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Institution

University of Lausanne

EducationLausanne, Switzerland
About: University of Lausanne is a education organization based out in Lausanne, Switzerland. It is known for research contribution in the topics: Population & Poison control. The organization has 20508 authors who have published 46458 publications receiving 1996655 citations. The organization is also known as: Université de Lausanne & UNIL.


Papers
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Journal ArticleDOI
TL;DR: A proof-of-concept phase Ib/IIa trial where 6 aviremic HIV-1 infected adults received intravenous 5 mg/m2 romidepsin (Celgene) once weekly for 3 weeks while maintaining ART demonstrates that significant reversal of HIV- 1 latency in vivo is possible without blunting T cell-mediated immune responses.
Abstract: Pharmacologically-induced activation of replication competent proviruses from latency in the presence of antiretroviral treatment (ART) has been proposed as a step towards curing HIV-1 infection. However, until now, approaches to reverse HIV-1 latency in humans have yielded mixed results. Here, we report a proof-of-concept phase Ib/IIa trial where 6 aviremic HIV-1 infected adults received intravenous 5 mg/m2 romidepsin (Celgene) once weekly for 3 weeks while maintaining ART. Lymphocyte histone H3 acetylation, a cellular measure of the pharmacodynamic response to romidepsin, increased rapidly (maximum fold range: 3.7–7.7 relative to baseline) within the first hours following each romidepsin administration. Concurrently, HIV-1 transcription quantified as copies of cell-associated un-spliced HIV-1 RNA increased significantly from baseline during treatment (range of fold-increase: 2.4–5.0; p = 0.03). Plasma HIV-1 RNA increased from <20 copies/mL at baseline to readily quantifiable levels at multiple post-infusion time-points in 5 of 6 patients (range 46–103 copies/mL following the second infusion, p = 0.04). Importantly, romidepsin did not decrease the number of HIV-specific T cells or inhibit T cell cytokine production. Adverse events (all grade 1–2) were consistent with the known side effects of romidepsin. In conclusion, romidepsin safely induced HIV-1 transcription resulting in plasma HIV-1 RNA that was readily detected with standard commercial assays demonstrating that significant reversal of HIV-1 latency in vivo is possible without blunting T cell-mediated immune responses. These finding have major implications for future trials aiming to eradicate the HIV-1 reservoir. Trial Registration clinicaltrials.gov NTC02092116

428 citations

Journal ArticleDOI
TL;DR: Initial evidence is described which revealed that genes in CNV regions are expressed at lower and more variable levels than genes mapping elsewhere, and also that CNV not only affects the expression of genes varying in copy number, but also has a global influence on the transcriptome.
Abstract: Copy number variation (CNV) has recently gained considerable interest as a source of genetic variation likely to play a role in phenotypic diversity and evolution. Much effort has been put into the identification and mapping of regions that vary in copy number among seemingly normal individuals in humans and a number of model organisms, using bioinformatics or hybridization-based methods. These have allowed uncovering associations between copy number changes and complex diseases in whole-genome association studies, as well as identify new genomic disorders. At the genome-wide scale, however, the functional impact of CNV remains poorly studied. Here we review the current catalogs of CNVs, their association with diseases and how they link genotype and phenotype. We describe initial evidence which revealed that genes in CNV regions are expressed at lower and more variable levels than genes mapping elsewhere, and also that CNV not only affects the expression of genes varying in copy number, but also have a global influence on the transcriptome. Further studies are warranted for complete cataloguing and fine mapping of CNVs, as well as to elucidate the different mechanisms by which they influence gene expression.

427 citations

Journal ArticleDOI
TL;DR: In this paper, the authors propose a framework for prioritizing lead time reduction in a demand chain improvement project, using a typology of demand chains to identify and recommend trajectories to achieve desirable levels of market mediation performance.

426 citations

Journal ArticleDOI
TL;DR: In this article, the authors present a consensus guideline for the use of therapeutic drug monitoring (TDM) in psychopharmakologie and pharmacopsychiatrie in psychiatry.
Abstract: Therapeutic Drug Monitoring (TDM) is a valid tool to optimise pharmacotherapy. It enables the clinician to adjust the dosage of drugs according to the characteristics of the individual patient. In psychiatry, TDM is an established procedure for lithium, some antidepressants and antipsychotics. In spite of its obvious advantages, however, the use of TDM in everyday clinical practice is far from optimal. The interdisciplinary TDM group of the Arbeitsgemeinschaft fur Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) has therefore worked out consensus guidelines to assist psychiatrists and laboratories involved in psychotropic drug analysis to optimise the use of TDM of psychotropic drugs. Five research-based levels of recommendation were defined with regard to routine monitoring of plasma concentrations for dose titration of 65 psychoactive drugs: (1) strongly recommended, (2) recommended, (3) useful, (4) probably useful and (5) not recommended. A second approach defined indications to use TDM, e. g. control of compliance, lack of clinical response or adverse effects at recommended doses, drug interactions, pharmacovigilance programs, presence of a genetic particularity concerning the drug metabolism, children, adolescents and elderly patients. Indications for TDM are relevant for all drugs either with or without validated therapeutic ranges. When studies on therapeutic ranges are lacking, target ranges should be plasma concentrations that are normally observed at therapeutic doses of the drug. Therapeutic ranges of plasma concentrations that are considered to be optimal for treatment are proposed for those drugs, for which the evaluation of the literature demonstrated strong evidence. Moreover, situations are defined when pharmacogenetic (phenotyping or genotyping) tests are informative in addition to TDM. Finally, practical instructions are given how to use TDM. They consider preparation of TDM, analytical procedures, reporting and interpretation of results and the use of information for patient treatment. Using the consensus guideline will help to ensure optimal clinical benefit of TDM in psychiatry.

425 citations

Journal ArticleDOI
Frank Koopmans1, Pim van Nierop1, Maria Andres-Alonso2, Andrea Byrnes3, Tony Cijsouw4, Marcelo P. Coba5, L. Niels Cornelisse1, Ryan J. Farrell6, Hana L. Goldschmidt7, Daniel P. Howrigan3, Natasha K. Hussain7, Natasha K. Hussain8, Cordelia Imig9, Arthur P.H. de Jong10, Hwajin Jung11, Mahdokht Kohansal-Nodehi9, Barbara Kramarz, Noa Lipstein9, Ruth C. Lovering, Harold D. MacGillavry12, Vittoria Mariano13, Vittoria Mariano14, Huaiyu Mi5, Momchil Ninov9, David Osumi-Sutherland15, Rainer Pielot2, Karl-Heinz Smalla2, Haiming Tang5, Katherine Tashman3, Ruud F. Toonen1, Chiara Verpelli16, Rita Reig-Viader17, Kyoko Watanabe1, Jan R.T. van Weering1, Tilmann Achsel14, Tilmann Achsel13, Ghazaleh Ashrafi6, Nimra Asi3, Tyler C. Brown3, Pietro De Camilli18, Marc Feuermann19, Rebecca E. Foulger, Pascale Gaudet19, Anoushka Joglekar6, Alexandros K. Kanellopoulos13, Alexandros K. Kanellopoulos14, Robert C. Malenka20, Roger A. Nicoll21, Camila Pulido6, Jaime de Juan-Sanz6, Morgan Sheng22, Thomas C. Südhof23, Hagen Tilgner6, Claudia Bagni13, Claudia Bagni14, Àlex Bayés17, Thomas Biederer4, Nils Brose9, John Jia En Chua24, Daniela C. Dieterich2, Eckart D. Gundelfinger2, Casper C. Hoogenraad12, Richard L. Huganir8, Richard L. Huganir7, Reinhard Jahn9, Pascal S. Kaeser10, Eunjoon Kim11, Michael R. Kreutz2, Peter S. McPherson25, Neale Bm3, Vincent O'Connor26, Danielle Posthuma1, Timothy A. Ryan6, Carlo Sala16, Guoping Feng3, Steven E. Hyman3, Paul Thomas5, August B. Smit1, Matthijs Verhage1 
17 Jul 2019-Neuron
TL;DR: It is shown that synaptic genes are exceptionally well conserved and less tolerant to mutations than other genes, and among de novo variants associated with neurodevelopmental disorders, including schizophrenia.

425 citations


Authors

Showing all 20911 results

NameH-indexPapersCitations
Peer Bork206697245427
Aaron R. Folsom1811118134044
Kari Alitalo174817114231
Ralph A. DeFronzo160759132993
Johan Auwerx15865395779
Silvia Franceschi1551340112504
Matthias Egger152901184176
Bart Staels15282486638
Fernando Rivadeneira14662886582
Christopher George Tully1421843111669
Richard S. J. Frackowiak142309100726
Peter Timothy Cox140126795584
Jürg Tschopp14032886900
Stylianos E. Antonarakis13874693605
Michael Weller134110591874
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Performance
Metrics
No. of papers from the Institution in previous years
YearPapers
2023249
2022635
20213,969
20203,508
20193,091
20182,776