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- Bousquet, J., et al.
(author)
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Scaling up strategies of the chronic respiratory disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3: Area 5)
- 2016
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In: Clinical and Translational Allergy. - : Wiley. - 2045-7022. ; 6:1, s. 1-18
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Research review (peer-reviewed)abstract
- Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) focuses on the integrated care of chronic diseases. Area 5 (Care Pathways) was initiated using chronic respiratory diseases as a model. The chronic respiratory disease action plan includes (1) AIRWAYS integrated care pathways (ICPs), (2) the joint initiative between the Reference site MACVIA-LR (Contre les MAladies Chroniques pour un VIeillissement Actif) and ARIA (Allergic Rhinitis and its Impact on Asthma), (3) Commitments for Action to the European Innovation Partnership on Active and Healthy Ageing and the AIRWAYS ICPs network. It is deployed in collaboration with the World Health Organization Global Alliance against Chronic Respiratory Diseases (GARD). The European Innovation Partnership on Active and Healthy Ageing has proposed a 5-step framework for developing an individual scaling up strategy: (1) what to scale up: (1-a) databases of good practices, (1-b) assessment of viability of the scaling up of good practices, (1-c) classification of good practices for local replication and (2) how to scale up: (2-a) facilitating partnerships for scaling up, (2-b) implementation of key success factors and lessons learnt, including emerging technologies for individualised and predictive medicine. This strategy has already been applied to the chronic respiratory disease action plan of the European Innovation Partnership on Active and Healthy Ageing.
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- Chang-Claude, Jenny, et al.
(author)
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Age at menarche and menopause and breast cancer risk in the International BRCA1/2 Carrier Cohort Study
- 2007
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In: Cancer Epidemiology Biomarkers and Prevention. - 1055-9965. ; 16:4, s. 740-746
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Journal article (peer-reviewed)abstract
- Background: Early menarche and late menopause are important risk factors for breast cancer, but their effects on breast cancer risk in BRCA1 and BRCA2 carriers are unknown. Methods: We assessed breast cancer risk in a large series of 1,187 BRCA1 and 414 BRCA2 carriers from the International BRCA1/2 Carrier Cohort Study. Rate ratios were estimated using a weighted Cox-regression approach. Results: Breast cancer risk was not significantly related to age at menopause {hazard ratio [HR] for menopause below age 35 years, 0.60 [95% confidence interval (95% CI), 0.25-1.44]; 35 to 40 years, 1.15 [0.65-2.04]; 45 to 54 years, 1.02 [0.65-1.60]; ≥55 years, 1.12 [0.12-5.02], as compared with premenopausal women}. However, there was some suggestion of a reduction in risk after menopause in BRCA2 carriers. There was some evidence of a protective effect of oophorectomy (HR, 0.56; 95% CI, 0.29-1.09) and a significant trend of decreasing risk with increasing time since oophorectomy, but no apparent effect of natural menopause. There was no association between age at menarche and breast cancer risk, nor any apparent association with the estimated total duration of breast mitotic activity. Conclusions: These results are consistent with other observations suggesting a protective effect of oophorectomy, similar in relative effect to that in the general population. The absence of an effect of age at natural menopause is, however, not consistent with findings in the general population and may reflect the different natural history of the disease in carriers.
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- Calistri, A, et al.
(author)
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The New Generation hDHODH Inhibitor MEDS433 Hinders the In Vitro Replication of SARS-CoV-2 and Other Human Coronaviruses
- 2021
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In: Microorganisms. - : MDPI AG. - 2076-2607. ; 9:8
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Journal article (peer-reviewed)abstract
- Although coronaviruses (CoVs) have long been predicted to cause zoonotic diseases and pandemics with high probability, the lack of effective anti-pan-CoVs drugs rapidly usable against the emerging SARS-CoV-2 actually prevented a promptly therapeutic intervention for COVID-19. Development of host-targeting antivirals could be an alternative strategy for the control of emerging CoVs infections, as they could be quickly repositioned from one pandemic event to another. To contribute to these pandemic preparedness efforts, here we report on the broad-spectrum CoVs antiviral activity of MEDS433, a new inhibitor of the human dihydroorotate dehydrogenase (hDHODH), a key cellular enzyme of the de novo pyrimidine biosynthesis pathway. MEDS433 inhibited the in vitro replication of hCoV-OC43 and hCoV-229E, as well as of SARS-CoV-2, at low nanomolar range. Notably, the anti-SARS-CoV-2 activity of MEDS433 against SARS-CoV-2 was also observed in kidney organoids generated from human embryonic stem cells. Then, the antiviral activity of MEDS433 was reversed by the addition of exogenous uridine or the product of hDHODH, the orotate, thus confirming hDHODH as the specific target of MEDS433 in hCoVs-infected cells. Taken together, these findings suggest MEDS433 as a potential candidate to develop novel drugs for COVID-19, as well as broad-spectrum antiviral agents exploitable for future CoVs threats.
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- Larsson, B., et al.
(author)
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The ISO-LWS map of the Serpens cloud core. I. The SEDs of the IR/SMM sources
- 2000
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In: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 363, s. 253-268
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Journal article (peer-reviewed)abstract
- Iso-Lws mapping observations of the Serpens molecular cloud core are presented. The spectral range is 50 - 200 μ m and the map size is 8',x 8'. These observations suffer from severe source confusion at Fir wavelengths and we employ a Maximum Likelihood Method for the spectro-spatial deconvolution. The strong and fairly isolated source SMM 1/FIRS 1 presented a test case, whose modelled spectral energy distribution (SED), within observational errors, is identical to the observed one. The model results for the other infrared and submillimetre sources are therefore likely to represent their correct SEDs. Simulations demonstrating the reliability and potential of the developed method support this view. It is found that some sources do not exhibit significant Fir emission and others are most likely not pointlike at long wavelengths. In contrast, the SEDs of a number of SMMs are well fit by modified single-temperature blackbodies over the entire accessible spectral range. For the majority of sources the peak of the SEDs is found within the spectral range of the Lws and derived temperatures are generally higher (>= 30 K) than have been found by earlier deconvolution attempts using Iras data. SMM sizes are found to be only a few arcsec in diameter. In addition, the SMMs are generally optically thick even at Lws wavelengths, i.e. estimated lambda (TAu=1) are in the range 160-270 μ m. The Rayleigh-Jeans tails are less steep than expected for optically thin dust emission. This indicates that the SMMs are optically thick out to longer wavelengths than previously assumed, an assertion confirmed by self-consistent radiative transfer calculations. Models were calculated for five sources, for which sufficient data were available, viz. SMM 1, 2, 3, 4 and 9. These models are optically thick out to millimetre wavelengths (wavelength of unit optical depth 900 to 1 400 μ m). Envelope masses for these SMMs are in the range 2-6 Msun, which is of course considerably more massive than estimates based on the optically thin assumption. The luminosities are in the range 10-70 Lsun, suggesting the formation of low-mass to intermediate mass stars, so that the existence of such massive envelopes argues for extreme youth of the SMMs in the Serpens cloud core. Finally, we present, for the first time, the full infrared SEDs for the outburst source DEOS, both at high and low intensity states. Based on observations with Iso, an Esa project with instruments funded by Esa Member States (especially the PI countries: France, Germany, the Netherlands and the United Kingdom) and with the participation of Isas and Nasa.
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