Dr Valentina CiprianiSenior Lecturer in Statistical GenomicsCentre: Clinical Pharmacology and Precision MedicineEmail: v.cipriani@qmul.ac.ukTwitter: @Val3CiprianiProfileResearchPublicationsSponsorsCollaboratorsNewsProfileI hold a Degree in ‘Statistics’ (Sapienza University, Rome, 2004) and a PhD in ‘Public Health and Education’ (University of Pavia, Italy, 2009; including 2-year visiting PhD student at Prof. Balding's group, Imperial College London), with a thesis on meta-analytic methods for family-based genetic association studies. A successful post-doc (2009-2012) at the UCL Institute of Ophthalmology (London) with the publication of the first genome-wide association study (GWAS) of age-related macular degeneration (AMD) in the UK (Cipriani et al., HMG, 2012) led me to be recognised as an expert in the complex genetics of AMD both in the UK and internationally. I have been an active analyst of the International AMD Genomics Consortium (IAMDGC) with several other high-impact publications (see publication list). I was then funded through a 5-year NIHR-BRC grant (2012-2017) as the referent genetic statistician at Moorfields Eye Hospital and the UCL Institute of Ophthalmology, where I expanded my research activities beyond complex genetics into rare disease diagnostics and gene discovery, and built a solid network of collaborators that landed my current affiliation at QMUL, first as a ‘Senior Bioinformatics Research Fellow’ (2017-2020, Prof. Smedley’s group), then as a faculty member ('Lecturer' in Statistical Genomics [March 2020 -July 2022], progressing to ‘Senior Lecturer’ in August 2022). I am a member of the Centre for Translational Bioinformatics. Twitter: @QMUL_C4TB. I am a Fellow at the Queen Mary's Digital Environment Research Institute (DERI) (August 2022 - present).ResearchGroup members Miss Apoorva Sarah Perepogu (MSc in Bioinformatics student, 2022-2023); project title: “Extending the rare variant burden analysis to the non-coding genome with an application to the 100,000 Genomes Project data” Miss Amy Evans (Barts charity PhD student, 2023- ); project title: “Genetic determinants of pituitary adenomas” Contact me at v.cipriani@qmul.ac.uk or check out my Twitter account @Val3Cipriani for currently available PhD student and post-doc research positions. Alumni Miss Catherine Kelly (MSc in Bioinformatics, 2020-2021); Kelly C, …Cipriani V, Phenotype-aware prioritisation of rare Mendelian disease variants. Trends Genet, 38:1271-1283, 2022 Miss Penpitcha Thawong (MSc in Bioinformatics, 2018-2019); Cipriani V, …, Thawong P, et al. An Improved Phenotype-Driven Tool for Rare Mendelian Variant Prioritization: Benchmarking Exomiser on Real Patient Whole-Exome Data. Genes, 11:460, 2020 Summary My research aims to help elucidate the genetic determinants of both common complex and rare Mendelian human diseases by using cutting-edge computational tools in genotyping and sequencing association studies. The divide between common and rare diseases has been decreasing over the past years with many common disorders presenting with their closely linked monogenic familial forms, as well as many Mendelian disorders showing incomplete penetrance and variable expressivity due, for example, to the effect of modifier genes and/or environmental factors. I am currently involved in many national and international human genetic projects, including studies of the complex genetics of age-related macular degeneration (AMD) and the analysis of genomic data from the 100,000 Genomes Project (100KGP) and the University College London (UCL) exome consortium (UCLex). My research output has a high clinical impact with potential implications for novel therapeutics in complex genetics and demonstrated increases in the diagnostic yield in rare diseases. Exomiser; rare disease diagnostics and gene discoveryI have been an active member of the Monarch Initiative and Human Phenotype Ontology community, contributing to the improvement and assessment of flagship Exomiser tool for phenotype-based variant prioritisation. Such tools often lack extensive validation on real patient data. I have recently shown an effective Exomiser performance on a large rare disease whole-exome patient dataset (Cipriani et al., Genes, 2020) and supervised an in-depth review of phenotype-based variant prioritisation tools (Kelly et al., Trends Genet, 2022). Furthermore, I co-led the application of an Exomiser-based gene burden analysis pipeline to the pilot phase of the 100KGP pilot (Smedley&Smith&Martin&Thomas&McDonagh&Cipriani&Ellingford&Arno&Tucci& Vandrovcova&Chan&Williams et al., NEJM, 2021) that has already resulted in three confirmed gene discoveries (including Bourinaris&Smedley&Cipriani et al., EJHG, 2020) as well as new gene discoveries (Park&Tucci&Cipriani et al., Genet Med, 2022). Family-based genetic association analysesI have recently led a comprehensive analysis that used a combination of haplotype-sharing, genotyping and sequencing family-based methods and successfully identified non-coding SNVs and duplications in 13 families affected by rare autosomal dominant North Carolina macular dystrophy (NCMD) (Cipriani et al., Sci Rep, 2017). This was a long-awaited result, with the chromosome 5 linkage region for this disorder being known for 15 years. These results have recently triggered further studies that gained insights into the cis-regulatory mechanisms of NCMD and support that NCMD is a retinal enhanceropathy (Van de Sompele et al., bioRxiv 2022.03.08.481329, 2022). Complex genetics of age-related macular degenerationI was the leading statistician for the first genome-wide association study (GWAS) of AMD in the UK (Cipriani et al., HMG, 2012). The study allowed me to become a member of the International AMD Genomics Consortium (IAMDGC). The IAMDGC performed the largest GWAS of AMD with the discovery of 16 novel risk loci. I presented the corresponding findings at the 64th ASHG meeting (San Diego, 2014) and contributed to the last IAMDGC GWAS manuscript (Fritsche et al., Nat Genet, 2016). Building on this experience, I have been pursuing a much-needed dissection of the well-established AMD-association at the CFH locus (known since 2005) with national and international experts in AMD and the complement system. I have led a wealth of statistical genetic data analyses that brought to the identification of FHR proteins as major players in AMD pathogenesis with concrete potential implications for complement inhibiting therapeutics (e.g., Complement Therapeutics Limited, CTx) (Cipriani et al, AJHG, 2021; Cipriani et al, Nat Commun, 2020). I am a Senior Editor for the Annals of Human Genetics.PublicationsGoogle scholar statistics (as of June 2023), Citations: 5134; h-index: 23; i10-index: 31 Leong IUS, Cabrera CP, Cipriani V et al. (2024). Large-Scale Pharmacogenomics Analysis of Patients With Cancer Within the 100,000 Genomes Project Combining Whole-Genome Sequencing and Medical Records to Inform Clinical Practice.. nameOfConference DOI: 10.1200/jco.23.02761 QMRO: qmroHref Benkirane M, Bonhomme M, Morsy H et al. (2024). De novo and inherited monoallelic variants in TUBA4A cause ataxia and spasticity. nameOfConference DOI: 10.1093/brain/awae193 QMRO: https://qmro.qmul.ac.uk/xmlui/handle/123456789/100459 Pavinato L, Stanic J, Barzasi M et al. (2023). Missense variants in RPH3A cause defects in excitatory synaptic function and are associated with a clinically variable neurodevelopmental disorder. nameOfConference DOI: 10.1016/j.gim.2023.100922 QMRO: qmroHref Chen Z, Tucci A, Cipriani V et al. (2023). Functional genomics provide key insights to improve the diagnostic yield of hereditary ataxia. nameOfConference DOI: 10.1093/brain/awad009 QMRO: qmroHref Morsy H, Benkirane M, Cali E et al. (2023). Expanding SPTAN1 monoallelic variant associated disorders: From epileptic encephalopathy to pure spastic paraplegia and ataxia. nameOfConference DOI: 10.1016/j.gim.2022.09.013 QMRO: qmroHref Park J, Tucci A, Cipriani V et al. (2022). Heterozygous UCHL1 loss-of-function variants cause a neurodegenerative disorder with spasticity, ataxia, neuropathy, and optic atrophy. nameOfConference DOI: 10.1016/j.gim.2022.07.006 QMRO: qmroHref Kelly C, Szabo A, Pontikos N et al. (2022). Phenotype-aware prioritisation of rare Mendelian disease variants. nameOfConference DOI: 10.1016/j.tig.2022.07.002 QMRO: https://uat2-qmro.qmul.ac.uk/xmlui/handle/123456789/84818 Chen Z, Cipriani V, Zhang D et al. (2022). 022 Functional genomics and transcriptomics further characterise and potentially improve diagnostic yield of hereditary ataxias. nameOfConference DOI: 10.1136/jnnp-2022-abn.347 QMRO: qmroHref Jacobsen JOB, Kelly C, Cipriani V et al. (2022). Evaluation of phenotype-driven gene prioritization methods for Mendelian diseases. nameOfConference DOI: 10.1093/bib/bbac188 QMRO: https://uat2-qmro.qmul.ac.uk/xmlui/handle/123456789/84820 Jacobsen JOB, Kelly C, Cipriani V et al. (2022). Phenotype‐driven approaches to enhance variant prioritization and diagnosis of rare disease. nameOfConference DOI: 10.1002/humu.24380 QMRO: https://uat2-qmro.qmul.ac.uk/xmlui/handle/123456789/82621 Cipriani V, Lores-Motta L, Tierney A et al. (2022). Beyond factor H: Impact of genetic-variants associated with age-related macular degeneration on circulating FHR protein levels. nameOfConference DOI: doi QMRO: qmroHref Kuan V, Warwick A, Hingorani A et al. (2021). Association of Smoking, Alcohol Consumption, Blood Pressure, Body Mass Index, and Glycemic Risk Factors With Age-Related Macular Degeneration. nameOfConference DOI: 10.1001/jamaophthalmol.2021.4601 QMRO: qmroHref Smedley D, Smith KR, Martin AR et al. (2021). 100,000 Genomes Pilot on Rare-Disease Diagnosis in Health Care — Preliminary Report. nameOfConference DOI: 10.1056/nejmoa2035790 QMRO: https://qmro.qmul.ac.uk/xmlui/handle/123456789/79432 Cipriani V, Tierney A, Griffiths JR et al. (2021). Beyond factor H: The impact of genetic-risk variants for age-related macular degeneration on circulating factor-H-like 1 and factor-H-related protein concentrations. nameOfConference DOI: 10.1016/j.ajhg.2021.05.015 QMRO: qmroHref D’Angelo E, Espinosa I, Cipriani V et al. (2021). Atypical Endometrial Hyperplasia, Low-grade. nameOfConference DOI: 10.1097/pas.0000000000001705 QMRO: qmroHref Kuan V, Warwick A, Hingorani A et al. (2021). Effects of smoking, alcohol, blood pressure, body mass index and glycaemic risk factors on advanced age-related macular degeneration: a mendelian randomisation study. nameOfConference DOI: doi QMRO: qmroHref Bourinaris T, Smedley D, Cipriani V et al. (publicationYear). Identification of UBAP1 mutations in juvenile hereditary spastic paraplegia in the 100,000 Genomes Project. nameOfConference DOI: 10.1038/s41431-020-00720-w QMRO: https://uat2-qmro.qmul.ac.uk/xmlui/handle/123456789/67071 Cipriani V, Pontikos N, Arno G et al. (publicationYear). An Improved Phenotype-Driven Tool for Rare Mendelian Variant Prioritization: Benchmarking Exomiser on Real Patient Whole-Exome Data. nameOfConference DOI: 10.3390/genes11040460 QMRO: https://uat2-qmro.qmul.ac.uk/xmlui/handle/123456789/68197 Cipriani V, Lorés-Motta L, He F et al. (2020). Increased circulating levels of Factor H-Related Protein 4 are strongly associated with age-related macular degeneration. nameOfConference DOI: 10.1038/s41467-020-14499-3 QMRO: https://uat2-qmro.qmul.ac.uk/xmlui/handle/123456789/63088 Smedley D, Abbs S, Arno G et al. (2020). The impact of the 100,000 Genomes Project on rare disease in national healthcare. nameOfConference DOI: doi QMRO: https://uat2-qmro.qmul.ac.uk/xmlui/handle/123456789/70170 Shefchek KA, Harris NL, Gargano M et al. (2020). The Monarch Initiative in 2019: an integrative data and analytic platform connecting phenotypes to genotypes across species. nameOfConference DOI: 10.1093/nar/gkz997 QMRO: qmroHref D’Angelo E, Espinosa I, Cipriani V et al. (2019). 257 Atypical endometrial hyperplasia, low-grade: ‘much ADO About nothing’. E-Poster viewings DOI: 10.1136/ijgc-2019-igcs.257 QMRO: qmroHref Carnt NA, Cipriani V, Stapleton FJ et al. (2019). Association study of single nucleotide polymorphisms in IL-10 and IL-17 genes with the severity of microbial keratitis. nameOfConference DOI: 10.1016/j.clae.2019.06.007 QMRO: qmroHref Silva RS, Arno G, Cipriani V et al. (2019). Unique noncoding variants upstream of PRDM13 are associated with a spectrum of developmental retinal dystrophies including progressive bifocal chorioretinal atrophy. nameOfConference DOI: 10.1002/humu.23715 QMRO: qmroHref Arno G, Silva RS, Pontikos N et al. (2019). A recurrent intergenic variant upstream of PRDM13 causes autosomal dominant progressive bifocal chorioretinal atrophy in two unrelated pedigrees. nameOfConference DOI: doi QMRO: qmroHref Silva RS, Kraft K, Arno G et al. (2019). Congenital Macular Dystrophy is caused by non-coding duplications downstream of IRXAlocus. nameOfConference DOI: doi QMRO: qmroHref Silva RS, Kraft K, Arno G et al. (2019). Congenital Macular Dystrophy is caused by non-coding duplications downstream of the IRXA cluster. nameOfConference DOI: doi QMRO: qmroHref Cipriani V, Lores-Motta L, Fathalla D et al. (2019). FACTOR H-RELATED PROTEIN 4 DRIVES COMPLEMENT DYSREGULATION IN AGE-RELATED MACULAR DEGENERATION. nameOfConference DOI: doi QMRO: qmroHref Cipriani V, de Motta LL, He F et al. (2019). Factor H-Related Protein 4 (FHR-4) drives complement dysregulation in age-related macular degeneration. nameOfConference DOI: doi QMRO: qmroHref Köhler S, Carmody L, Vasilevsky N et al. (2019). Expansion of the Human Phenotype Ontology (HPO) knowledge base and resources. nameOfConference DOI: 10.1093/nar/gky1105 QMRO: qmroHref Silva RS, Kraft K, Arno G et al. (2018). CRISPR-derived mouse model of North Carolina Macular Dystrophy reveals in trans tissue-specific upregulation of PRDM13. nameOfConference DOI: doi QMRO: qmroHref Cipriani V, Silva RS, Arno G et al. (publicationYear). Duplication events downstream of IRX1 cause North Carolina macular dystrophy at the MCDR3 locus. nameOfConference DOI: 10.1038/s41598-017-06387-6 QMRO: https://uat2-qmro.qmul.ac.uk/xmlui/handle/123456789/67007 Borman AD, Rachitskaya A, Suzani M et al. (2017). Benign Yellow Dot Maculopathy A New Macular Phenotype. nameOfConference DOI: 10.1016/j.ophtha.2017.02.026 QMRO: qmroHref Grassmann F, Kiel C, Zimmermann ME et al. (2017). Genetic pleiotropy between age-related macular degeneration and 16 complex diseases and traits. nameOfConference DOI: 10.1186/s13073-017-0418-0 QMRO: https://uat2-qmro.qmul.ac.uk/xmlui/handle/123456789/67015 Pontikos N, Yu J, Moghul I et al. (2017). Phenopolis: An open platform for harmonization and analysis of genetic and phenotypic data. nameOfConference DOI: 10.1093/bioinformatics/btx147 QMRO: https://uat2-qmro.qmul.ac.uk/xmlui/handle/123456789/62706 Cipriani V, Kalhoro A, Arno G et al. (2017). Genome-wide linkage and haplotype sharing analysis implicates the MCDR3 locus as a candidate region for a developmental macular disorder in association with digit abnormalities. nameOfConference DOI: 10.1080/13816810.2017.1289544 QMRO: qmroHref Cipriani V, Pontikos N, Arno G et al. (2017). An Improved Bioinformatics Tool for Rare Disease Variant Prioritization: The Exomiser 9.0.1 in Clinical Practice. nameOfConference DOI: doi QMRO: qmroHref Köhler S, Vasilevsky NA, Engelstad M et al. (2017). The Human Phenotype Ontology in 2017. nameOfConference DOI: 10.1093/nar/gkw1039 QMRO: https://uat2-qmro.qmul.ac.uk/xmlui/handle/123456789/18234 Pontikos N, Yu J, Blanco-Kelly F et al. (publicationYear). Phenopolis: an open platform for harmonization and analysis of sequencing and phenotype data. nameOfConference DOI: 10.1101/084582 QMRO: qmroHref Polley S, Cipriani V, Khan JC et al. (2016). Analysis of copy number variation at DMBT1 and age-related macular degeneration. nameOfConference DOI: 10.1186/s12881-016-0311-5 QMRO: https://uat2-qmro.qmul.ac.uk/xmlui/handle/123456789/66900 Chan MPY, Grossi CM, Khawaja AP et al. (2016). Associations with Intraocular Pressure in a Large Cohort Results from the UK Biobank. nameOfConference DOI: 10.1016/j.ophtha.2015.11.031 QMRO: qmroHref Bunce C, Quartilho A, Freemantle N et al. (2016). Ophthalmic statistics note 8: missing data—exploring the unknown. nameOfConference DOI: 10.1136/bjophthalmol-2015-307821 QMRO: qmroHref Patel PJ, Foster PJ, Grossi CM et al. (2016). Spectral-Domain Optical Coherence Tomography Imaging in 67 321 Adults Associations with Macular Thickness in the UK Biobank Study. nameOfConference DOI: 10.1016/j.ophtha.2015.11.009 QMRO: qmroHref Fritsche LG, Igl W, Bailey JNC et al. (2016). A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants. nameOfConference DOI: 10.1038/ng.3448 QMRO: https://uat2-qmro.qmul.ac.uk/xmlui/handle/123456789/69886 Cumberland PM, Bao Y, Hysi PG et al. (publicationYear). Frequency and Distribution of Refractive Error in Adult Life: Methodology and Findings of the UK Biobank Study. nameOfConference DOI: 10.1371/journal.pone.0139780 QMRO: https://uat2-qmro.qmul.ac.uk/xmlui/handle/123456789/68986 Shweikh Y, Ko F, Chan MPY et al. (2015). Measures of socioeconomic status and self-reported glaucoma in the UK Biobank cohort. nameOfConference DOI: 10.1038/eye.2015.157 QMRO: https://uat2-qmro.qmul.ac.uk/xmlui/handle/123456789/69891 Cipriani V, Quartilho A, Bunce C et al. (2015). Ophthalmic statistics note 7: multiple hypothesis testing—to adjust or not to adjust. nameOfConference DOI: 10.1136/bjophthalmol-2015-306784 QMRO: qmroHref MacGillivray TJ, Cameron JR, Zhang Q et al. (publicationYear). Suitability of UK Biobank Retinal Images for Automatic Analysis of Morphometric Properties of the Vasculature. nameOfConference DOI: 10.1371/journal.pone.0127914 QMRO: https://uat2-qmro.qmul.ac.uk/xmlui/handle/123456789/69890 Saunders LJ, Zhu H, Bunce C et al. (2015). Ophthalmic statistics note 5: diagnostic tests—sensitivity and specificity. nameOfConference DOI: 10.1136/bjophthalmol-2014-306055 QMRO: https://uat2-qmro.qmul.ac.uk/xmlui/handle/123456789/69888 Nash R, Bunce C, Freemantle N et al. (2014). Ophthalmic Statistics Note 4: analysing data from randomised controlled trials with baseline and follow-up measurements. nameOfConference DOI: 10.1136/bjophthalmol-2014-305614 QMRO: https://uat2-qmro.qmul.ac.uk/xmlui/handle/123456789/69889 Lenassi E, Saihan Z, Cipriani V et al. (2014). Natural History and Retinal Structure in Patients with Usher Syndrome Type 1 Owing to MYO7A Mutation. nameOfConference DOI: 10.1016/j.ophtha.2013.09.017 QMRO: qmroHref Zhan X, Larson DE, Wang C et al. (2013). Identification of a rare coding variant in complement 3 associated with age-related macular degeneration. nameOfConference DOI: 10.1038/ng.2758 QMRO: https://uat2-qmro.qmul.ac.uk/xmlui/handle/123456789/69887 (2013). Seven new loci associated with age-related macular degeneration. nameOfConference DOI: 10.1038/ng.2578 QMRO: https://qmro.qmul.ac.uk/xmlui/handle/123456789/69885 Cipriani V, Leung H-T, Plagnol V et al. (2012). Genome-wide association study of age-related macular degeneration identifies associated variants in the TNXB–FKBPL–NOTCH4 region of chromosome 6p21.3. nameOfConference DOI: 10.1093/hmg/dds225 QMRO: qmroHref Sofat R, Casas JP, Webster AR et al. (2012). Complement factor H genetic variant and age-related macular degeneration: effect size, modifiers and relationship to disease subtype. nameOfConference DOI: 10.1093/ije/dyr204 QMRO: qmroHref Cipriani V, Matharu BK, Khan JC et al. (2012). No evidence of association between complement factor I genetic variant rs10033900 and age-related macular degeneration. nameOfConference DOI: 10.1038/ejhg.2011.118 QMRO: qmroHref Cipriani V, Matharu BK, Khan JC et al. (2012). Genetic variation in complement regulators and susceptibility to age-related macular degeneration. nameOfConference DOI: 10.1016/j.imbio.2011.09.002 QMRO: qmroHref McKay GJ, Patterson CC, Chakravarthy U et al. (2011). Evidence of association of APOE with age‐related macular degeneration ‐ a pooled analysis of 15 studies. nameOfConference DOI: 10.1002/humu.21577 QMRO: qmroHref Shahid H, Khan JC, Cipriani V et al. (2012). Age-related macular degeneration: the importance of family history as a risk factor. nameOfConference DOI: 10.1136/bjophthalmol-2011-300193 QMRO: qmroHref Khandhadia S, Cipriani V, Yates JRW et al. (2012). Age-related macular degeneration and the complement system. nameOfConference DOI: 10.1016/j.imbio.2011.07.019 QMRO: qmroHref McKay GJ, Silvestri G, Chakravarthy U et al. (2011). Variations in Apolipoprotein E Frequency With Age in a Pooled Analysis of a Large Group of Older People. nameOfConference DOI: 10.1093/aje/kwr015 QMRO: qmroHref Shahid H, Khan J, Cipriani V et al. (2011). AGE-RELATED MACULAR DEGENERATION: THE IMPORTANCE OF FAMILY HISTORY AS A RISK FACTOR. nameOfConference DOI: doi QMRO: qmroHref Cipriani V, Mannucci PM, Ardissino D et al. (2010). Familial aggregation of early-onset myocardial infarction. nameOfConference DOI: 10.1016/j.ejim.2010.07.017 QMRO: qmroHref Sponsors Rosetrees Trust, UK, “A ciliopathies approach to understanding the genetic basis of bronchiectasis”, Co-PI, £199,942 (2023-2026) Barts Charity, UK, “Genetic determinants of pituitary adenomas”, Co-PI, £417,939 (2022-2025) Dunhill Medical Trust, UK, “Investigating the causal role of lipid pathways in age-related macular degeneration (AMD)”, Co-PI, £268,848 (2018-2021) Medical Research Centre (MRC), UK, “Investigating the influence of genetic variation associated with AMD on plasma levels of complement regulatory proteins”, Named researcher with over-heads, £521,307 (2017-2020) National Institute of Health, USA (25% of salary, 2022-2025) International Age-Related Macular Degeneration Genomics Consortium (IAMDGC), USA (travel and lodging grant for participation in the IAMDGC Annual Meeting, Belfast, Sept 2022) National Institute for Health and Care Research (NIHR), UK (full salary, 2012-2017) The Guide Dogs for the Blind Association, UK (full salary, 2009-2012) Erasmus+, EU (staff training mobility grant; May-June 2016) British Council, UK (travel and lodging grant for participation in the British Council Researcher Links WorkshopMexico-UK, June 2015) CollaboratorsInternal Professor Sir Mark Caulfield Professor Marta Korbonits External Prof. Peter Robinson (JAX, USA) Dr. Richard Unwin (University of Manchester) Prof. Simon Clark (Tübingen University, Germany) Dr. Nikolas Pontikos (UCL) Prof. Reecha Sofat (UCL) Prof. Andrew Webster (UCL) Dr. Amanda Carr (UCL) Dr. Arianna Tucci (MRC Fellow, Genomics England) Prof. Mina Ryten (UCL) Prof. Giorgia Girotto (IRCCS Burlo Garofolo, Italy) News Macular degeneration: Link found in eye disease treatment, February 2020 Back to top