Interactively modelling land profitability to estimate European agricultural and forest land use under future scenarios of climate, socio-economics and adaptation

Studies of climate change impacts on agricultural land use generally consider sets of climates combined with fixed socio-economic scenarios, making it impossible to compare the impact of specific factors within these scenario sets. Analysis of the impact of specific scenario factors is extremely difficult due to prohibitively long run-times of the complex models. This study produces and combines metamodels of crop and forest yields and farm profit, derived from previously developed very complex models, to enable prediction of European land use under any set of climate and socio-economic data. Land use is predicted based on the profitability of the alternatives on every soil within every 10' grid across the EU. A clustering procedure reduces 23,871 grids with 20+ soils per grid to 6,714 clusters of common soil and climate. Combined these reduce runtime 100 thousand-fold. Profit thresholds define land as intensive agriculture (arable or grassland), extensive agriculture or managed forest, or finally unmanaged forest or abandoned land. The demand for food as a function of population, imports, food preferences and bioenergy, is a production constraint, as is irrigation water available. An iteration adjusts prices to meet these constraints. A range of measures are derived at 10' grid-level such as diversity as well as overall EU production. There are many ways to utilise this ability to do rapidWhat-If analysis of both impact and adaptations. The paper illustrates using two of the 5 different GCMs (CSMK3, HADGEM with contrasting precipitation and temperature) and two of the 4 different socio-economic scenarios ("We are the world", "Should I stay or should I go" which have contrasting demands for land), exploring these using two of the 13 scenario parameters (crop breeding for yield and population) . In the first scenario, population can be increased by a large amount showing that food security is far from vulnerable. In the second scenario increasing crop yield shows that it improves the food security problem

Method and theory in the psychology of art

The unsatisfactory state of the psychology of art as a field of enquiry is analysed and two explanations are offered. The current state of psychology is also analysed and recommendations for change are made which should also improve the psychology of art, particularly in terms of effectiveness and relevance. This is followed by a detailed discussion of three major approaches to the subject, viz. Psycho-analysis, Gestalt psychology and experimental aesthetics. The empirical approach is further analysed in terms of the specific problems of aesthetic measurement. Certain procedures and kinds of measurement are strongly discouraged, whereas other forms are encouraged. The ideas of the preceding four chapters are integrated in chapter five within the frame-work of implicit aesthetic theories, which can structure both the individual's and a culture's encounter with art. In addition it can be used to structure the field of enquiry, particularly with reference to the model of aesthetic perception which is discussed in chapter five. In general, an enlightened empiricism is called for which is based on a model of man akin to that of 'the man in the street'. The psychology of art should deal directly with the phenomenal experience of real works of art. To this end introspection is regarded as an indispensible source of hypotheses which can be tested within an empirical framework. It is unlikely that problems in psychological aesthetics can be resolved except through multilevel, multi-disciplinary explanations. The next four chapters contain discussions of major topics in the psychology of art, viz. the structure of aesthetic reactions; the influences and determinants of aesthetic reactions; the development of aesthetic appreciation; and the problem of meaning in visual art. The final chapter presents a summary and overview.<p

Parameterized Directed kk-Chinese Postman Problem and kk Arc-Disjoint Cycles Problem on Euler Digraphs

In the Directed $k$-Chinese Postman Problem ($k$-DCPP), we are given a connected weighted digraph $G$ and asked to find $k$ non-empty closed directed walks covering all arcs of $G$ such that the total weight of the walks is minimum. Gutin, Muciaccia and Yeo (Theor. Comput. Sci. 513 (2013) 124--128) asked for the parameterized complexity of $k$-DCPP when $k$ is the parameter. We prove that the $k$-DCPP is fixed-parameter tractable. We also consider a related problem of finding $k$ arc-disjoint directed cycles in an Euler digraph, parameterized by $k$. Slivkins (ESA 2003) showed that this problem is W[1]-hard for general digraphs. Generalizing another result by Slivkins, we prove that the problem is fixed-parameter tractable for Euler digraphs. The corresponding problem on vertex-disjoint cycles in Euler digraphs remains W[1]-hard even for Euler digraphs

A γ-secretase inhibitor, but not a γ-secretase modulator, induced defects in BDNF axonal trafficking and signaling: evidence for a role for APP.

Clues to Alzheimer disease (AD) pathogenesis come from a variety of different sources including studies of clinical and neuropathological features, biomarkers, genomics and animal and cellular models. An important role for amyloid precursor protein (APP) and its processing has emerged and considerable interest has been directed at the hypothesis that Aβ peptides induce changes central to pathogenesis. Accordingly, molecules that reduce the levels of Aβ peptides have been discovered such as γ-secretase inhibitors (GSIs) and modulators (GSMs). GSIs and GSMs reduce Aβ levels through very different mechanisms. However, GSIs, but not GSMs, markedly increase the levels of APP CTFs that are increasingly viewed as disrupting neuronal function. Here, we evaluated the effects of GSIs and GSMs on a number of neuronal phenotypes possibly relevant to their use in treatment of AD. We report that GSI disrupted retrograde axonal trafficking of brain-derived neurotrophic factor (BDNF), suppressed BDNF-induced downstream signaling pathways and induced changes in the distribution within neuronal processes of mitochondria and synaptic vesicles. In contrast, treatment with a novel class of GSMs had no significant effect on these measures. Since knockdown of APP by specific siRNA prevented GSI-induced changes in BDNF axonal trafficking and signaling, we concluded that GSI effects on APP processing were responsible, at least in part, for BDNF trafficking and signaling deficits. Our findings argue that with respect to anti-amyloid treatments, even an APP-specific GSI may have deleterious effects and GSMs may serve as a better alternative

Can clinical audits be enhanced by pathway simulation and machine learning? An example from the acute stroke pathway

OBJECTIVE: To evaluate the application of clinical pathway simulation in machine learning, using clinical audit data, in order to identify key drivers for improving use and speed of thrombolysis at individual hospitals

New Heuristic Algorithms for the Windy Rural Postman Problem

[EN] In this paper we deal with the windy rural postman problem. This problem generalizes several important arc routing problems and has interesting real-life applications. Here, we present several heuristics whose study has lead to the design of a scatter search algorithm for the windy rural postman problem. Extensive computational experiments over different sets of instances, with sizes up to 988 nodes and 3952 edges, are also presented. (c) 2004 Elsevier Ltd. All rights reserved.Benavent, E.; Corberán, A.; Piñana, E.; Plana. I.; Sanchís Llopis, JM. (2005). New Heuristic Algorithms for the Windy Rural Postman Problem. Computers & Operations Research. 32(12):3111-3128. doi:10.1016/j.cor.2004.04.007S31113128321

Feasibility of a hyper-acute stroke unit model of care across England: a modelling analysis.

The policy of centralising hyperacute stroke units (HASUs) in England aims to provide stroke care in units that are both large enough to sustain expertise (>600 admissions/year) and dispersed enough to rapidly deliver time-critical treatments (<30 min maximum travel time). Currently, just over half (56%) of patients with stroke access care in such a unit. We sought to model national configurations of HASUs that would optimise both institutional size and geographical access to stroke care, to maximise the population benefit from the centralisation of stroke care.This article is freely available via Open Access. Click on the Additional Link above to access the full-text via the publisher's site.Publishe

Efficacy and safety of co-careldopa as an add-on therapy to occupational and physical therapy in patients after stroke (DARS): a randomised, double-blind, placebo controlled trial

Background Dopamine is a key modulator of striatal function and learning and might improve motor recovery after stroke. Previous small trials of dopamine agonists after stroke provide equivocal evidence of effectiveness on improving motor recovery. We aimed to assess the safety and efficacy of co-careldopa plus routine occupational and physical therapy during early rehabilitation after stroke. Methods This double-blind, multicentre, randomised controlled trial of co-careldopa versus placebo in addition to routine NHS occupational and physical therapy was done at 51 UK NHS acute inpatient stroke rehabilitation services. We recruited patients with new or recurrent clinically diagnosed ischaemic or haemorrhagic (excluding subarachnoid haemorrhage) stroke 5–42 days before randomisation, who were unable to walk 10 m or more, had a score of less than 7 points on the Rivermead Mobility Index, were expected to need rehabilitation, and were able to access rehabilitation after discharge from hospital. Participants were assigned (1:1) using stratified random blocks to receive 6 weeks of oral co-careldopa or matched placebo in addition to routine NHS physiotherapy and occupational therapy. The initial two doses of co-careldopa were 62·5 mg (50 mg of levodopa and 12·5 mg of carbidopa) and the remaining doses were 125 mg (100 mg of levodopa and 25 mg of carbidopa). Participants were required to take a single oral tablet 45–60 min before physiotherapy or occupational therapy session. The primary outcome was ability to walk independently, defined as a Rivermead Mobility Index score of 7 or more, at 8 weeks. Primary and safety analyses were done in the intention-to-treat population. The trial is registered on the ISRCTN registry, number ISRCTN99643613.Findings Between May 30, 2011, and March 28, 2014, of 1574 patients found eligible, 593 (mean age 68·5 years) were randomly assigned to either the co-careldopa group (n=308) or to the placebo group (n=285), on an average 18 days after stroke onset. Primary outcome data were available for all 593 patients. We found no evidence that the ability to walk independently improved with co-careldopa (125 [41%] of 308 patients) compared with placebo (127 [45%] of 285 patients; odds ratio 0·78 [95% CI 0·53–1·15]) at 8 weeks. Mortality at 12 months did not differ between the two groups (22 [7%] vs 17 [6%]). Serious adverse events were largely similar between groups. Vomiting during therapy sessions, after taking the study drug, was the most frequent adverse event and was more frequent in the co-careldopa group than the placebo group (19 [6·2%] vs 9 [3·2%]).Interpretation Co-careldopa in addition to routine occupational and physical therapy does not seem to improve walking after stroke. Further research might identify subgroups of patients with stroke who could benefit from dopaminergic therapy at different doses or times after stroke with more intensive motor therap

Use of clinical pathway simulation and machine learning to identify key levers for maximizing the benefit of intravenous thrombolysis in acute stroke.

This is the final version. Available from Wolters Kluwer Health via the DOI in this record. BACKGROUND: Expert opinion is that about 20% of emergency stroke patients should receive thrombolysis. Currently, 11% to 12% of patients in England and Wales receive thrombolysis, ranging from 2% to 24% between hospitals. The aim of this study was to assess how much variation is due to differences in local patient populations, and how much is due to differences in clinical decision-making and stroke pathway performance, while estimating a realistic target thrombolysis use. METHODS: Anonymised data for 246 676 emergency stroke admissions to 132 acute hospitals in England and Wales between 2016 and 2018 was obtained from the Sentinel Stroke National Audit Programme data. We used machine learning to learn decisions on who to give thrombolysis to at each hospital. We used clinical pathway simulation to model effects of changing pathway performance. Qualitative research was used to assess clinician attitudes to these methods. Three changes were modeled: (1) arrival-to-treatment in 30 minutes, (2) proportion of patients with determined stroke onset times set to at least the national upper quartile, (3) thrombolysis decisions made based on majority vote of a benchmark set of hospitals. RESULTS: Of the modeled changes, any single change was predicted to increase national thrombolysis use from 11.6% to between 12.3% to 14.5% (clinical decision-making having the most effect). Combined, these changes would be expected to increase thrombolysis to 18.3%, but there would still be significant variation between hospitals depending on local patient population. Clinicians engaged well with the modeling, but those from hospitals with lower thrombolysis use were most cautious about the methods. CONCLUSIONS: Machine learning and clinical pathway simulation may be applied at scale to national stroke audit data, allowing extended use and analysis of audit data. Stroke thrombolysis rates of at least 18% look achievable in England and Wales, but each hospital should have its own target.National Institute for Health Researc