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  • 1.
    Christakoudi, Sofia
    et al.
    Kings Coll London, MRC Ctr Transplantat, London SE1 9RT, England;Kings Coll London, Inst Psychiat Psychol & Neurosci, Biostat & Hlth Informat Dept, 16 Crespigny Pk, London SE5 8AF, England.
    Runglall, Manohursingh
    Guys & St Thomas NHS Fdn Trust, NIHR Biomed Res Ctr, London SE1 9RT, England;Kings Coll London, London SE1 9RT, England.
    Mobillo, Paula
    Kings Coll London, MRC Ctr Transplantat, London SE1 9RT, England.
    Rebollo-Mesa, Irene
    Kings Coll London, MRC Ctr Transplantat, London SE1 9RT, England;Kings Coll London, Inst Psychiat Psychol & Neurosci, Biostat & Hlth Informat Dept, 16 Crespigny Pk, London SE5 8AF, England;UCB Pharma SA, UCB Celltech, Brussels, Belgium.
    Tsui, Tjir-Li
    Kings Coll London, MRC Ctr Transplantat, London SE1 9RT, England;Guys & St Thomas NHS Fdn Trust, London SE1 9RT, England.
    Nova-Lamperti, Estefania
    Kings Coll London, MRC Ctr Transplantat, London SE1 9RT, England;Univ Concepcion, Pharm Fac, Dept Clin Biochem & Immunol, Lab Mol & Translat Immunol, Concepcion, Chile.
    Norris, Sonia
    Kings Coll London, MRC Ctr Transplantat, London SE1 9RT, England;UCL, London, England.
    Kamra, Yogesh
    Kings Coll London, MRC Ctr Transplantat, London SE1 9RT, England;Kings Coll London, Peter Gorer Dept Immunobiol, London, England.
    Hilton, Rachel
    Guys & St Thomas NHS Fdn Trust, London SE1 9RT, England.
    Bhandari, Sunil
    Hull & East Yorkshire Hosp NHS Trust, Anlaby Rd, Kingston Upon Hull HU3 2JZ, N Humberside, England.
    Baker, Richard
    St James Univ Hosp, Beckett St, Leeds LS9 7TF, W Yorkshire, England.
    Berglund, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Carr, Sue
    Leicester Gen Hosp, Gwendolen Rd, Leicester LE5 4PW, Leics, England.
    Game, David
    Guys & St Thomas NHS Fdn Trust, London SE1 9RT, England.
    Griffin, Sian
    Cardiff & Vale Univ Hlth Board, Cardiff CF14 4XW, S Glam, Wales.
    Kalra, Philip A.
    Salford Royal NHS Fdn Trust, Stott Ln, Salford M6 8HD, Lancs, England.
    Lewis, Robert
    Queen Alexandra Hosp, Southwick Hill Rd, Portsmouth PO6 3LY, Hants, England.
    Mark, Patrick B.
    Univ Glasgow, Univ Ave, Glasgow G12 8QQ, Lanark, Scotland.
    Marks, Stephen D.
    Great Ormond St Hosp Children NHS Fdn Trust, Great Ormond St,London, London WC1N 3JH, England.
    Macphee, Lain
    St George Hosp, Blackshaw Rd, London SW17 0QT, England.
    McKane, William
    Northern Gen Hosp, Herries Rd, Sheffield S5 7AU, S Yorkshire, England.
    Mohaupt, Markus G.
    Univ Hosp, Univ Spital Dept Nephrol Hypertens & Clin Pharmac, INSELSPITAL, Freiburgstr 8, CH-3010 Bern, Switzerland.
    Pararajasingam, Ravi
    Manchester Royal Infirm, Oxford Rd, Manchester M13 9WL, Lancs, England.
    Kon, Sui Phin
    Kings Coll Hosp NHS Fdn Trust, Denmark Hill, London SE5 9RS, England.
    Seron, Daniel
    Hosp Univ Vali dHebron, Passeig Vali dHebron 119-129, Barcelona 08035, Spain.
    Sinha, Manish
    Evelina London Childrens Hosp, Westminster Bridge Rd, London SE1 7EH, England.
    Tucker, Beatriz
    Kings Coll Hosp NHS Fdn Trust, Denmark Hill, London SE5 9RS, England.
    Viklicky, Ondrej
    IKEM, Transplantacni Lab, Videnska 1958-9, Prague 14021 4, Czech Republic.
    Lechler, Robert, I
    Kings Coll London, MRC Ctr Transplantat, London SE1 9RT, England;Guys Hosp, Kings Hlth Partners, London SE1 9RT, England.
    Lord, Graham M.
    Kings Coll London, MRC Ctr Transplantat, London SE1 9RT, England;Guys & St Thomas NHS Fdn Trust, NIHR Biomed Res Ctr, London SE1 9RT, England;Kings Coll London, London SE1 9RT, England;Guys & St Thomas NHS Fdn Trust, London SE1 9RT, England.
    Stahl, Daniel
    Kings Coll London, Inst Psychiat Psychol & Neurosci, Biostat & Hlth Informat Dept, 16 Crespigny Pk, London SE5 8AF, England.
    Hernandez-Fuentes, Maria P.
    Kings Coll London, MRC Ctr Transplantat, London SE1 9RT, England;Guys Hosp, Kings Hlth Partners, London SE1 9RT, England;UCB Pharma SA, UCB Celltech, Brussels, Belgium.
    Steroid regulation: An overlooked aspect of tolerance and chronic rejection in kidney transplantation2018In: Molecular and Cellular Endocrinology, ISSN 0303-7207, E-ISSN 1872-8057, Vol. 473, p. 205-216Article in journal (Refereed)
    Abstract [en]

    Steroid conversion (HSD11B1, HSD11B2, H6PD) and receptor genes (NR3C1, NR3C2) were examined in kidney-transplant recipients with "operational tolerance" and chronic rejection (CR), independently and within the context of 88 tolerance-associated genes. Associations with cellular types were explored. Peripheral whole-blood gene-expression levels (RT-qPCR-based) and cell counts were adjusted for immunosuppressant drug intake. Tolerant (n = 17), stable (n = 190) and CR patients (n = 37) were compared. Healthy controls (n= 14) were used as reference. The anti-inflammatory glucocorticoid receptor (NR3C1) and the cortisol-activating HSD11B1 and H6PD genes were up-regulated in CR and were lowest in tolerant patients. The pro-inflammatory mineralocorticoid gene (NR3C2) was downregulated in stable and CR patients. NR3C1 was associated with neutrophils and NR3C2 with T-cells. Steroid conversion and receptor genes, alone, enabled classification of tolerant patients and were major contributors to gene-expression signatures of both, tolerance and CR, alongside known tolerance-associated genes, revealing a key role of steroid regulation and response in kidney transplantation. 

  • 2.
    Fusar-Poli, Paolo
    et al.
    Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Psychosis Studies, Early Psychosis Intervent & Clin Detect EPIC Lab, London, England;South London & Maudsley Natl Hlth Serv Fdn Trust, OASIS Serv, London, England;Univ Pavia, Dept Brain & Behav Sci, Pavia, Italy.
    Hijazi, Ziad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Stahl, Daniel
    Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Biostat & Hlth Informat, London, England.
    Steyerberg, Ewout W.
    Leiden Univ, Med Ctr, Dept Biomed Data Sci Med Stat & Med Decis Making, Leiden, Netherlands.
    The Science of Prognosis in Psychiatry: A Review2018In: JAMA psychiatry, ISSN 2168-6238, E-ISSN 2168-622X, Vol. 75, no 12, p. 1289-1297Article, review/survey (Refereed)
    Abstract [en]

    IMPORTANCE Prognosis is a venerable component of medical knowledge introduced by Hippocrates (460-377 BC). This educational review presents a contemporary evidence-based approach for how to incorporate clinical risk prediction models in modern psychiatry. The article is organized around key methodological themes most relevant for the science of prognosis in psychiatry. Within each theme, the article highlights key challenges and makes pragmatic recommendations to improve scientific understanding of prognosis in psychiatry.

    OBSERVATIONS The initial step to building clinical risk prediction models that can affect psychiatric care involves designing the model: preparation of the protocol and definition of the outcomes and of the statistical methods (theme 1). Further initial steps involve carefully selecting the predictors, preparing the data, and developing the model in these data. A subsequent step is the validation of the model to accurately test its generalizability (theme 2). The next consideration is that the accuracy of the clinical prediction model is affected by the incidence of the psychiatric condition under investigation (theme 3). Eventually, clinical prediction models need to be implemented in real-world clinical routine, and this is usually the most challenging step (theme 4). Advanced methods such as machine learning approaches can overcome some problems that undermine the previous steps (theme 5). The relevance of each of these themes to current clinical risk prediction modeling in psychiatry is discussed and recommendations are given.

    CONCLUSIONS AND RELEVANCE Together, these perspectives intend to contribute to an integrative, evidence-based science of prognosis in psychiatry. By focusing on the outcome of the individuals, rather than on the disease, clinical risk prediction modeling can become the cornerstone for a scientific and personalized psychiatry.

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