This study aimed to test the hypothesis that lymphovascular invasion adds prognostic information to histological grade and tumour size in node-negative invasive carcinoma of the breast. ...Lymphovascular invasion was assessed in haematoxylin and eosin tumour sections from 2760 patients with node-negative invasive breast carcinoma treated with definitive surgery. Patients were divided into two groups: 990 in the no adjuvant therapy series (diagnosed in 1974–1988) with median follow-up of 13 years; and 1765 in the selective adjuvant therapy series (1988–2000) with median follow-up of 6.8 years. Lymphovascular invasion was identified in 19% of tumours and was associated with larger tumour size, higher histological grade and younger age. Overall, survival was associated on multivariate analysis with lymphovascular invasion, histological grade and tumour size in both patient series, and with histological type in the no adjuvant therapy series. In conclusion, lymphovascular invasion is an independent prognostic factor in node-negative breast cancer and should be considered in decisions about adjuvant treatment in this group of women.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Presently only limited sets of tropospheric ammonia (NH3) measurements in the Earth's atmosphere have been reported from satellite and surface station measurements, despite the well-documented ...negative impact of NH3 on the environment and human health. Presented here is a detailed description of the satellite retrieval strategy and analysis for the Tropospheric Emission Spectrometer (TES) using simulations and measurements. These results show that: (i) the level of detectability for a representative boundary layer TES NH3 mixing ratio value is ~0.4 ppbv, which typically corresponds to a profile that contains a maximum level value of ~1 ppbv; (ii) TES NH3 retrievals generally provide at most one degree of freedom for signal (DOFS), with peak sensitivity between 700 and 900 mbar; (iii) TES NH3 retrievals show significant spatial and seasonal variability of NH3 globally; (iv) initial comparisons of TES observations with GEOS-CHEM estimates show TES values being higher overall. Important differences and similarities between modeled and observed seasonal and spatial trends are noted, with discrepancies indicating areas where the timing and magnitude of modeled NH3 emissions from agricultural sources, and to lesser extent biomass burning sources, need further study.
Ammonia (NH3) has significant impacts on biodiversity, eutrophication, and acidification. Widespread uncertainty in the magnitude and seasonality of NH3 emissions hinders efforts to address these ...issues. In this work, we constrain U.S. NH3 sources using observations from the TES satellite instrument with the GEOS‐Chem model and its adjoint. The inversion framework is first validated using simulated observations. We then assimilate TES observations for April, July, and October of 2006 through 2009. The adjoint‐based inversion allows emissions to be adjusted heterogeneously; they are found to increase in California throughout the year, increase in different regions of the West depending upon season, and exhibit smaller increases and occasional decreases in the Eastern U.S. Evaluations of the inversion using independent surface measurements show reduced model underestimates of surface NH3 and wet deposited NHx in April and October; however, the constrained simulation in July leads to overestimates of these quantities, while TES observations are still under predicted. Modeled sulfate and nitrate aerosols concentrations do not change significantly, and persistent nitrate overestimation is noted, consistent with previous studies. Overall, while satellite‐based constraints on NH3 emissions improve model simulations in several aspects, additional assessment at higher horizontal resolution of spatial sampling bias, nitric acid formation, and diurnal variability and bi‐directionality of NH3 sources may be necessary to enhance year‐round model performance across the full range of gas and aerosol evaluations.
Key PointsInverse modeling with TES satellite data helps constrain ammonia emissionsImprovements beyond NH3 sources are needed for better ammonium aerosol modelingNH3 emissions may be broadly underestimated throughout the U.S
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
During the second Texas Air Quality Study 2006 (TexAQS II), a full range of pollutants was measured by aircraft in eastern Texas during successive transects of power plant plumes (PPPs). A regional ...photochemical model is applied to simulate the physical and chemical evolution of the plumes. The observations reveal that SO2 and NOy were rapidly removed from PPPs on a cloudy day but not on the cloud-free days, indicating efficient aqueous processing of these compounds in clouds. The model reasonably represents observed NOx oxidation and PAN formation in the plumes, but fails to capture the rapid loss of SO2 (0.37 h−1) and NOy (0.24 h−1) in some plumes on the cloudy day. Adjustments to the cloud liquid water content (QC) and the default metal concentrations in the cloud module could explain some of the SO2 loss. However, NOy in the model was insensitive to QC. These findings highlight cloud processing as a major challenge to atmospheric models. Model-based estimates of ozone production efficiency (OPE) in PPPs are 20–50 % lower than observation-based estimates for the cloudy day.
Long-term analysis of a randomised trial in Nottingham comparing tamoxifen versus surgery as initial treatment demonstrated that in oestrogen receptor (ER)-unselected cases, surgery achieved better ...local control, with no difference in overall survival. It was suggested that for patients with ER-rich tumours, local control and survival may be comparable. We now present long-term follow-up of a randomised trial designed to address this clinical scenario.
One hundred and fifty three fit elderly (≥70 years) women with clinically node-negative primary invasive breast carcinoma <5 cm of high ER content histochemical (H) score ≥100 were randomised 2:1 to primary tamoxifen (Tam) (N=100) or mastectomy with adjuvant tamoxifen (Mx+Tam) (N=53).
With median follow-up of 78 months, there was no statistically significant difference in 10-year rates of regional recurrence (9.0% versus 7.5%), metastasis (8.0% versus 13.2%), breast cancer-specific survival (89.0% versus 86.8%) or overall survival (64.0% versus 66.0%) between Tam and Mx+Tam; however, local control was inferior with Tam (local failure rates 43.0% versus 1.9%; P<0.001).
Irrespective of the degree of ER positivity, surgery achieved better local control. However, there was excellent and similar survival in both groups. Tam could be considered in those who are ‘frail’, refuse or prefer not to initially undergo surgery.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This paper examines the operational performance of the Community Multiscale Air Quality (CMAQ) model simulations for 2002–2006 using both 36-km and 12-km horizontal grid spacing, with a primary focus ...on the performance of the CMAQ model in predicting wet deposition of sulfate (SO4=), ammonium (NH4+) and nitrate (NO3−). Performance of the wet deposition estimates from the model is determined by comparing CMAQ predicted concentrations to concentrations measured by the National Acid Deposition Program (NADP), specifically the National Trends Network (NTN). For SO4= wet deposition, the CMAQ model estimates were generally comparable between the 36-km and 12-km simulations for the eastern US, with the 12-km simulation giving slightly higher estimates of SO4= wet deposition than the 36-km simulation on average. The result is a slightly larger normalized mean bias (NMB) for the 12-km simulation; however both simulations had annual biases that were less than ±15 % for each of the five years. The model estimated SO4= wet deposition values improved when they were adjusted to account for biases in the model estimated precipitation. The CMAQ model underestimates NH4+ wet deposition over the eastern US, with a slightly larger underestimation in the 36-km simulation. The largest underestimations occur in the winter and spring periods, while the summer and fall have slightly smaller underestimations of NH4+ wet deposition. The underestimation in NH4+ wet deposition is likely due in part to the poor temporal and spatial representation of ammonia (NH3) emissions, particularly those emissions associated with fertilizer applications and NH3 bi-directional exchange. The model performance for estimates of NO3− wet deposition are mixed throughout the year, with the model largely underestimating NO3− wet deposition in the spring and summer in the eastern US, while the model has a relatively small bias in the fall and winter. Model estimates of NO3− wet deposition tend to be slightly lower for the 36-km simulation as compared to the 12-km simulation, particularly in the spring. The underestimation of NO3− wet deposition in the spring and summer is due in part to a lack of lightning generated NO emissions in the upper troposphere, which can be a large source of NO in the spring and summer when lightning activity is the high. CMAQ model simulations that include production of NO from lightning show a significant improvement in the NO3− wet deposition estimates in the eastern US in the summer. Overall, performance for the 36-km and 12-km CMAQ model simulations is similar for the eastern US, while for the western US the performance of the 36-km simulation is generally not as good as either eastern US simulation, which is not entire unexpected given the complex topography in the western US.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Neuroendocrine differentiation and prognosis in breast adenocarcinoma
Aims: Neuroendocrine differentiation has been detected, and its prognostic value studied, in a number of common human carcinomas. ...To date there are few detailed studies examining its relevance in breast carcinoma. In this study we evaluate the frequency and prognostic importance of neuroendocrine differentiation in breast adenocarcinoma.
Methods and results: The presence of neuroendocrine differentiation, defined as positive reactivity for three markers, neuron‐specific enolase (NSE), chromogranin A and/or synaptophysin, has been evaluated in 99 patients with primary operable breast cancer using standard immunocytochemical techniques. A consecutive cohort of patients were selected from the Nottingham/Tenovus series. Comprehensive patient and tumour records have been maintained, and patients were followed up according to a defined protocol. Eighteen cases were positive for NSE, 10 for chromogranin A and 13 for synaptophysin. Eleven percent were positive with more than one neuroendocrine marker. No significant association was found between neuroendocrine differentiation and tumour size, grade, stage or the prevalence of vascular invasion. There was no significant difference in either overall or disease‐free survival between patients with or without neuroendocrine differentiation.
Conclusions: In this study we confirm that neuroendocrine differentiation can be identified in a subset (10–18%) of human breast carcinomas. This phenomenon appears to have no relationship to established prognostic factors or patient outcome.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Abstract ONCOPOOL is a retrospectively compiled database of primary operable invasive breast cancers treated in the 1990s in 10 European breast cancer Units. Sixteen thousand and nine hundred and ...forty four cases were entered, with tumours less than 5 cm diameter in women aged 70 or less (mean age 55). Data Data were date of birth, mode of diagnosis, pathology (size, lymph node status, grade, type, lympho-vascular invasion and hormone receptor) and therapies and outcome measures: first local, regional or distant recurrences, contralateral primary, date and cause of death. Tumour characteristics Mean diameter 1.8 cm, 66% lymph node negative, 24% 1–3 lymph nodes involved and 10% had 4 or more involved. Grade 1, 29%; Grade 2, 41%; and Grade 3, 30%. Polynomial relationships were established between grade, stage and size. Seventy-five percent were oestrogen receptor (ER) positive. ER closely related to grade. Outcomes Overall Survival was 89% at 5 years from diagnosis, 80% 10 years and 73% 15 years; Breast Cancer-Specific survivals were 91%, 84% and 79%. Survival strongly related to the Nottingham Prognostic Index (NPI). Cases detected at screening had 84% 10-year survival, those presenting symptomatically 76%. ER positive cases treated with adjuvant hormone therapy had a reduction in risk of death of 13% over those not receiving adjuvant therapy ( p = 0.000). ER negative cases treated with chemotherapy showed a risk reduction of 23% over those not receiving chemotherapy ( p = 0.000).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
An inverse modeling method was developed and tested for identifying possible biases in emission inventories using satellite observations. The relationships between emission inputs and modeled ambient ...concentrations were estimated using sensitivities calculated with the decoupled direct method in three dimensions (DDM-3D) implemented within the framework of the Community Multiscale Air Quality (CMAQ) regional model. As a case study to test the approach, the method was applied to regional ground-level NOx emissions in the southeastern United States as constrained by observations of NO2 column densities derived from the Scanning Imaging Absorption Spectrometer for Atmospheric Chartography (SCIAMACHY) satellite instrument. A controlled "pseudodata" scenario with a known solution was used to establish that the methodology can achieve the correct solution, and the approach was then applied to a summer 2004 period where the satellite data are available. The results indicate that emissions biases differ in urban and rural areas of the southeast. The method suggested slight downward (less than 10%) adjustment to urban emissions, while rural region results were found to be highly sensitive to NOx processes in the upper troposphere. As such, the bias in the rural areas is likely not solely due to biases in the ground-level emissions. It was found that CMAQ was unable to predict the significant level of NO2 in the upper troposphere that was observed during the NASA Intercontinental Chemical Transport Experiment (INTEX) measurement campaign. The best correlation between satellite observations and modeled NO2 column densities, as well as comparison to ground-level observations of NO2, was obtained by performing the inverse while accounting for the significant presence of NO2 in the upper troposphere not captured by the regional model.
Previous inventories of ammonia emissions for the United States have not characterized the seasonal and geographic variations that are necessary for accurately predicting ambient concentrations of ...ammonium nitrate and ammonium sulfate aerosol. This research calculates the seasonal and geographic variation in ammonia emissions from dairy cows in the United States. Monthly, county-level emission factors are calculated with a process-based model of dairy farm emissions, the national distribution of farming practices, seasonal climate conditions, and animal populations. Annual, county-level emission factors are estimated to range between 13.1 and 55.5, with a national average of 23.9
kg
NH
3 cow
−1 yr
−1. The seasonal variation of the emission factor is estimated to be as high as a factor of seven in some counties. Emissions are predicted to be the highest in the spring and fall, because of high manure application rates during the spring planting and after the fall harvest. Summer emissions are higher than winter, resulting from the temperature dependence of housing and storage emissions. In the summer and winter, the majority of emissions are from animal housing. In the spring and fall, the majority of emissions are from field applied manure. The 5% and 95% confidence interval about the national annual average emission factor is between 18 and 36
kg
NH
3
cow
−1
yr
−1. Uncertainties in farming practices contribute most to the total uncertainty, yet uncertainty in the timing of manure application, the quantity of manure and nitrogen excreted by cows, and the physical processes of volatilization affecting applied manure are also significant.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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