Estrogen receptor (ER) expression is the main indicator of potential responses to endocrine therapy (ET), and approximately 70% of human breast cancers (BCs) are hormone-dependent and ER-positive. ...The introduction of adjuvant systemic therapy led to a significant improvement in post-surgical survival and a reduction in disease relapse, especially in women with early BC and those with ER+ tumors, who may receive ET alone or in combination with cytotoxic therapy. Adjuvant ET currently consists of (i) ovarian suppression, (ii) selective estrogen receptor modulators (SERMs) and down-regulators, and (iii) aromatase inhibitors (AIs). In patients with ER+ tumors pharmacologic ovary suppression with gonadotropin-releasing hormone agonists in combination with standard adjuvant therapy is generally more effective than adjuvant chemotherapy alone. Tamoxifen is the best established SERM, has favorable effects on BC control and bone metabolism, but also has adverse effects due to its estrogenic activity in other tissues. For these reasons, other SERMs have been developed. Fulvestrant is an ER down-regulator with several potential advantages over SERMs, including a 100-fold increase in its affinity for ER compared with tamoxifen and no estrogen-like activity in the uterus. The inhibition of the aromatase system with third-generation AIs is associated with improved survival in patients with advanced BC compared with SERMs. In postmenopausal patients with ER+ BC adjuvant treatment with AIs should be performed, either as sequential treatment after tamoxifen or as upfront therapy. Studies evaluating the role of AIs as first-line therapy are ongoing and the results are encouraging.
Endocrine therapy of breast cancer Lumachi, F; Luisetto, G; Basso, S M M ...
Current medicinal chemistry,
02/2011, Volume:
18, Issue:
4
Journal Article
Peer reviewed
Breast cancer remains one of the first leading causes of death in women, and currently endocrine treatment is of major therapeutic value in patients with estrogen-receptor positive tumors. Selective ...estrogen-receptor modulators (SERMs), such as tamoxifen and raloxifene, aromatase inhibitors, and GnRH agonists are the drugs of choice. Tamoxifen, a partial nonsteroidal estrogen agonist, is a type II competitive inhibitor of estradiol at its receptor, and the prototype of SERMs. Aromatase inhibitors significantly lower serum estradiol concentration in postmenopausal patients, having no detectable effects on adrenocortical steroids formation, while GnRH agonists suppress ovarian function, inducing a menopause-like condition in premenopausal women. Endocrine therapy has generally a relatively low morbidity, leading to a significant reduction of mortality for breast cancer. The aim of chemoprevention is to interfere early with the process of carcinogenesis, reducing the risk of cancer development. As preventive agents, raloxifene and tamoxifene are equivalent, while raloxifene has more potent antiresorptive effects in postmenopausal osteoporosis. Endocrine treatment is usually considered a standard choice for patients with estrogen-receptor positive cancers and non-life-threatening advanced disease, or for older patients unfit for aggressive chemotherapy regimens. Several therapeutic protocols used in patients with breast cancer are associated with bone loss, which may lead to an increased risk of fracture. Bisphosphonates are the drugs of choice to treat such a drug-induced bone disease. The aim of this review is to outline current understanding on endocrine therapy of breast cancer.
Analyzing a response of catchments to rainfall inputs allows for deeper insights on the mechanisms of runoff generation at catchment scale. In this study an automated time series‐based event ...separation procedure consisting of available base flow separation, runoff event identification, and rainfall attribution methods and of a novel iterative procedure for the adjustment of thresholds used to identify single‐peak components of multiple‐peak events is proposed. Event runoff coefficient, time scale, rise time, and peak discharge of more than 220,000 identified rainfall‐runoff events are then used to analyze dynamics of event runoff response in 185 catchments at multiple temporal scales. In mountainous catchments with poor storage event runoff response is strongly controlled by the characteristics of rainfall and is generated by event‐fed saturation or infiltration excess. A distinct switch between saturated and unsaturated states occurs in these catchments. A weak relation between rainfall and runoff event properties is instead observed in lowland and hilly catchments with substantial storage, where a gradual transformation between functioning states occurs and the response is driven by preevent saturation. The seasonality of their event characteristics is governed by the contribution of snowmelt and the seasonality of the aridity index rather than of rainfall properties. Long‐term changes of total precipitation amount alone do not explain season‐specific long‐term changes of event characteristics that are rather consistent with changes of seasonal indicators of the wetness state. The effects of land use changes are detectable only in a few cases and display themselves mostly in the characteristic response time of catchments.
Key Points
Rainfall‐runoff events are identified from continuous time series (1951‐2013) for a large scale data set covering the whole of Germany
Temporal variability of event characteristics identify regions where infiltration excess and event‐fed or preevent saturation dominate
Runoff response nonstationarity is caused by modification of the intraannual seasonality rather than of the total precipitation amount
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Demographic Structure and Macroeconomic Trends Aksoy, Yunus; Basso, Henrique S.; Smith, Ron P. ...
American economic journal. Macroeconomics,
01/2019, Volume:
11, Issue:
1
Journal Article
Peer reviewed
Open access
We estimate the effect of changes in demographic structure on long-term trends of key macroeconomic variables using a panel VAR for 21 OECD economies from 1970–2014. The panel data variation assists ...the identification of demographic effects, while the dynamic structure, incorporating multiple channels of influence, uncovers long-term effects. We propose a theoretical model, relating demographics, innovation, and growth, whose simulations match our empirical findings. The current trend of population aging and low fertility is projected to reduce output growth, investment, and real interest rates across OECD countries.
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BFBNIB, CEKLJ, NMLJ, NUK, PNG, UL, UM, UPUK
Amazonia hosts the Earth's largest tropical forests and has been shown to be an important carbon sink over recent decades.sup.1-3. This carbon sink seems to be in decline, however, as a result of ...factors such as deforestation and climate change.sup.1-3. Here we investigate Amazonia's carbon budget and the main drivers responsible for its change into a carbon source. We performed 590 aircraft vertical profiling measurements of lower-tropospheric concentrations of carbon dioxide and carbon monoxide at four sites in Amazonia from 2010 to 2018.sup.4. We find that total carbon emissions are greater in eastern Amazonia than in the western part, mostly as a result of spatial differences in carbon-monoxide-derived fire emissions. Southeastern Amazonia, in particular, acts as a net carbon source (total carbon flux minus fire emissions) to the atmosphere. Over the past 40 years, eastern Amazonia has been subjected to more deforestation, warming and moisture stress than the western part, especially during the dry season, with the southeast experiencing the strongest trends.sup.5-9. We explore the effect of climate change and deforestation trends on carbon emissions at our study sites, and find that the intensification of the dry season and an increase in deforestation seem to promote ecosystem stress, increase in fire occurrence, and higher carbon emissions in the eastern Amazon. This is in line with recent studies that indicate an increase in tree mortality and a reduction in photosynthesis as a result of climatic changes across Amazonia.sup.1,10.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
Mixture of runoff generation processes poses a challenge for predicting upper flood quantiles. We examined transformations of generation processes from all identifiable runoff events to frequent and ...upper tail floods for a large set of mesoscale catchments and observed a substantial change of the dominant processes. Two trajectories of transformation were detected. In regions where floods occur almost exclusively in winter the dominance of processes related to snowmelt consistently increases from small events to frequent and upper tail floods. In catchments characterized by frequent winter‐spring floods and occasional summer‐autumn flood events triggered by rare meteorological phenomena (e.g., Vb cyclones), processes that dominate upper tails are not adequately represented in the sample of frequent floods. Predictions of extremes and projections of flood changes might remain highly uncertain in the latter cases.
Plain Language Summary
Prediction of floods remains a challenging task for the engineering practice. Floods triggered by different physical mechanisms have contrasting statistical attributes. Mixture of these processes hinders reliable prediction of the largest floods. In this study we classified a large number of streamflow events observed in a wide range of German river basins according to their generation processes. We analyzed changes in the frequency of occurrence of different generation processes, from the smallest identifiable runoff events to annual floods to rarer events corresponding to larger river flows. Interestingly, for some river basins certain processes tend to consistently increase their frequency from small streamflow events to common and larger floods. In other cases, we observed an opposite tendency. Certain processes become less important for the generation of annual floods compared to small streamflow events but then dominate generation of the largest floods. This has important implications for our ability to predict extreme floods and their possible changes.
Key Points
We analyzed transformation of processes from small runoff events to larger floods using a process‐based framework for event characterization
A substantial transformation of the frequency of processes from small runoff events to frequent and upper tail floods is observed
Differences in trajectories of process transformation among catchments suggest regionally variable predictability of extremes
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Increasing the water‐holding capacity of sandy soils will help improve efficiency of water use in agricultural production, and may be critical for providing enough energy and food for an increasing ...global population. We hypothesized that addition of biochar will increase the water‐holding capacity of a sandy loam soil, and that the depth of biochar incorporation will influence the rate of biochar surface oxidation in the amended soils. Hardwood fast pyrolysis biochar was mixed with soil (0%, 3%, and 6% w/w) and placed into columns in either the bottom 11.4 cm or the top 11.4 cm to simulate deep banding in rows (DBR) and uniform topsoil mixing (UTM) applications, respectively. Four sets of 18 columns were incubated at 30 °C and 80% RH. Every 7 days, 150 mL of 0.001 M calcium chloride solution was added to the columns to produce leaching. Sets of columns were harvested after 1, 15, 29, and 91 days. Addition of biochar increased the gravity‐drained water content 23% relative to the control. Bulk density of the control soils increased with incubation time (from 1.41 to 1.45 g cm−3), whereas bulk density of biochar‐treated soils was up to 9% less than the control and remained constant throughout the incubation period. Biochar did not affect the CEC of the soil. The results suggest that biochar added to sandy loam soil increases water‐holding capacity and might increase water available for crop use.
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BFBNIB, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Wetlands are the largest global source of atmospheric methane (CH
), a potent greenhouse gas. However, methane emission inventories from the Amazon floodplain, the largest natural geographic source ...of CH
in the tropics, consistently underestimate the atmospheric burden of CH
determined via remote sensing and inversion modelling, pointing to a major gap in our understanding of the contribution of these ecosystems to CH
emissions. Here we report CH
fluxes from the stems of 2,357 individual Amazonian floodplain trees from 13 locations across the central Amazon basin. We find that escape of soil gas through wetland trees is the dominant source of regional CH
emissions. Methane fluxes from Amazon tree stems were up to 200 times larger than emissions reported for temperate wet forests and tropical peat swamp forests, representing the largest non-ebullitive wetland fluxes observed. Emissions from trees had an average stable carbon isotope value (δ
C) of -66.2 ± 6.4 per mil, consistent with a soil biogenic origin. We estimate that floodplain trees emit 15.1 ± 1.8 to 21.2 ± 2.5 teragrams of CH
a year, in addition to the 20.5 ± 5.3 teragrams a year emitted regionally from other sources. Furthermore, we provide a 'top-down' regional estimate of CH
emissions of 42.7 ± 5.6 teragrams of CH
a year for the Amazon basin, based on regular vertical lower-troposphere CH
profiles covering the period 2010-2013. We find close agreement between our 'top-down' and combined 'bottom-up' estimates, indicating that large CH
emissions from trees adapted to permanent or seasonal inundation can account for the emission source that is required to close the Amazon CH
budget. Our findings demonstrate the importance of tree stem surfaces in mediating approximately half of all wetland CH
emissions in the Amazon floodplain, a region that represents up to one-third of the global wetland CH
source when trees are combined with other emission sources.
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IJS, KISLJ, NUK, SBMB, UL, UM, UPUK
Abstract
Magnitude and frequency are prominent features of river floods informing design of engineering structures, insurance premiums and adaptation strategies. Recent advances yielding a formal ...characterization of these variables from a joint description of soil moisture and daily runoff dynamics in river basins are here systematized to highlight their chief outcome: the PHysically-based Extreme Value (PHEV) distribution of river flows. This is a physically-based alternative to empirical estimates and purely statistical methods hitherto used to characterize extremes of hydro-meteorological variables. Capabilities of PHEV for predicting flood magnitude and frequency are benchmarked against a standard distribution and the latest statistical approach for extreme estimation, by using both an extensive observational dataset and long synthetic series of streamflow generated for river basins from contrasting hydro-climatic regions. The analyses outline the domain of applicability of PHEV and reveal its fairly unbiased capabilities to estimate flood magnitudes with return periods much longer than the sample size used for calibration in a wide range of case studies. The results also emphasize reduced prediction uncertainty of PHEV for rare floods, notably if the flood magnitude-frequency curve displays an inflection point. These features, arising from the mechanistic understanding embedded in the novel distribution of the largest river flows, are key for a reliable assessment of the actual flooding hazard associated to poorly sampled rare events, especially when lacking long observational records.
•Diverse versions of a stochastic model compared in terms of high flow statistics.•Key role of non-linear storage–discharge to reproduce frequencies of high flows.•Importance of studying individual ...recessions to portray the basin hydrologic response.•Emergence of heavy tails linked to non-linearity of catchment response.•Implications for floods, riparian vegetation dynamics and sediment transport.
The right tail of streamflow distributions quantifies the occurrence probability of high flows, which play an important role in the dynamics of many eco-hydrological processes and eventually contribute to shape riverine environments. In this paper, the ability of a mechanistic analytical model for streamflow distributions to capture the statistical features of high flows has been investigated. The model couples a stochastic description of soil moisture dynamics with a simplified hydrologic response based on a catchment-scale storage–discharge relationship. Different types of relations between catchment water storage and discharge have been investigated, and alternative methods for parameter estimation have been compared using informal performance metrics and formal model selection criteria. The study highlights the pivotal role of non-linear storage–discharge relations in reproducing observed frequencies of high flows, and reveals the importance of analyzing the behavior of individual events for a reliable characterization of recession parameters. The emergence of heavy-tailed streamflow distributions is mechanistically linked to the degree of non-linearity of the catchment hydrologic response, with implications for the understanding of rivers’ flooding potential and related ecologic and morphological processes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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