Stopping clinical trials because of treatment ineffectiveness: a comparison of a futility design with a method of stochastic curtailment

This paper introduces a simple futility design that allows a comparative clinical trial to be stopped due to lack of effect at any of a series of planned interim analyses. Stopping due to apparent benefit is not permitted. The design is for use when any positive claim should be based on the maximum sample size, for example to allow subgroup analyses or the evaluation of safety or secondary efficacy responses. A final frequentist analysis can be performed that is valid for the type of design employed. Here the design is described and its properties are presented. Its advantages and disadvantages relative to the use of stochastic curtailment are discussed. Copyright (C) 2003 John Wiley Sons, Ltd.

Bode's maximum available feedback and phase margin

'Maximum Available Feedback' is Bode's term for the highest possible loop gain over a given bandwidth, with specified stability margins, in a single loop feedback system. His work using asymptotic analysis allowed Bode to develop a methodology for achieving this. However, the actual system performance differs from that specified, due to the use of asymptotic approximations, and the author[2] has described how, for instance, the actual phase margin is often much lower than required when the bandwidth is high, and proposed novel modifications to the asymptotes to address the issue. This paper gives some new analysis of such systems, showing that the method also contravenes Bode's definition of phase margin, and shows how the author's modifications can be used for different amounts of bandwidth.

A continuous wavelet transform and classification method for delirium motoric subtyping

The usefulness of motor subtypes of delirium is unclear due to inconsistency in subtyping methods and a lack of validation with objective measures of activity. The activity of 40 patients was measured over 24 h with a discrete accelerometer-based activity monitor. The continuous wavelet transform (CWT) with various mother wavelets were applied to accelerometry data from three randomly selected patients with DSM-IV delirium that were readily divided into hyperactive, hypoactive, and mixed motor subtypes. A classification tree used the periods of overall movement as measured by the discrete accelerometer-based monitor as determining factors for which to classify these delirious patients. This data used to create the classification tree were based upon the minimum, maximum, standard deviation, and number of coefficient values, generated over a range of scales by the CWT. The classification tree was subsequently used to define the remaining motoric subtypes. The use of a classification system shows how delirium subtypes can be categorized in relation to overall motoric behavior. The classification system was also implemented to successfully define other patient motoric subtypes. Motor subtypes of delirium defined by observed ward behavior differ in electronically measured activity levels.

Simplifying Bode's maximum available feedback design

Bode's method for obtaining 'maximum obtainable feedback' is a good example of a nontrivial feedback system design technique, but it is largely overlooked. This paper shows how the associated mathematics can be simplified and linear elements used in its implementation, so as to make it accessible for teaching to undergraduates.

Achieving or exceeding maximum available feedback

A feedback system for control or electronics should have high loop gain, so that its output is close to its desired state, and the effects of changes in the system and of disturbances are minimised. Bode proposed a method for single loop feedback systems to obtain the maximum available feedback, defined as the largest possible loop gain over a bandwidth pertinent to the system, with appropriate gain and phase margins. The method uses asymptotic approximations, and this paper describes some novel adjustments to the asymptotes, so that the final system often exceeds the maximum available feedback. The implementation of the method requires the cascading of a series of lead-lag element. This paper describes a new way to determine how many elements should be used.

A variational method to retrieve the extinction profile in liquid clouds using multiple field-of-view lidar

Liquid clouds play a profound role in the global radiation budget but it is difficult to remotely retrieve their vertical profile. Ordinary narrow field-of-view (FOV) lidars receive a strong return from such clouds but the information is limited to the first few optical depths. Wideangle multiple-FOV lidars can isolate radiation scattered multiple times before returning to the instrument, often penetrating much deeper into the cloud than the singly-scattered signal. These returns potentially contain information on the vertical profile of extinction coefficient, but are challenging to interpret due to the lack of a fast radiative transfer model for simulating them. This paper describes a variational algorithm that incorporates a fast forward model based on the time-dependent two-stream approximation, and its adjoint. Application of the algorithm to simulated data from a hypothetical airborne three-FOV lidar with a maximum footprint width of 600m suggests that this approach should be able to retrieve the extinction structure down to an optical depth of around 6, and total opticaldepth up to at least 35, depending on the maximum lidar FOV. The convergence behavior of Gauss-Newton and quasi-Newton optimization schemes are compared. We then present results from an application of the algorithm to observations of stratocumulus by the 8-FOV airborne “THOR” lidar. It is demonstrated how the averaging kernel can be used to diagnose the effective vertical resolution of the retrieved profile, and therefore the depth to which information on the vertical structure can be recovered. This work enables exploitation of returns from spaceborne lidar and radar subject to multiple scattering more rigorously than previously possible.

Assessment of the Wind Gust Estimate Method in mesoscale modelling of storm events over West Germany

A physically based gust parameterisation is added to the atmospheric mesoscale model FOOT3DK to estimate wind gusts associated with storms over West Germany. The gust parameterisation follows the Wind Gust Estimate (WGE) method and its functionality is verified in this study. The method assumes that gusts occurring at the surface are induced by turbulent eddies in the planetary boundary layer, deflecting air parcels from higher levels down to the surface under suitable conditions. Model simulations are performed with horizontal resolutions of 20 km and 5 km. Ten historical storm events of different characteristics and intensities are chosen in order to include a wide range of typical storms affecting Central Europe. All simulated storms occurred between 1990 and 1998. The accuracy of the method is assessed objectively by validating the simulated wind gusts against data from 16 synoptic stations by means of “quality parameters”. Concerning these parameters, the temporal and spatial evolution of the simulated gusts is well reproduced. Simulated values for low altitude stations agree particularly well with the measured gusts. For orographically exposed locations, the gust speeds are partly underestimated. The absolute maximum gusts lie in most cases within the bounding interval given by the WGE method. Focussing on individual storms, the performance of the method is better for intense and large storms than for weaker ones. Particularly for weaker storms, the gusts are typically overestimated. The results for the sample of ten storms document that the method is generally applicable with the mesoscale model FOOT3DK for mid-latitude winter storms, even in areas with complex orography.

Mid-holocene and last glacial maximum climate simulations with the IPSL model-part I: comparing IPSLCM5A to IPSLCM4

The climates of the mid-Holocene (MH), 6,000 years ago, and of the Last Glacial Maximum (LGM), 21,000 years ago, have extensively been simulated, in particular in the framework of the Palaeoclimate Modelling Intercomparion Project. These periods are well documented by paleo-records, which can be used for evaluating model results for climates different from the present one. Here, we present new simulations of the MH and the LGM climates obtained with the IPSL_CM5A model and compare them to our previous results obtained with the IPSL_CM4 model. Compared to IPSL_CM4, IPSL_CM5A includes two new features: the interactive representation of the plant phenology and marine biogeochemistry. But one of the most important differences between these models is the latitudinal resolution and vertical domain of their atmospheric component, which have been improved in IPSL_CM5A and results in a better representation of the mid-latitude jet-streams. The Asian monsoon’s representation is also substantially improved. The global average mean annual temperature simulated for the pre-industrial (PI) period is colder in IPSL_CM5A than in IPSL_CM4 but their climate sensitivity to a CO2 doubling is similar. Here we show that these differences in the simulated PI climate have an impact on the simulated MH and LGM climatic anomalies. The larger cooling response to LGM boundary conditions in IPSL_CM5A appears to be mainly due to differences between the PMIP3 and PMIP2 boundary conditions, as shown by a short wave radiative forcing/feedback analysis based on a simplified perturbation method. It is found that the sensitivity computed from the LGM climate is lower than that computed from 2 × CO2 simulations, confirming previous studies based on different models. For the MH, the Asian monsoon, stronger in the IPSL_CM5A PI simulation, is also more sensitive to the insolation changes. The African monsoon is also further amplified in IPSL_CM5A due to the impact of the interactive phenology. Finally the changes in variability for both models and for MH and LGM are presented taking the example of the El-Niño Southern Oscillation (ENSO), which is very different in the PI simulations. ENSO variability is damped in both model versions at the MH, whereas inconsistent responses are found between the two versions for the LGM. Part 2 of this paper examines whether these differences between IPSL_CM4 and IPSL_CM5A can be distinguished when comparing those results to palaeo-climatic reconstructions and investigates new approaches for model-data comparisons made possible by the inclusion of new components in IPSL_CM5A.

Reconstructing paleosalinity from δ18O: coupled model simulations of the Last Glacial Maximum, Last Interglacial and Late Holocene

Reconstructions of salinity are used to diagnose changes in the hydrological cycle and ocean circulation. A widely used method of determining past salinity uses oxygen isotope (δOw) residuals after the extraction of the global ice volume and temperature components. This method relies on a constant relationship between δOw and salinity throughout time. Here we use the isotope-enabled fully coupled General Circulation Model (GCM) HadCM3 to test the application of spatially and time-independent relationships in the reconstruction of past ocean salinity. Simulations of the Late Holocene (LH), Last Glacial Maximum (LGM), and Last Interglacial (LIG) climates are performed and benchmarked against existing compilations of stable oxygen isotopes in carbonates (δOc), which primarily reflect δOw and temperature. We find that HadCM3 produces an accurate representation of the surface ocean δOc distribution for the LH and LGM. Our simulations show considerable variability in spatial and temporal δOw-salinity relationships. Spatial gradients are generally shallower but within ∼50% of the actual simulated LH to LGM and LH to LIG temporal gradients and temporal gradients calculated from multi-decadal variability are generally shallower than both spatial and actual simulated gradients. The largest sources of uncertainty in salinity reconstructions are found to be caused by changes in regional freshwater budgets, ocean circulation, and sea ice regimes. These can cause errors in salinity estimates exceeding 4 psu. Our results suggest that paleosalinity reconstructions in the South Atlantic, Indian and Tropical Pacific Oceans should be most robust, since these regions exhibit relatively constant δOw-salinity relationships across spatial and temporal scales. Largest uncertainties will affect North Atlantic and high latitude paleosalinity reconstructions. Finally, the results show that it is difficult to generate reliable salinity estimates for regions of dynamic oceanography, such as the North Atlantic, without additional constraints.

MODELING VERY LONG BASELINE INTERFEROMETRIC IMAGES WITH THE CROSS-ENTROPY GLOBAL OPTIMIZATION TECHNIQUE

We present a new technique for obtaining model fittings to very long baseline interferometric images of astrophysical jets. The method minimizes a performance function proportional to the sum of the squared difference between the model and observed images. The model image is constructed by summing N(s) elliptical Gaussian sources characterized by six parameters: two-dimensional peak position, peak intensity, eccentricity, amplitude, and orientation angle of the major axis. We present results for the fitting of two main benchmark jets: the first constructed from three individual Gaussian sources, the second formed by five Gaussian sources. Both jets were analyzed by our cross-entropy technique in finite and infinite signal-to-noise regimes, the background noise chosen to mimic that found in interferometric radio maps. Those images were constructed to simulate most of the conditions encountered in interferometric images of active galactic nuclei. We show that the cross-entropy technique is capable of recovering the parameters of the sources with a similar accuracy to that obtained from the very traditional Astronomical Image Processing System Package task IMFIT when the image is relatively simple (e. g., few components). For more complex interferometric maps, our method displays superior performance in recovering the parameters of the jet components. Our methodology is also able to show quantitatively the number of individual components present in an image. An additional application of the cross-entropy technique to a real image of a BL Lac object is shown and discussed. Our results indicate that our cross-entropy model-fitting technique must be used in situations involving the analysis of complex emission regions having more than three sources, even though it is substantially slower than current model-fitting tasks (at least 10,000 times slower for a single processor, depending on the number of sources to be optimized). As in the case of any model fitting performed in the image plane, caution is required in analyzing images constructed from a poorly sampled (u, v) plane.

Consistency in approximate entropy given by a volumetric estimate

Non-linear methods for estimating variability in time-series are currently of widespread use. Among such methods are approximate entropy (ApEn) and sample approximate entropy (SampEn). The applicability of ApEn and SampEn in analyzing data is evident and their use is increasing. However, consistency is a point of concern in these tools, i.e., the classification of the temporal organization of a data set might indicate a relative less ordered series in relation to another when the opposite is true. As highlighted by their proponents themselves, ApEn and SampEn might present incorrect results due to this lack of consistency. In this study, we present a method which gains consistency by using ApEn repeatedly in a wide range of combinations of window lengths and matching error tolerance. The tool is called volumetric approximate entropy, vApEn. We analyze nine artificially generated prototypical time-series with different degrees of temporal order (combinations of sine waves, logistic maps with different control parameter values, random noises). While ApEn/SampEn clearly fail to consistently identify the temporal order of the sequences, vApEn correctly do. In order to validate the tool we performed shuffled and surrogate data analysis. Statistical analysis confirmed the consistency of the method. (C) 2008 Elsevier Ltd. All rights reserved.

Entropy-Based Approach to Analyze and Classify Mineral Aggregates

This paper presents an automatic method to detect and classify weathered aggregates by assessing changes of colors and textures. The method allows the extraction of aggregate features from images and the automatic classification of them based on surface characteristics. The concept of entropy is used to extract features from digital images. An analysis of the use of this concept is presented and two classification approaches, based on neural networks architectures, are proposed. The classification performance of the proposed approaches is compared to the results obtained by other algorithms (commonly considered for classification purposes). The obtained results confirm that the presented method strongly supports the detection of weathered aggregates.

Texture analysis based on maximum contrast walker

Recently, the deterministic tourist walk has emerged as a novel approach for texture analysis. This method employs a traveler visiting image pixels using a deterministic walk rule. Resulting trajectories provide clues about pixel interaction in the image that can be used for image classification and identification tasks. This paper proposes a new walk rule for the tourist which is based on contrast direction of a neighborhood. The yielded results using this approach are comparable with those from traditional texture analysis methods in the classification of a set of Brodatz textures and their rotated versions, thus confirming the potential of the method as a feasible texture analysis methodology. (C) 2010 Elsevier B.V. All rights reserved.

Bismuth germanate films prepared by Pechini method

Bismuth germanate films were prepared by dip coating and spin coating techniques and the dependence of the luminescent properties of the samples on the resin viscosity and deposition technique was investigated. The resin used for the preparation of the films was obtained via Pechini method, employing the precursors Bi(2)O(3) and GeO(2). Citric acid and ethylene glycol were used as chelating and cross-linking agents, respectively. Results from X-ray diffraction and Raman spectroscopy indicated that the films sintered at 700 degrees C for 10 h presented the single crystalline phase Bi(4)Ge(3)O(12). SEM images of the films have shown that homogeneous flat films can be produced by the two techniques investigated. All the samples presented the typical Bi(4)Ge(3)O(12) emission band centred at 505 nm. Films with 3.1 mu m average thickness presented 80% of the luminescence intensity registered for the single crystal at the maximum wavelength. Published by Elsevier B.V.

Continuous GRASP with a local active-set method for bound-constrained global optimization

Global optimization seeks a minimum or maximum of a multimodal function over a discrete or continuous domain. In this paper, we propose a hybrid heuristic-based on the CGRASP and GENCAN methods-for finding approximate solutions for continuous global optimization problems subject to box constraints. Experimental results illustrate the relative effectiveness of CGRASP-GENCAN on a set of benchmark multimodal test functions.