Using longitudinal targeted maximum likelihood estimation in complex settings with dynamic interventions.

Longitudinal targeted maximum likelihood estimation (LTMLE) has very rarely been used to estimate dynamic treatment effects in the context of time-dependent confounding affected by prior treatment when faced with long follow-up times, multiple time-varying confounders, and complex associational relationships simultaneously. Reasons for this include the potential computational burden, technical challenges, restricted modeling options for long follow-up times, and limited practical guidance in the literature. However, LTMLE has desirable asymptotic properties, ie, it is doubly robust, and can yield valid inference when used in conjunction with machine learning. It also has the advantage of easy-to-calculate analytic standard errors in contrast to the g-formula, which requires bootstrapping. We use a topical and sophisticated question from HIV treatment research to show that LTMLE can be used successfully in complex realistic settings, and we compare results to competing estimators. Our example illustrates the following practical challenges common to many epidemiological studies: (1) long follow-up time (30 months); (2) gradually declining sample size; (3) limited support for some intervention rules of interest; (4) a high-dimensional set of potential adjustment variables, increasing both the need and the challenge of integrating appropriate machine learning methods; and (5) consideration of collider bias. Our analyses, as well as simulations, shed new light on the application of LTMLE in complex and realistic settings: We show that (1) LTMLE can yield stable and good estimates, even when confronted with small samples and limited modeling options; (2) machine learning utilized with a small set of simple learners (if more complex ones cannot be fitted) can outperform a single, complex model, which is tailored to incorporate prior clinical knowledge; and (3) performance can vary considerably depending on interventions and their support in the data, and therefore critical quality checks should accompany every LTMLE analysis. We provide guidance for the practical application of LTMLE

Biografo: An integrated tool for forensic writer identification

The final publication is available at Springer via http://dx.doi.org/10.1007/978-3-319-20125-2_17The design and performance of a practical integrated tool for writer identification in forensic scenarios is presented. The tool has been designed to help forensic examiners along the complete identification process: from the data acquisition to the recognition itself, as well as with the management of large writer-related databases. The application has been implemented using JavaScript running over a relational database which provides the whole system with some very desirable and unique characteristics such as the possibility to perform all type of queries (e.g., find individuals with some very discriminative character, find a specific document, display all the samples corresponding to one writer, etc.), or a complete control over the set of parameters we want to use in a specific recognition task (e.g., users in the database to be used as control set, set of characters to be used in the identification, size of the ranked list we want as final result, etc.). The identification performance of the tool is evaluated on a real-case forensic database showing some very promising results.This work has been partially supported by the Spanish Dirección General de la Guardia Civil, and projects Contexts (S2009/TIC-1485) from CAM, Bio-Challenge (TEC2009-11186) from Spanish MICINN, BBfor2 (ITN-2008-238803) from the European Commision, and Cátedra UAM-Telefónica

A HPMT based set-up to characterize scintillating crystals

We have developed a fully automatic measurement set-up, capable of measuring light yields arising from scintillating crystals in a linear range of about four orders of magnitude. The photodetector is a Hybrid Photomultiplier Tube especially developed to optimize linear range and photon detection. Crystal and photodetector are temperature controlled by a closed water circuit, as this is essential when measuring low light yield scintillating crystals with a marked temperature dependence of their light yield. Gamma sources can be placed either on top or on the side of the crystal. In this latter case, the source can be automatically moved by a computer-controlled step motor to provide a uniformity profile of the light yield along the crystal. Tagged and not-tagged operation modes are possible. The whole set-up is computer-controlled in an effort to provide fast and reliable measurements, to characterize many crystals per day. This is important for the quality control of the Lead Tungstate crystals that will be applied in the electromagnetic calorimeter of the CMS-detector at the LHC at CERN

Elevation and cholera: an epidemiological spatial analysis of the cholera epidemic in Harare, Zimbabwe, 2008-2009

BACKGROUND: In highly populated African urban areas where access to clean water is a challenge, water source contamination is one of the most cited risk factors in a cholera epidemic. During the rainy season, where there is either no sewage disposal or working sewer system, runoff of rains follows the slopes and gets into the lower parts of towns where shallow wells could easily become contaminated by excretes. In cholera endemic areas, spatial information about topographical elevation could help to guide preventive interventions. This study aims to analyze the association between topographic elevation and the distribution of cholera cases in Harare during the cholera epidemic in 2008 and 2009. METHODS: We developed an ecological study using secondary data. First, we described attack rates by suburb and then calculated rate ratios using whole Harare as reference. We illustrated the average elevation and cholera cases by suburbs using geographical information. Finally, we estimated a generalized linear mixed model (under the assumption of a Poisson distribution) with an Empirical Bayesian approach to model the relation between the risk of cholera and the elevation in meters in Harare. We used a random intercept to allow for spatial correlation of neighboring suburbs. RESULTS: This study identifies a spatial pattern of the distribution of cholera cases in the Harare epidemic, characterized by a lower cholera risk in the highest elevation suburbs of Harare. The generalized linear mixed model showed that for each 100 meters of increase in the topographical elevation, the cholera risk was 30% lower with a rate ratio of 0.70 (95% confidence interval=0.66-0.76). Sensitivity analysis confirmed the risk reduction with an overall estimate of the rate ratio between 20% and 40%. CONCLUSION: This study highlights the importance of considering topographical elevation as a geographical and environmental risk factor in order to plan cholera preventive activities linked with water and sanitation in endemic areas. Furthermore, elevation information, among other risk factors, could help to spatially orientate cholera control interventions during an epidemic

Wettability characteristics of an Al2O3/SiO2-based ceramic modified with CO2, Nd:YAG, excimer and high-power diode lasers

Interaction of CO2, Nd:YAG, excimer and high power diode laser (HPDL) radiation with the surface of an Al2O3/SiO2 based ceramic was found to effect significant changes in the wettability characteristics of the material. It was observed that interaction with CO2, Nd:YAG and HPDL radiation reduced the enamel contact angle from 1180 to 310, 340 and 330 respectively. In contrast, interaction with excimer laser radiation resulted an increase in the contact angle to 1210. Such changes were identified as being due to: (i) the melting and partial vitrification of the Al2O3/SiO2 based ceramic surface as a result of interaction with CO2, Nd:YAG HPDL radiation. (ii) the surface roughness of the Al2O3/SiO2 based ceramic increasing after interaction with excimer laser radiation. (iii) the surface oxygen content of the Al2O3/SiO2 based ceramic increasing after interaction with CO2, Nd:YAG and HPDL radiation. The work has shown that the wettability characteristics of the Al2O3/SiO2 based ceramic could be controlled and/or modified with laser surface treatment. In particular, whether the laser radiation had the propensity to cause surface melting. However, a wavelength dependance of the change of the wetting properties could not be deduced from the findings of this work

Learning to Grasp 3D Objects using Deep Residual U-Nets

Grasp synthesis is one of the challenging tasks for any robot object manipulation task. In this paper, we present a new deep learning-based grasp synthesis approach for 3D objects. In particular, we propose an end-to-end 3D Convolutional Neural Network to predict the objects’ graspable areas. We named our approach Res-U-Net since the architecture of the network is designed based on U-Net structure and residual network-styled blocks. It devised to plan 6-DOF grasps for any desired object, be efficient to compute and use, and be robust against varying point cloud density and Gaussian noise. We have performed extensive experiments to assess the performance of the proposed approach concerning graspable part detection, grasp success rate, and robustness to varying point cloud density and Gaussian noise. Experiments validate the promising performance of the proposed architecture in all aspects. A video showing the performance of our approach in the simulation environment can be found at http://youtu.be/5_yAJCc8owo<br/

Structures of Five \u3cem\u3etrans\u3c/em\u3e-2-Hydroxy and \u3cem\u3etrans\u3c/em\u3e-2-Methoxy-2-methyl-3,4-dihydro-4-aryl- 2\u3cem\u3eH\u3c/em\u3e,5\u3cem\u3eH\u3c/em\u3e-pyrano[3,2-\u3cem\u3ec\u3c/em\u3e]benzopyran-5-ones

Derivatives of 2-methyl-3,4-dihydro-2H,5H-pyrano[3,2-c][1]benzopyran-5-one. (1) Racemic trans-methoxy-4-phenyl, Mr = 322·4, monoclinic, P21/n, a = 5·858 (1), b = 16· 732 (9), c = 16·383 (9) Å, β = 94·82 (3)°, V = 1600·1 Å3, Z = 4, Dx = 1·338 g cm-3, λ(Mo Kα) = 0·71073 Å, μ = 0·866 cm-1, F(000) = 680, T = 298 K, final R = 0·047 for 1513 intensities. The trans methyl ketal of warfarin (C20H18O4) contains a half-chair dihydropyran ring distorted toward the d,e-diplanar conformation. (2) Resolved (2R,4R)-trans-2-methoxy-4-phenyl, Mr = 322·4, orthorhombic, P212121, a = 11·521(1), b = 14·061 (2), c = 10·055(2) Å, V = 1628·9 Å3 , Z = 4, Dx= 1·314 g cm-3, λ(Mo Kα) = 0·71073 Å, μ = 0·851 cm-1, F(000) = 680, T = 298 K, final R = 0·056 for 1660 intensities. The trans methyl ketal (C20H18O4) from R(+)-warfarin; its dihydropyran ring is a half- chair distorted toward the d,e-diplanar conformation. (3) Resolved trans-2-hydroxy-4-(4-methoxyphenyl), Mr = 338·4, orthorhombic, P212121, a = 10·584 (1), b = 10·621(5), c = 14·778 (2) Å, V = 1661·2 Å3, Z = 4, Dx = 1·353 g cm-3, λ(Mo Kα) = 0·71073 Å, μ = 0·908 cm-1, F(000) = 712, T = 298 K, final R = 0·044 for 1165 unique intensities. Compound C20H18O5 spontaneously resolves on crystallization from acetone and water, and absolute configuration of data specimen was not determined. It has a dihydropyran ring with a half-chair conformation; hydroxyl and lactone carbonyl are intermolecularly H-bonded at O···O = 2·79 Å. (4) Racemic trans-2-hydroxy-4-(2-methyl-6-methoxyphenyl), Mr = 372·4, monoclinic, P21/n, a = 9·637 (2), b = 14·345 (4), c = 13·224 (2) Å, β = 91·09 (1)°, V = 1827·8 Å3, Z = 4, Dx = 1·353 g cm-3, λ(Mo Kα) = 0·71073 Å, μ = 0·961 cm-1, F(000) = 784, T = 298 K, final R= 0·048 for 2339 unique intensities. A synthetic derivative of warfarin, it crystallizes as the hydrate C20H18O6.H2O and has a dihydropyran ring with a half-chair conformation and intermolecular H bonds with O···O distances between 2·67 and 2·77 Å. (5) Racemic trans-2-hydroxy-4-(4-dimethylaminophenyl), Mr = 369·4, triclinic, PĪ, a = 9·066 (3), b = 9·509 (2)°, c = 12·681 (3) Å, α = 98·50 (2), β = 91·25 (3), γ = 116·96 (2)°, V = 958·8 Å3, Z = 2, Dx = 1·279 g cm-3, λ(Mo Kα) = 0·71073 Å, μ = 0·854 cm-1, F(000) = 392, T = 298 K, final R = 0·045 on 2773 unique intensities. A synthetic derivative of warfarin, it also crystallizes as a hydrate, C21H21NO4.H2O, and has a dihydropyran ring with a half-chair conformation and intermolecular H bonds with O···O distances between 2·70 and 3·07 Å

Structures of Four \u3ci\u3etrans\u3c/i\u3e-2-Hydroxy- and Methoxy-2-methyl-3,4-dihydro-4-alkyl-2\u3ci\u3eH\u3c/i\u3e,5\u3ci\u3eH\u3c/i\u3e-pyrano[3,2-c][1]benzopyran-5-ones

Derivatives of 2-methyl-3,4-dihydro-2H,5H-pyrano[ 3,2-c][1]benzopyran-5-one. ( l) Racemic trans- 2-methoxy-4-(2-propyl), Mr= 288·3, monoclinic, P2i/c, a = 13·737 (3), b = 13·228 (6), c = 17·229(4) Å, β = l02·93(2)° , V = 3051·4 Å3, Z = 8 (two molecules/asymmetric unit), Dx = 1·255 g cm- 3, λ(Mo Kα) = O·71073 Å, μ = 0·908 cm-1 , F(OOO) = 1232, T = 298 K, final R = 0·050 for 3988 unique intensities. Dihydropyran rings in C17H2004 are halfchairs, one being distorted toward the d,e-diplanar form. (2) Resolved trans-2-methoxy-4-cyclohexyl, Mr = 328-4, orthorhombic, P212121, a = 10·468 (5), b = 11·245 (5). c = 14·465 (4) Å, V= 1702·7 Å3, Z=4, Dx= 1·281 g cm-3, λ(Mo Kα) = 0·71073 Å, μ = 0·823 cm- 1 , F(OOO) = 704, T = 298 K, final R = 0·051 for 2481 unique intensities. Compound, C20H2404, spontaneously resolves on crystallization from methanol: acetone; data specimen determined to be 2R,4R by circular dichroism spectrum and comparison with structures of known configuration. Dihydropyran ring has a d,e-diplanar conformation. (3) Racemic trans- 2-hydroxy-4-(2-propyl). Compound crystallizes as the hemihydrate C16H1804. ½H20; Mr= 283-3, triclinic, P1, a = 9·015 (4), b = 10·216 (4), c = 16·208 (5) Å, α = 103·08 (3), β = 95·42 (3), γ = 95·28 (3)° , V = 1437·6 Å3, Z = 4 (two molecules/asymmetric unit), Dx = 1·309 g cm-3 , λ(Mo Kα) = O·71073 Å, μ = 0·890 cm-1, F(OOO) = 604, T = 298 K, final R = 0·040 for 4656 unique reflections. One dihydropyran ring is a half-chair, the other has an ef-diplanar conformation. Intermolecular hydrogen bonding occurs between the water and the hydroxyls and lactone carbonyls of each coumarin with O···O distances between 2·82 and 2·90 Å. (4) Racemic trans-2-hydroxyl-4-(2-propyl) derivative also cocrystallizes with 4-hydroxy-2H-benzopyran- 2-one (1:1), Mr = 436·4, triclinic, P1, a= 8·669 (2), b = 10·506 (4), c = 12.559 (2) Å, α = 102·98 (2), β = 107·56 (2), γ = 93·63 (2)°, V = 1052·0 Å3, Z=2, Dx= 1·378g cm-3, γ(Mo Kα) = 0·71073 Å, μ = 0·941 cm-1, F(OOO) = 460, T = 298 K, final R = 0·041 for 3322 unique reflections. Cocrystalline C16H1804C9H603 shows chains of H bonds linking the hydroxyls of the coumarins alternately with the lactone carbonyls, O···O distances 2·68 and 2·75 Å. The dihydropyran ring has a half-chair conformation