Size constancy in bat biosonar?

Perception and encoding of object size is an important feature of sensory systems. In the visual system object size is encoded by the visual angle (visual aperture) on the retina, but the aperture depends on the distance of the object. As object distance is not unambiguously encoded in the visual system, higher computational mechanisms are needed. This phenomenon is termed "size constancy". It is assumed to reflect an automatic re-scaling of visual aperture with perceived object distance. Recently, it was found that in echolocating bats, the 'sonar aperture', i.e., the range of angles from which sound is reflected from an object back to the bat, is unambiguously perceived and neurally encoded. Moreover, it is well known that object distance is accurately perceived and explicitly encoded in bat sonar. Here, we addressed size constancy in bat biosonar, recruiting virtual-object techniques. Bats of the species Phyllostomus discolor learned to discriminate two simple virtual objects that only differed in sonar aperture. Upon successful discrimination, test trials were randomly interspersed using virtual objects that differed in both aperture and distance. It was tested whether the bats spontaneously assigned absolute width information to these objects by combining distance and aperture. The results showed that while the isolated perceptual cues encoding object width, aperture, and distance were all perceptually well resolved by the bats, the animals did not assign absolute width information to the test objects. This lack of sonar size constancy may result from the bats relying on different modalities to extract size information at different distances. Alternatively, it is conceivable that familiarity with a behaviorally relevant, conspicuous object is required for sonar size constancy, as it has been argued for visual size constancy. Based on the current data, it appears that size constancy is not necessarily an essential feature of sonar perception in bats

Application of antisense conjugates for the treatment of myotonic dystrophy type 1

Myotonic dystrophy type 1 (DM1) is one of the most common muscular dystrophies and can be potentially treated with antisense therapy decreasing mutant DMPK, targeting miRNAs or their binding sites or via a blocking mechanism for MBNL1 displacement from the repeats. Unconjugated antisense molecules are able to correct the disease phenotype in mouse models, but they show poor muscle penetration upon systemic delivery in DM1 patients. In order to overcome this challenge, research has focused on the improvement of the therapeutic window and biodistribution of antisense therapy using bioconjugation to lipids, cell penetrating peptides or antibodies. Antisense conjugates are able to induce the long-lasting correction of DM1 pathology at both molecular and functional levels and also efficiently penetrate hard-to-reach tissues such as cardiac muscle. Delivery to the CNS at clinically relevant levels remains challenging and the use of alternative administration routes may be necessary to ameliorate some of the symptoms experienced by DM1 patients. With several antisense therapies currently in clinical trials, the outlook for achieving a clinically approved treatment for patients has never looked more promising

Optimising use of electronic health records to describe the presentation of rheumatoid arthritis in primary care: a strategy for developing code lists

Background Research using electronic health records (EHRs) relies heavily on coded clinical data. Due to variation in coding practices, it can be difficult to aggregate the codes for a condition in order to define cases. This paper describes a methodology to develop ‘indicator markers’ found in patients with early rheumatoid arthritis (RA); these are a broader range of codes which may allow a probabilistic case definition to use in cases where no diagnostic code is yet recorded. Methods We examined EHRs of 5,843 patients in the General Practice Research Database, aged ≥30y, with a first coded diagnosis of RA between 2005 and 2008. Lists of indicator markers for RA were developed initially by panels of clinicians drawing up code-lists and then modified based on scrutiny of available data. The prevalence of indicator markers, and their temporal relationship to RA codes, was examined in patients from 3y before to 14d after recorded RA diagnosis. Findings Indicator markers were common throughout EHRs of RA patients, with 83.5% having 2 or more markers. 34% of patients received a disease-specific prescription before RA was coded; 42% had a referral to rheumatology, and 63% had a test for rheumatoid factor. 65% had at least one joint symptom or sign recorded and in 44% this was at least 6-months before recorded RA diagnosis. Conclusion Indicator markers of RA may be valuable for case definition in cases which do not yet have a diagnostic code. The clinical diagnosis of RA is likely to occur some months before it is coded, shown by markers frequently occurring ≥6 months before recorded diagnosis. It is difficult to differentiate delay in diagnosis from delay in recording. Information concealed in free text may be required for the accurate identification of patients and to assess the quality of care in general practice

Spiky Strings and Giant Holes

We analyse semiclassical strings in AdS in the limit of one large spin. In this limit, classical string dynamics is described by a finite number of collective coordinates corresponding to spikes or cusps of the string. The semiclassical spectrum consists of two branches of excitations corresponding to "large" and "small" spikes respectively. We propose that these states are dual to the excitations known as large and small holes in the spin chain description of N=4 SUSY Yang-Mills. The dynamics of large spikes in classical string theory can be mapped to that of a classical spin chain of fixed length. In turn, small spikes correspond to classical solitons propagating on the background formed by the large spikes. We derive the dispersion relation for these excitations directly in the finite gap formalism.Comment: 36 pages, 9 figure

Understanding patient-reported knowledge of hernia surgery: a quantitative study

Abdominal wall; Knowledge; PatientPared abdominal; Conocimiento; PacienteParet abdominal; Coneixement; PacientPurpose The objective of this study was to gather information on patient-reported knowledge (PRK) in the field of hernia surgery. Methods A prospective quantitative study was designed to explore different aspects of PRK and opinions regarding hernia surgery. Patients referred for the first time to a surgical service with a presumed diagnosis of hernia and eventual hernia repair were eligible, and those who gave consent completed a simple self-assessment questionnaire before the clinical visit. Results The study population included 449 patients (72.8% men, mean age 61.5). Twenty (4.5%) patients did not have hernia on physical examination. The patient’s perceived health status was “neither bad nor good” or “good” in 56.6% of cases. Also, more patients considered that hernia repair would be an easy procedure (35.1%) rather than a difficult one (9.8%). Although patients were referred by their family physicians, 32 (7.1%) answered negatively to the question of coming to the visit to assess the presence of a hernia. The most important reason of the medical visit was to receive medical advice (77.7%), to be operated on as soon as possible (40.1%) or to be included in the surgical waiting list (35.9%). Also, 46.1% of the patients considered that they should undergo a hernia repair and 56.8% that surgery will be a definitive solution. Conclusion PRK of patients referred for the first time to an abdominal wall surgery unit with a presumed diagnosis of hernia was quite limited and there is still a long way towards improving knowledge of hernia surgery.Open Access Funding provided by Universitat Autonoma de Barcelona

MultiBaC: A strategy to remove batch effects between different omic data types

[EN] Diversity of omic technologies has expanded in the last years together with the number of omic data integration strategies. However, multiomic data generation is costly, and many research groups cannot afford research projects where many different omic techniques are generated, at least at the same time. As most researchers share their data in public repositories, different omic datasets of the same biological system obtained at different labs can be combined to construct a multiomic study. However, data obtained at different labs or moments in time are typically subjected to batch effects that need to be removed for successful data integration. While there are methods to correct batch effects on the same data types obtained in different studies, they cannot be applied to correct lab or batch effects across omics. This impairs multiomic meta-analysis. Fortunately, in many cases, at least one omics platform-i.e. gene expression- is repeatedly measured across labs, together with the additional omic modalities that are specific to each study. This creates an opportunity for batch analysis. We have developed MultiBaC (multiomic Multiomics Batch-effect Correction correction), a strategy to correct batch effects from multiomic datasets distributed across different labs or data acquisition events. Our strategy is based on the existence of at least one shared data type which allows data prediction across omics. We validate this approach both on simulated data and on a case where the multiomic design is fully shared by two labs, hence batch effect correction within the same omic modality using traditional methods can be compared with the MultiBaC correction across data types. Finally, we apply MultiBaC to a true multiomic data integration problem to show that we are able to improve the detection of meaningful biological effects.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work is part of a research project that is totally funded by Conselleria d'Educacio, Cultura i Esport (Generalitat Valenciana) through PROMETEO grants program for excellence research groups.Ugidos, M.; Tarazona Campos, S.; Prats-Montalbán, JM.; Ferrer, A.; Conesa, A. (2020). MultiBaC: A strategy to remove batch effects between different omic data types. Statistical Methods in Medical Research. 29(10):2851-2864. https://doi.org/10.1177/0962280220907365S285128642910Kupfer, P., Guthke, R., Pohlers, D., Huber, R., Koczan, D., & Kinne, R. W. (2012). Batch correction of microarray data substantially improves the identification of genes differentially expressed in Rheumatoid Arthritis and Osteoarthritis. BMC Medical Genomics, 5(1). doi:10.1186/1755-8794-5-23Gregori, J., Villarreal, L., Méndez, O., Sánchez, A., Baselga, J., & Villanueva, J. (2012). Batch effects correction improves the sensitivity of significance tests in spectral counting-based comparative discovery proteomics. Journal of Proteomics, 75(13), 3938-3951. doi:10.1016/j.jprot.2012.05.005Ritchie, M. E., Phipson, B., Wu, D., Hu, Y., Law, C. W., Shi, W., & Smyth, G. K. (2015). limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Research, 43(7), e47-e47. doi:10.1093/nar/gkv007Gagnon-Bartsch, J. A., & Speed, T. P. (2011). Using control genes to correct for unwanted variation in microarray data. Biostatistics, 13(3), 539-552. doi:10.1093/biostatistics/kxr034Nueda, M. j., Ferrer, A., & Conesa, A. (2011). ARSyN: a method for the identification and removal of systematic noise in multifactorial time course microarray experiments. Biostatistics, 13(3), 553-566. doi:10.1093/biostatistics/kxr042Jansen, J. J., Hoefsloot, H. C. J., van der Greef, J., Timmerman, M. E., Westerhuis, J. A., & Smilde, A. K. (2005). ASCA: analysis of multivariate data obtained from an experimental design. Journal of Chemometrics, 19(9), 469-481. doi:10.1002/cem.952Nueda, M. J., Conesa, A., Westerhuis, J. A., Hoefsloot, H. C. J., Smilde, A. K., Talón, M., & Ferrer, A. (2007). Discovering gene expression patterns in time course microarray experiments by ANOVA–SCA. Bioinformatics, 23(14), 1792-1800. doi:10.1093/bioinformatics/btm251Giordan, M. (2013). A Two-Stage Procedure for the Removal of Batch Effects in Microarray Studies. Statistics in Biosciences, 6(1), 73-84. doi:10.1007/s12561-013-9081-1Nyamundanda, G., Poudel, P., Patil, Y., & Sadanandam, A. (2017). A Novel Statistical Method to Diagnose, Quantify and Correct Batch Effects in Genomic Studies. Scientific Reports, 7(1). doi:10.1038/s41598-017-11110-6Reese, S. E., Archer, K. J., Therneau, T. M., Atkinson, E. J., Vachon, C. M., de Andrade, M., … Eckel-Passow, J. E. (2013). A new statistic for identifying batch effects in high-throughput genomic data that uses guided principal component analysis. Bioinformatics, 29(22), 2877-2883. doi:10.1093/bioinformatics/btt480Papiez, A., Marczyk, M., Polanska, J., & Polanski, A. (2018). BatchI: Batch effect Identification in high-throughput screening data using a dynamic programming algorithm. Bioinformatics, 35(11), 1885-1892. doi:10.1093/bioinformatics/bty900Keel, B. N., Zarek, C. M., Keele, J. W., Kuehn, L. A., Snelling, W. M., Oliver, W. T., … Lindholm-Perry, A. K. (2018). RNA-Seq Meta-analysis identifies genes in skeletal muscle associated with gain and intake across a multi-season study of crossbred beef steers. BMC Genomics, 19(1). doi:10.1186/s12864-018-4769-8Li, M. D., Burns, T. C., Morgan, A. A., & Khatri, P. (2014). Integrated multi-cohort transcriptional meta-analysis of neurodegenerative diseases. Acta Neuropathologica Communications, 2(1). doi:10.1186/s40478-014-0093-yAndres-Terre, M., McGuire, H. M., Pouliot, Y., Bongen, E., Sweeney, T. E., Tato, C. M., & Khatri, P. (2015). Integrated, Multi-cohort Analysis Identifies Conserved Transcriptional Signatures across Multiple Respiratory Viruses. Immunity, 43(6), 1199-1211. doi:10.1016/j.immuni.2015.11.003Sandhu, V., Labori, K. J., Borgida, A., Lungu, I., Bartlett, J., Hafezi-Bakhtiari, S., … Haibe-Kains, B. (2019). Meta-Analysis of 1,200 Transcriptomic Profiles Identifies a Prognostic Model for Pancreatic Ductal Adenocarcinoma. JCO Clinical Cancer Informatics, (3), 1-16. doi:10.1200/cci.18.00102Huang, H., Liu, C.-C., & Zhou, X. J. (2010). Bayesian approach to transforming public gene expression repositories into disease diagnosis databases. Proceedings of the National Academy of Sciences, 107(15), 6823-6828. doi:10.1073/pnas.0912043107Pelechano, V., & Pérez-Ortín, J. E. (2010). There is a steady-state transcriptome in exponentially growing yeast cells. Yeast, 27(7), 413-422. doi:10.1002/yea.1768Garcı́a-Martı́nez, J., Aranda, A., & Pérez-Ortı́n, J. E. (2004). Genomic Run-On Evaluates Transcription Rates for All Yeast Genes and Identifies Gene Regulatory Mechanisms. Molecular Cell, 15(2), 303-313. doi:10.1016/j.molcel.2004.06.004Pelechano, V., Chávez, S., & Pérez-Ortín, J. E. (2010). A Complete Set of Nascent Transcription Rates for Yeast Genes. PLoS ONE, 5(11), e15442. doi:10.1371/journal.pone.0015442Zid, B. M., & O’Shea, E. K. (2014). Promoter sequences direct cytoplasmic localization and translation of mRNAs during starvation in yeast. Nature, 514(7520), 117-121. doi:10.1038/nature13578Freeberg, M. A., Han, T., Moresco, J. J., Kong, A., Yang, Y.-C., Lu, Z., … Kim, J. K. (2013). Pervasive and dynamic protein binding sites of the mRNA transcriptome in Saccharomyces cerevisiae. Genome Biology, 14(2), R13. doi:10.1186/gb-2013-14-2-r13McKinlay, A., Araya, C. L., & Fields, S. (2011). Genome-Wide Analysis of Nascent Transcription in Saccharomyces cerevisiae. G3 Genes|Genomes|Genetics, 1(7), 549-558. doi:10.1534/g3.111.000810Castells-Roca, L., García-Martínez, J., Moreno, J., Herrero, E., Bellí, G., & Pérez-Ortín, J. E. (2011). Heat Shock Response in Yeast Involves Changes in Both Transcription Rates and mRNA Stabilities. PLoS ONE, 6(2), e17272. doi:10.1371/journal.pone.0017272Wold, S., Sjöström, M., & Eriksson, L. (2001). PLS-regression: a basic tool of chemometrics. Chemometrics and Intelligent Laboratory Systems, 58(2), 109-130. doi:10.1016/s0169-7439(01)00155-1Folch-Fortuny, A., Vitale, R., de Noord, O. E., & Ferrer, A. (2017). Calibration transfer between NIR spectrometers: New proposals and a comparative study. Journal of Chemometrics, 31(3), e2874. doi:10.1002/cem.2874García Muñoz, S., MacGregor, J. F., & Kourti, T. (2005). Product transfer between sites using Joint-Y PLS. Chemometrics and Intelligent Laboratory Systems, 79(1-2), 101-114. doi:10.1016/j.chemolab.2005.04.009Andrade, J. M., Gómez-Carracedo, M. P., Krzanowski, W., & Kubista, M. (2004). Procrustes rotation in analytical chemistry, a tutorial. Chemometrics and Intelligent Laboratory Systems, 72(2), 123-132. doi:10.1016/j.chemolab.2004.01.007Hurley, J. R., & Cattell, R. B. (2007). The procrustes program: Producing direct rotation to test a hypothesized factor structure. Behavioral Science, 7(2), 258-262. doi:10.1002/bs.3830070216Hartigan, J. A., & Wong, M. A. (1979). Algorithm AS 136: A K-Means Clustering Algorithm. Applied Statistics, 28(1), 100. doi:10.2307/234683

Analysis of antenal sensilla patterns of Rhodnius prolixus from Colombia and Venezuela

Antennal sensilla patterns were used to analyze population variation of domestic Rhodnius prolixus from six departments and states representing three biogeographical regions of Colombia and Venezuela. Discriminant analysis of the patterns of mechanoreceptors and of three types of chemoreceptors on the pedicel and flagellar segments showed clear differentiation between R. prolixus populations east and west of the Andean Cordillera. The distribution of thick and thin-walled trichoids on the second flagellar segment also showed correlation with latitude, but this was not seen in the patterns of other sensilla. The results of the sensilla patterns appear to be reflecting biogeographic features or population isolation rather than characters associated with different habitats and lend support to the idea that domestic R. prolixus originated in the eastern region of the Andes.Fil: Esteban, Lyda. Universidad Industrial de Santander; ColombiaFil: Angulo, Víctor Manuel. Universidad Industrial de Santander; ColombiaFil: Dora Feliciangeli, M.. Universidad de Carabobo; VenezuelaFil: Catala, Silvia Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja. - Universidad Nacional de La Rioja. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja. - Universidad Nacional de Catamarca. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja. - Secretaría de Industria y Minería. Servicio Geológico Minero Argentino. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja. - Provincia de La Rioja. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja; Argentin

A pipeline structure for the block QR update in digital signal processing

[EN] There exist problems in the field of digital signal processing, such as filtering of acoustic signals that require processing a large amount of data in real time. The beamforming algorithm, for instance, is a process that can be modeled by a rectangular matrix built on the input signals of an acoustic system and, thus, changes in real time. To obtain the output signals, it is required to compute its QR factorization. In this paper, we propose to organize the concurrent computational resources of a given multicore computer in a pipeline structure to perform this factorization as fast as possible. The pipeline has been implemented using both the application programming interface OpenMP and GrPPI, a library interface to design parallel applications based on parallel patterns. We tackle not only the performance challenge but also the programmability of our idea using parallel programming frameworks.This work was supported by the Spanish Ministry of Economy and Competitiveness under MINECO and FEDER projects TIN2014-53495-R and TEC2015-67387-C4-1-R.Dolz, MF.; Alventosa, FJ.; Alonso-Jordá, P.; Vidal Maciá, AM. (2019). A pipeline structure for the block QR update in digital signal processing. The Journal of Supercomputing. 75(3):1470-1482. https://doi.org/10.1007/s11227-018-2666-1S14701482753Huang Y, Benesty J, Chen J (2006) Acoustic MIMO signal processing (signals and communication technology). Springer, BerlinRamiro C, Vidal AM, González A (2015) MIMOPack: a high performance computing library for MIMO communication systems. J Supercomput 71:751–760Alventosa FJ, Alonso P, Piñero G, Vidal AM (2016) Implementation of the Beamformer algorithm for the NVIDIA Jetson. In: Actas de la Conferencia, Granada, Spain, pp 201–211. ISBN 978-3-319-49955-0Alventosa FJ, Alonso P, Vidal AM, Piñero G, Quintana-Ortí ES (2018) Fast block QR update in digital signal processing. J Supercomput. https://doi.org/10.1007/s11227-018-2298-5del Rio D, Dolz MF, Fernández J, García JD (2017) A generic parallel pattern interface for stream and data processing. Concurr Comput Pract Exp 29(24):e4175Benesty J, Chen J, Huang Y, Dmochowski J (2007) On microphone-array Beamforming from a MIMO acoustic signal processing perspective. IEEE Trans Audio Speech Lang Process 15(3):1053–1065Lorente J, Piñero G, Vidal AM, Belloch JA, González A (2011) Parallel implementations of Beamforming design and filtering for microphone array applications. In: 19th European Signal Processing Conference (EUSIPCO), Barcelona, Spain, pp 501–505Belloch JA, Ferrer M, González A, Martínez-Zaldívar FJ, Vidal AM (2013) Headphone-based virtual spatialization of sound with a GPU accelerator. J Audio Eng Soc 61:546–561Belloch JA, González A, Martínez-Zaldívar FJ, Vidal AM (2011) Real-time massive convolution for audio applications on GPU. J Supercomput 58(3):449–457Golub GH, Van Loan CF (2013) Matrix computations. Johns Hopkins studies in the mathematical sciences. Johns Hopkins University Press, BaltimoreGunter BC, van de Geijn RA (2005) Parallel out-of-core computation and updating the QR factorization. ACM Trans Math Softw 31(1):60–78Buttari A, Langou J, Kurzak J, Dongarra J (2009) A class of parallel tiled linear algebra algorithms for multicore architectures. Parallel Comput 35(1):38–53Dolz MF, Alventosa FJ, Alonso-Jordá P, Vidal AM (2018) A pipeline for the QR update in digital signal processing. In: Proceedings of the 18th International Conference on Computational and Mathematical Methods in Science and Engineering (CMMSE 2018), Rota, Cádiz, Spain, pp 1–5Quintana-Ortí G, Quintana-Ortí ES, Van De Geijn RA, Van Zee FG, Chan E (2009) Programming matrix algorithms-by-blocks for thread-level parallelism. ACM Trans Math Softw 36(3):14:1–14:2

Antimicrobial stewardship programs in solid-organ transplant recipients in Switzerland.

INTRODUCTION: Antimicrobial stewardship programs (ASPs) are essential for minimizing the emergence of antimicrobial resistance, while improving patient outcomes. The current status of ASP in the field of organ transplantation in Switzerland has not been well characterized. METHODS: We describe in this article the current status of ASP and discuss challenges and opportunities of implementing ASP dedicated to solid-organ transplant (SOT) recipients in Switzerland. RESULTS: ASP have been implemented in the Swiss healthcare system over the last years, although specific strategies for SOT recipients are mostly based on transplant infectious diseases (TID) consultations rather than structured institutional interventions. Even so, there is a unique opportunity for developing a successful ASP in Switzerland that also specifically addresses areas of practice relevant to SOT recipients. This is due to the existent network of TID specialists in close collaboration with transplant physicians, the small number of centers involved in the care of transplant recipients, and the development of the Swiss Transplant Cohort Study (STCS), a prospective nationwide cohort of SOT recipients in Switzerland. The STCS can identify actual challenges through the updated reports on the epidemiology on transplant infections, accurately monitor the impact of potential antimicrobial stewardship interventions, and represent an opportunity for nesting of pragmatic randomized controlled trials to address key questions about optimized antibiotic use for SOT recipients. CONCLUSIONS: Although ASP in SOT recipients rely more on specific TID consultations than in general antimicrobial stewardship teams, we identified several opportunities for the implementation of a successful ASP in Switzerland