| 1. |
- Buus, Richard, et al.
(författare)
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Novel 18-gene signature for predicting relapse in ER-positive, HER2-negative breast cancer
- 2018
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Several prognostic signatures for early oestrogen receptor-positive (ER+) breast cancer have been established with a 10-year follow-up. We tested the hypothesis that signatures optimised for 0-5-year and 5-10-year follow-up separately are more prognostic than a single signature optimised for 10 years. Methods: Genes previously identified as prognostic or associated with endocrine resistance were tested in publicly available microarray data set using Cox regression of 747 ER+/HER2- samples from post-menopausal patients treated with 5 years of endocrine therapy. RNA expression of the selected genes was assayed in primary ER+/HER2- tumours from 948 post-menopausal patients treated with 5 years of anastrozole or tamoxifen in the TransATAC cohort. Prognostic signatures for 0-10, 0-5 and 5-10 years were derived using a penalised Cox regression (elastic net). Signature comparison was performed with likelihood ratio statistics. Validation was done by a case-control (POLAR) study in 422 samples derived from a cohort of 1449. Results: Ninety-three genes were selected by the modelling of microarray data; 63 of these were significantly prognostic in TransATAC, most similarly across each time period. Contrary to our hypothesis, the derived early and late signatures were not significantly more prognostic than the 18-gene 10-year signature. The 18-gene 10-year signature was internally validated in the TransATAC validation set, showing prognostic information similar to that of Oncotype DX Recurrence Score, PAM50 risk of recurrence score, Breast Cancer Index and IHC4 (score based on four IHC markers), as well as in the external POLAR case-control set. Conclusions: The derived 10-year signature predicts risk of metastasis in patients with ER+/HER2- breast cancer similar to commercial signatures. The hypothesis that early and late prognostic signatures are significantly more informative than a single signature was rejected.
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| 2. |
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| 3. |
- Chaurasia, Chandra S., et al.
(författare)
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AAPS-FDA workshop white paper : microdialysis principles, application and regulatory perspectives
- 2007
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Ingår i: Pharmaceutical research. - : Springer Science and Business Media LLC. - 0724-8741 .- 1573-904X. ; 24:5, s. 1014-1025
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Tidskriftsartikel (refereegranskat)abstract
- Many decisions in drug development and medical practice are based on measuring blood concentrations of endogenous and exogenous molecules. Yet most biochemical and pharmacological events take place in the tissues. Also, most drugs with few notable exceptions exert their effects not within the bloodstream, but in defined target tissues into which drugs have to distribute from the central compartment. Assessing tissue drug chemistry has, thus, for long been viewed as a more rational way to provide clinically meaningful data rather than gaining information from blood samples. More specifically, it is often the extracellular (interstitial) tissue space that is most closely related to the site of action (biophase) of the drug. Currently microdialysis (microD) is the only tool available that explicitly provides data on the extracellular space. Although microD as a preclinical and clinical tool has been available for two decades, there is still uncertainty about the use of microD in drug research and development, both from a methodological and a regulatory point of view. In an attempt to reduce this uncertainty and to provide an overview of the principles and applications of microD in preclinical and clinical settings, an AAPS-FDA workshop took place in November 2005 in Nashville, TN, USA. Stakeholders from academia, industry and regulatory agencies presented their views on microD as a tool in drug research and development.
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| 4. |
- Chaurasia, Chandra S., et al.
(författare)
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AAPS-FDA Workshop White Paper : microdialysis principles, application, and regulatory perspectives
- 2007
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Ingår i: Journal of clinical pharmacology. - : Wiley. - 0091-2700 .- 1552-4604. ; 47:5, s. 589-603
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Tidskriftsartikel (refereegranskat)abstract
- Many decisions in drug development and medical practice are based on measuring blood concentrations of endogenous and exogenous molecules. Yet most biochemical and pharmacological events take place in the tissues. Also, most drugs with few notable exceptions exert their effects not within the bloodstream, but in defined target tissues into which drugs have to distribute from the central compartment. Assessing tissue drug chemistry has, thus, for long been viewed as a more rational way to provide clinically meaningful data rather than gaining information from blood samples. More specifically, it is often the extracellular (interstitial) tissue space that is most closely related to the site of action (biophase) of the drug. Currently microdialysis (μD) is the only tool available that explicitly provides data on the extracellular space. Although μD as a preclinical and clinical tool has been available for two decades, there is still uncertainty about the use of μD in drug research and development, both from a methodological and a regulatory point of view. In an attempt to reduce this uncertainty and to provide an overview of the principles and applications of μD in preclinical and clinical settings, an AAPS-FDA workshop took place in November 2005 in Nashville, TN, USA. Stakeholders from academia, industry and regulatory agencies presented their views on μD as a tool in drug research and development.
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| 5. |
- Diaz, Sandra, et al.
(författare)
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The IPBES Conceptual Framework - connecting nature and people
- 2015
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Ingår i: Current Opinion in Environmental Sustainability. - : Elsevier BV. - 1877-3435 .- 1877-3443. ; 14, s. 1-16
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Tidskriftsartikel (refereegranskat)abstract
- The first public product of the Intergovernmental Platform on Biodiversity and Ecosystem Services (IPBES) is its Conceptual Framework. This conceptual and analytical tool, presented here in detail, will underpin all IPBES functions and provide structure and comparability to the syntheses that IPBES will produce at different spatial scales, on different themes, and in different regions. Salient innovative aspects of the IPBES Conceptual Framework are its transparent and participatory construction process and its explicit consideration of diverse scientific disciplines, stakeholders, and knowledge systems, including indigenous and local knowledge. Because the focus on co-construction of integrative knowledge is shared by an increasing number of initiatives worldwide, this framework should be useful beyond IPBES, for the wider research and knowledge-policy communities working on the links between nature and people, such as natural, social and engineering scientists, policy-makers at different levels, and decision-makers in different sectors of society.
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| 6. |
- Yéo, Alain, et al.
(författare)
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Establishment of a Gonococcal Antimicrobial Surveillance Programme, in Accordance With World Health Organization Standards, in Côte d'Ivoire, Western Africa, 2014-2017
- 2019
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Ingår i: Sexually Transmitted Diseases. - : Lippincott Williams & Wilkins. - 0148-5717 .- 1537-4521. ; 46:3, s. 179-184
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is compromising the treatment of gonorrhea globally. Recent AMR data are extremely limited in Africa, and mainly totally lacking in Western Africa, including Côte d'Ivoire. This study (i) established a quality-assured gonococcal antimicrobial surveillance program, according to World Health Organization quality criteria, (ii) investigated the AMR to 8 therapeutic antimicrobials in gonococcal isolates from 2014 to 2017, and (iii) provided evidence for updating the National Sexually Transmitted Disease Syndromic Management Guidelines in Côte d'Ivoire.METHODS: During 2014 to 2017, gonococcal isolates were obtained from sexually active symptomatic or asymptomatic males and females in 14 sites in Côte d'Ivoire. It was a special focus on symptomatic males, and their sexual partners, due to the higher culture positivity rates in symptomatic males. Patient metadata were collected, including age, gender, sexual orientation, and symptoms. Minimum inhibitory concentrations of 8 antimicrobials were determined by Etest and interpreted using European Committee on Antimicrobial Susceptibility Testing breakpoints. β-lactamase production was detected using cefinase disks.RESULTS: The level of resistance, examining 212 gonococcal isolates, was as follows: 84.9% to tetracycline, 68.9% to benzylpenicillin, 62.7% to ciprofloxacin, 6.1% to azithromycin, and 1.4% to gentamicin. All isolates were susceptible to ceftriaxone, cefixime and spectinomycin.CONCLUSIONS: We provide the first gonococcal AMR data, quality assured according to World Health Organization standards, from Côte d'Ivoire since more than 20 years. The high ciprofloxacin resistance, which informed a revision of the national syndromic management guideline during study, and relatively high resistance to azithromycin demand an improved gonococcal antimicrobial surveillance program and increased awareness when prescribing treatment in Côte d'Ivoire.
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