Discounting and the environment should current impacts be weighted differently than impacts harming future generations?

Background  In Life-Cycle Assessment (LCA), decision makers are often faced with tradeoffs between current and future impacts. One typical example is waste incineration, where immediate emissions to the air from the incineration process have to be weighted against future emissions of slag landfills. Long-term impacts are either completely taken into account or they are entirely disregarded in case of a temporal cut-off. Temporal cutoffs are a special case of discounting. Objective  In this paper, discounting is defined as valuing damages differently at different points of time using a positive or negative discount rate. Apart from temporal cut-offs, discounting has rarely been applied in LCA so far. It is the goal of this paper to discuss the concept of discounting and its applicability in the context of LCA. Methods  For this purpose, we first review the arguments for discounting and its principles in economic sciences. Discounting in economics can be motivated by pure time preference, productivity of capital, diminishing marginal utility of consumption, and uncertainties. The nominal discount rate additionally includes changes in the price level. These arguments and their justification are discussed in the context of environmental impacts harming future generations. Results and Discussion  It is concluded that discounting across generations because of pure time preference contradicts fundamental ethical values and should therefore not be applied in LCA. However, it has to be acknowledged that in practice decision makers often use positive discount rates because of pure time preference — either because they might profit from imposing environmental damage on others instead of themselves or because people in the far future are not of immediate concern to them. Discounting because of the productivity of capital assumes a relationship between monetary values and environmental impact. If such a relationship is accepted, discounting could be applied. However, future generations should be compensated for the environmental damage. It is likely that they would demand a higher compensation if the real per capita income increases. As both the compensation and the discount rate are related to economic growth, the overall discount rate might be close to zero. It is shown that the overall discount rate might even be negative considering that the required compensation could increase (even to infinite) if natural assets remain scarce, whereas the utility of consumption diminishes with increasing income. Uncertainties could justify both positive and negative discount rates. Since the relationship between uncertainties and the magnitude of damage is generally not exponential, we recommend to model changes in the magnitude of damage in scenario analysis instead of considering it in discounting (which requires an exponential function of time in the case of a constant discount rate). We investigated the influence of discounting in a case study of heavy metal emissions from slag landfills. It could be shown that even small discount rates of less than 1 % lead to a significant reduction of the impact score, whereas negative discount rates inflate the results. Conclusions and Recommendations  Discounting is only applicable when temporally differentiated data is available. In some cases, such a temporal differentiation is necessary to take sound decisions, especially when long emission periods are involved. An example is the disposal of nuclear or heavy metal-containing waste. In these cases, the results might completely depend on the discount rate. This paper helps to structure arguments and thus to support the decision about whether or not discounting should be applied in an LCA.     

Development of synaptic responses and plasticity at the SC-CA1 and MF-CA3 synapses in rat hippocampus

1. The development of synaptic transmission and indicators of short- and long-term plasticity was studied by recording from areas CA1 and CA3 upon activation of monosy- naptic excitatory inputs in rat hippocampal brain slices obtained from Wistar rats of different ages.2. Although population field excitatory postsynaptic potentials (fEPSPS) are small in animals at postnatal day 10 (P10), both areas already exhibited short-term [posttetanic potentiation (PTP) and paired pulse potentiation (PPF)] and long-term [long-term potentiation (LTP)] plastic responses.3. The amplitudes of the fEPSP and LTP increased with age in both regions, but peaked at P30 in CA3 while they were still increasing at the oldest age studied (P60) in CA1. In CA3, but not CA1, LTP at P60 was less than at P30.4. PTP did not show clear alterations with age in either region. PPF decreased with age in CA1 but not CA3.     

The use of a conventional tissue culture plate as an optically accessible perfusion chamber for in situ assays and for long-term cultivation of mammalian cells

An alternative culture system has been developed based on a conventional tissue culture plate (3.5 cm diameter) which is changed into a closed perfusion chamber. The system can easily be scaled up from one to several chambers. The shape and the size of the area of cell growth may be designed to individual experimental demands. The whole culture chamber is optically accessible, so cell growth and morphology can be evaluated by light microscopy. Furthermore the cellular physiology can be characterised by any fluorimetric assay using a bottom type fluorescence reader. A peristaltic pump sustains a constant medium flow through the chamber thus creating true homeostasis. The use of HPLC-valves and connectors allows the switching between different media or assay solutions. Thus it is possible to perform in situ assays also measuring transient effects. A protocol for vitality tests using calcein-AM is worked out for an adherent cell line and for a suspension cell line. The lower detection limits are 7 × 10² cells cm^-2 for the adherent cells and 5 × 10⁴ cells mL^-1 for the suspension cells. The upper limits are 1–2 × 10⁵ cells cm^-2 respectively 8 × 10⁶ cells mL^-1.     

Hemopoiesis in long-term stroma-dependent cultures from lymphoid tissue: Production of cells with myeloid/dendritic characteristics

Summary A long-term stroma-dependent culture system (LTC) has been developed which continuously produces hemopoietic cells providing an in vitro system for the study of cell differentiation. These nonadherent cell populations contain a large subpopulation of dendritic cells (DC). LTC producing DC were easily generated from spleen, but could also be established from bone marrow (BM) and lymph node with less success. It was difficult to establish DC-producing LTC from thymus. The properties of splenic and thymic stroma have been compared. Spleen stroma developed more complicated networks of fibroblasts, endothelial cells, macrophages, and DC. Thymic stromal monolayers were dominated by epithelial cells and fibroblasts, with a lower proportion of macrophages and endothelial cells. They had a relatively sparse structure of cell networks compared with spleen stroma. Cells with dendritiform morphology first appeared in cultures by 2–3 wk. The majority of cells produced were large cells which expressed DC-specific cell surface markers, major histocompatibility complex (MHC) Class II molecules, and the CD80/CD86(B7) costimulator. A high proportion of cells also expressed myeloid cell markers. No T or B lymphoid cells or granulocytes were present in the cultures. LTC continued to produce nonadherent cells resembling myeloid/DC for long periods, even after passage of stromal cells and stem cells at about 3–4 mo. after culture establishment. The LTC system offers potential to study the in vitro differentiation of myeloid/DC.     

Somatic embryogenesis in pearl millet (Pennisetum glaucum): Strategies to reduce genotype limitation and to maintain long-term totipotency

Three genotypes of Pearl millet were screened in vitro for induction of embryogenic callus, somatic embryogenesis and regeneration. Shoot apices excised from in vitro germinated seedlings or immature embryos isolated from green house established plants were used as primary explants. The frequency of embryogenic callus initiation was significantly higher in shoot apices in comparison with immature zygotic embryos. Moreover, differences between genotypes were minimal when using shoot apices. Friable embryogenic calli (type II) developed on the initial nodular calli after 1 to 3 months of culture. The frequency of type II callus is related to the composition of the maintenance medium and they were more often found in ageing cultures. The transfer of embryogenic calli onto auxin-free medium was sufficient for inducing somatic embryo development in short-term culture (3 months) while a progressive loss in regeneration potential was observed with increasing time of subcultures. Maturation of embryogenic calli on medium supplemented with activated charcoal, followed by germination of somatic embryos on medium supplemented with gibberellic acid, restored regeneration in long-term cultures. This revised version was published online in June 2006 with corrections to the Cover Date.     

Weekly osimertinib dosing prevents EGFR mutant tumor cells destined to home mouse lungs

The recently conducted ADAURA trial concludes daily dosing of adjuvant osimertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI), improves disease-free survival with stage IB/II/IIIA EGFR -mutated non-small cell lung cancer patients in comparison to placebo. We have developed a preclinical orthotopic mouse model, using luciferase tagged lung adenocarcinoma cells harboring EGFR TKI sensitive exon 19 deletion to model and extend trial implications comparing a weekly vs daily dosing outcome of osimertinib to a first-generation TKI- erlotinib. We find that 100% of mice in both the groups receiving osimertinib daily or weekly before injection of cells show a complete absence of homing of cells in mice''s lungs from day three until day 18 post-injection of cells. On the other hand, 25% and 75% of mice receiving erlotinib daily and weekly before injecting cells show homing of cells to the lungs. The tumors observed in the lungs, when dissected at day 30, confirmed the colonization of the injected cells homing to the organ. Thus, our study establishes the efficacy of pretreatment with osimertinib in reducing tumor cells'' homing to mouse lungs in an in vivo mouse model.     

Effects of European colonization on indigenous ecosystems: post-settlement changes in tree stand structures in Eucalyptus–Callitris woodlands in central New South Wales, Australia

Aim There has been considerable debate about pre‐settlement stand structures in temperate woodlands in south‐eastern Australia. Traditional histories assumed massive tree losses across the region, whereas a number of recent histories propose that woodlands were originally open and trees regenerated densely after settlement. To reconcile these conflicting models, we gathered quantitative data on pre‐settlement stand structures in Eucalyptus–Callitris woodlands in central New South Wales Australia, including: (1) tree density, composition, basal area and canopy cover at the time of European settlement; and (2) post‐settlement changes in these attributes. Location Woodlands dominated by Eucalyptus species and Callitris glaucophylla, which originally occupied approximately 100,000 km² in central New South Wales, Australia. Methods We recorded all evidence of pre‐settlement trees, including stumps, stags and veteran trees, from 39 relatively undisturbed 1‐ha stands within 16 State Forests evenly distributed across the region. Current trees were recorded in a nested 900 m² quadrat at each site. Allometric relationships were used to estimate girth over bark at breast height, tree basal area, and crown diameter from the girth of cut stumps. A post‐settlement disturbance index was developed to assess correlations between post‐settlement disturbance and attributes of pre‐settlement stands. Results The densities of all large trees (> 60 cm girth over bark at breast height) were significantly greater in current stands than at the time of European settlement (198 vs. 39 trees ha^?1). Pre‐settlement and current stands did not differ in basal area. However, the proportional representation of Eucalyptus and Callitris changed completely. At the time of settlement, stands were dominated by Eucalyptus (78% of basal area), whereas current stands are dominated by Callitris (74%). On average, Eucalyptus afforded 83% of crown cover at the time of settlement. Moreover, the estimated density, basal area and crown cover of Eucalyptus at the time of settlement were significantly negatively correlated with post‐settlement disturbance, which suggests that these results underestimate pre‐settlement Eucalyptus representation in the most disturbed stands. Main conclusions These results incorporate elements of traditional and recent vegetation histories. Since European settlement, State Forests have been transformed from Eucalyptus to Callitris dominance as a result of the widespread clearance of pre‐settlement Eucalyptus and dense post‐settlement recruitment of Callitris. Tree densities did increase greatly after European settlement, but most stands were much denser at the time of settlement than recent histories suggest. The original degree of dominance by Eucalyptus was unexpected, and has been consistently underestimated in the past. This study has greatly refined our understanding of post‐settlement changes in woodland stand structures, and will strengthen the foundation for management policies that incorporate historical benchmarks of landscape vegetation changes.     

Adjusting for Ordinal Covariates by Inducing a Partial Ordering

In the context of randomized clinical trials, multiplicity arises in many forms. One prominent example is when a key endpoint is measured and analyzed both at baseline and after treatment. It is common to analyze each separately, but more efficient to adjust the post‐treatment comparisons for the baseline values. Adjustment techniques generally treat the covariate (baseline value, in this case) as either nominal or continuous. Either is problematic when applied to an ordinal covariate, the former because it fails to exploit the natural ordering and the latter because it relies on an artifical notion of linear prediction and differences between values. We propose new methods for adjusting for ordinal covariates without having to treat them as nominal or continuous. Specifically, the information‐preserving composite endpoint consists of the pair of values for each patient, one at baseline and one after treatment. Some of these patterns will indicate more improvement than others, yet some pairs of patterns are not comparable. Hence, the ordering is only partial. We develop an approach to testing and deriving estimators of magnitudes of the treatment effect based on comparing each observation in one group to each observation in the other group to which it is comparable. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Long-term patterns of mass loss during the decomposition of leaf and fine root litter: an intersite comparison

Decomposition is a critical process in global carbon cycling. During decomposition, leaf and fine root litter may undergo a later, relatively slow phase; past long-term experiments indicate this phase occurs, but whether it is a general phenomenon has not been examined. Data from Long-term Intersite Decomposition Experiment Team, representing 27 sites and nine litter types (for a total of 234 cases) was used to test the frequency of this later, slow phase of decomposition. Litter mass remaining after up to 10 years of decomposition was fit to models that included (dual exponential and asymptotic) or excluded (single exponential) a slow phase. The resultant regression equations were evaluated for goodness of fit as well as biological realism. Regression analysis indicated that while the dual exponential and asymptotic models statistically and biologically fit more of the litter type–site combinations than the single exponential model, the latter was biologically reasonable for 27–65% of the cases depending on the test used. This implies that a slow phase is common, but not universal. Moreover, estimates of the decomposition rate of the slowly decomposing component averaged 0.139–0.221 year⁻¹ (depending on method), higher than generally observed for mineral soil organic matter, but one-third of the faster phase of litter decomposition. Thus, this material may be slower than the earlier phases of litter decomposition, but not as slow as mineral soil organic matter. Comparison of the long-term integrated decomposition rate (which included all phases of decomposition) to that for the first year of decomposition indicated the former was on average 75% that of the latter, consistent with the presence of a slow phase of decomposition. These results indicate that the global store of litter estimated using short-term decomposition rates would be underestimated by at least one-third.