Abstract Background The incidence of local recurrence (LR) after conservative surgery for early breast cancer without adjuvant therapy is unacceptably high even with favourable tumours. The aim of ...this study was to examine the effect of adjuvant therapies in tumours with excellent prognostic features. Methods Patients with primary invasive breast cancer <2 cm diameter, grade 1 or good prognosis special type, and node negative, treated by wide local excision (WLE) with clear margins were randomised into a 2 × 2 clinical trial of factorial design with or without radiotherapy and with or without tamoxifen. Trial entry was allowed to either comparison or both. Findings The actuarial breast cancer specific survival in 1135 randomised patients at 10 years was 96%. Analysis by intention to treat showed that LR after WLE was reduced in patients randomised to radiotherapy (RT) (HR 0.37, CI 0.22-0.61 p < 0.001) and to tamoxifen (HR 0.33, CI 0.15 – 0.70 p < 0.004). Actuarial analysis of patients entered into the four-way randomisation showed that LR after WLE alone was 1.9% per annum (PA) versus 0.7% with RT alone and 0.8% with tamoxifen alone. No patient randomised to both adjuvant treatments developed LR. Analysis by treatment received showed LR at 2.2% PA for surgery alone versus 0.8% for either adjuvant radiotherapy or tamoxifen and 0.2% for both treatments. Conclusions Even in these patients with tumours of excellent prognosis, LR after conservative surgery without adjuvant therapy was still very high. This was reduced to a similar extent by either radiotherapy or tamoxifen but to a greater extent by the receipt of both treatments.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
We use the adjoint of a global 3‐D chemical transport model (GEOS‐Chem) to optimize ammonia (NH3) emissions in the U.S., European Union, and China by inversion of 2005–2008 network data for NH4+ wet ...deposition fluxes. Optimized emissions are derived on a 2° × 2.5° grid for individual months and years. Error characterization in the optimization includes model errors in precipitation. Annual optimized emissions are 2.8 Tg NH3−N a−1 for the contiguous U.S., 3.1 Tg NH3−N a−1 for the European Union, and 8.4 Tg NH3−N a−1 for China. Comparisons to previous inventories for the U.S. and European Union show consistency (∼±15%) in annual totals but some large spatial and seasonal differences. We develop a new global bottom‐up inventory of NH3 emissions (Magnitude And Seasonality of Agricultural Emissions model for NH3 (MASAGE_NH3)) to interpret the results of the adjoint optimization. MASAGE_NH3 provides information on the magnitude and seasonality of NH3 emissions from individual crop and livestock sources on a 0.5° × 0.5° grid. We find that U.S. emissions peak in the spring in the Midwest due to corn fertilization and in the summer elsewhere due to manure. The seasonality of European emissions is more homogeneous with a well‐defined maximum in spring associated with manure and mineral fertilizer application. There is some evidence for the effect of European regulations of NH3 emissions, notably a large fall decrease in northern Europe. Emissions in China peak in summer because of the summertime application of fertilizer for double cropping.
Key Points
Adjoint‐based inversion of ammonium wet deposition in the U.S., Europe, and ChinaMuch larger spatial and temporal variability of U.S. emission than in the a prioriNew model of NH3 emissions reproduces the patterns of the optimized emissions
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
A lightning-nitrogen oxide (NO) algorithm is implemented in the Community Multiscale Air Quality Model (CMAQ) and used to evaluate the impact of lightning-NO emissions (LNOx) on tropospheric ...photochemistry over the United States during the summer of 2006. For a 500 mole per flash lightning-NO source, the mean summertime tropospheric NO2 column agrees with satellite-retrieved columns to within −5 to +13%. Temporal fluctuations in the column are moderately well simulated; however, the addition of LNOx does not lead to a better simulation of day-to-day variability. The contribution of lightning-NO to the model column ranges from ∼10% in the northern US to >45% in the south-central and southeastern US. Lightning-NO adds up to 20 ppbv to upper tropospheric model ozone and 1.5–4.5 ppbv to 8-h maximum surface layer ozone, although, on average, the contribution of LNOx to model surface ozone is 1–2 ppbv less on poor air quality days. LNOx increases wet deposition of oxidized nitrogen by 43% and total deposition of nitrogen by 10%. This additional deposition reduces the mean magnitude of the CMAQ low-bias in nitrate wet deposition with respect to National Atmospheric Deposition monitors to near zero. Differences in urban/rural biases between model and satellite-retrieved NO2 columns were examined to identify possible problems in model chemistry and/or transport. CMAQ columns were too large over urban areas. Biases at other locations were minor after accounting for the impacts of lightning-NO emissions and the averaging kernel on model columns. In order to obtain an upper bound on the contribution of uncertainties in NOy chemistry to upper tropospheric NOx low biases, sensitivity calculations with updated chemistry were run for the time period of the Intercontinental Chemical Transport Experiment (INTEX-A) field campaign (summer 2004). After adjusting for possible interferences in NO2 measurements and averaging over the entire campaign, these updates reduced 7–9 km biases from 32 to 17% and 9–12 km biases from 57 to 46%. While these changes lead to better agreement, a considerable unexplained NO2 low-bias remains in the uppermost troposphere.
The epidermal growth factor receptor (EGFR) family plays an important role in breast carcinogenesis. Much interest has been focused recently on its members because of their potential role as ...prognostic indicators in breast cancer and their involvement in cancer therapy. We have evaluated more than 1500 cases of invasive breast carcinoma immunohistochemically using tissue microarray technology to examine the expression of EGFR family receptor proteins. We have found that 20.1 and 31.8% of cases were positive for EGFR and c-erbB-2, respectively, and 45 and 45.1% of tumours overexpressed for c-erbB-3 and c-erbB-4, respectively. The expression of either EGFR or c-erbB-2 was associated with other bad prognostic features and with poor outcome. Neither c-erbB-3 nor c-erbB-4 had any association with survival. c-erbB-2 had an independent prognostic effect on overall and disease-free survival (DFS) in all cases, as well as in the subset of breast carcinoma patients with nodal metastases. Several hetero- and homodimeric combinations have been reported between the EGFR members. Those dimers can evoke diverse signal transduction pathways with variable cellular responses. We stratified cases according to their co-expression of receptors into distinct groups with different receptor-positive combinations. Patients whose tumours co-expressed c-erbB-2 and c-erbB-3, as well as those whose tumours co-expressed EGFR, c-erbB-2 and c-erbB-4 showed an unfavourable outcome compared with other groups, while combined c-erbB-3 and c-erbB-4 expression was associated with a better outcome. In cases showing expression of one family member only (homodimers), we found a significant association between c-erbB-4 homodimer-expressing tumours and better DFS. In contrast, patients with c-erbB-2 homodimer-expressing tumours had a significant poorer DFS compared with other cases. These data imply that the combined profile expression patterns of the four receptor family members together provide more accurate information on the tumour behaviour than studying the expression of each receptor individually.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The CMAQ (Community Multiscale Air Quality) us model in combination with observations for INTEX-NA/ICARTT (Intercontinental Chemical Transport Experiment–North America/International Consortium for ...Atmospheric Research on Transport and Transformation) 2004 are used to evaluate recent advances in isoprene oxidation chemistry and provide constraints on isoprene nitrate yields, isoprene nitrate lifetimes, and NOx recycling rates. We incorporate recent advances in isoprene oxidation chemistry into the SAPRC-07 chemical mechanism within the US EPA (United States Environmental Protection Agency) CMAQ model. The results show improved model performance for a range of species compared against aircraft observations from the INTEX-NA/ICARTT 2004 field campaign. We further investigate the key processes in isoprene nitrate chemistry and evaluate the impact of uncertainties in the isoprene nitrate yield, NOx (NOx = NO + NO2) recycling efficiency, dry deposition velocity, and RO2 + HO2 reaction rates. We focus our examination on the southeastern United States, which is impacted by both abundant isoprene emissions and high levels of anthropogenic pollutants. We find that NOx concentrations increase by 4–9% as a result of reduced removal by isoprene nitrate chemistry. O3 increases by 2 ppbv as a result of changes in NOx. OH concentrations increase by 30%, which can be primarily attributed to greater HOx production. We find that the model can capture observed total alkyl and multifunctional nitrates (∑ANs) and their relationship with O3 by assuming either an isoprene nitrate yield of 6% and daytime lifetime of 6 hours or a yield of 12% and lifetime of 4 h. Uncertainties in the isoprene nitrates can impact ozone production by 10% and OH concentrations by 6%. The uncertainties in NOx recycling efficiency appear to have larger effects than uncertainties in isoprene nitrate yield and dry deposition velocity. Further progress depends on improved understanding of isoprene oxidation pathways, the rate of NOx recycling from isoprene nitrates, and the fate of the secondary, tertiary, and further oxidation products of isoprene.
Abstract The Nottingham Prognostic Index (NPI) is a well established and widely used method of predicting survival of operable primary breast cancer. Aims Primary : To present the updated survival ...figures for each NPI Group. Secondary : From the observations to suggest reasons for the reported fall in mortality from breast cancer. Methods The NPI is compiled from grade, size and lymph node status of the primary tumour. Consecutive cases diagnosed and treated at Nottingham City Hospital in 1980–1986 ( n = 892) and 1990–1999 ( n = 2238) are compared. Changes in protocols towards earlier diagnosis and better case management were made in the late 1980s between the two data sets. Results Case survival (Breast Cancer Specific) at 10 years has improved overall from 55% to 77%. Within all Prognostic groups there are high relative and absolute risk reductions. The distribution of cases to Prognostic groups shows only a small increase in the numbers in better groups. Conclusion The updated survival figures overall and for each Prognostic group for the NPI are presented.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Recent regulations require large‐scale emission reductions of NOx and SO2 in the eastern United States. These emission changes will alter the partitioning of ammonia between the gas and particle ...phases. Furthermore, ammonia emissions are expected to increase in the future. How will these changes impact the contribution of ammonia to inorganic particulate matter and nitrogen deposition? We use a chemical transport model and emission scenarios representing years 2001, 2010, and 2020 to estimate the future change of the sensitivity of iPM2.5 to ammonia emission reductions and change in nitrogen deposition to ecosystems. We find that during winter conditions, particulate matter concentrations in several locations in the Midwestern US continue to have significant sensitivity to NH3 emissions. In addition, the total nitrogen deposition near NH3 emission sources increases 10–40%
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Excess reactive Nitrogen (Nr) has become one of the most pressing environmental problems leading to air pollution, acidification and eutrophication of ecosystems, biodiversity impacts, leaching of ...nitrates into groundwater and global warming. This paper investigates how current inventories cover emissions of Nr to the atmosphere in Europe, the United States of America, and China. The focus is on anthropogenic sources, assessing the state-of-the-art of quantifying emissions of Ammonia (NH3), Nitrogen Oxides (NOx) and Nitrous Oxide (N2O), the different purposes for which inventories are compiled, and to which extent current inventories meet the needs of atmospheric dispersion modelling. The paper concludes with a discussion of uncertainties involved and a brief outlook on emerging trends in the three regions investigated is conducted. Key issues are substantial differences in the overall magnitude, but as well in the relative sectoral contribution of emissions in the inventories that have been assessed. While these can be explained by the use of different methodologies and underlying data (e.g. emission factors or activity rates), they may lead to quite different results when using the emission datasets to model ambient air quality or the deposition with atmospheric dispersion models. Hence, differences and uncertainties in emission inventories are not merely of academic interest, but can have direct policy implications when the development of policy actions is based on these model results. The level of uncertainty of emission estimates varies greatly between substances, regions and emission source sectors. This has implications for the direction of future research needs and indicates how existing gaps between modelled and measured concentration or deposition rates could be most efficiently addressed. The observed current trends in emissions display decreasing NOx emissions and only slight reductions for NH3 in both Europe and the US. However, in China projections indicate a steep increase of both.
Existing descriptions of bi-directional ammonia (NH3) land–atmosphere exchange incorporate temperature and moisture controls, and are beginning to be used in regional chemical transport models. ...However, such models have typically applied simpler emission factors to upscale the main NH3 emission terms. While this approach has successfully simulated the main spatial patterns on local to global scales, it fails to address the environment- and climate-dependence of emissions. To handle these issues, we outline the basis for a new modelling paradigm where both NH3 emissions and deposition are calculated online according to diurnal, seasonal and spatial differences in meteorology. We show how measurements reveal a strong, but complex pattern of climatic dependence, which is increasingly being characterized using ground-based NH3 monitoring and satellite observations, while advances in process-based modelling are illustrated for agricultural and natural sources, including a global application for seabird colonies. A future architecture for NH3 emission–deposition modelling is proposed that integrates the spatio-temporal interactions, and provides the necessary foundation to assess the consequences of climate change. Based on available measurements, a first empirical estimate suggests that 5°C warming would increase emissions by 42 per cent (28–67%). Together with increased anthropogenic activity, global NH3 emissions may increase from 65 (45–85) Tg N in 2008 to reach 132 (89–179) Tg by 2100.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
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