| 11. |
- Tutt, A. N. J., et al.
(författare)
-
Adjuvant Olaparib for Patients with BRCA1- or BRCA2-Mutated Breast Cancer
- 2021
-
Ingår i: New England Journal of Medicine. - 0028-4793. ; 384:25, s. 2394-2405
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Poly(adenosine diphosphate-ribose) polymerase inhibitors target cancers with defects in homologous recombination repair by synthetic lethality. New therapies are needed to reduce recurrence in patients with BRCA1 or BRCA2 germline mutation-associated early breast cancer. METHODS We conducted a phase 3, double-blind, randomized trial involving patients with human epidermal growth factor receptor 2 (HER2)-negative early breast cancer with BRCA1 or BRCA2 germline pathogenic or likely pathogenic variants and high-risk clinicopathological factors who had received local treatment and neoadjuvant or adjuvant chemotherapy. Patients were randomly assigned (in a 1:1 ratio) to 1 year of oral olaparib or placebo. The primary end point was invasive disease-free survival. RESULTS A total of 1836 patients underwent randomization. At a prespecified event-driven interim analysis with a median follow-up of 2.5 years, the 3-year invasive disease-free survival was 85.9% in the olaparib group and 77.1% in the placebo group (difference, 8.8 percentage points; 95% confidence interval [CI], 4.5 to 13.0; hazard ratio for invasive disease or death, 0.58; 99.5% CI, 0.41 to 0.82; P<0.001). The 3-year distant disease-free survival was 87.5% in the olaparib group and 80.4% in the placebo group (difference, 7.1 percentage points; 95% CI, 3.0 to 11.1; hazard ratio for distant disease or death, 0.57; 99.5% CI, 0.39 to 0.83; P<0.001). Olaparib was associated with fewer deaths than placebo (59 and 86, respectively) (hazard ratio, 0.68; 99% CI, 0.44 to 1.05; P=0.02); however, the between-group difference was not significant at an interim-analysis boundary of a P value of less than 0.01. Safety data were consistent with known side effects of olaparib, with no excess serious adverse events or adverse events of special interest. CONCLUSIONS Among patients with high-risk, HER2-negative early breast cancer and germline BRCA1 or BRCA2 pathogenic or likely pathogenic variants, adjuvant olaparib after completion of local treatment and neoadjuvant or adjuvant chemotherapy was associated with significantly longer survival free of invasive or distant disease than was placebo. Olaparib had limited effects on global patient-reported quality of life.
|
|
| 12. |
- Jin, J.J., et al.
(författare)
-
Co-located ACE-FTS and Odin/SMR stratospheric-mesospheric CO 2004 measurements and comparison with a GCM
- 2005
-
Ingår i: Geophysical Research Letters. - 1944-8007 .- 0094-8276. ; 32:15
-
Tidskriftsartikel (refereegranskat)abstract
- This paper presents a comparison of co-located and near simultaneous CO measurements from January to May, 2004 and from the Arctic to southern polar regions using the ACE-FTS, in solar occultation mode, and the Odin/SMR, which measures atmospheric emission. We find that there is excellent agreement between the two instruments at the locations investigated over 4 orders of magnitude from the lower stratosphere to the lower thermosphere. There is also good agreement with the CMAM model simulation from 20 km to 90 km in sub-tropical and tropical latitudes but poorer agreement in the upper stratosphere and lower mesosphere in winter polar regions. For the Arctic in March 2004 this can be attributed, at least partly, to the unique dynamical processes in the stratosphere in the winter of 2003 - 2004. Clearly CO measurements from these instruments will provide a useful tool for testing model transport from the troposphere to the thermosphere.
|
|
| 13. |
- Chen, XD, et al.
(författare)
-
Non-invasive early detection of cancer four years before conventional diagnosis using a blood test
- 2020
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 3475-
-
Tidskriftsartikel (refereegranskat)abstract
- Early detection has the potential to reduce cancer mortality, but an effective screening test must demonstrate asymptomatic cancer detection years before conventional diagnosis in a longitudinal study. In the Taizhou Longitudinal Study (TZL), 123,115 healthy subjects provided plasma samples for long-term storage and were then monitored for cancer occurrence. Here we report the preliminary results of PanSeer, a noninvasive blood test based on circulating tumor DNA methylation, on TZL plasma samples from 605 asymptomatic individuals, 191 of whom were later diagnosed with stomach, esophageal, colorectal, lung or liver cancer within four years of blood draw. We also assay plasma samples from an additional 223 cancer patients, plus 200 primary tumor and normal tissues. We show that PanSeer detects five common types of cancer in 88% (95% CI: 80–93%) of post-diagnosis patients with a specificity of 96% (95% CI: 93–98%), We also demonstrate that PanSeer detects cancer in 95% (95% CI: 89–98%) of asymptomatic individuals who were later diagnosed, though future longitudinal studies are required to confirm this result. These results demonstrate that cancer can be non-invasively detected up to four years before current standard of care.
|
|
| 14. |
|
|
| 15. |
- Sigl, M., et al.
(författare)
-
Timing and climate forcing of volcanic eruptions for the past 2,500 years
- 2015
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 523:7562, s. 543-549
-
Tidskriftsartikel (refereegranskat)abstract
- Volcanic eruptions contribute to climate variability, but quantifying these contributions has been limited by inconsistencies in the timing of atmospheric volcanic aerosol loading determined from ice cores and subsequent cooling from climate proxies such as tree rings. Here we resolve these inconsistencies and show that large eruptions in the tropics and high latitudes were primary drivers of interannual-to-decadal temperature variability in the Northern Hemisphere during the past 2,500 years. Our results are based on new records of atmospheric aerosol loading developed from high-resolution, multi-parameter measurements from an array of Greenland and Antarctic ice cores as well as distinctive age markers to constrain chronologies. Overall, cooling was proportional to the magnitude of volcanic forcing and persisted for up to ten years after some of the largest eruptive episodes. Our revised timescale more firmly implicates volcanic eruptions as catalysts in the major sixth-century pandemics, famines, and socioeconomic disruptions in Eurasia and Mesoamerica while allowing multi-millennium quantification of climate response to volcanic forcing.
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
- Jin, J.J., et al.
(författare)
-
Comparison of CMAM simulations of carbon monoxide (CO), nitrous oxide (N2O), and methane (CH4) with observations from Odin/SMR, ACE-FTS, and Aura/MLS
- 2009
-
Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 9, s. 3233-3252
-
Tidskriftsartikel (refereegranskat)abstract
- Simulations of CO, N2O and CH4 from a coupled chemistry-climate model (CMAM) are compared with satellite measurements from Odin Sub-Millimeter Radiometer (Odin/SMR), Atmospheric Chemistry Experiment Fourier Transform Spectrometer (ACE-FTS), and Aura Microwave Limb Sounder (Aura/MLS). Pressure-latitude cross-sections and seasonal time series demonstrate that CMAM reproduces the observed global CO, N2O, and CH4 distributions quite well. Generally, excellent agreement with measurements is found between CO simulations and observations in the stratosphere and mesosphere. Differences between the simulations and the ACE-FTS observations are generally within 30%, and the differences between CMAM results and SMR and MLS observations are slightly larger. These differences are comparable with the difference between the instruments in the upper stratosphere and mesosphere. Comparisons of N2O show that CMAM results are usually within 15% of the measurements in the lower and middle stratosphere, and the observations are close to each other. However, the standard version of CMAM has a low N2O bias in the upper stratosphere. The CMAM CH4 distribution also reproduces the observations in the lower stratosphere, but has a similar but smaller negative bias in the upper stratosphere. The negative bias may be due to that the gravity drag is not fully resolved in the model. The simulated polar CO evolution in the Arctic and Antarctic agrees with the ACE and MLS observations. CO measurements from 2006 show evidence of enhanced descent of air from the mesosphere into the stratosphere in the Arctic after strong stratospheric sudden warmings (SSWs). CMAM also shows strong descent of air after SSWs. In the tropics, CMAM captures the annual oscillation in the lower stratosphere and the semiannual oscillations at the stratopause and mesopause seen in Aura/MLS CO and N2O observations and in Odin/SMR N2O observations. The Odin/SMR and Aura/MLS N2O observations also show a quasi-biennial oscillation (QBO) in the upper stratosphere, whereas, the CMAM does not have QBO included. This study confirms that CMAM is able to simulate middle atmospheric transport processes reasonably well.
|
|
| 19. |
- McConnell, M. L., et al.
(författare)
-
POET : A SMEX mission for gamma ray burst polarimetry
- 2014
-
Ingår i: Proceedings of SPIE, the International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. ; 9144
-
Tidskriftsartikel (refereegranskat)abstract
- Polarimeters for Energetic Transients (POET) is a mission concept designed to t within the envelope of a NASA Small Explorer (SMEX) mission. POET will use X-ray and gamma-ray polarimetry to uncover the energy release mechanism associated with the formation of stellar-mass black holes and investigate the physics of extreme magnetic ields in the vicinity of compact objects. Two wide-FoV, non-imaging polarimeters will provide polarization measurements over the broad energy range from about 2 keV up to about 500 keV. A Compton scatter polarimeter, using an array of independent scintillation detector elements, will be used to collect data from 50 keV up to 500 keV. At low energies (215 keV), data will be provided by a photoelectric polarimeter based on the use of a Time Projection Chamber for photoelectron tracking. During a two-year baseline mission, POET will be able to collect data that will allow us to distinguish between three basic models for the inner jet of gamma-ray bursts.
|
|
| 20. |
- Nassar, R., et al.
(författare)
-
A global inventory of stratospheric chlorine in 2004
- 2006
-
Ingår i: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 111:22
-
Tidskriftsartikel (refereegranskat)abstract
- Total chlorine (CITOT) in the stratosphere has been determined using the Atmospheric Chemistry Experiment Fourier Transform Spectrometer (ACE-FTS) measurements of HCl, ClONO2, CH3Cl, CCl4, CCl3F (CFC-11), CCl2F2 (CFC-12), CHClF2 (HCFC-22), CCl2FCClF2 (CFC-113), CH3CClF2 (HCFC-142b), COClF, and ClO supplemented by data from several other sources, including both measurements and models. Separate chlorine inventories were carried out in five latitude zones (60°-82°N, 30°-60°N, 30°S-30°N, 30°-60°S, and 60°-82°S), averaging the period of February 2004 to January 2005 inclusive, when possible, to deal with seasonal variations. The effect of diurnal variation was avoided by only using measurements taken at local sunset. Mean stratospheric ClTOT values of 3.65 ppbv were determined for both the northern and southern midlatitudes (with an estimated 1σ, accuracy of ±0.13 ppbv and a precision of ±.09 ppbv), accompanied by a slightly lower value in the tropics and slightly higher values at high latitudes. Stratospheric ClTOT profiles in all five latitude zones are nearly linear with a slight positive slope in ppbv /km. Both the observed slopes and pattern of latitudinal variation can be interpreted as evidence of the beginning of a decline in global stratospheric chlorine, which is qualitatively consistent with the mean stratospheric circulation pattern and time lag necessary for transport.
|
|
