Comparación de pruebas para la detección de Virus de Papiloma Humano (VPH) en cérvix y orina de mujeres infectadas con Virus de Inmunodeficiencia Humana (VIH)

En el desarrollo y progresión de Cáncer de Cérvix (CC), además de la infección con Virus de Papiloma Humano (VPH), existen factores asociados como la inmunosupresión ocasionada por el Virus de Inmunodeficiencia Humana (VIH). Los programas de prevención de CC basados en la citología, presentan limitaciones que han llevado a explorar muestras alternativas como la de orina. El objetivo de este trabajo fue determinar las frecuencias de infección y distribución tipo-especifica de VPH en cérvix y orina en mujeres VIH positivas, y establecer sus características operativas. Se determinó una alta prevalencia de infección por VPH (70,1% en cérvix y 63,9% en orina), siendo el tipo VPH-16 el más prevalente en los dos tipos de muestra. Las características operativas de las dos fuentes de muestra fueron comparables. Adicionalmente, se encontró una asociación positiva entre anormalidad cervical y la detección viral en orina. En conclusión, la detección de VPH en muestra de orina es una herramienta que contribuye en el mejoramiento de los programas de tamización cervical, por su economía, practicidad, aceptabilidad y características operativas similares a las ofrecidas por la muestra cervical.Abstract: In addition to the infection with Human Papillomavirus (HPV), other factors are associated with the development and progression of Cervical Cancer (CC), such as the immunosuppression caused by the Human Immunodeficiency Virus (HIV). The CC prevention programs based on cytology have certain limitations that have led to explore alternative sample sources, such as urine. This study aimed at determining the frequency of infection and type-specific distribution of HPV in cervical and urine samples from HIVinfected women, and to determine the operative characteristics. High prevalence of HPV infection was found (70.1% in cervical and 63.9% in urine samples, respectively); HPV-16 was the most prevalent viral type in both sample sources, being the operating characteristics of them comparable. Positive association was found between cervical abnormalities and viral detection in urine. In conclusion, the detection of HPV in urine might become a useful tool to improve cervical screening programs due to its low cost, ease to obtain, acceptability and operational characteristics similar to those offered by the cervical sample.Maestrí

POWAR: Power-Aware Routing in HPC Networks with On/Off Links

[EN] In order to save energy in HPC interconnection networks, one usual proposal is to switch idle links into a low-power mode after a certain time without any transmission, as IEEE Energy Efficient Ethernet standard proposes. Extending the low-power mode mechanism, we propose POWer-Aware Routing (POWAR), a simple power-aware routing and selection function for fat-tree and torus networks. POWAR adapts the amount of network links that can be used, taking into account the network load, and obtaining great energy savings in the network (55%-65%) and the entire system (9%-10%) with negligible performance overhead.This work has been supported by the Spanish MINECO and European Commission (FEDER funds) under project TIN2015-66972-C5-1-R. Francisco J. Andujar has been partially funded by the Spanish MICINN and by the ERDF program of the European Union: PCAS Project (TIN2017-88614-R), CAPAP-H6 (TIN2016-81840-REDT), and Junta de Castilla y Leon FEDER Grant VA082P17 (PROPHET Project).Andújar-Muñoz, FJ.; Coll, S.; Alonso Díaz, M.; López Rodríguez, PJ.; Martínez-Rubio, J. (2019). POWAR: Power-Aware Routing in HPC Networks with On/Off Links. ACM Transactions on Architecture and Code Optimization. 15(4):1-22. https://doi.org/10.1145/3293445S122154Abts, D., Marty, M. R., Wells, P. M., Klausler, P., & Liu, H. (2010). Energy proportional datacenter networks. Proceedings of the 37th annual international symposium on Computer architecture - ISCA ’10. doi:10.1145/1815961.1816004Adiga, N. R., Blumrich, M. A., Chen, D., Coteus, P., Gara, A., Giampapa, M. E., … Vranas, P. (2005). Blue Gene/L torus interconnection network. IBM Journal of Research and Development, 49(2.3), 265-276. doi:10.1147/rd.492.0265M. Alonso S. Coll J. M. Martínez V. Santonja and P. López. 2015. Power consumption management in fat-tree interconnection networks. Parallel Comput. 48 C (Oct. 2015) 59--80. 10.1016/j.parco.2015.03.007 M. Alonso S. Coll J. M. Martínez V. Santonja and P. López. 2015. Power consumption management in fat-tree interconnection networks. Parallel Comput. 48 C (Oct. 2015) 59--80. 10.1016/j.parco.2015.03.007Marina Alonso, Coll, S., Martínez, J.-M., Santonja, V., López, P., & Duato, J. (2010). Power saving in regular interconnection networks. Parallel Computing, 36(12), 696-712. doi:10.1016/j.parco.2010.08.003Bob Alverson Edwin Froese Larry Kaplan and Duncan Roweth. 2012. Cray XC series network. Cray Inc. White Paper WP-Aries01-1112 (2012). Bob Alverson Edwin Froese Larry Kaplan and Duncan Roweth. 2012. Cray XC series network. Cray Inc. White Paper WP-Aries01-1112 (2012).Anderson, T. E., Owicki, S. S., Saxe, J. B., & Thacker, C. P. (1993). High-speed switch scheduling for local-area networks. ACM Transactions on Computer Systems, 11(4), 319-352. doi:10.1145/161541.161736Andujar, F. J., Villar, J. A., Sanchez, J. L., Alfaro, F. J., & Escudero-Sahuquillo, J. (2015). VEF Traces: A Framework for Modelling MPI Traffic in Interconnection Network Simulators. 2015 IEEE International Conference on Cluster Computing. doi:10.1109/cluster.2015.141Barroso, L. A., & Hölzle, U. (2007). The Case for Energy-Proportional Computing. Computer, 40(12), 33-37. doi:10.1109/mc.2007.443Camacho, J., & Flich, J. (2011). HPC-Mesh: A Homogeneous Parallel Concentrated Mesh for Fault-Tolerance and Energy Savings. 2011 ACM/IEEE Seventh Symposium on Architectures for Networking and Communications Systems. doi:10.1109/ancs.2011.17Chen, D., Parker, J. J., Eisley, N. A., Heidelberger, P., Senger, R. M., Sugawara, Y., … Steinmacher-Burow, B. (2011). The IBM Blue Gene/Q interconnection network and message unit. Proceedings of 2011 International Conference for High Performance Computing, Networking, Storage and Analysis on - SC ’11. doi:10.1145/2063384.2063419Chen, L., & Pinkston, T. M. (2012). NoRD: Node-Router Decoupling for Effective Power-gating of On-Chip Routers. 2012 45th Annual IEEE/ACM International Symposium on Microarchitecture. doi:10.1109/micro.2012.33Christensen, K., Reviriego, P., Nordman, B., Bennett, M., Mostowfi, M., & Maestro, J. (2010). IEEE 802.3az: the road to energy efficient ethernet. IEEE Communications Magazine, 48(11), 50-56. doi:10.1109/mcom.2010.5621967Dally, & Seitz. (1987). Deadlock-Free Message Routing in Multiprocessor Interconnection Networks. IEEE Transactions on Computers, C-36(5), 547-553. doi:10.1109/tc.1987.1676939Das, R., Narayanasamy, S., Satpathy, S. K., & Dreslinski, R. G. (2013). Catnap. Proceedings of the 40th Annual International Symposium on Computer Architecture - ISCA ’13. doi:10.1145/2485922.2485950Derradji, S., Palfer-Sollier, T., Panziera, J.-P., Poudes, A., & Atos, F. W. (2015). The BXI Interconnect Architecture. 2015 IEEE 23rd Annual Symposium on High-Performance Interconnects. doi:10.1109/hoti.2015.15Jack Dongarra Hans W. Meuer and Erich Strohmaier. 2018. TOP500 Supercomputer Sites. Retrieved from https://www.top500.org. Jack Dongarra Hans W. Meuer and Erich Strohmaier. 2018. TOP500 Supercomputer Sites. Retrieved from https://www.top500.org.Duato, J. (1993). A new theory of deadlock-free adaptive routing in wormhole networks. IEEE Transactions on Parallel and Distributed Systems, 4(12), 1320-1331. doi:10.1109/71.250114José Duato Sudhakar Yalamanchili and Lionel Ni. 2003. Interconnection Networks. An Engineering Approach. Morgan Kaufmann Publishers Inc. San Francisco CA. José Duato Sudhakar Yalamanchili and Lionel Ni. 2003. Interconnection Networks. An Engineering Approach. Morgan Kaufmann Publishers Inc. San Francisco CA.GALGO 2017. GALGO—Albacete Research Institute of Informatics Supercomputer Center homepage. Retrieved from http://www.i3a.uclm.es/galgo. GALGO 2017. GALGO—Albacete Research Institute of Informatics Supercomputer Center homepage. Retrieved from http://www.i3a.uclm.es/galgo.Greenberg, A., Hamilton, J., Maltz, D. A., & Patel, P. (2008). The cost of a cloud. ACM SIGCOMM Computer Communication Review, 39(1), 68-73. doi:10.1145/1496091.1496103HPCC {n.d.}. HPC Challenge Benchmark. Retrieved from http://icl.cs.utk.edu/hpcc/index.html. HPCC {n.d.}. HPC Challenge Benchmark. Retrieved from http://icl.cs.utk.edu/hpcc/index.html.Hluchyj, M. G., & Karol, M. J. (1988). Queueing in high-performance packet switching. IEEE Journal on Selected Areas in Communications, 6(9), 1587-1597. doi:10.1109/49.12886Koibuchi, M., Otsuka, T., Hiroki Matsutani, & Amano, H. (2009). An on/off link activation method for low-power ethernet in PC clusters. 2009 IEEE International Symposium on Parallel & Distributed Processing. doi:10.1109/ipdps.2009.5161069Phillips, J. C., Braun, R., Wang, W., Gumbart, J., Tajkhorshid, E., Villa, E., … Schulten, K. (2005). Scalable molecular dynamics with NAMD. Journal of Computational Chemistry, 26(16), 1781-1802. doi:10.1002/jcc.20289Pronk, S., Páll, S., Schulz, R., Larsson, P., Bjelkmar, P., Apostolov, R., … Lindahl, E. (2013). GROMACS 4.5: a high-throughput and highly parallel open source molecular simulation toolkit. Bioinformatics, 29(7), 845-854. doi:10.1093/bioinformatics/btt055Reviriego, P., Hernandez, J., Larrabeiti, D., & Maestro, J. (2009). Performance evaluation of energy efficient ethernet. IEEE Communications Letters, 13(9), 697-699. doi:10.1109/lcomm.2009.090880K. P. Saravanan and P. Carpenter. 2018. PerfBound: Conserving energy with bounded overheads in on/off-based HPC interconnects. IEEE Trans. Comput. (2018) 1--1. 10.1109/TC.2018.2790394 K. P. Saravanan and P. Carpenter. 2018. PerfBound: Conserving energy with bounded overheads in on/off-based HPC interconnects. IEEE Trans. Comput. (2018) 1--1. 10.1109/TC.2018.2790394Saravanan, K. P., Carpenter, P. M., & Ramirez, A. (2013). Power/performance evaluation of energy efficient Ethernet (EEE) for High Performance Computing. 2013 IEEE International Symposium on Performance Analysis of Systems and Software (ISPASS). doi:10.1109/ispass.2013.6557171Soteriou, V., & Li-Shiuan Peh. (s. f.). Dynamic power management for power optimization of interconnection networks using on/off links. 11th Symposium on High Performance Interconnects, 2003. Proceedings. doi:10.1109/conect.2003.1231472Totoni, E., Jain, N., & Kale, L. V. (2013). Toward Runtime Power Management of Exascale Networks by on/off Control of Links. 2013 IEEE International Symposium on Parallel & Distributed Processing, Workshops and Phd Forum. doi:10.1109/ipdpsw.2013.191VEF 2017. 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Creación de un entorno pedagógico que reproduzca el sistema y las condiciones de trabajo de una agencia de comunicación: La agencia junior “El Estudio”

La Agencia de Comunicación Junior El Estudio fue creada en julio 2015 por el Prof. Giorgio De Marchis para atender las necesidades formativas de los alumnos de Publicidad y Relaciones Públicas de la Universidad Complutense de Madrid (UCM). La idea era crear una agencia formada y gestionada por estudiantes para ofrecer servicios de comunicación a empresas startups

Energy efficient HPC network topologies with on/off links

[EN] Energy efficiency is a must in today HPC systems. To achieve this goal, a holistic design based on the use of power-aware components should be performed. One of the key components of an HPC system is the high-speed interconnect. In this paper, we compare and evaluate several design options for the interconnection network of an HPC system, including torus, fat-trees and dragonflies. State of the art low power modes are also used in the interconnection networks. The paper does not only consider energy efficiency at the interconnection network level but also at the system as a whole.The analysis is performed by using a simple yet realistic power model of the system. The model has been adjusted using actual power consumption values measured on a real system. Using this model, realistic multi-job trace-based workloads have been used, obtaining the execution time and energy consumed. The results are presented to ease choosing a system, depending on which parameter, performance or energy consumption, receives the most importance.This work has been supported by the Spanish Ministerio de Ciencia e Innovacion (MICINN, formerly MINECO) , and the European Commission (FEDER funds) under the projects PID2019- 105903RB-100 and PID2021-123627OB-C5, and by Junta de Comunidades de Castilla -La Mancha under the project SBPLY/21/180501/000248.Andújar-Muñoz, FJ.; Coll, S.; Alonso Díaz, M.; Martínez-Rubio, J.; López Rodríguez, PJ.; Sánchez García, JL.; Alfaro Cortés, FJ. (2023). Energy efficient HPC network topologies with on/off links. Future Generation Computer Systems. 139:126-138. https://doi.org/10.1016/j.future.2022.09.01212613813

Use of Eculizumab in Pediatric Patients With Transplant Associated Thrombotic Microangiopathy

Complement inhibitor; Eculizumab; Hematopoietic stem cell transplant (HSCT)Inhibidor del complemento; Eculizumab; Trasplante de células madre hematopoyéticas (TCMH)Inhibidor del complement; Eculizumab; Trasplantament de cèl·lules mare hematopoètiques (HSCT)Background: Transplant-associated thrombotic microangiopathy (TA-TMA) is a serious complication of hematopoietic stem cell transplantation (HSCT) associated with high morbidity and mortality. High-risk TA-TMA (hrTA-TMA) is characterized by multifactorial endothelial damage caused by environmental stressors, dysregulation of the complement system, and genetic predisposition. Complement inhibitors have significantly decreased mortality and are the current treatment of choice. In this article, we describe our experience with the use of eculizumab in pediatric patients diagnosed with hrT-TMA after HSCT. Method: Retrospective study of pediatric patients with hrTA-TMA treated with eculizumab between January 2016 and December 2020. Results: Four pediatric patients aged 1, 12, 14, and 17 years at the time of HSCT were diagnosed with hrTA-TMA and treated with eculizumab during the study. At diagnosis, they all had renal impairment with proteinuria, and hypertension under treatment with at least two antihypertensive drugs. The patient who presented multisystemic involvement died instead of treatment. The three patients with exclusive renal involvement achieved TA-TMA resolution after treatment with eculizumab for 65, 52, and 40.6 weeks and were able to stop treatment. The two patients with follow-up data one year after eculizumab withdrawal sustained a favorable response. Eculizumab was well tolerated, and with adequate vaccination and antibiotic prophylaxis, did not increase the risk of infection. Conclusions: Eculizumab appears to be both safe and effective for the treatment of hrTA-TMA in patients with renal impairment. Early diagnosis and initiation of treatment may improve response. Eculizumab withdrawal can be contemplated in patients who achieve laboratory and clinical resolution of TA-TMA

KRAS4A induces metastatic lung adenocarcinomas in vivo in the absence of the KRAS4B isoform.

In mammals, the KRAS locus encodes two protein isoforms, KRAS4A and KRAS4B, which differ only in their C terminus via alternative splicing of distinct fourth exons. Previous studies have shown that whereas KRAS expression is essential for mouse development, the KRAS4A isoform is expendable. Here, we have generated a mouse strain that carries a terminator codon in exon 4B that leads to the expression of an unstable KRAS4B154 truncated polypeptide, hence resulting in a bona fide Kras4B-null allele. In contrast, this terminator codon leaves expression of the KRAS4A isoform unaffected. Mice selectively lacking KRAS4B expression developed to term but died perinatally because of hypertrabeculation of the ventricular wall, a defect reminiscent of that observed in embryos lacking the Kras locus. Mouse embryonic fibroblasts (MEFs) obtained from Kras4B-/- embryos proliferated less than did wild-type MEFs, because of limited expression of KRAS4A, a defect that can be compensated for by ectopic expression of this isoform. Introduction of the same terminator codon into a Kras FSFG12V allele allowed expression of an endogenous KRAS4AG12V oncogenic isoform in the absence of KRAS4B. Exposure of Kras +/FSF4AG12V4B- mice to Adeno-FLPo particles induced lung tumors with complete penetrance, albeit with increased latencies as compared with control Kras +/FSFG12V animals. Moreover, a significant percentage of these mice developed proximal metastasis, a feature seldom observed in mice expressing both mutant isoforms. These results illustrate that expression of the KRAS4AG12V mutant isoform is sufficient to induce lung tumors, thus suggesting that selective targeting of the KRAS4BG12V oncoprotein may not have significant therapeutic consequences.We thank Marta San Roman, Raquel Villar, and Nuria Cabrera for excellent technical assistance; Mayte Lamparero and Isabel Blanco (Animal Facility) for mouse work; the Histopathology Unit for processing of mouse tissues; Lola Martinez (Flow Cytometry Unit) for her help with flow cytometry analyses; Diego Megias and Manuel Perez (Confocal Microscopy Unit) for assistance with confocal microscopy; and the Mouse Genome Editing Unit for support with the generation of the mouse strains described here. We also thank Ignacio Perez de Castro (Instituto de Salud Carlos III, Madrid, Spain) for sharing the EGFP-KRAS4B plasmid and Orlando Dominguez (Genomics Unit) and Pedro P. Lopez-Casas (Clinical Research Program) for their advice on exome sequencing. This work was supported by grants from the European Research Council (ERC-2015-AdG/695566, THERACAN), the Spanish Ministry of Science, Innovation and Universities (RTC-2017-6576-1), and the Autonomous Community of Madrid (B2017/BMD-3884 iLUNG-CM); a grant from the CRIS Cancer Foundation (to M.B.); and a grant from the Spanish Ministry of Science, Innovation and Universities (RTI2018-094664-B-I00, to M.B. and M.M.). M.B. is a recipient of an Endowed Chair from the AXA Research Fund. M.S. was supported by predoctoral contract "Severo Ochoa" (BES-2016-079096) from the SpanishMinistry of Science, Innovation and Universities. G.P. was a recipient of a "Young Ph.D." grant from the Government of the Community of Madrid. F.F.-G. was supported by a formacion de profesorado universitario (FPU) fellowship from the Spanish Ministry of Science, Innovation and Universities.S

The Response to Biologics is Better in Patients with Severe Asthma Than in Patients with Asthma–COPD Overlap Syndrome

Although biologics have demonstrated to be effective in T2-high asthma patients, there is little experience with these drugs in asthma-COPD overlap (ACO). The aim of this study was to compare the effectiveness of biologics in these two conditions. We included 318 patients (24 ACO and 297 asthma) treated with monoclonal antibodies and followed for at least 12 months Omalizumab was the most frequently employed biologic agent both in patients with ACO and asthma. Asthma control test (ACT) scores after at least 12 months of biologic therapy were not significantly different between groups. The percentage of patients with >= 1 exacerbation and >= 1 corticosteroid burst was significantly higher in ACO patients (70.8 vs 27.3 and 83.3% vs 37.5%, respectively), whereas the percentage of controlled patients (with no exacerbations, no need for corticosteroids and ACT >= 20) was significantly lower (16.7% vs 39.7%). In conclusion, this report suggests that patients with ACO treated with biologics reach worse outcomes than asthma patients