System Level Synthesis via Dynamic Programming

System Level Synthesis (SLS) parametrization facilitates controller synthesis for large, complex, and distributed systems by incorporating system level constraints (SLCs) into a convex SLS problem and mapping its solution to stable controller design. Solving the SLS problem at scale efficiently is challenging, and current attempts take advantage of special system or controller structures to speed up the computation in parallel. However, those methods do not generalize as they rely on the specific system/controller properties. We argue that it is possible to solve general SLS problems more efficiently by exploiting the structure of SLS constraints. In particular, we derive dynamic programming (DP) algorithms to solve SLS problems. In addition to the plain SLS without any SLCs, we extend DP to tackle infinite horizon SLS approximation and entrywise linear constraints, which form a superclass of the locality constraints. Comparing to convex program solver and naive analytical derivation, DP solves SLS 4 to 12 times faster and scales with little computation overhead. We also quantize the cost of synthesizing a controller that stabilizes the system in a finite horizon through simulations

Distributed Linear Quadratic Regulator Robust to Communication Dropouts

We present a solution to deal with information package dropouts in distributed controllers for large-scale networks. We do this by leveraging the System Level Synthesis approach, a control framework particularly suitable for large-scale networks that addresses information exchange in a very transparent manner. To this end, we propose two different schemes for controller synthesis and implementation. The first one synthesizes a controller inherently robust to dropouts, which is later implemented in an offline fashion. For the second approach, we synthesize a collection of controllers offline and then switch between different controllers online depending on the current dropouts detected in the system. The two approaches are illustrated and compared by means of a simulation example.Comment: Accepted contribution to the 21st World Congress of the International Federation of Automatic Control, 202

Benthic oxygen fluxes in a coastal upwelling system (Ria de Vigo, NW Iberia) measured by aquatic eddy covariance

Organic carbon mineralization and nutrient cycling in benthic environments are critically important for their biogeochemical functioning, but are poorly understood in coastal up - welling systems. The main objective of this study was to determine benthic oxygen fluxes in a muddy sediment in the Ria de Vigo (NW Iberian coastal upwelling), by applying the aquatic eddy covariance (AEC) technique during 2 campaigns in different seasons (June and October 2017). The main drivers of benthic fluxes were studied and compared among days in each season and between seasons. The 2 campaigns were characterized by an upwelling-relaxation period followed by a downwelling event, the last of which was due to the extratropical cyclone Ophelia in October. The mean (±SD) seasonal benthic oxygen fluxes were not significantly different for the 2 campaigns despite differences in hydrodynamic and biogeochemical conditions (June: -20.9 ± 7.1 mmol m-2d-1vs. October: -26.5 ± 3.1 mmol m-2d-1). Benthic fluxes were controlled by different drivers depending on the season. June was characterized by sinking labile organic material, which enhanced benthic fluxes in the downwelling event, whereas October had a significantly higher bottom velocity that stimulated the benthic fluxes. Finally, a comparison with a large benthic chamber (0.50 m2) was made during October. Despite methodological differences between AEC and chamber measurements, concurrent fluxes agreed within an acceptable margin (AEC:benthic chamber ratio = 0.78 ± 0.13; mean ± SD). Bottle incubations of water sampled from the chamber interior indicated that mineralization could explain this difference. These results show the importance of using non-invasive techniques such as AEC to resolve benthic flux dynamicsPostprin

Gender and functional CYP2C and NAT2 polymorphisms determine the metabolic profile of metamizole

Metamizole is a pain-killer drug that has been banned in some countries because of its toxicity, but it is still used in many countries due to its effective analgesic and antispasmodic properties. Although large variability in the biodisposition and adverse effects of metamizole are known, factors underlying this variability are poorly understood. We analyzed the urinary recovery of metabolites, as well as the association of these profiles with genetic and non-genetic factors, in a group of 362 healthy individuals. Gender and functional polymorphisms are strongly related to metabolic profiles. N-demethylation of the active metabolite MAA is diminished in carriers of the CYP2C19*2 allele and in NAT2-slow acetylators. Acetylation of the secondary metabolite AA is decreased in men, in drinkers and in NAT2-slow acetylators with a differential effect of NAT2*5 and NAT2*6 alleles. The formylation of MAA is diminished in older subjects and in carriers of defect CYP2C9 and CYP2C19 alleles. Two novel arachidonoyl metabolites were identified for the first time in humans. Women and NAT2-slow acetylators show higher concentrations, whereas the presence of the rapid CYP2C19*17 allele is associated with lower concentrations of these metabolites. All genetic associations show a gene-dose effect. We identified for the first time genetic and non-genetic factors related to the oxidative metabolism of analgesic drug metamizole, as well as new active metabolites in humans. The phenotypic and genetic factors identified in this study have a potential application as biomarkers of metamizole biotransformation and toxicity.We are grateful to Prof. James McCue for assistance in language editing. Financed by grants PS09/00943, PS09/00469, PI12/00241, PI12/00324 and RETICS RD07/0064/0016 and RD12/0013/0002 and RD12/0013/0009 from Fondo de Investigacion Sanitaria, Instituto de Salud Carlos III, Madrid, Spain; GR10068 from Junta de Extremadura, Spain. Financed in part with FEDER funds from the European Union. I.A. is supported by a Servet Contract CP11/00154.Martínez, C.; Andreu Ros, MI.; Amo, G.; Miranda Alonso, MÁ.; Esguevillas, G.; Torres, MJ.; Blanca López, N.... (2014). Gender and functional CYP2C and NAT2 polymorphisms determine the metabolic profile of metamizole. Biochemical Pharmacology. 92(3):457-466. https://doi.org/10.1016/j.bcp.2014.09.005S45746692

Epidemiologic Features and Control Measures during Monkeypox Outbreak, Spain, June 2022

During June 2022, Spain was one of the countries most affected worldwide by a multicountry monkeypox outbreak with chains of transmission without identified links to disease-endemic countries. We provide epidemiologic features of cases reported in Spain and the coordinated measures taken to respond to this outbreak.S

Validation of the Spanish Version of the ICECAP-O for Nursing Home Residents with Dementia

Background Measurement of health-related quality of life (HRQoL) is important for a chronic disease, such as dementia, which impairs the quality of life of affected patients in addition to their length of life. This is important in the context of economic evaluations when interventions do not (only) affect HRQoL and these other factors also affect overall quality of life. Objective To validate the Spanish translation of the ICECAP-O's capability to measure Health-related quality of life in elderly with dementia who live in nursing homes. Method Cross-sectional study. For 217 residents living in 8 Spanish nursing homes, questionnaires were completed by nursing professionals serving as proxy respondents. We analyzed the internal consistency and other psychometric properties. We investigated the convergent validity of the ICECAP-O with other HRQoL instruments, the EQ-5D extended with a cognitive dimension (EQ-5D+C), the Alzheimer's Disease Related Quality of Life (ADRQL) measures, and the Barthel Index measure of activities of daily living (ADL). Results The ICECAP-O presents satisfactory internal consistency (alpha 0.820). The factorial analysis indicated a structure of five principal dimensions that explain 66.57% of the total variance. Convergent validity between the ICECAP-O, EQ-5D+C, ADRQL, and Barthel Index scores was moderate to good (with correlations of 0.62, 0.61, and 0.68, respectively), but differed between dimensions of the instruments. Discriminant validity was confirmed by finding differences in ICECAP-O scores between subgroups based on ADL scores (0.70 low, 0.59 medium, and 0.39 high level care), dementia severity (0.72 mild, 0.63 medium, and 0.50 severe), and ages (0.59 below 75 years and 0.84 above 75 years). Conclusions This study presented the first use of a Spanish version of the ICECAP-O. The results indicate that the ICECAP-O appears to be a reliable Health-related quality of life measurement instrument showing good convergent and discriminant validity for people with dementia

Using Interpretable Machine Learning to Identify Baseline Predictive Factors of Remission and Drug Durability in Crohn’s Disease Patients on Ustekinumab

Ustekinumab has shown efficacy in Crohn's Disease (CD) patients. To identify patient profiles of those who benefit the most from this treatment would help to position this drug in the therapeutic paradigm of CD and generate hypotheses for future trials. The objective of this analysis was to determine whether baseline patient characteristics are predictive of remission and the drug durability of ustekinumab, and whether its positioning with respect to prior use of biologics has a significant effect after correcting for disease severity and phenotype at baseline using interpretable machine learning. Patients' data from SUSTAIN, a retrospective multicenter single-arm cohort study, were used. Disease phenotype, baseline laboratory data, and prior treatment characteristics were documented. Clinical remission was defined as the Harvey Bradshaw Index <= 4 and was tracked longitudinally. Drug durability was defined as the time until a patient discontinued treatment. A total of 439 participants from 60 centers were included and a total of 20 baseline covariates considered. Less exposure to previous biologics had a positive effect on remission, even after controlling for baseline disease severity using a non-linear, additive, multivariable model. Additionally, age, body mass index, and fecal calprotectin at baseline were found to be statistically significant as independent negative risk factors for both remission and drug survival, with further risk factors identified for remission

Long-Term Real-World Effectiveness and Safety of Ustekinumab in Crohn’s Disease Patients: The SUSTAIN Study

Background Large real-world-evidence studies are required to confirm the durability of response, effectiveness, and safety of ustekinumab in Crohn’s disease (CD) patients in real-world clinical practice. Methods A retrospective, multicentre study was conducted in Spain in patients with active CD who had received ≥1 intravenous dose of ustekinumab for ≥6 months. Primary outcome was ustekinumab retention rate; secondary outcomes were to identify predictive factors for drug retention, short-term remission (week 16), loss of response and predictive factors for short-term efficacy and loss of response, and ustekinumab safety. Results A total of 463 patients were included. Mean baseline Harvey-Bradshaw Index was 8.4. A total of 447 (96.5%) patients had received prior biologic therapy, 141 (30.5%) of whom had received ≥3 agents. In addition, 35.2% received concomitant immunosuppressants, and 47.1% had ≥1 abdominal surgery. At week 16, 56% had remission, 70% had response, and 26.1% required dose escalation or intensification; of these, 24.8% did not subsequently reduce dose. After a median follow-up of 15 months, 356 (77%) patients continued treatment. The incidence rate of ustekinumab discontinuation was 18% per patient-year of follow-up. Previous intestinal surgery and concomitant steroid treatment were associated with higher risk of ustekinumab discontinuation, while a maintenance schedule every 12 weeks had a lower risk; neither concomitant immunosuppressants nor the number of previous biologics were associated with ustekinumab discontinuation risk. Fifty adverse events were reported in 39 (8.4%) patients; 4 of them were severe (2 infections, 1 malignancy, and 1 fever). Conclusions Ustekinumab is effective and safe as short- and long-term treatment in a refractory cohort of CD patients in real-world clinical practice