Model-Based Decision Support for Industry-Environment Interactions

Applied systems analysis is -- or should be -- a tool in the hands of planners and decision makers who have to deal with the complex and growing problems of modern society. There is, however, an obvious gap between the ever-increasing complexity and volume of scientific and technological information and tools of analysis relevant to large socio-technical and environmental systems, and the information requirements at a strategic planning and policy level. The Advanced Computer Applications (ACA) project builds on IIASA's traditional strength in the methodological foundations of operations research and applied systems analysis, and its rich experience in numerous application areas including the environment, technology, and risk. The ACA group draws on this infrastructure and combines it with elements of AI and advanced information and computer technology. Several completely externally-funded research and development projects in the field of model-based decision support and applied Artificial Intelligence (AI) are currently under way. As an example of this approach to information and decision support systems, one of the components of an R&D project sponsored by the CEC's EURATOM Joint Research Centre (JRC) at Ispra, Italy, in the area of hazardous substances and industrial risk management, is described in this paper. The PDA (Production Distribution Area) is an interactive optimization code (based on DIDASS, one of a family of multicriteria decision support tools developed at IIASA) and a linear problem solver, for chemical industry structures, configured for the pesticide industry of a hypothetical region. The user can select optimization criteria, define allowable ranges or constraints on these criteria, define reference points for the multi-criteria trade-off, and display various levels of model output, including the waste streams generated by the different industrial structure alternatives. These waste streams can then be used to provide input conditions for the environmental impact models. With the emphasis on a directly understandable problem representation and dynamic color graphics, and the user interface as a key element of interactive decision support systems, this is a step toward increased direct practical usability of IIASA's research results

Efficacy of salbutamol via Easyhaler®unaffected by low inspiratory flow

AbstractThe fine particle dose delivered via dry powder inhalers (DPIs) is often affected by the inspiratory flow rate generated during inhalation. This has clinical implications, since the fine particle dose determines the amount of drug reaching the lungs. With Easyhaler®DPI the fine particle dose remains relatively constant over the range of inspiratory flow rates from 30–60 l min−1. The aim of this study was to confirm that clinical efficacy is maintained even at low flow rates by comparing the bronchodilating effect of salbutamol (100 μ g) delivered via Easyhaler®at a target inspiratory flow of 30 l min−1with the same dose of salbutamol via pressurised metered-dose inhaler (pMDI) plus spacer.This was a double-blind, randomized, cross-over study with double-dummy technique. Twenty-one paediatric and adult asthmatic patients completed the study, which was conducted over 2 study days. The main outcome parameter was forced expiratory volume in 1 sec (FEV1). The patients were trained to generate a low peak inspiratory flow rate (PIFR) of 30 l min−1, and the actual PIFR through Easyhaler®was recorded.The average PIFR through Easyhaler®was 28·7 l min−1. The difference in the maximum value of FEV1(FEV1max) between the treatments after drug inhalation was 0·01 l. The mean of FEV1maxwas 2·67 l after pMDI plus spacer compared to 2·69 l after Easyhaler®. Improvements in FEV1were clinically significant. No significant differences between treatments were found.A reasonably low inspiratory flow rate through Easyhaler®produces an equivalent improvement in lung function to a correctly used pMDI plus spacer. Hence, Easyhaler®can be used with confidence in patients who may have difficulty in generating a high inspiratory flow rate, such as children and the elderly

Temperature dependence of the Brewer global UV measurements

Spectral measurements of global UV irradiance recorded by Brewer spectrophotometers can be significantly affected by instrument-specific optical and mechanical features. Thus, proper corrections are needed in order to reduce the associated uncertainties to within acceptable levels. The present study aims to contribute to the reduction of uncertainties originating from changes in the Brewer internal temperature, which affect the performance of the optical and electronic parts, and subsequently the response of the instrument. Until now, measurements of the irradiance from various types of lamps at different temperatures have been used to characterize the instruments' temperature dependence. The use of 50 W lamps was found to induce errors in the characterization due to changes in the transmissivity of the Teflon diffuser as it warms up by the heat of the lamp. In contrast, the use of 200 or 1000 W lamps is considered more appropriate because they are positioned at longer distances from the diffuser so that warming is negligible. Temperature gradients inside the instrument can cause mechanical stresses which can affect the instrument's optical characteristics. Therefore, during the temperature-dependence characterization procedure warming or cooling must be slow enough to minimize these effects. In this study, results of the temperature characterization of eight different Brewer spectrophotometers operating in Greece, Finland, Germany and Spain are presented. It was found that the instruments' response changes differently in different temperature regions due to different responses of the diffusers' transmittance. The temperature correction factors derived for the Brewer spectrophotometers operating at Thessaloniki, Greece, and Sodankylä, Finland, were evaluated and were found to remove the temperature dependence of the instruments' sensitivity.This article is based upon work from COST Action ES1207 “A European Brewer Network (EUBREWNET)”, supported by COST (European Cooperation in Science and Technology) and from the ENV59-ATMOZ (“Traceability for atmospheric total column ozone”) Joint Research Programme (JRP)

High frequency of TTK mutations in microsatellite-unstable colorectal cancer and evaluation of their effect on spindle assembly checkpoint

Frameshift mutations frequently accumulate in microsatellite-unstable colorectal cancers (MSI CRCs) typically leading to downregulation of the target genes due to nonsense-mediated messenger RNA decay. However, frameshift mutations that occur in the 3' end of the coding regions can escape decay, which has largely been ignored in previous works. In this study, we characterized nonsense-mediated decay-escaping frameshift mutations in MSI CRC in an unbiased, genome wide manner. Combining bioinformatic search with expression profiling, we identified genes that were predicted to escape decay after a deletion in a microsatellite repeat. These repeats, located in 258 genes, were initially sequenced in 30 MSI CRC samples. The mitotic checkpoint kinase TTK was found to harbor decay-escaping heterozygous mutations in exon 22 in 59% (105/179) of MSI CRCs, which is notably more than previously reported. Additional novel deletions were found in exon 5, raising the mutation frequency to 66%. The exon 22 of TTK contains an A(9)-G(4)-A(7) locus, in which the most common mutation was a mononucleotide deletion in the A(9) (c.2560delA). When compared with identical non-coding repeats, TTK was found to be mutated significantly more often than expected without selective advantage. Since TTK inhibition is known to induce override of the mitotic spindle assembly checkpoint (SAC), we challenged mutated cancer cells with the microtubule-stabilizing drug paclitaxel. No evidence of checkpoint weakening was observed. As a conclusion, heterozygous TTK mutations occur at a high frequency in MSI CRCs. Unexpectedly, the plausible selective advantage in tumourigenesis does not appear to be related to SAC

Insect herbivory dampens Subarctic birch forest C sink response to warming

Climate warming is anticipated to make high latitude ecosystems stronger C sinks through increasing plant production. This effect might, however, be dampened by insect herbivores whose damage to plants at their background, non-outbreak densities may more than double under climate warming. Here, using an open-air warming experiment among Subarctic birch forest field layer vegetation, supplemented with birch plantlets, we show that a 2.3 degrees C air and 1.2 degrees C soil temperature increase can advance the growing season by 1-4 days, enhance soil N availability, leaf chlorophyll concentrations and plant growth up to 400%, 160% and 50% respectively, and lead up to 122% greater ecosystem CO2 uptake potential. However, comparable positive effects are also found when insect herbivory is reduced, and the effect of warming on C sink potential is intensified under reduced herbivory. Our results confirm the expected warming-induced increase in high latitude plant growth and CO2 uptake, but also reveal that herbivorous insects may significantly dampen the strengthening of the CO2 sink under climate warming. Warming is expected to increase C sink capacity in high-latitude ecosystems, but plant-herbivore interactions could moderate or offset this effect. Here, Silfver and colleagues test individual and interactive effects of warming and insect herbivory in a field experiment in Subarctic forest, showing that even low intensity insect herbivory strongly reduces C sink potential

Thalamic Atrophy Without Whole Brain Atrophy Is Associated With Absence of 2-Year NEDA in Multiple Sclerosis

Purpose: To study which brain volume measures best differentiate early relapsing MS (RMS) and secondary progressive MS (SPMS) patients and correlate with disability and cognition. To test whether isolated thalamic atrophy at study baseline correlates with NEDA (no evidence of disease activity) at 2 years.Methods: Total and regional brain volumes were measured from 24 newly diagnosed RMS patients 6 months after initiation of therapy and 2 years thereafter, and in 36 SPMS patients. Volumes were measured by SIENAX and cNeuro. The patients were divided into subgroups based on whole brain parenchyma (BP) and thalamic atrophy at baseline. Standard scores (z-scores) were computed by comparing individual brain volumes against healthy controls. A z-score cut-off of - 1.96 was applied to separate atrophic from normal brain volumes. The Expanded Disability Status Scale (EDSS) and Symbol Digit Modalities Test (SDMT) were assessed at baseline and at 2 years. Differences in achieving NEDA-3, NEDA-4, EDSS progression, and SDMT change were analyzed between patients with no thalamic or BP atrophy and in patients with isolated thalamic atrophy at baseline.Results: At baseline, 7 SPMS and 12 RMS patients had no brain atrophy, 8 SPMS and 10 RMS patients had isolated thalamic atrophy and 2 RMS and 20 SPMS patients had both BP and thalamic atrophy. NEDA-3 was reached in 11/19 patients with no brain atrophy but only in 2/16 patients with isolated thalamic atrophy (p = 0.012). NEDA-4 was reached in 7/19 patients with no brain atrophy and in 1/16 of the patients with isolated thalamic atrophy (p = 0.047). At 2 years, EDSS was same or better in 16/19 patients with no brain atrophy but only in 5/17 patients with isolated thalamic atrophy (p = 0.002). There was no significant difference in the EDSS, relapses or SDMT between patients with isolated thalamic atrophy and no atrophy at baseline.Conclusion: Patients with isolated thalamic atrophy were at a higher risk for not reaching 2-year NEDA-3 and for EDSS increase than patients with no identified brain atrophy. The groups were clinically indistinguishable. A single measurement of thalamic and whole brain atrophy could help identify patients needing most effective therapies from early on

The influence of soil communities on the temperature sensitivity of soil respiration

Soil respiration represents a major carbon flux between terrestrial ecosystems and the atmosphere, and is expected to accelerate under climate warming. Despite its importance in climate change forecasts, however, our understanding of the effects of temperature on soil respiration (RS) is incomplete. Using a metabolic ecology approach we link soil biota metabolism, community composition and heterotrophic activity, to predict RS rates across five biomes. We find that accounting for the ecological mechanisms underpinning decomposition processes predicts climatological RS variations observed in an independent dataset (n = 312). The importance of community composition is evident because without it RS is substantially underestimated. With increasing temperature, we predict a latitudinal increase in RS temperature sensitivity, with Q10 values ranging between 2.33 ±0.01 in tropical forests to 2.72 ±0.03 in tundra. This global trend has been widely observed, but has not previously been linked to soil communities