| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Abe, O, et al.
(författare)
-
Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
- 2005
-
Ingår i: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
-
Tidskriftsartikel (refereegranskat)abstract
- Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, &GE; 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes. Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
|
|
| 5. |
- Lagrange, A. M., et al.
(författare)
-
Unveiling the beta Pictoris system, coupling high contrast imaging, interferometric, and radial velocity data
- 2020
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 642
-
Tidskriftsartikel (refereegranskat)abstract
- Context. The nearby and young beta Pictoris system hosts a well resolved disk, a directly imaged massive giant planet orbiting at similar or equal to 9 au, as well as an inner planet orbiting at similar or equal to 2.7 au, which was recently detected through radial velocity (RV). As such, it offers several unique opportunities for detailed studies of planetary system formation and early evolution.Aims. We aim to further constrain the orbital and physical properties of beta Pictoris b and c using a combination of high contrast imaging, long base-line interferometry, and RV data. We also predict the closest approaches or the transit times of both planets, and we constrain the presence of additional planets in the system.Methods. We obtained six additional epochs of SPHERE data, six additional epochs of GRAVITY data, and five additional epochs of RV data. We combined these various types of data in a single Markov-chain Monte Carlo analysis to constrain the orbital parameters and masses of the two planets simultaneously. The analysis takes into account the gravitational influence of both planets on the star and hence their relative astrometry. Secondly, we used the RV and high contrast imaging data to derive the probabilities of presence of additional planets throughout the disk, and we tested the impact of absolute astrometry.Results. The orbital properties of both planets are constrained with a semi-major axis of 9.8 0.4 au and 2.7 +/- 0.02 au for b and c, respectively, and eccentricities of 0.09 +/- 0.1 and 0.27 +/- 0.07, assuming the HIPPARCOS distance. We note that despite these low fitting error bars, the eccentricity of beta Pictoris c might still be over-estimated. If no prior is provided on the mass of beta Pictoris b, we obtain a very low value that is inconsistent with what is derived from brightness-mass models. When we set an evolutionary model motivated prior to the mass of beta Pictoris b, we find a solution in the 10-11 M-Jup range. Conversely, beta Pictoris c's mass is well constrained, at 7.8 +/- 0.4 M-Jup, assuming both planets are on coplanar orbits. These values depend on the assumptions on the distance of the beta Pictoris system. The absolute astrometry HIPPARCOS-Gaia data are consistent with the solutions presented here at the 2 sigma level, but these solutions are fully driven by the relative astrometry plus RV data. Finally, we derive unprecedented limits on the presence of additional planets in the disk. We can now exclude the presence of planets that are more massive than about 2.5 M-Jup closer than 3 au, and more massive than 3.5 M-Jup between 3 and 7.5 au. Beyond 7.5 au, we exclude the presence of planets that are more massive than 1-2 M-Jup.Conclusions. Combining relative astrometry and RVs allows one to precisely constrain the orbital parameters of both planets and to give lower limits to potential additional planets throughout the disk. The mass of beta Pictoris c is also well constrained, while additional RV data with appropriate observing strategies are required to properly constrain the mass of beta Pictoris b.
|
|
| 6. |
- Lacour, S., et al.
(författare)
-
The mass of β Pictoris c from β Pictoris b orbital motion
- 2021
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 654
-
Tidskriftsartikel (refereegranskat)abstract
- Aims. We aim to demonstrate that the presence and mass of an exoplanet can now be effectively derived from the astrometry of another exoplanet.Methods. We combined previous astrometry of β Pictoris b with a new set of observations from the GRAVITY interferometer. The orbital motion of β Pictoris b is fit using Markov chain Monte Carlo simulations in Jacobi coordinates. The inner planet, β Pictoris c, was also reobserved at a separation of 96 mas, confirming the previous orbital estimations.Results. From the astrometry of planet b only, we can (i) detect the presence of β Pictoris c and (ii) constrain its mass to 10.04(-3.10)(+4.53) M-Jup. If one adds the astrometry of β Pictoris c, the mass is narrowed down to 9.15(-1.06)(+1.08) M-Jup. The inclusion of radial velocity measurements does not affect the orbital parameters significantly, but it does slightly decrease the mass estimate to 8.89(-0.75)(+0.75) M-Jup. With a semimajor axis of 2.68 +/- 0.02 au, a period of 1221 +/- 15 days, and an eccentricity of 0.32 +/- 0.02, the orbital parameters of β Pictoris c are now constrained as precisely as those of β Pictoris b. The orbital configuration is compatible with a high-order mean-motion resonance (7:1). The impact of the resonance on the planets' dynamics would then be negligible with respect to the secular perturbations, which might have played an important role in the eccentricity excitation of the outer planet.
|
|
| 7. |
- Liu, JJ, et al.
(författare)
-
Germline HOXB13 mutations p.G84E and p.R217C do not confer an increased breast cancer risk
- 2020
-
Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 9688-
-
Tidskriftsartikel (refereegranskat)abstract
- In breast cancer, high levels of homeobox protein Hox-B13 (HOXB13) have been associated with disease progression of ER-positive breast cancer patients and resistance to tamoxifen treatment. Since HOXB13 p.G84E is a prostate cancer risk allele, we evaluated the association between HOXB13 germline mutations and breast cancer risk in a previous study consisting of 3,270 familial non-BRCA1/2 breast cancer cases and 2,327 controls from the Netherlands. Although both recurrent HOXB13 mutations p.G84E and p.R217C were not associated with breast cancer risk, the risk estimation for p.R217C was not very precise. To provide more conclusive evidence regarding the role of HOXB13 in breast cancer susceptibility, we here evaluated the association between HOXB13 mutations and increased breast cancer risk within 81 studies of the international Breast Cancer Association Consortium containing 68,521 invasive breast cancer patients and 54,865 controls. Both HOXB13 p.G84E and p.R217C did not associate with the development of breast cancer in European women, neither in the overall analysis (OR = 1.035, 95% CI = 0.859–1.246, P = 0.718 and OR = 0.798, 95% CI = 0.482–1.322, P = 0.381 respectively), nor in specific high-risk subgroups or breast cancer subtypes. Thus, although involved in breast cancer progression, HOXB13 is not a material breast cancer susceptibility gene.
|
|
| 8. |
|
|
| 9. |
- Brinkman, D. J., et al.
(författare)
-
Essential Competencies in Prescribing: A First European Cross-Sectional Study Among 895 Final-Year Medical Students
- 2017
-
Ingår i: Clinical Pharmacology and Therapeutics. - : WILEY-BLACKWELL. - 0009-9236 .- 1532-6535. ; 101:2, s. 281-289
-
Tidskriftsartikel (refereegranskat)abstract
- European medical students should have acquired adequate prescribing competencies before graduation, but it is not known whether this is the case. In this international multicenter study, we evaluated the essential knowledge, skills, and attitudes in clinical pharmacology and therapeutics (CPT) of final-year medical students across Europe. In a cross-sectional design, 26 medical schools from 17 European countries were asked to administer a standardized assessment and questionnaire to 50 final-year students. Although there were differences between schools, our results show an overall lack of essential prescribing competencies among final-year students in Europe. Students had a poor knowledge of drug interactions and contraindications, and chose inappropriate therapies for common diseases or made prescribing errors. Our results suggest that undergraduate teaching in CPT is inadequate in many European schools, leading to incompetent prescribers and potentially unsafe patient care. A European core curriculum with clear learning outcomes and assessments should be urgently developed.
|
|
| 10. |
|
|
