Improved statistical evaluation of group differences in connectomes by screening-filtering strategy with application to study maturation of brain connections between childhood and adolescence.

Detecting local differences between groups of connectomes is a great challenge in neuroimaging, because the large number of tests that have to be performed and the impact on multiplicity correction. Any available information should be exploited to increase the power of detecting true between-group effects. We present an adaptive strategy that exploits the data structure and the prior information concerning positive dependence between nodes and connections, without relying on strong assumptions. As a first step, we decompose the brain network, i.e., the connectome, into subnetworks and we apply a screening at the subnetwork level. The subnetworks are defined either according to prior knowledge or by applying a data driven algorithm. Given the results of the screening step, a filtering is performed to seek real differences at the node/connection level. The proposed strategy could be used to strongly control either the family-wise error rate or the false discovery rate. We show by means of different simulations the benefit of the proposed strategy, and we present a real application of comparing connectomes of preschool children and adolescents.

A Motion compensated filtering approach to remove sunlight flicker in shallow water images

A common problem in video surveys in very shallow waters is the presence of strong light fluctuations, due to sun light refraction. Refracted sunlight casts fast moving patterns, which can significantly degrade the quality of the acquired data. Motivated by the growing need to improve the quality of shallow water imagery, we propose a method to remove sunlight patterns in video sequences. The method exploits the fact that video sequences allow several observations of the same area of the sea floor, over time. It is based on computing the image difference between a given reference frame and the temporal median of a registered set of neighboring images. A key observation is that this difference will have two components with separable spectral content. One is related to the illumination field (lower spatial frequencies) and the other to the registration error (higher frequencies). The illumination field, recovered by lowpass filtering, is used to correct the reference image. In addition to removing the sunflickering patterns, an important advantage of the approach is the ability to preserve the sharpness in corrected image, even in the presence of registration inaccuracies. The effectiveness of the method is illustrated in image sets acquired under strong camera motion containing non-rigid benthic structures. The results testify the good performance and generality of the approach

A limited area model intercomparison on the "Montserrat-2000" flash-flood event using statistical and deterministic methods

In the scope of the European project Hydroptimet, INTERREG IIIB-MEDOCC programme, limited area model (LAM) intercomparison of intense events that produced many damages to people and territory is performed. As the comparison is limited to single case studies, the work is not meant to provide a measure of the different models' skill, but to identify the key model factors useful to give a good forecast on such a kind of meteorological phenomena. This work focuses on the Spanish flash-flood event, also known as "Montserrat-2000" event. The study is performed using forecast data from seven operational LAMs, placed at partners' disposal via the Hydroptimet ftp site, and observed data from Catalonia rain gauge network. To improve the event analysis, satellite rainfall estimates have been also considered. For statistical evaluation of quantitative precipitation forecasts (QPFs), several non-parametric skill scores based on contingency tables have been used. Furthermore, for each model run it has been possible to identify Catalonia regions affected by misses and false alarms using contingency table elements. Moreover, the standard "eyeball" analysis of forecast and observed precipitation fields has been supported by the use of a state-of-the-art diagnostic method, the contiguous rain area (CRA) analysis. This method allows to quantify the spatial shift forecast error and to identify the error sources that affected each model forecasts. High-resolution modelling and domain size seem to have a key role for providing a skillful forecast. Further work is needed to support this statement, including verification using a wider observational data set.

A filtering method to correct time-lapse 3D ERT data and improve imaging of natural aquifer dynamics

We have developed a processing methodology that allows crosshole ERT (electrical resistivity tomography) monitoring data to be used to derive temporal fluctuations of groundwater electrical resistivity and thereby characterize the dynamics of groundwater in a gravel aquifer as it is infiltrated by river water. Temporal variations of the raw ERT apparent-resistivity data were mainly sensitive to the resistivity (salinity), temperature and height of the groundwater, with the relative contributions of these effects depending on the time and the electrode configuration. To resolve the changes in groundwater resistivity, we first expressed fluctuations of temperature-detrended apparent-resistivity data as linear superpositions of (i) time series of riverwater-resistivity variations convolved with suitable filter functions and (ii) linear and quadratic representations of river-water-height variations multiplied by appropriate sensitivity factors; river-water height was determined to be a reliable proxy for groundwater height. Individual filter functions and sensitivity factors were obtained for each electrode configuration via deconvolution using a one month calibration period and then the predicted contributions related to changes in water height were removed prior to inversion of the temperature-detrended apparent-resistivity data. Applications of the filter functions and sensitivity factors accurately predicted the apparent-resistivity variations (the correlation coefficient was 0.98). Furthermore, the filtered ERT monitoring data and resultant time-lapse resistivity models correlated closely with independently measured groundwater electrical resistivity monitoring data and only weakly with the groundwater-height fluctuations. The inversion results based on the filtered ERT data also showed significantly less inversion artefacts than the raw data inversions. We observed resistivity increases of up to 10% and the arrival time peaks in the time-lapse resistivity models matched those in the groundwater resistivity monitoring data.

Suboptimal filtering and nonlinear time scale transformation for the analysis of multiexponential decays

Multiexponential decays may contain time-constants differing in several orders of magnitudes. In such cases, uniform sampling results in very long records featuring a high degree of oversampling at the final part of the transient. Here, we analyze a nonlinear time scale transformation to reduce the total number of samples with minimum signal distortion, achieving an important reduction of the computational cost of subsequent analyses. We propose a time-varying filter whose length is optimized for minimum mean square error

Phylogenetic relatedness and proboscis length contribute to structuring bumblebee communities in the extremes of abiotic and biotic gradients

Aim To improve our understanding of how biological communities assemble, we investigated changes in bumblebee communities in space along an elevation gradient. We assessed how much deterministic abiotic and biotic factors shape community assembly. We focused on proboscis length (influencing the species' dietary regime) and phylogenetic relatedness to investigate if competition and environmental filtering occur in more and less productive climates, respectively. Location Western Swiss Alps. Methods We recorded bumblebee species in 149 plots along a 1800-m wide elevation gradient. We contrasted two major clades of bumblebees, a short-tongued and a long-tongued clade. We calculated the phylogenetic and proboscis-length diversity of the bumblebee communities and compared these observed data with a random distribution to detect clustering likely to be caused by environmental filtering or overdispersion likely to be caused by competition. We compared the prevalence of clustered and overdispersed communities along the gradients of plant species richness (biotic) and temperature (abiotic). Results Under colder conditions, where plant species richness is lower and floral resources are scarcer, the clade with shorter proboscides prevails over the clade with longer proboscides, and communities are functionally and phylogenetic clustered. Under warmer conditions, we found phylogenetic but not functional overdispersion in communities. Main conclusions We show for the first time a strong correlation between phylogenetic relatedness, proboscis length and species distribution along temperature and plant richness gradients shaping bumblebee communities. The low temperatures and low levels of plant species richness limit the dispersal of the species from the long-tongued clade, which have more specialized diets, into high-elevation areas. Competition under warmer conditions may produce communities composed of less closely related species that share distinct ecological preferences. Our empirical results corroborate theoretical expectation as well as experiments on the prevalence of deterministic processes in the most severe and most productive parts of environmental gradients.

Hysteresis and return-point memory in deterministic cellular automata

We have investigated hysteresis and the return-point memory (RPM) property in deterministic cellular automata with avalanche dynamics. The RPM property reflects a partial ordering of metastable states, preserved by the dynamics. Recently, Sethna et al. [Phys. Rev. Lett. 70, 3347 (1993)] proved this behavior for a homogeneously driven system with static disorder. This Letter shows that the partial ordering and the RPM can be displayed as well by systems driven heterogeneously, as a result of its own evolution dynamics. In particular, we prove the RPM property for a deterministic 2D sandpile automaton driven at a central site.

Spin filtering through ferromagnetic BiMnO3 tunnel barriers

We report on experiments of spin filtering through ultrathin single-crystal layers of the insulating and ferromagnetic oxide BiMnO3 (BMO). The spin polarization of the electrons tunneling from a gold electrode through BMO is analyzed with a counterelectrode of the half-metallic oxide La2/3Sr1/3MnO3 (LSMO). At 3 K we find a 50% change of the tunnel resistances according to whether the magnetizations of BMO and LSMO are parallel or opposite. This effect corresponds to a spin-filtering efficiency of up to 22%. Our results thus show the potential of complex ferromagnetic insulating oxides for spin filtering and injection.

Nonlinear filtering in object and Fourier space in a joint transform optical correlator: comparison and experimental realization

The use of different kinds of nonlinear filtering in a joint transform correlator are studied and compared. The study is divided into two parts, one corresponding to object space and the second to the Fourier domain of the joint power spectrum. In the first part, phase and inverse filters are computed; their inverse Fourier transforms are also computed, thereby becoming the reference in the object space. In the Fourier space, the binarization of the power spectrum is realized and compared with a new procedure for removing the spatial envelope. All cases are simulated and experimentally implemented by a compact joint transform correlator.

Free conjunctival autologous graft for bleb repair and bleb reduction after trabeculectomy and nonpenetrating filtering surgery.

PURPOSE: To describe methods and outcomes of excisional revision of a filtering bleb (bleb revision) using free conjunctival autologous graft either for bleb repair or for bleb reduction after trabeculectomy and deep sclerectomy with an implant. METHODS: Retrospective medical records were reviewed for a consecutive non-comparative case series comprising patients who underwent excisional revision of a filtering bleb between May 1998-January 2001. Excisional revision using free conjunctival autologous graft (bleb revision) was performed either for bleb repair, to treat early and late leaks and hypotony with maculopathy, or for bleb reduction, to improve ocular pain, discomfort, burning, foreign body sensation, tearing, and fluctuations of visual acuity. The revision consisted of bleb excision and free conjunctival autologous graft. The bleb histopathology was analyzed in patients who underwent bleb repair. RESULTS: Sixteen patients were included in the study, consisting of nine patients who had a trabeculectomy and seven patients who had a deep sclerectomy with an implant. Bleb revision was necessary in 14 patients due to leaking filtering bleb (bleb repair), and in 2 patients due to bleb dysesthesia (bleb reduction). After a follow-up of 15.1 +/- 8.4 months, the mean intraocular pressure (IOP) rose from 7.8 +/- 6.3 mm Hg to 14.3 +/- 6.5 mm Hg, and the visual acuity from 0.4 +/- 0.3 to 0.7 +/- 0.3, with a P value of 0.008 and 0.03, respectively. The complete success rate at 32 months, according to the Kaplan-Meier survival curve, was 38.3%, and the qualified success rate was 83.3%. Four patients (25%) required additional suturing for persistent bleb leak. To control IOP, antiglaucoma medical therapy was needed for six patients (37.5%) and repeated glaucoma surgery was needed for one patient. CONCLUSION: Free conjunctival autologous graft is a safe and successful procedure for bleb repair and bleb reduction. However, patients should be aware of the postoperative possibility of requiring medical or surgical intervention for IOP control after revision.

A probabilistic approach to niche-based community models for spatial forecasts of assemblage properties and their uncertainties

Aim Conservation strategies are in need of predictions that capture spatial community composition and structure. Currently, the methods used to generate these predictions generally focus on deterministic processes and omit important stochastic processes and other unexplained variation in model outputs. Here we test a novel approach of community models that accounts for this variation and determine how well it reproduces observed properties of alpine butterfly communities. Location The western Swiss Alps. Methods We propose a new approach to process probabilistic predictions derived from stacked species distribution models (S-SDMs) in order to predict and assess the uncertainty in the predictions of community properties. We test the utility of our novel approach against a traditional threshold-based approach. We used mountain butterfly communities spanning a large elevation gradient as a case study and evaluated the ability of our approach to model species richness and phylogenetic diversity of communities. Results S-SDMs reproduced the observed decrease in phylogenetic diversity and species richness with elevation, syndromes of environmental filtering. The prediction accuracy of community properties vary along environmental gradient: variability in predictions of species richness was higher at low elevation, while it was lower for phylogenetic diversity. Our approach allowed mapping the variability in species richness and phylogenetic diversity projections. Main conclusion Using our probabilistic approach to process species distribution models outputs to reconstruct communities furnishes an improved picture of the range of possible assemblage realisations under similar environmental conditions given stochastic processes and help inform manager of the uncertainty in the modelling results

Regional deterministic characterization of fracture networks and its application to GIS-based rock fall risk assessment

The study investigates the possibility to incorporate fracture intensity and block geometry as spatially continuous parameters in GIS-based systems. For this purpose, a deterministic method has been implemented to estimate block size (Bloc3D) and joint frequency (COLTOP). In addition to measuring the block size, the Bloc3D Method provides a 3D representation of the shape of individual blocks. These two methods were applied using field measurements (joint set orientation and spacing) performed over a large field area, in the Swiss Alps. This area is characterized by a complex geology, a number of different rock masses and varying degrees of metamorphism. The spatial variability of the parameters was evaluated with regard to lithology and major faults. A model incorporating these measurements and observations into a GIS system to assess the risk associated with rock falls is proposed. The analysis concludes with a discussion on the feasibility of such an application in regularly and irregularly jointed rock masses, with persistent and impersistent discontinuities.

Controlled delivery of 5-chlorouracil using poly(ortho esters) in filtering surgery for glaucoma.

PURPOSE: To evaluate the antimitotic and toxic effects of 5-chlorouracil (5-CU) and 5-fluorouracil (5-FU) and study their potential to delay filtering bleb closure in the rabbit eye when released by poly(ortho esters) (POE). METHODS: Rabbit Tenon fibroblasts and human conjunctival cells were incubated with various 5-CU and 5-FU concentrations. Antiproliferative effects and toxicity were evaluated at 24 and 72 hours by monotetrazolium, neutral red, and Hoechst tests and cell counting. Mechanisms of cell death were evaluated using TUNEL assay, annexin V binding, immunohistochemistry for anti-apoptosis-inducing factor (AIF) and LEI/L-DNase II. Trabeculectomy was performed in pigmented rabbits. Two hundred microliters of POE loaded with 1% wt/wt 5-FU or 5-CU was injected into the subconjunctival space after surgery. Intraocular pressure (IOP) and bleb persistence were monitored for 150 days. RESULTS: In vitro, 5-FU showed a higher antiproliferative effect and a more toxic effect than 5-CU. 5-FU induced cell necrosis, whereas 5-CU induced mostly apoptosis. The apoptosis induced by 5-CU was driven through a non-caspase-dependent pathway involving AIF and LEI/L-DNase II. In vivo, at 34 days after surgery, the mean IOP in the POE/5-CU-treated group was 83% of the baseline level and only 40% in the POE/5-FU-treated group. At 100 days after surgery, IOP was still decreased in the POE/5-CU group when compared with the controls and still inferior to the preoperative value. The mean long-term IOP, with all time points considered, was significantly (P < 0.0001) decreased in the POE/5-CU-treated group (6.0 +/- 2.4 mm Hg) when compared with both control groups, the trabeculectomy alone group (7.6 +/- 2.9 mm Hg), and the POE alone group (7.5 +/- 2.6 mm Hg). Histologic analysis showed evidence of functioning blebs in the POE-5-CU-treated eyes along with a preserved structure of the conjunctiva epithelium. CONCLUSIONS: The slow release of 5-CU from POE has a longstanding effect on the decrease of IOP after glaucoma-filtering surgery in the rabbit eye. Thus, the slow release of POE/5-CU may be beneficial for the prevention of bleb closure in patients who undergo complicated trabeculectomy.

Automatic filtering and substantiation of drug safety signals

Drug safety issues pose serious health threats to the population and constitute a major cause of mortality worldwide. Due to the prominent implications to both public health and the pharmaceutical industry, it is of great importance to unravel the molecular mechanisms by which an adverse drug reaction can be potentially elicited. These mechanisms can be investigated by placing the pharmaco-epidemiologically detected adverse drug reaction in an information-rich context and by exploiting all currently available biomedical knowledge to substantiate it. We present a computational framework for the biological annotation of potential adverse drug reactions. First, the proposed framework investigates previous evidences on the drug-event association in the context of biomedical literature (signal filtering). Then, it seeks to provide a biological explanation (signal substantiation) by exploring mechanistic connections that might explain why a drug produces a specific adverse reaction. The mechanistic connections include the activity of the drug, related compounds and drug metabolites on protein targets, the association of protein targets to clinical events, and the annotation of proteins (both protein targets and proteins associated with clinical events) to biological pathways. Hence, the workflows for signal filtering and substantiation integrate modules for literature and database mining, in silico drug-target profiling, and analyses based on gene-disease networks and biological pathways. Application examples of these workflows carried out on selected cases of drug safety signals are discussed. The methodology and workflows presented offer a novel approach to explore the molecular mechanisms underlying adverse drug reactions

Augmented state Kalman filtering for AUV navigation

Addresses the problem of estimating the motion of an autonomous underwater vehicle (AUV), while it constructs a visual map ("mosaic" image) of the ocean floor. The vehicle is equipped with a down-looking camera which is used to compute its motion with respect to the seafloor. As the mosaic increases in size, a systematic bias is introduced in the alignment of the images which form the mosaic. Therefore, this accumulative error produces a drift in the estimation of the position of the vehicle. When the arbitrary trajectory of the AUV crosses over itself, it is possible to reduce this propagation of image alignment errors within the mosaic. A Kalman filter with augmented state is proposed to optimally estimate both the visual map and the vehicle position