The potential of an observational data set for calibration of a computationally expensive computer model

PublishedJournal ArticleWe measure the potential of an observational data set to constrain a set of inputs to a complex and computationally expensive computer model. We use each member in turn of an ensemble of output from a computationally expensive model, corresponding to an observable part of a modelled system, as a proxy for an observational data set. We argue that, given some assumptions, our ability to constrain uncertain parameter inputs to a model using its own output as data, provides a maximum bound for our ability to constrain the model inputs using observations of the real system. The ensemble provides a set of known parameter input and model output pairs, which we use to build a computationally effic. © 2013 Author(s).This work was supported by funding from the ice2sea programme from the European Union 7th Framework Programme, grant number 226375. Ice2sea contribution number 154

Exhaled breath profiling for diagnosing acute respiratory distress syndrome

The acute respiratory distress syndrome (ARDS) is a common, devastating complication of critical illness that is characterized by pulmonary injury and inflammation. The clinical diagnosis may be improved by means of objective biological markers. Electronic nose (eNose) technology can rapidly and non-invasively provide breath prints, which are profiles of volatile metabolites in the exhaled breath. We hypothesized that breath prints could facilitate accurate diagnosis of ARDS in intubated and ventilated intensive care unit (ICU) patients. Prospective single-center cohort study with training and temporal external validation cohort. Breath of newly intubated and mechanically ventilated ICU-patients was analyzed using an electronic nose within 24 hours after admission. ARDS was diagnosed and classified by the Berlin clinical consensus definition. The eNose was trained to recognize ARDS in a training cohort and the diagnostic performance was evaluated in a temporal external validation cohort. In the training cohort (40 patients with ARDS versus 66 controls) the diagnostic model for ARDS showed a moderate discrimination, with an area under the receiver-operator characteristic curve (AUC-ROC) of 0.72 (95%-confidence interval (CI): 0.63-0.82). In the external validation cohort (18 patients with ARDS versus 26 controls) the AUC-ROC was 0.71 [95%-CI: 0.54 - 0.87]. Restricting discrimination to patients with moderate or severe ARDS versus controls resulted in an AUC-ROC of 0.80 [95%-CI: 0.70 - 0.90]. The exhaled breath profile from patients with cardiopulmonary edema and pneumonia was different from that of patients with moderate/severe ARDS. An electronic nose can rapidly and non-invasively discriminate between patients with and without ARDS with modest accuracy. Diagnostic accuracy increased when only moderate and severe ARDS patients were considered. This implicates that breath analysis may allow for rapid, bedside detection of ARDS, especially if our findings are reproduced using continuous exhaled breath profiling. NTR2750, registered 11 February 201

Global data for ecology and epidemiology: a novel algorithm for temporal Fourier processing MODIS data

Background. Remotely-sensed environmental data from earth-orbiting satellites are increasingly used to model the distribution and abundance of both plant and animal species, especially those of economic or conservation importance. Time series of data from the MODerate-resolution Imaging Spectroradiometer (MODIS) sensors on-board NASA's Terra and Aqua satellites offer the potential to capture environmental thermal and vegetation seasonality, through temporal Fourier analysis, more accurately than was previously possible using the NOAA Advanced Very High Resolution Radiometer (AVHRR) sensor data. MODIS data are composited over 8- or 16-day time intervals that pose unique problems for temporal Fourier analysis. Applying standard techniques to MODIS data can introduce errors of up to 30% in the estimation of the amplitudes and phases of the Fourier harmonics. Methodology/Principal Findings. We present a novel spline-based algorithm that overcomes the processing problems of composited MODIS data. The algorithm is tested on artificial data generated using randomly selected values of both amplitudes and phases, and provides an accurate estimate of the input variables under all conditions. The algorithm was then applied to produce layers that capture the seasonality in MODIS data for the period from 2001 to 2005. Conclusions/Significance. Global temporal Fourier processed images of 1 km MODIS data for Middle Infrared Reflectance, day- and night-time Land Surface Temperature (LST), Normalised Difference Vegetation Index (NDVI), and Enhanced Vegetation Index (EVI) are presented for ecological and epidemiological applications. The finer spatial and temporal resolution, combined with the greater geolocational and spectral accuracy of the MODIS instruments, compared with previous multi-temporal data sets, mean that these data may be used with greater confidence in species' distribution modelling

Cost-Effective Use of Silver Dressings for the Treatment of Hard-to-Heal Chronic Venous Leg Ulcers

Aim To estimate the cost-effectiveness of silver dressings using a health economic model based on time-to-wound-healing in hard-to-heal chronic venous leg ulcers (VLUs). Background Chronic venous ulceration affects 1–3% of the adult population and typically has a protracted course of healing, resulting in considerable costs to the healthcare system. The pathogenesis of VLUs includes excessive and prolonged inflammation which is often related to critical colonisation and early infection. The use of silver dressings to control this bioburden and improve wound healing rates remains controversial. Methods A decision tree was constructed to evaluate the cost-effectiveness of treatment with silver compared with non-silver dressings for four weeks in a primary care setting. The outcomes: ‘Healed ulcer’, ‘Healing ulcer’ or ‘No improvement’ were developed, reflecting the relative reduction in ulcer area from baseline to four weeks of treatment. A data set from a recent meta-analysis, based on four RCTs, was applied to the model. Results Treatment with silver dressings for an initial four weeks was found to give a total cost saving (£141.57) compared with treatment with non-silver dressings. In addition, patients treated with silver dressings had a faster wound closure compared with those who had been treated with non-silver dressings. Conclusion The use of silver dressings improves healing time and can lead to overall cost savings. These results can be used to guide healthcare decision makers in evaluating the economic aspects of treatment with silver dressings in hard-to-heal chronic VLUs

Limited response of peatland CH4 emissions to abrupt Atlantic Ocean circulation changes in glacial climates

Ice-core records show that abrupt Dansgaard–Oeschger (D–O) climatic warming events of the last glacial period were accompanied by large increases in the atmospheric CH4 concentration (up to 200 ppbv). These abrupt changes are generally regarded as arising from the effects of changes in the Atlantic Ocean meridional overturning circulation and the resultant climatic impact on natural CH4 sources, in particular wetlands. We use two different ecosystem models of wetland CH4 emissions to simulate northern CH4 sources forced with coupled general circulation model simulations of five different time periods during the last glacial to investigate the potential influence of abrupt ocean circulation changes on atmospheric CH4 levels during D–O events. The simulated warming over Greenland of 7–9 °C in the different time periods is at the lower end of the range of 11–15 °C derived from ice cores, but is associated with strong impacts on the hydrological cycle, especially over the North Atlantic and Europe during winter. We find that although the sensitivity of CH4 emissions to the imposed climate varies significantly between the two ecosystem emissions models, the model simulations do not reproduce sufficient emission changes to satisfy ice-core observations of CH4 increases during abrupt events. The inclusion of permafrost physics and peatland carbon cycling in one model (LPJ-WHyMe) increases the climatic sensitivity of CH44 emissions relative to the Sheffield Dynamic Global Vegetation Model (SDGVM) model, which does not incorporate these processes. For equilibrium conditions this additional sensitivity is mostly due to differences in carbon cycle processes, whilst the increased sensitivity to the imposed abrupt warmings is also partly due to the effects of freezing on soil thermodynamics. These results suggest that alternative scenarios of climatic change could be required to explain the abrupt glacial CH4 variations, perhaps with a more dominant role for tropical wetland CH4 sources

The Energy Landscape, Folding Pathways and the Kinetics of a Knotted Protein

The folding pathway and rate coefficients of the folding of a knotted protein are calculated for a potential energy function with minimal energetic frustration. A kinetic transition network is constructed using the discrete path sampling approach, and the resulting potential energy surface is visualized by constructing disconnectivity graphs. Owing to topological constraints, the low-lying portion of the landscape consists of three distinct regions, corresponding to the native knotted state and to configurations where either the N- or C-terminus is not yet folded into the knot. The fastest folding pathways from denatured states exhibit early formation of the N-terminus portion of the knot and a rate-determining step where the C-terminus is incorporated. The low-lying minima with the N-terminus knotted and the C-terminus free therefore constitute an off-pathway intermediate for this model. The insertion of both the N- and C-termini into the knot occur late in the folding process, creating large energy barriers that are the rate limiting steps in the folding process. When compared to other protein folding proteins of a similar length, this system folds over six orders of magnitude more slowly.Comment: 19 page

A Comparison of Stride Length and Lower Extremity Kinematics during Barefoot and Shod Running in Well Trained Distance Runners

Stride length, hip, knee and ankle angles were compared during barefoot and shod running on a treadmill at two speeds. Nine well-trained (1500m time: 3min:59.80s ± 14.7 s) male (22 ±3 years; 73 ±9 kg; 1.79 ±0.4 m) middle distance (800 m – 5,000 m) runners performed 2 minutes of running at 3.05 m·s-1 and 4.72 m·s-1 on an treadmill. This approach allowed continuous measurement of lower extremity kinematic data and calculation of stride length. Statistical analysis using a 2X2 factorial ANOVA revealed speed to have a main effect on stride length and hip angle and footwear to have a main effect on hip angle. There was a significant speed*footwear interaction for knee and ankle angles. Compared to shod running at the lower speed (3.05 m·s-1), well trained runners have greater hip, knee and ankle angles when running barefoot. Runners undertake a high volume (~75%) of training at lower intensities and therefore knowledge of how barefoot running alters running kinematics at low and high speeds may be useful to the runner