Multiple Imputation for Multilevel Data with Continuous and Binary Variables

We present and compare multiple imputation methods for multilevel continuous and binary data where variables are systematically and sporadically missing. The methods are compared from a theoretical point of view and through an extensive simulation study motivated by a real dataset comprising multiple studies. The comparisons show that these multiple imputation methods are the most appropriate to handle missing values in a multilevel setting and why their relative performances can vary according to the missing data pattern, the multilevel structure and the type of missing variables. This study shows that valid inferences can only be obtained if the dataset includes a large number of clusters. In addition, it highlights that heteroscedastic multiple imputation methods provide more accurate inferences than homoscedastic methods, which should be reserved for data with few individuals per cluster. Finally, guidelines are given to choose the most suitable multiple imputation method according to the structure of the data

Processing of functional fine scale ceramic structures by ink-jet printing

International audienceThis review illustrates the potentiality of ink-jet printing for the fabrication of functional fine scale ceramic structures corresponding to two different kinds of micro-pillar arrays i.e. (i) PZT skeletons, etc..

Five-Year Survival Outcomes With Nivolumab Plus Ipilimumab Versus Chemotherapy as First-Line Treatment for Metastatic Non-Small-Cell Lung Cancer in CheckMate 227

[Purpose] We present 5-year results from CheckMate 227 Part 1, in which nivolumab plus ipilimumab improved overall survival (OS) versus chemotherapy in patients with metastatic non–small-cell lung cancer, regardless of tumor programmed death ligand 1 (PD-L1) status.[Methods] Adults with stage IV/recurrent non–small-cell lung cancer without EGFR mutations or ALK alterations and with tumor PD-L1 ≥ 1% or < 1% (n = 1739) were randomly assigned. Patients with tumor PD-L1 ≥ 1% were randomly assigned to first-line nivolumab plus ipilimumab, nivolumab alone, or chemotherapy. Patients with tumor PD-L1 < 1% were randomly assigned to nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy. End points included exploratory 5-year results for efficacy, safety, and quality of life.[Results] At a minimum follow-up of 61.3 months, 5-year OS rates were 24% versus 14% for nivolumab plus ipilimumab versus chemotherapy (PD-L1 ≥ 1%) and 19% versus 7% (PD-L1 < 1%). The median duration of response was 24.5 versus 6.7 months (PD-L1 ≥ 1%) and 19.4 versus 4.8 months (PD-L1 < 1%). Among patients surviving 5 years, 66% (PD-L1 ≥ 1%) and 64% (PD-L1 < 1%) were off nivolumab plus ipilimumab without initiating subsequent systemic anticancer treatment by the 5-year time point. Survival benefit continued after nivolumab plus ipilimumab discontinuation because of treatment-related adverse events, with a 5-year OS rate of 39% (combined PD-L1 ≥ 1% and < 1% populations). Quality of life in 5-year survivors treated with nivolumab plus ipilimumab was similar to that in the general US population through the 5-year follow-up. No new safety signals were observed.[Conclusion] With all patients off immunotherapy treatment for ≥ 3 years, nivolumab plus ipilimumab increased 5-year survivorship versus chemotherapy, including long-term, durable clinical benefit regardless of tumor PD-L1 expression. These data support nivolumab plus ipilimumab as an effective first-line treatment for patients with metastatic non–small-cell lung cancer.Peer reviewe

Updating the approaches to define susceptibility and resistance to anti-tuberculosis agents: implications for diagnosis and treatment

11 páginas, 2 figuras, 1 tablaInappropriately high breakpoints have resulted in systematic false-susceptible AST results to anti-TB drugs. MIC, PK/PD and clinical outcome data should be combined when setting breakpoints to minimise the emergence and spread of antimicrobial resistance.I. Comas was supported by PID2019-104477RB-I00 from the Spanish Science Ministry and by ERC (CoG 101001038)Peer reviewe

Uniquely-determined thinning of the tie-zone watershed based on label frequency

There are many watershed transform algorithms in literature but most of them do not exactly correspond to their respective definition. The solution given by such algorithms depends on their implementation. Others fit with their definition which allows multiple solutions. The solution chosen by such algorithms depends on their implementation too. It is the case of the watershed by image foresting transform that consists in building a forest of trees with minimum path-costs. The recently introduced tie-zone watershed (TZW) has the advantage of not depending on arbitrary implementation choices: it provides a unique and, thereby, unbiased solution. Indeed, the TZW considers all possible solutions of the watershed transform and keeps only the common parts of them as catchment basins whereas parts that differ form a tie zone disputed by many solutions. Although the TZW insures the uniqueness of the solution, it does not prevent from possible large tie zones, sometimes unwanted in segmentation applications. This paper presents a special thinning of the tie zone that leads to a unique solution. Observing all the possible solutions of the watershed by image foresting transform, one can deduce the frequency of the labels associated with each pixel. The thinning consists in assigning the most frequent label while preserving the segmented region connectivity. We demonstrate that the label frequency can be computed both from an immersion-like recursive formula and the proposed fragmented drop paradigm. Finally, we propose an algorithm under the IFT framework that computes the TZW, the label frequency and the thinning simultaneously and without explicit calculation of all the watershed solutions.27215717

Duality Between The Watershed By Image Foresting Transform And The Fuzzy Connectedness Segmentation Approaches

This paper makes a rereading of two successful image segmentation approaches, the fuzzy connectedness (FC) and the watershed (WS) approaches, by analyzing both by means of the Image Foresting Transform (IFT). This graphbased transform provides a sound framework for analyzing and implementing these methods. This paradigm allows to show the duality existing between the WS by IFT and the FC segmentation approaches. Both can be modeled by an optimal forest computation in a dual form (maximization of the similarities or minimization of the dissimilarities), the main difference being the input parameters: the weights associated to each arc of the graph representing the image. In the WS approach, such weights are based on the (possibly filtered) image gradient values whereas they are based on much more complex affinity values in the FC theory. An efficient algorithm for both FC and IFT-WS computation is proposed. Segmentation robustness issue is also discussed. © 2006 IEEE.5360Audigier, R., Lotufo, R., Tie-zone watershed, bottlenecks and segmentation robustness analysis (2005) XVIII Brazilian Symp. on Comp. Graph, and Image Proc. (SIBGRAPI'05), pp. 55-62. , Natal, Brazil, Oct, IEEE PressAudigier, R., Lotufo, R., Couprie, M., The tie-zone watershed: Definition, algorithm and applications (2005) Proceedings of IEEE Int. Conf. on Image Processing (ICIP'05), 2, pp. 654-657. , Genova, Italy, SeptBerge, C., (1958) Théorie des graphes et ses applications, , Dunod, Paris, FranceBeucher, S., Lantuéjoul, C., Use of watersheds in contour detection (1979) International Workshop on Image Processing, Real-Time Edge and Motion Detection/Estimation, , Rennes, FranceBeucher, S., Meyer, F., The Morphological Approach to Segmentation: The Watershed Transform (1993) Mathematical Morphology in Image Processing, pp. 433-481. , E. R. Dougherty, editor, chapter 12, Marcel Dekker, Inc, New York NY, USACouprie, M., Bertrand, G., Topological grayscale watershed transformation (1997) SPIE Vision Geometry V Proceedings, 3168, pp. 136-146Dijkstra, E., A note on two problems in connexion with graphs (1959) Numerische MathematikDougherty, E., Lotufo, R., (2003) Hands-on Morphological Image Processing, , SPIE, The International Society for Optical Engineering, Bellingham Washington, USA, AugFalcão, A., Stolfi, J., Lotufo, R., The image foresting transform: Theory, algorithms, and applications (2004) IEEE Trans. Pattern Anal. Mach. Intell, 26 (1), pp. 19-29. , JanHerman, G.T., Carvalho, B.M., Multiseeded segmentation using fuzzy connectedness (2001) IEEE Trans. Pattern Anal. Mach. Intell, 23 (5), pp. 460-474Lotufo, R., Falcão, A., The Ordered Queue and the Optimality of the Watershed Approaches (2000) 5th International Symposium on Mathematical Morphology, pp. 341-350. , Palo Alto CA, USA, June, Kluwer AcademicLotufo, R., Falcão, A., Zampirolli, F., IFT-watershed from gray-scale marker (2002) XV Brazilian Symp. on Computer Graph, and Image Proc, pp. 146-152. , Fortaleza CE, Brazil, Oct, IEEE Computer SocietyMeyer, F., Topographic distance and watershed lines (1994) Signal Processing, 38, pp. 113-125Meyer, F., Beucher, S., Morphological segmentation (1990) Journal of Visual Comm. and Image Repr, 1 (1), pp. 21-46Najman, L., Schmitt, M., Watershed of a continuous function (1994) Signal Processing, 38 (1), pp. 99-112J. Roerdink and A. Meijster. The watershed transform: Definitions, algorithms and parallelization strategies. Fundamenta Informaticae, 41(1-2):187-228, Jan. 2000. Special issue on mathematical morphologySaha, P., Udupa, J., Relative fuzzy connectedness among multiple objects: Theory, algorithms, and applications in image segmentation (2001) Computer Vision and Image Understanding, 82 (1), pp. 42-56. , AprilSaha, P., Udupa, J., Odhner, D., Scale-based fuzzy connected image segmentation: Theory, algorithms, and validation (2000) Computer Vision and Image Understanding, 77 (2), pp. 145-174. , FebruaryUdupa, J., Saha, P., Lotufo, R., Relative fuzzy connectedness and object definition: Theory, algorithms, and applications in image segmentation (2002) IEEE Trans. Pattern Anal. Mach. Intell, 24 (11), pp. 1485-1500. , NovemberUdupa, J.K., Samarasekera, S., Fuzzy connectedness and object definition: Theory, algorithms, and applications in image segmentation (1996) Graph. Models Image Process, 58 (3), pp. 246-261. , MayVincent, L., Soille, P., Watersheds in digital spaces: An efficient algorithm based on immersion simulations (1991) IEEE Trans. PatternAnal Mach. Intell, 13 (6), pp. 583-598Zhuge, Y., Udupa, J., Saha, P., Vectorial scale-based fuzzy-connected image segmentation (2006) Computer Vision and Image Understanding, 101 (3), pp. 177-193. , Marc

Tie-zone Watershed, Bottlenecks And Segmentation Robustness Analysis

In a recent paper [1], a new type of watershed (WS) transform was introduced: the tie-zone watershed (TZWS). This region-based watershed transform does not depend on arbitrary implementation and provides a unique (and thereby unbiased) optimal solution. Indeed, many optimal solutions are sometimes possible when segmenting an image by WS. The TZWS assigns each pixel to a catchment basin (CB) if in all solutions it belongs to this CB. Otherwise, the pixel is said to belong to a tie-zone (TZ). An efficient algorithm computing the TZWS and based on the Image Foresting Transform (IFT) was also proposed. In this article, we define the new concept of "bottlenecks" in the watermerging paradigm. Intuitively, the bottlenecks are the first contact points between at least two different wave fronts. They are pixels in the image where different colored waters meet and tie and from which may begin, therefore, the tie-zones. They represent the origin points or the access of the tie-zones (regions that cannot be labeled without making arbitrary choices). If they are preferentially assigned to one or another colored water according to an arbitrary processing order, as occurs in most of watershed algorithm, an entire region (its influence zone -the "bottle"!) is conquered together. The bottlenecks play therefore an important role in the bias that could be introduced by a WS implementation. It is why we show in this paper that both tie-zones and bottlenecks analysis can be associated with the robustness of a segmentation. © 2005 IEEE.20055562Audigier, R., Lotufo, R., Couprie, M., The tie-zone watershed: Definition, algorithm and applications (2005) IEEE Proceedings of ICIP'05, , Genova, Italy, Sept, In pressBeucher, S., Lantuéjoul, C., Use of watersheds in contour detection (1979) International Workshop on Image Processing, Real-Time Edge and Motion Detection/Estimation, , Rennes, FranceCouprie, M., Bertrand, G., Topological grayscale watershed transformation (1997) SPIE Vision Geometry VI Proceedings, 3168, pp. 136-146Dijkstra, E., A note on two problems in connexion with graphs (1959) Numerische MathematikFalcão, A., da Cunha, B., Lotufo, R., Design of connected operators using the image foresting transform (2001) SPIE on Medical Imaging, 4322, pp. 468-479. , Feb. 17-23Falcão, A., Stolfi, J., Lotufo, R., The image foresting transform: Theory, algorithms, and applications (2004) IEEE Trans. on Pattern Analysis and Machine Intelligence, 26 (1), pp. 19-29. , JanLotufo, R., Falcão, A., The ordered queue and the optimality of the watershed approaches (2000) 5th International Symposium on Mathematical Morphology, pp. 341-350. , Palo Alto CA, USA, June, Kluwer AcademicLotufo, R., Falcão, A., Zampirolli, F., IFT-watershed from gray-scale marker (2002) Proceedings of the 15th Brazilian Symposium on Computer Graphics and Image Processing, pp. 146-152. , Fortaleza CE, Brazil, October, IEEE Computer SocietyMeyer, F., Topographic distance and watershed lines (1994) Signal Processing, 38 (1), pp. 113-125Meyer, F., Beucher, S., Morphological segmentation (1990) Journal of Visual Communication and Image Processing, 1 (1), pp. 21-46Najman, L., Couprie, M., Watershed algorithms and contrast preservation (2003) Lecture Notes in Computer Science, 2886, pp. 62-71. , Discrete geometry for computer imagery, of, SpringerRoerdink, J., Meijster, A., The watershed transform: Definitions, algorithms and parallelization strategies (2000) Fundamenta Informaticae, 41 (1-2), pp. 187-228. , JanuaryVincent, L., Soille, P., Watersheds in digital spaces: An efficient algorithm based on immersion simulations (1991) IEEE Trans, on Pattern Analysis and Machine Intelligence, 13 (6), pp. 583-59