Different aspects of workflow scheduling in large-scale distributed systems

As large-scale distributed systems gain momentum, the scheduling of workflow applications with multiple requirements in such computing platforms has become a crucial area of research. In this paper, we investigate the workflow scheduling problem in large-scale distributed systems, from the Quality of Service (QoS) and data locality perspectives. We present a scheduling approach, considering two models of synchronization for the tasks in a workflow application: (a) communication through the network and (b) communication through temporary files. Specifically, we investigate via simulation the performance of a heterogeneous distributed system, where multiple soft real-time workflow applications arrive dynamically. The applications are scheduled under various tardiness bounds, taking into account the communication cost in the first case study and the I/O cost and data locality in the second.The work presented in this paper has been partially supported by EU, under the COST program Action IC1305, “Network for Sustainable Ultrascale Computing (NESUS)”, and by the Ministerio de Economía y Competitividad, Spain, under the project TIN2013-41350-P, “Scalable Data Management Techniques for High-End Computing Systems”

Cell cycle-dependent expression of Kv3.4 channels modulates proliferation of human uterine artery smooth muscle cells

Producción CientíficaAims: Vascular smooth muscle cell (VSMC) proliferation is involved in cardiovascular pathologies associated with unwanted arterial wall remodelling. Coordinated changes in the expression of several K+ channels have been found to be important elements in the phenotypic switch of VSMCs towards proliferation. We have previously demonstrated the association of functional expression of Kv3.4 channels with proliferation of human uterine VSMCs. Here, we sought to gain deeper insight on the relationship between Kv3.4 channels and cell cycle progression in this preparation. Methods and results: Expression and function of Kv3.4 channels along the cell cycle was explored in uterine VSMCs synchronized at different checkpoints, combining real-time PCR, western blotting, and electrophysiological techniques. Flow cytometry, Ki67 expression and BrdU incorporation techniques allowed us to explore the effects of Kv3.4 channels blockade on cell cycle distribution. We found cyclic changes in Kv3.4 and MiRP2 mRNA and protein expression along the cell cycle. Functional studies showed that Kv3.4 current amplitude and Kv3.4 channels contribution to cell excitability increased in proliferating cells. Finally, both Kv3.4 blockers and Kv3.4 knockdown with siRNA reduced the proportion of proliferating VSMCs. Conclusion: Our data indicate that Kv3.4 channels exert a permissive role in the cell cycle progression of proliferating uterine VSMCs, as their blockade induces cell cycle arrest after G2/M phase completion. The modulation of resting membrane potential (VM) by Kv3.4 channels in proliferating VSMCs suggests that their role in cell cycle progression could be at least in part mediated by their contribution to the hyperpolarizing signal needed to progress through the G1 phase.Ministerio de Sanidad, Consumo y Bienestar Social - Instituto de Salud Carlos III (grants R006/009 and PI041044)Ministerio de Ciencia, Innovación y Universidades (grants BFU2004-05551 and BFU2007-61524)Junta de Castilla y León (grant GR242

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

DPPX modifies TEA sensitivity of the Kv4 channels in rabbit carotid body chemoreceptor cells

El pdf del trabajo es la versión post-print.Chemoreceptor cells from rabbit carotid body (CB) exhibit transient outward currents reversibly inhibited by low P(o2). Molecular and functional dissection of the components of these outward currents indicates that at least two different channels (Kv4.3 and Kv3.4) contribute to this current. Furthermore, several lines of evidence support the conclusion that Kv4 channel subfamily members (either Kv4.3 alone or Kv4.3/Kv4.1 heteromultimers) are the oxygen sensitive K channels (K(o2)) in rabbit CB chemoreceptor cells. However, the pharmacological characterization of these currents shows that they are almost completely blocked by high external TEA concentrations, while Kv4 channels have been shown to be TEA-insensitive. We hypothesized that the expression of regulatory subunits in chemoreceptor cells could modify TEA sensitivity of Kv4 channels. Here, we explore the presence and functional contribution of DPPX to K(o2) currents in rabbit CB chemoreceptor cells by using DPPX functional knockdown with siRNA. Our data suggest that DPPX proteins are integral components of K(o2) currents, and that their association with Kv4 subunits modulate the pharmacological profile of the heteromultimers.This work was supported by Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III grants R006/009 (Red Heracles) and PI041044 (JRLL), Ministerio de Educación y Ciencia grant BFU2004-05551 (MTPG) and Junta de Castilla y León grant VA011C05.Peer Reviewe

Functional contribution of DPPX to transient outward K currents of rabbit CB chemoreceptor cells

(A) Validation of siRNA DPPX was performed, quantifying the amount of DPPX protein by Western blot and the amount of DPPX mRNA by real-time PCR. The figure shows a Western blot of lysates from HEK cells untransfected (control lane) or transfected with DPPX alone (DPPX) or DPPX+DPPX siRNA (siRNA lane), probed with anti-DPPX antibody. The arrow indicates the estimated molecular weight of DPPX protein. The reduction of the levels of DPPX mRNA was determined by qRT-PCR and analyzed with the 2 method as described in the Materials and methods section. Total mRNA was extracted from HEK cells transfected with rabbit DPPX alone or in combination with DPPX siRNA as indicated in the figure. (B) Currents recorded from two individual CB chemoreceptor cells after electroporation of GFP + negative control siRNA (siRNA nC) or GFP+DPPX siRNA (siRNA DPPX). In both cases, the currents were elicited with the voltage protocol shown at the bottom, in which 500-ms depolarizing steps to +40 mV follow 6.5-s prepulses to two different potentials, −80 mV (thicker trace) and 0 mV (thinner trace). The difference between the current amplitude at +40 mV in these two pulses is defined throughout the paper as the transient outward current. The black thick line shows the fit of the currents to a double-exponential function. (C) Inactivation fitting parameters obtained in both conditions (control and siRNA cells) indicate a significant change in the relative amplitudes of the two components of inactivation, A and A. The bar plot shows the relative proportion of the fast component. Data are mean ± SEM of 8–10 cells in each group; *, P < 0.05. (D) Peak current densities recorded in control or siRNA DPPX electroporated cells were obtained with the two pulse protocol described in B. I represents the peak current amplitude at +40 mV after the −80-mV prepulse, I was calculated as indicated above, and I is the current amplitude at +40 mV after the 0-mV prepulse. *, P < 0.05, = 10 cells in each group. (E) The normalized steady-state inactivation curves and the conductance–voltage curves from the two groups of cells were obtained and constructed as described in . Lines represent the best fit of the data to Boltzmann functions. Each point is the mean ± SEM of 8–10 determinations. The bar plot shows the differences in the V for activation obtained from the individual fit of the cells in both groups.<p><b>Copyright information:</b></p><p>Taken from "A Role for DPPX Modulating External TEA Sensitivity of Kv4 Channels"</p><p></p><p>The Journal of General Physiology 2008;131(5):455-471.</p><p>Published online Jan 2008</p><p>PMCID:PMC2346566.</p><p></p

Consensus document for severe asthma in adults. 2022 update Documento de consenso de asma grave en adultos. Actualización 2022

Severe asthma is a heterogeneous syndrome with several clinical variants and often represents a complex disease requiring a specialized and multidisciplinary approach, as well as the use of multiple drugs. The prevalence of severe asthma varies from one country to another, and it is estimated that 50% of these patients present a poor control of their disease. For the best management of the patient, it is necessary a correct diagnosis, an adequate follow-up and undoubtedly to offer the best available treatment, including biologic treatments with monoclonal antibodies. With this objective, this consensus process was born, which began in its first version in 2018, whose goal is to offer the patient the best possible management of their disease in order to minimize their symptomatology. For this 2020 consensus update, a literature review was conducted by the authors. Subsequently, through a two-round interactive Delphi process, a broad panel of asthma experts from SEPAR and the regional pulmonology societies proposed the recommendations and conclusions contained in this document

Patients awaiting surgery for neurosurgical diseases during the first wave of the COVID-19 pandemic in Spain: a multicentre cohort study.

The large number of infected patients requiring mechanical ventilation has led to the postponement of scheduled neurosurgical procedures during the first wave of the COVID-19 pandemic. The aims of this study were to investigate the factors that influence the decision to postpone scheduled neurosurgical procedures and to evaluate the effect of the restriction in scheduled surgery adopted to deal with the first outbreak of the COVID-19 pandemic in Spain on the outcome of patients awaiting surgery. This was an observational retrospective study. A tertiary-level multicentre study of neurosurgery activity between 1 March and 30 June 2020. A total of 680 patients awaiting any scheduled neurosurgical procedure were enrolled. 470 patients (69.1%) were awaiting surgery because of spine degenerative disease, 86 patients (12.6%) due to functional disorders, 58 patients (8.5%) due to brain or spine tumours, 25 patients (3.7%) due to cerebrospinal fluid (CSF) disorders and 17 patients (2.5%) due to cerebrovascular disease. The primary outcome was mortality due to any reason and any deterioration of the specific neurosurgical condition. Second, we analysed the rate of confirmed SARS-CoV-2 infection. More than one-quarter of patients experienced clinical or radiological deterioration. The rate of worsening was higher among patients with functional (39.5%) or CSF disorders (40%). Two patients died (0.4%) during the waiting period, both because of a concurrent disease. We performed a multivariate logistic regression analysis to determine independent covariates associated with maintaining the surgical indication. We found that community SARS-CoV-2 incidence (OR=1.011, p Patients awaiting neurosurgery experienced significant collateral damage even when they were considered for scheduled procedures