A comparison of statistical emulation methodologies for multi-wave calibration of environmental models

Expensive computer codes, particularly those used simulating environmental or geological processes such as climate models, require calibration (sometimes called tuning). When calibrating expensive simulators using uncertainty quantification methods, it is usually necessary to use a statistical model called an emulator in place of the computer code when running the calibration algorithm. Though emulators based on Gaussian processes are typically many orders of magnitude faster to evaluate than the simulator they mimic, many applications have sought to speed up the computations by using regression-only emulators within the calculations instead, arguing that the extra sophistication brought using the Gaussian process is not worth the extra computational power. This was the case for the analysis that produced the UK climate projections in 2009. In this paper we compare the effectiveness of both emulation approaches upon a multi-wave calibration framework that is becoming popular in the climate modelling community called \history matching". We find that Gaussian processes offer significant benefits to the reduction of parametric uncertainty over regression-only approaches. We find that in a multi-wave experiment, a combination of regression-only emulators initially, followed by Gaussian process emulators for refocussing experiments can be nearly as effective as using Gaussian processes throughout for a fraction of the computational cost. We also discover a number of design and emulator-dependent features of the multi-wave history matching approach that can cause apparent, yet premature, convergence of our estimates of parametric uncertainty. We compare these approaches to calibration in idealised examples and apply it to a well-known geological reservoir mode

Quantitative assessment of sewer overflow performance with climate change in northwest England

Changes in rainfall patterns associated with climate change can affect the operation of a combined sewer system, with the potential increase in rainfall amount. This could lead to excessive spill frequencies and could also introduce hazardous substances into the receiving waters, which, in turn, would have an impact on the quality of shellfish and bathing waters. This paper quantifies the spilling volume, duration and frequency of 19 combined sewer overflows (CSOs) to receiving waters under two climate change scenarios, the high (A1FI), and the low emissions (B1) scenarios, simulated by three global climate models (GCMs), for a study catchment in northwest England. The future rainfall is downscaled, using climatic variables from HadCM3, CSIRO and CGCM2 GCMs, with the use of a hybrid generalized linear–artificial neural network model. The results from the model simulation for the future in 2080 showed an annual increase of 37% in total spill volume, 32% in total spill duration, and 12% in spill frequency for the shellfish water limiting requirements. These results were obtained, under the high emissions scenario, as projected by the HadCM3 as maximum. Nevertheless, the catchment drainage system is projected to cope with the future conditions in 2080 by all three GCMs. The results also indicate that under scenario B1, a significant drop was projected by CSIRO, which in the worst case could reach up to 50% in spill volume, 39% in spill duration and 25% in spill frequency. The results further show that, during the bathing season, a substantial drop is expected in the CSO spill drivers, as predicted by all GCMs under both scenarios

The ROAM/EORTC-1308 trial: Radiation versus Observation following surgical resection of Atypical Meningioma: study protocol for a randomised controlled trial

BACKGROUND Atypical meningiomas are an intermediate grade brain tumour with a recurrence rate of 39-58 %. It is not known whether early adjuvant radiotherapy reduces the risk of tumour recurrence and whether the potential side-effects are justified. An alternative management strategy is to perform active monitoring with magnetic resonance imaging (MRI) and to treat at recurrence. There are no randomised controlled trials comparing these two approaches. METHODS/DESIGN A total of 190 patients will be recruited from neurosurgical/neuro-oncology centres across the United Kingdom, Ireland and mainland Europe. Adult patients undergoing gross total resection of intracranial atypical meningioma are eligible. Patients with multiple meningioma, optic nerve sheath meningioma, previous intracranial tumour, previous cranial radiotherapy and neurofibromatosis will be excluded. Informed consent will be obtained from patients. This is a two-stage trial (both stages will run in parallel): Stage 1 (qualitative study) is designed to maximise patient and clinician acceptability, thereby optimising recruitment and retention. Patients wishing to continue will proceed to randomisation. Stage 2 (randomisation) patients will be randomised to receive either early adjuvant radiotherapy for 6 weeks (60 Gy in 30 fractions) or active monitoring. The primary outcome measure is time to MRI evidence of tumour recurrence (progression-free survival (PFS)). Secondary outcome measures include assessing the toxicity of the radiotherapy, the quality of life, neurocognitive function, time to second line treatment, time to death (overall survival (OS)) and incremental cost per quality-adjusted life year (QALY) gained. DISCUSSION ROAM/EORTC-1308 is the first multi-centre randomised controlled trial designed to determine whether early adjuvant radiotherapy reduces the risk of tumour recurrence following complete surgical resection of atypical meningioma. The results of this study will be used to inform current neurosurgery and neuro-oncology practice worldwide. TRIAL REGISTRATION ISRCTN71502099 on 19 May 2014

Summer weather becomes more persistent in a 2 °C world

Heat and rainfall extremes have intensified over the past few decades and this trend is projected to continue with future global warming1–3. A long persistence of extreme events often leads to societal impacts with warm-and-dry conditions severely affecting agriculture and consecutive days of heavy rainfall leading to flooding. Here we report systematic increases in the persistence of boreal summer weather in a multi-model analysis of a world 2 °C above pre-industrial compared to present-day climate. Averaged over the Northern Hemisphere mid-latitude land area, the probability of warm periods lasting longer than two weeks is projected to increase by 4% (2–6% full uncertainty range) after removing seasonal-mean warming. Compound dry–warm persistence increases at a similar magnitude on average but regionally up to 20% (11–42%) in eastern North America. The probability of at least seven consecutive days of strong precipitation increases by 26% (15–37%) for the mid-latitudes. We present evidence that weakening storm track activity contributes to the projected increase in warm and dry persistence. These changes in persistence are largely avoided when warming is limited to 1.5 °C. In conjunction with the projected intensification of heat and rainfall extremes, an increase in persistence can substantially worsen the effects of future weather extremes

Anti-cancer effects and mechanism of actions of aspirin analogues in the treatment of glioma cancer

INTRODUCTION: In the past 25 years only modest advancements in glioma treatment have been made, with patient prognosis and median survival time following diagnosis only increasing from 3 to 7 months. A substantial body of clinical and preclinical evidence has suggested a role for aspirin in the treatment of cancer with multiple mechanisms of action proposed including COX 2 inhibition, down regulation of EGFR expression, and NF-κB signaling affecting Bcl-2 expression. However, with serious side effects such as stroke and gastrointestinal bleeding, aspirin analogues with improved potency and side effect profiles are being developed. METHOD: Effects on cell viability following 24 hr incubation of four aspirin derivatives (PN508, 517, 526 and 529) were compared to cisplatin, aspirin and di-aspirin in four glioma cell lines (U87 MG, SVG P12, GOS – 3, and 1321N1), using the PrestoBlue assay, establishing IC50 and examining the time course of drug effects. RESULTS: All compounds were found to decrease cell viability in a concentration and time dependant manner. Significantly, the analogue PN517 (IC50 2mM) showed approximately a twofold increase in potency when compared to aspirin (3.7mM) and cisplatin (4.3mM) in U87 cells, with similar increased potency in SVG P12 cells. Other analogues demonstrated similar potency to aspirin and cisplatin. CONCLUSION: These results support the further development and characterization of novel NSAID derivatives for the treatment of glioma

Environmental differences between sites control the diet and nutrition of the carnivorous plant Drosera rotundifolia

Background and aims: Carnivorous plants are sensitive to small changes in resource availability, but few previous studies have examined how differences in nutrient and prey availability affect investment in and the benefit of carnivory. We studied the impact of site-level differences in resource availability on ecophysiological traits of carnivory for Drosera rotundifolia L. Methods: We measured prey availability, investment in carnivory (leaf stickiness), prey capture and diet of plants growing in two bogs with differences in N deposition and plant available N: Cors Fochno (0.62 g m−2 yr.−1, 353 μg l−1), Whixall Moss (1.37 g m−2 yr.−1, 1505 μg l−1). The total N amount per plant and the contributions of prey/root N to the plants’ N budget were calculated using a single isotope natural abundance method. Results: Plants at Whixall Moss invested less in carnivory, were less likely to capture prey, and were less reliant on prey-derived N (25.5% compared with 49.4%). Actual prey capture did not differ between sites. Diet composition differed – Cors Fochno plants captured 62% greater proportions of Diptera. Conclusions: Our results show site-level differences in plant diet and nutrition consistent with differences in resource availability. Similarity in actual prey capture may be explained by differences in leaf stickiness and prey abundance

Changes in the annual cycle of heavy precipitation across the British Isles within the 21st century

We investigate future changes in the annual cycle of heavy daily precipitation events across the British Isles in the periods 2021–2060 and 2061–2100, relative to present day climate. Twelve combinations of regional and global climate models forced with the A1B scenario are used. The annual cycle is modelled as an inhomogeneous Poisson process with sinusoidal models for location and scale parameters of the generalized extreme value distribution. Although the peak times of the annual cycle vary considerably between projections for the 2061–2100 period, a robust shift towards later peak times is found for the south-east, while in the north-west there is evidence for a shift towards earlier peak times. In the remaining parts of the British Isles no changes in the peak times are projected. For 2021–2060 this signal is weak. The annual cycle’s relative amplitude shows no robust signal, where differences in projected changes are dominated by global climate model differences. The relative contribution of anthropogenic forcing and internal climate variability to changes in the relative amplitude cannot be identified with the available ensemble. The results might be relevant for the development of adequate risk-reduction strategies, for insurance companies and for the management and planning of water resource