sequencing-based studies. Our view of the resistome and its diversity is therefore incomplete, which hampers our ability to assess risk for promotion and spread of yet undiscovered resistance determinants. RESULTS: A reference database consisting of both established and latent ARGs (ARGs not present in current resistance gene repositories) was created. By analyzing more than 10,000 metagenomic samples, we showed that latent ARGs were more abundant and diverse than established ARGs in all studied environments, including the human- and animal-associated microbiomes. The pan-resistomes, i.e., all ARGs present in an environment, were heavily dominated by latent ARGs. In comparison, the core-resistome, i.e., ARGs that were commonly encountered, comprised both latent and established ARGs. We identified several latent ARGs shared between environments and/or present in human pathogens. Context analysis of these genes showed that they were located on mobile genetic elements, including conjugative elements. We, furthermore, identified that wastewater microbiomes had a surprisingly large pan- and core-resistome, which makes it a potentially high-risk environment for the mobilization and promotion of latent ARGs. CONCLUSIONS: Our results show that latent ARGs are ubiquitously present in all environments and constitute a diverse reservoir from which new resistance determinants can be recruited to pathogens. Several latent ARGs already had high mobile potential and were present in human pathogens, suggesting that they may constitute emerging threats to human health. We conclude that the full resistome-including both latent and established ARGs-needs to be considered to properly assess the risks associated with antibiotic selection pressures. Video Abstract.
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33.
  • Johansson, Anette, et al. (författare)
  • Severity of past aggression coupled to higher baseline oxygenated hemoglobin in right dorsolateral prefrontal cortex in schizophrenia
  • 2019
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Objective: Are there differences in working memory task related oxygenated hemoglobin (HbO) in dorsolateral prefrontal cortex in those with schizophrenia, who had committed instrumental violence as opposed to reactive aggression? Is there any relationship to the severity of such aggression?Methods: 22 stable forensic psychiatric inpatients with schizophrenia spectrum disorders (20 schizophrenia) were rated on symptom scales. Their most severe aggressive act was rated according to Cornell’s classification of instrumental or reactive aggression. The severity of aggression was also noted. Subjects completed a computerized Corsi-block-tapping test during functional near infrared spectroscopy (fNIRS). Correlation analyses and GLM were used to identify factors that correlated with oxygenated hemoglobin signal in optodes 1 and 15 (dorsolateral prefrontal cortex DLPFC).Results / Discussion: Spearman Rank correlations with task-minus-baseline HbO in optode 1(left DLPFC) were found for total antipsychotic daily dose and scores on block 5 of the Corsi task, as well as between daily dose and negative symptom scores. Correlations were found between baseline HbO in optode 1 and 15, as well as in task-minus-baseline.  There was no effect of type of aggression on optode 1 or 15 baseline or task-minus-baseline HbO when controlled for the above. Past severe aggression, controlled for SANS, daily dose and Corsi correct responses correlated with higher HbO at baseline in optode 15 (F=9.45 p=0.007, adj R2=0.33, p=0.032) as opposed to task related HbO. Baseline and task-minus baseline optode 1 HbO correlated only with antipsychotic dose and Corsi score.
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34.
  • Johnning, Anna, 1985, et al. (författare)
  • Acquired genetic mechanisms of a multiresistant bacterium isolated from a treatment plant receiving wastewater from antibiotic production.
  • 2013
  • Ingår i: Applied and environmental microbiology. - 1098-5336 .- 0099-2240. ; 79:23, s. 7256-63
  • Tidskriftsartikel (refereegranskat)abstract
    • The external environment, particularly wastewater treatment plants (WWTPs), where environmental bacteria meet human commensals and pathogens in large numbers, has been highlighted as a potential breeding ground for antibiotic resistance. We have isolated the extensively drug-resistant Ochrobactrum intermedium CCUG 57381 from an Indian WWTP receiving industrial wastewater from pharmaceutical production contaminated with high levels of quinolones. Antibiotic susceptibility testing against 47 antibiotics showed that the strain was 4 to >500 times more resistant to sulfonamides, quinolones, tetracyclines, macrolides, and the aminoglycoside streptomycin than the type strain O. intermedium LMG 3301(T). Whole-genome sequencing identified mutations in the Indian strain causing amino acid substitutions in the target enzymes of quinolones. We also characterized three acquired regions containing resistance genes to sulfonamides (sul1), tetracyclines [tet(G) and tetR], and chloramphenicol/florfenicol (floR). Furthermore, the Indian strain harbored acquired mechanisms for horizontal gene transfer, including a type I mating pair-forming system (MPFI), a MOBP relaxase, and insertion sequence transposons. Our results highlight that WWTPs serving antibiotic manufacturing may provide nearly ideal conditions for the recruitment of resistance genes into human commensal and pathogenic bacteria.
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35.
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36.
  • Johnning, Anna, 1985, et al. (författare)
  • Quinolone resistance mutations in the faecal microbiota of Swedish travellers to India
  • 2015
  • Ingår i: BMC Microbiology. - : Springer Science and Business Media LLC. - 1471-2180. ; 15
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: International travel contributes to the spread of antibiotic resistant bacteria over the world. Most studies addressing travel-related changes in the faecal flora have focused on specific mobile resistance genes, or depended on culturing of individual bacterial isolates. Antibiotic resistance can, however, also spread via travellers colonized by bacteria carrying chromosomal antibiotic resistance mutations, but this has received little attention so far. Here we aimed at exploring the abundance of chromosomal quinolone resistance mutations in Escherichia communities residing in the gut of Swedish travellers, and to determine potential changes after visiting India. Sweden is a country with a comparably low degree of quinolone use and quinolone resistance, whereas the opposite is true for India. Methods: Massively parallel amplicon sequencing targeting the quinolone-resistance determining region of gyrA and parC was applied to total DNA extracted from faecal samples. Paired samples were collected from 12 Swedish medical students before and after a 4-15 week visit to India. Twelve Indian residents were included for additional comparisons. Methods known resistance mutations were common in Swedes before travel as well as in Indians, with a trend for all mutations to be more common in the Indian sub group. There was a significant increase in the abundance of the most common amino acid substitution in GyrA (S83L, from 44 to 72 %, p = 0.036) in the samples collected after return to Sweden. No other substitution, including others commonly associated with quinolone resistance (D87N in GyrA, S80I in ParC) changed significantly. The number of distinct genotypes encoded in each traveller was significantly reduced after their visit to India for both GyrA (p = 0.0020) and ParC (p = 0.0051), indicating a reduced genetic diversity, similar to that found in the Indians. Conclusions: International travel can alter the composition of the Escherichia communities in the faecal flora, favouring bacteria carrying certain resistance mutations, and, thereby, contributes to the global spread of antibiotic resistance. A high abundance of specific mutations in Swedish travellers before visiting India is consistent with the hypothesis that these mutation have no fitness cost even in the absence of an antibiotic selection pressure.
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37.
  • Johnning, Anna, 1985, et al. (författare)
  • Resistance Mutations in gyrA and parC are Common in Escherichia Communities of both Fluoroquinolone-Polluted and Uncontaminated Aquatic Environments
  • 2015
  • Ingår i: Frontiers in Microbiology. - : Frontiers Media SA. - 1664-302X. ; 6
  • Tidskriftsartikel (refereegranskat)abstract
    • Alterations in the target proteins of fluoroquinolones, especially in GyrA and ParC, are known to cause resistance. Here, we investigated environmental Escherichia communities to explore the possible link between the abundance of mutations, and the exposure to fluoroquinolones. Sediment samples were collected from a relatively pristine lake, up and downstream from a sewage treatment plant, and from several industrially polluted sites. The quinolone resistance-determining regions of gyrA and parC were analyzed using amplicon sequencing of metagenomic DNA. Five non-synonymous substitutions were present in all samples, and all of these mutations have been previously linked to fluoroquinolone resistance in Escherichia coli. In GyrA, substitutions S83L and D87N were on average detected at frequencies of 86 and 32%, respectively, and 31% of all amplicons encoded both substitutions. In ParC, substitutions S80I, E84G, and E84V were detected in 42, 0.9, and 6.0% of the amplicons, respectively, and 6.5% encoded double substitutions. There was no significant correlation between the level of fluoroquinolone pollution and the relative abundance of resistance mutations, with the exception of the most polluted site, which showed the highest abundance of said substitutions in both genes. Our results demonstrate that resistance mutations can be common in environmental Escherichia, even in the absence of a fluoroquinolone selective pressure.
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38.
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39.
  • Johnning, Anna, 1985, et al. (författare)
  • The resistomes of six carbapenem-resistant pathogens - a critical genotype-phenotype analysis
  • 2018
  • Ingår i: Microbial Genomics. - : Microbiology Society. - 2057-5858. ; 4:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Carbapenem resistance is a rapidly growing threat to our ability to treat refractory bacterial infections. To understand how carbapenem resistance is mobilized and spread between pathogens, it is important to study the genetic context of the underlying resistance mechanisms. In this study, the resistomes of six clinical carbapenem-resistant isolates of five different species - Acinetobacter baumannii, Escherichia colt, two Klebsiella pneumoniae, Proteus mirabilis and Pseudomonas aeruginosa - were characterized using whole genome sequencing. All Enterobacteriaceae isolates and the A. baumannii isolate had acquired a large number of antimicrobial resistance genes (7-18 different genes per isolate), including the following encoding carbapenemases: bla(KPC-2), bla(OXA-48), bla(OXA-72), bla(NDM-1), bla(NDm-7) and bla(VIM-1). In addition, a novel version of bla(SHv) was discovered. Four new resistance plasmids were identified and their fully assembled sequences were verified using optical DNA mapping. Most of the resistance genes were colocalized on these and other plasmids, suggesting a risk for coselection. In contrast, five out of six carbapenemase genes were present on plasmids with no or few other resistance genes. The expected level of resistance - based on acquired resistance determinants - was concordant with measured levels in most cases. There were, however, several important discrepancies for four of the six isolates concerning multiple classes of antibiotics. In conclusion, our results further elucidate the diversity of carbapenemases, their mechanisms of horizontal transfer and possible patterns of co-selection. The study also emphasizes the difficulty of using whole genome sequencing for antimicrobial susceptibility testing of pathogens with complex genotypes.
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40.
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41.
  • Juul-Dam, KL, et al. (författare)
  • Deep Sequencing of Leukemia-specific Mutations in Peripheral Blood Identifies Children with Imminent Relapse of Acute Myeloid Leukemia
  • 2019
  • Ingår i: NOPHO Annual Meeting 2019.
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Relapse remains the major problem in childhood acute myeloid leukemia (AML). The outcome in children with imminent relapse may improve if preemptive therapy is initiated at first evidence of leukemia regrowth. This requires measurable residual disease (MRD) monitoring after therapy completion, but only 40% of children with AML harbor genetic abnormalities applicable for quantification using standardized qPCR assays. To enable disease surveillance for all patients, we investigated the potential of early relapse detection in peripheral blood (PB) using patient-tailored deep sequencing (DS) MRD analysis. PB samples were collected at monthly intervals during follow-up from 45 children diagnosed with AML and treated according to the NOPHO-DBH AML 2012 protocol between January 2013 and May 2016 in Denmark, Norway, Sweden and Finland (508 samples, median 11 samples/patient, range 3–27). In relapsed patients, MRD-suitable leukemia-specific single nucleotide variants (SNVs) were identified with exome sequencing (ES) in diagnostic samples and verified at relapse. SNVs were analyzed in PB samples obtained during the months before overt relapse using DS with a sensitivity of 0.02% variant allele frequency (VAF). Until October 1st 2017, 14 patients experienced relapse within 18 months from therapy completion, and in 6 patients analysis has been completed. ES identified 37 leukemia-specific SNVs at diagnosis (median 4 SNVs/patient, range 2–12) of which 23 were also present at relapse (median 3 SNVs/patient, range 1–9). Fourteen MRD-suitable SNVs (1–3/patient) were quantified with DS. In all patients, at least one SNV was detected in PB before overt relapse occurred. The first PB sample showing MRD positivity (median error corrected VAF 0.15%, range 0.03–0.85) preceded hematological relapse at a median interval of 2.3 months (range 0.6–4.7). In conclusion, high-sensitivity quantification of leukemia-specific SNVs can facilitate early detection of imminent relapse and provide a chance for initiation of preemptive treatment.
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42.
  • Juul-Dam, KL, et al. (författare)
  • Patient-Tailored Deep Sequencing of Peripheral Blood Enables Early Detection of Relapse in Childhood Acute Myeloid Leukemia
  • 2019
  • Ingår i: Blood Vpl 134 Suppl 1 1456. - : American Society of Hematology. - 0006-4971 .- 1528-0020.
  • Konferensbidrag (refereegranskat)abstract
    • Relapse remains a major therapeutic challenge in children with acute myeloid leukemia (AML). Outcome after relapse may improve if preemptive therapy is initiated at first evidence of leukemia regrowth. Early detection of imminent relapse requires molecular measurable residual disease (MRD) monitoring after therapy completion. Today, this is possible only in about 40% of children with AML that harbor genetic abnormalities applicable for quantification using standardized qPCR assays. To enable disease surveillance for all patients, we developed patient-tailored deep sequencing (DS) MRD analysis, which provides highly sensitive detection of leukemia-specific mutations. We investigated the potential of this method for early relapse detection in peripheral blood (PB), the only easily accessible source for MRD sampling in children. PB samples were collected at monthly intervals during follow-up from 45 children diagnosed with AML and treated according to The Nordic Society of Pediatric Haematology and Oncology (NOPHO)-DBH AML 2012 protocol between January 2013 and May 2016 in Denmark, Norway, Sweden and Finland (508 samples, median 11 samples/patient, range 3-27). Nine patients with relapse (median age 5 years, range 0-8) had available diagnostic and relapse material and were included in this study. The patients displayed core binding factor abnormalities (n=3), KMT2A-rearrangements (n=3), monosomy 7 (n=1) or normal karyotype (n=2) at AML diagnosis. Leukemia-specific single nucleotide variants (SNVs) were identified with exome sequencing (ES) of sorted leukemic cells with lymphocytes or remission PB as constitutive DNA template. A variant allele frequency (VAF) with 95% confidence interval including 50% indicates presence of the mutation in all leukemic cells at diagnosis. With the exception of 2 cases with only subclonal mutations at diagnosis, leukemia-specific SNVs with VAF of 50% at diagnosis and persistence at relapse were selected as MRD targets. MRD target mutations were quantified in PB samples preceding overt relapse using patient-tailored DS assays with sensitivity of VAF 0.02%. In diagnostic samples, ES identified 53 leukemia-specific SNVs (median 4 SNVs/patient, range 2-12) of which 33 were also present at relapse (median 2 SNVs/patient, range 1-9). The number of mutations identified at diagnosis increased with age (Rs 0.83, p=0.006). All patients had at least one leukemia-specific SNV detected at both diagnosis and relapse. Twenty-one MRD target mutations (median 2 SNVs/patient, range 1-3) were quantified in PB (55 samples, median sampling interval 28 days, range 11-80) using DS. In 8/9 patients, at least one SNV was detected in PB before overt relapse occurred. The first PB sample showing MRD positivity (median VAF 0.14%, range 0.03-0.44) preceded hematological relapse at a median interval of 3 months (range 0-7.9). In 6 patients not preemptively treated, the median doubling time based on VAF increments was 7 days, with great variability between individuals and genotypes (range 4-28 days). Three patients had molecular relapse diagnosed by qPCR used in clinical diagnostics and received individualized preemptive treatment. In these 3 patients, DS detected mutations in PB for >100 days preceding overt relapse and the doubling times were 14, 25 and 36 days. In conclusion, DS of leukemia-specific mutations at frequent intervals in PB enables early detection of relapse and ES at diagnosis may identify SNVs applicable for such longitudinal MRD monitoring. This approach facilitates molecular disease surveillance and initiation of preemptive therapy in AML patients without established qPCR targets.
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43.
  • Karlsson, Roger, 1975, et al. (författare)
  • Discovery of Species-unique Peptide Biomarkers of Bacterial Pathogens by Tandem Mass Spectrometry-based Proteotyping
  • 2020
  • Ingår i: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 19:3, s. 518-528
  • Tidskriftsartikel (refereegranskat)abstract
    • Mass spectrometry (MS) and proteomics offer comprehensive characterization and identification of microorganisms and discovery of protein biomarkers that are applicable for diagnostics of infectious diseases. The use of biomarkers for diagnostics is widely applied in the clinic and the use of peptide biomarkers is increasingly being investigated for applications in the clinical laboratory. Respiratory-tract infections are a predominant cause for medical treatment, although, clinical assessments and standard clinical laboratory protocols are time-consuming and often inadequate for reliable diagnoses. Novel methods, preferably applied directly to clinical samples, excluding cultivation steps, are needed to improve diagnostics of infectious diseases, provide adequate treatment and reduce the use of antibiotics and associated development of antibiotic resistance. This study applied nano-liquid chromatography (LC) coupled with tandem MS, with a bioinformatics pipeline and an in-house database of curated high-quality reference genome sequences to identify species-unique peptides as potential biomarkers for four bacterial pathogens commonly found in respiratory tract infections (RTIs): Staphylococcus aureus; Moraxella catarrhalis; Haemophilus influenzae and Streptococcus pneumoniae. The species-unique peptides were initially identified in pure cultures of bacterial reference strains, reflecting the genomic variation in the four species and, furthermore, in clinical respiratory tract samples, without prior cultivation, elucidating proteins expressed in clinical conditions of infection. For each of the four bacterial pathogens, the peptide biomarker candidates most predominantly found in clinical samples, are presented. Data are available via ProteomeXchange with identifier PXD014522. As proof-of-principle, the most promising species-unique peptides were applied in targeted tandem MS-analyses of clinical samples and their relevance for identifications of the pathogens, i.e. proteotyping, was validated, thus demonstrating their potential as peptide biomarker candidates for diagnostics of infectious diseases.
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44.
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45.
  • Kristiansson, Robert S., et al. (författare)
  • Introduction of specialized heart failure nurses in primary care and its impact on readmissions
  • 2022
  • Ingår i: Primary Health Care Research and Development. - : Cambridges Institutes Press. - 1463-4236 .- 1477-1128. ; 23
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Heart failure (HF) has a 2% prevalence in the population and is a major cause of morbidity and mortality. Multiple efforts have been made worldwide to improve quality of care and decrease unplanned readmissions for HF patients, one of which has been the introduction of specialist HF nurses (HFN) in primary health care. The present evidence on the benefits of HFN is contradicting. This study aims to evaluate the impact of a quality improvement intervention, availability of a HFN in Swedish primary care, on hospital readmissions.Methods: All patients over the age of 65 with a HF diagnosis and with complete information on availability of a HFN were included in this retrospective register-based study. Using propensity score matching (PSM) techniques, two comparable groups of 128 patients each were created according to the exposure status, availability or no availability of a HFN. The rate of readmission was compared between the groups.Results: Using PSM, 256 patients were matched, 128 in the HFN group and 128 in the no-HFN group. A total of 50% and 46.09% of patients in the HFN and no-HFN groups were readmitted, respectively. Mean number of readmissions per patient was 1.19 (SD 0.61) in the HFN group and 1.10 (SD 0.44) in the no-HFN group. Patients in the HFN had 17.6% higher odds of being readmitted during the study period, OR: 1.176 (CI: 0.716-1.932), and 3.8% lower odds of being readmitted within 30 days, OR: 0.962 (CI: 0.528-1.750).Conclusions: Availability of a HFN in primary care was not significantly associated with reduced readmissions for the patients included in this study. Further investigations are warranted looking at the impacts of availability and access to a HFN in primary care on readmissions and other patient outcomes.
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46.
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47.
  • Lennquist, Anna, 1978, et al. (författare)
  • Colour and melanophore function in rainbow trout after long term exposure to the new antifoulant medetomidine
  • 2010
  • Ingår i: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 80:9, s. 1050-1055
  • Tidskriftsartikel (refereegranskat)abstract
    • Medetomidine is a new antifouling agent, and its effects in non-target aquatic organisms have been investigated. Earlier short-term studies in fish have shown a skin lightening response to medetomidine, but effects after chronic exposure have not been studied. In fish, the dark pigment melanin is contained within specialized cells, melanophores. Medetomidine binds to the melanophore α2-adrenoceptor, which stimulates pigment aggregation resulting in the light appearance. In the present study, rainbow trout (Oncorhynchus mykiss) was long-term exposed to 0.5 and 5.0 nM of medetomidine via water for 54 d. The fish were then photographed for paleness quantification and the images were analyzed using ImageJ analysis software. Additionally, scales were removed and used for in vitro function studies of the melanophores, monitoring the response to melanophore stimulating hormone (MSH) and subsequent medetomidine addition. The number of melanophores was also investigated. As a result of the medetomidine exposure, fish from the 5 nM treatment were significantly paler than control fish and the melanophores from these fishes were also more aggregated. Melanophores from all the treatments were functional, responding to MSH by dispersion and to subsequent medetomidine by aggregation. However, the results indicate a difference in sensitivity among treatments. The number of melanophores in the scales did not change significantly after long term exposure to medetomidine. These results suggest that the observed paleness may be reversible, even after chronic exposure.
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48.
  • Lennquist, Anna, 1978, et al. (författare)
  • Physiology and mRNA expression in rainbow trout (Oncorhynchus mykiss) after long-term exposure to the new antifoulant medetomidine.
  • 2011
  • Ingår i: Comparative biochemistry and physiology. Toxicology & pharmacology : CBP. - : Elsevier BV. - 1532-0456. ; 154:3, s. 234-41
  • Tidskriftsartikel (refereegranskat)abstract
    • Medetomidine is under evaluation for use as an antifouling agent, and its effects on non-target aquatic organisms are therefore of interest. In this study, rainbow trout was exposed to low (0.5 and 5.0nM) concentrations of medetomidine for up to 54days. Recently we have reported on effects on paleness and melanophore aggregation of medetomidine in these fish. Here, specific growth rates were investigated together with a broad set of physiological parameters including plasma levels of growth hormone (GH), insulin-like growth factor-I (IGF-I) and leptin, glucose and haemoglobin (Hb), hematocrit (Ht), condition factor, liver and heart somatic indexes (LSI, HSI). Hepatic enzyme activities of CYP1A (EROD activity), glutathione S-transferases (GST) and glutathione reductase (GR) were also measured. Additionally, hepatic mRNA expression was analysed through microarray and quantitative PCR in fish sampled after 31days of exposure. Medetomidine at both concentrations significantly lowered blood glucose levels and the higher concentration significantly reduced the LSI. The mRNA expression analysis revealed few differentially expressed genes in the liver and the false discovery rate was high. Taken together, the results suggest that medetomidine at investigated concentrations could interfere with carbohydrate metabolism of exposed fish but without any clear consequences for growth.
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49.
  • Lindblom, Anna, et al. (författare)
  • The impact of the ST131 clone on recurrent ESBL-producing E. coli urinary tract infection: a prospective comparative study
  • 2022
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The global emergence of extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-E. coli), mainly causing urinary tract infections (UTI), is of great concern. Almost one third of patients with UTI, develop recurrent UTI (RUTI). We followed 297 patients for one year after their first episode of UTI due to ESBL-E. coli. Our aim was to evaluate the impact of the globally dominant sequence type (ST)131 clone and its clades, on the risk of subsequent recurrences with ESBL-E. coli. Isolates from patients developing RUTI (68/297) were compared with those from patients with sporadic UTI (SUTI, 229/297). No association was found between RUTI and the two most prevalent phylogroups B2 and D, bla(CTX-M) genes, or resistance profile. Half of the patients with RUTI were infected with ST131 isolates. Clade C2 were in dominance (50/119) among ST131 isolates. They were more common in patients with RUTI than SUTI (28% vs 13%) and multivariate analysis showed an increased odds-ratio (OR = 2.21, p = 0.033) for recurrences in patients infected with these isolates as compared to non-ST131 isolates. Detecting specific biomarkers, as ST131 clade C2, in ESBL-E. coli UTI isolates may aid in prediction of RUTI and improve diagnostics and care of patients with a risk of ESBL-E. coli recurrences.
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50.
  • Lu, Yingchang, et al. (författare)
  • New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk
  • 2016
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.
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