Universidad Andrés Bello

Wilkinson J.L., Boxall A.B., Kolpin D.W., Leung K.M., Lai R.W., Galbán-Malagón C., Adell A.D., Mondon J., Metian M., Marchant R.A., Bouzas-Monroy A., Cuni-Sanchez A., Coors A., Carriquiriborde P., Rojo M., et. al.

Significance Despite growing evidence of the deleterious effects on ecological and human health, little is known regarding the global occurrence of pharmaceuticals in rivers. Studies assessing their occurrence are available for 75 of 196 countries, with most research conducted in North America and Western Europe. This leaves large geographical regions relatively unstudied. Here, we present the findings of a global reconnaissance of pharmaceutical pollution in rivers. The study monitored 1,052 sampling sites along 258 rivers in 104 countries of all continents, thus representing the pharmaceutical fingerprint of 471.4 million people. We show that the presence of these contaminants in surface water poses a threat to environmental and/or human health in more than a quarter of the studied locations globally.

Agarwal A., Rochwerg B., Lamontagne F., Siemieniuk R.A., Agoritsas T., Askie L., Lytvyn L., Leo Y., Macdonald H., Zeng L., Amin W., da Silva A.R., Aryal D., Barragan F.A., Bausch F.J., et. al.

Abstract Updates This is the twelfth version (eleventh update) of the living guideline, replacing earlier versions (available as data supplements). New recommendations will be published as updates to this guideline. Clinical question What is the role of drugs in the treatment of patients with covid-19? Context The evidence base for therapeutics for covid-19 is evolving with numerous randomised controlled trials (RCTs) recently completed and under way. The emerging SARS-CoV-2 variants (such as omicron) and subvariants are also changing the role of therapeutics. This update provides updated recommendations for remdesivir, addresses the use of combination therapy with corticosteroids, interleukin-6 (IL-6) receptor blockers, and janus kinase (JAK) inhibitors in patients with severe or critical covid-19, and modifies previous recommendations for the neutralising monoclonal antibodies sotrovimab and casirivimab-imdevimab in patients with non-severe covid-19. New or updated recommendations • Remdesivir: a conditional recommendation for its use in patients with severe covid-19; and a conditional recommendation against its use in patients with critical covid-19. • Concomitant use of IL-6 receptor blockers (tocilizumab or sarilumab) and the JAK inhibitor baricitinib: these drugs may now be combined, in addition to corticosteroids, in patients with severe or critical covid-19. • Sotrovimab and casirivimab-imdevimab: strong recommendations against their use in patients with covid-19, replacing the previous conditional recommendations for their use. Understanding the new recommendations When moving from new evidence to updated recommendations, the Guideline Development Group (GDG) considered a combination of evidence assessing relative benefits and harms, values and preferences, and feasibility issues. For remdesivir, new trial data were added to a previous subgroup analysis and provided sufficiently trustworthy evidence to demonstrate benefits in patients with severe covid-19, but not critical covid-19. The GDG considered benefits of remdesivir to be modest and of moderate certainty for key outcomes such as mortality and mechanical ventilation, resulting in a conditional recommendation. For baricitinib, the GDG considered clinical trial evidence (RECOVERY) demonstrating reduced risk of death in patients already receiving corticosteroids and IL-6 receptor blockers. The GDG acknowledged that the clinical trials were not representative of the world population and that the risk-benefit balance may be less advantageous, particularly in patients who are immunosuppressed at higher risk of opportunistic infections (such as serious fungal, viral, or bacteria), those already deteriorating where less aggressive or stepwise addition of immunosuppressive medications may be preferred, and in areas where certain pathogens such as HIV or tuberculosis, are of concern. The panel anticipated that there would be situations where clinicians may opt for less aggressive immunosuppressive therapy or to combine medications in a stepwise fashion in patients who are deteriorating. The decision to combine the medications will depend on their availability, and the treating clinician's perception of the risk-benefit balance associated with combination immunosuppressive therapy, particularly in patient populations at risk of opportunistic infections who may have been under-represented in clinical trials. When making a strong recommendation against the use of monoclonal antibodies for patients with covid-19, the GDG considered in vitro neutralisation data demonstrating that sotrovimab and casirivimab-imdevimab evaluated in clinical trials have meaningfully reduced neutralisation activity of the currently circulating variants of SARS-CoV-2 and their subvariants. There was consensus among the panel that the absence of in vitro neutralisation activity strongly suggests absence of clinical effectiveness of these monoclonal antibodies. However, there was also consensus regarding the need for clinical trial evidence in order to confirm clinical efficacy of new monoclonal antibodies that reliably neutralise the circulating strains in vitro. Whether emerging new variants and subvariants might be susceptible to sotrovimab, casirivimab-imdevimab, or other anti-SARS-CoV-2 monoclonal antibodies cannot be predicted. Prior recommendations • Recommended for patients with severe or critical covid-19—strong recommendations for systemic corticosteroids; IL-6 receptor blockers (tocilizumab or sarilumab) in combination with corticosteroids; and baricitinib as an alternative to IL-6 receptor blockers, in combination with corticosteroids. • Recommended for patients with non-severe covid-19 at highest risk of hospitalisation—a strong recommendation for nirmatrelvir/ritonavir; conditional recommendations for molnupiravir and remdesivir. • Not recommended for patients with non-severe covid-19—a conditional recommendation against systemic corticosteroids; a strong recommendation against convalescent plasma; a recommendation against fluvoxamine, except in the context of a clinical trial; and a strong recommendation against colchicine. • Not recommended for patients with non-severe covid-19 at low risk of hospitalisation—a conditional recommendation against nirmatrelvir/ritonavir. • Not recommended for patients with severe or critical covid-19—a recommendation against convalescent plasma except in the context of a clinical trial; and a conditional recommendation against the JAK inhibitors ruxolitinib and tofacitinib. • Not recommended, regardless of covid-19 disease severity—a strong recommendations against hydroxychloroquine and against lopinavir/ritonavir; and a recommendation against ivermectin except in the context of a clinical trial. About this guideline This living guideline from the World Health Organization (WHO) incorporates new evidence to dynamically update recommendations for covid-19 therapeutics. The GDG typically evaluates a therapy when the WHO judges sufficient evidence is available to make a recommendation. While the GDG takes an individual patient perspective in making recommendations, it also considers resource implications, acceptability, feasibility, equity, and human rights. This guideline was developed according to standards and methods for trustworthy guidelines, making use of an innovative process to achieve efficiency in dynamic updating of recommendations. The methods are aligned with the WHO Handbook for Guideline Development and according to a pre-approved protocol (planning proposal) by the Guideline Review Committee (GRC). A box at the end of the article outlines key methodological aspects of the guideline process. MAGIC Evidence Ecosystem Foundation provides methodological support, including the coordination of living systematic reviews with network meta-analyses to inform the recommendations. The full version of the guideline is available online in MAGICapp and in PDF, with a summary version here in The BMJ . These formats should facilitate adaptation, which is strongly encouraged by WHO to contextualise recommendations in a healthcare system to maximise impact. Future recommendations Recommendations on anticoagulation are planned for the next update to this guideline.

Ruiz L.M., Libedinsky A., Elorza A.A.

Copper is essential for life processes like energy metabolism, reactive oxygen species detoxification, iron uptake, and signaling in eukaryotic organisms. Mitochondria gather copper for the assembly of cuproenzymes such as the respiratory complex IV, cytochrome c oxidase, and the antioxidant enzyme superoxide dismutase 1. In this regard, copper plays a role in mitochondrial function and signaling involving bioenergetics, dynamics, and mitophagy, which affect cell fate by means of metabolic reprogramming. In mammals, copper homeostasis is tightly regulated by the liver. However, cellular copper levels are tissue specific. Copper imbalances, either overload or deficiency, have been associated with many diseases, including anemia, neutropenia, and thrombocytopenia, as well as tumor development and cancer aggressivity. Consistently, new pharmacological developments have been addressed to reduce or exacerbate copper levels as potential cancer therapies. This review goes over the copper source, distribution, cellular uptake, and its role in mitochondrial function, metabolic reprograming, and cancer biology, linking copper metabolism with the field of regenerative medicine and cancer.

Seron P., Oliveros M., Gutierrez-Arias R., Fuentes-Aspe R., Torres-Castro R.C., Merino-Osorio C., Nahuelhual P., Inostroza J., Jalil Y., Solano R., Marzuca-Nassr G.N., Aguilera-Eguía R., Lavados-Romo P., Soto-Rodríguez F.J., Sabelle C., et. al.

Abstract Objective The purpose of this article was to summarize the available evidence from systematic reviews on telerehabilitation in physical therapy. Methods We searched Medline/PubMed, EMBASE, and Cochrane Library databases. In addition, the records in PROSPERO and Epistemonikos and PEDro were consulted. Systematic reviews of different conditions, populations, and contexts—where the intervention to be evaluated is telerehabilitation by physical therapy—were included. The outcomes were clinical effectiveness depending on specific condition, functionality, quality of life, satisfaction, adherence, and safety. Data extraction and risk of bias assessment were carried out by a reviewer with non-independent verification by a second reviewer. The findings are reported qualitatively in the tables and figures. Results Fifty-three systematic reviews were included, of which 17 were assessed as having low risk of bias. Fifteen reviews were on cardiorespiratory rehabilitation, 14 on musculoskeletal conditions, and 13 on neurorehabilitation. The other 11 reviews addressed other types of conditions and rehabilitation. Thirteen reviews evaluated with low risk of bias showed results in favor of telerehabilitation versus in-person rehabilitation or no rehabilitation, while 17 reported no differences between the groups. Thirty-five reviews with unclear or high risk of bias showed mixed results. Conclusions Despite the contradictory results, telerehabilitation in physical therapy could be comparable with in-person rehabilitation or better than no rehabilitation for conditions such as osteoarthritis, low-back pain, hip and knee replacement, and multiple sclerosis and also in the context of cardiac and pulmonary rehabilitation. It is imperative to conduct better quality clinical trials and systematic reviews. Impact Providing the best available evidence on the effectiveness of telerehabilitation to professionals, mainly physical therapists, will impact the decision-making process and therefore yield better clinical outcomes for patients, both in these times of the COVID-19 pandemic and in the future. The identification of research gaps will also contribute to the generation of relevant and novel research questions.

Luedtke J.A., Chanson J., Neam K., Hobin L., Maciel A.O., Catenazzi A., Borzée A., Hamidy A., Aowphol A., Jean A., Sosa-Bartuano Á., Fong G. A., de Silva A., Fouquet A., Angulo A., et. al.

AbstractSystematic assessments of species extinction risk at regular intervals are necessary for informing conservation action1,2. Ongoing developments in taxonomy, threatening processes and research further underscore the need for reassessment3,4. Here we report the findings of the second Global Amphibian Assessment, evaluating 8,011 species for the International Union for Conservation of Nature Red List of Threatened Species. We find that amphibians are the most threatened vertebrate class (40.7% of species are globally threatened). The updated Red List Index shows that the status of amphibians is deteriorating globally, particularly for salamanders and in the Neotropics. Disease and habitat loss drove 91% of status deteriorations between 1980 and 2004. Ongoing and projected climate change effects are now of increasing concern, driving 39% of status deteriorations since 2004, followed by habitat loss (37%). Although signs of species recoveries incentivize immediate conservation action, scaled-up investment is urgently needed to reverse the current trends.

Hu J., Shan Y., Guerrero J.M., Ioinovici A., Chan K.W., Rodriguez J.

The development of microgrids is an advantageous option for integrating rapidly growing renewable energies. However, the stochastic nature of renewable energies and variable power demand have created many challenges like unstable voltage/frequency and complicated power management and interaction with the utility grid. Recently, predictive control with its fast transient response and flexibility to accommodate different constraints has presented huge potentials in microgrid applications. This paper provides a comprehensive review of model predictive control (MPC) in individual and interconnected microgrids, including both converter-level and grid-level control strategies applied to three layers of the hierarchical control architecture. This survey shows that MPC is at the beginning of the application in microgrids and that it emerges as a competitive alternative to conventional methods in voltage regulation, frequency control, power flow management and economic operation optimization. Also, some of the most important trends in MPC development have been highlighted and discussed as future perspectives. • A comprehensive review of model predictive control (MPC) in microgrids, including both converter-level and grid-level control strategies applied to three layers of microgrid hierarchical architecture. • Illustrating MPC is at the beginning of the application to microgrids and it emerges as a competitive alternative to conventional methods. • Some of the most important trends in MPC development have been highlighted and discussed as future perspectives.

Salem A., Van Khang H., Robbersmyr K.G., Norambuena M., Rodriguez J.

Multilevel inverters (MLIs) have gained increasing interest for advanced energy-conversion systems due to their features of high-quality produced waveforms, modularity, transformerless operation, voltage, and current scalability, and fault-tolerant operation. However, these merits usually come with the cost of a high number of components. Over the past few years, proposing new MLIs with a lower component count has been one of the most active topics in power electronics. The first aim of this article is to update and summarize the recently developed multilevel topologies with a reduced component count, based on their advantages, disadvantages, construction, and specific applications. Within the framework, both single-phase and three-phase topologies with symmetrical and asymmetrical operations are taken into consideration via a detailed comparison in terms of the used component count and type. The second objective is to propose a comparative method with novel factors to take component ratings into account. The effectiveness of the proposed method is verified by a comparative study.

Shajib A.J., Birrer S., Treu T., Agnello A., Buckley-Geer E.J., Chan J.H., Christensen L., Lemon C., Lin H., Millon M., Poh J., Rusu C.E., Sluse D., Spiniello C., Chen G.C., et. al.

ABSTRACT We present a blind time-delay cosmographic analysis for the lens system DES J0408−5354. This system is extraordinary for the presence of two sets of multiple images at different redshifts, which provide the opportunity to obtain more information at the cost of increased modelling complexity with respect to previously analysed systems. We perform detailed modelling of the mass distribution for this lens system using three band Hubble Space Telescope imaging. We combine the measured time delays, line-of-sight central velocity dispersion of the deflector, and statistically constrained external convergence with our lens models to estimate two cosmological distances. We measure the ‘effective’ time-delay distance corresponding to the redshifts of the deflector and the lensed quasar $D_{\Delta t}^{\rm eff}=$$3382_{-115}^{+146}$ Mpc and the angular diameter distance to the deflector Dd = $1711_{-280}^{+376}$ Mpc, with covariance between the two distances. From these constraints on the cosmological distances, we infer the Hubble constant H0= $74.2_{-3.0}^{+2.7}$ km s−1 Mpc−1 assuming a flat ΛCDM cosmology and a uniform prior for Ωm as $\Omega _{\rm m} \sim \mathcal {U}(0.05, 0.5)$. This measurement gives the most precise constraint on H0 to date from a single lens. Our measurement is consistent with that obtained from the previous sample of six lenses analysed by the H0 Lenses in COSMOGRAIL’s Wellspring (H0LiCOW) collaboration. It is also consistent with measurements of H0 based on the local distance ladder, reinforcing the tension with the inference from early Universe probes, for example, with 2.2σ discrepancy from the cosmic microwave background measurement.

Ahrendt C., Perez-Venegas D.J., Urbina M., Gonzalez C., Echeveste P., Aldana M., Pulgar J., Galbán-Malagón C.

We exposed juvenile intertidal fish to different amounts of Poly(styrene-co-divinylbenzene) microplastics in their diet. We fed ten individuals with pellets containing 0.01 g, another ten fish with pellets containing 0.1 g of PS, and ten fish without plastic as control. After 45 days of treatment, the whole intestine was removed, and the histological evaluation started immediately. We evaluated inflammation due to leukocyte infiltration (Lk), circulatory disorders like Hypermeia (Hyp), and regressive changes in the intestinal tissue, assessing Crypt cell loss (Ccl) and Villi cell loss (Vcl). The severity of the lesions increased according to the microplastic concentration. In the fish group feeding on microplastics, we found that leukocyte infiltration and hyperemia were more severe in the higher exposure group compared to the lower exposure; and crypt cell loss and villi cell loss increased significantly due to Poly(styrene-co-divinylbenzene) microplastic physical abrasion.

Adriaenssens E.M., Sullivan M.B., Knezevic P., van Zyl L.J., Sarkar B.L., Dutilh B.E., Alfenas-Zerbini P., Łobocka M., Tong Y., Brister J.R., Moreno Switt A.I., Klumpp J., Aziz R.K., Barylski J., Uchiyama J., et. al.

This article is a summary of the activities of the ICTV’s Bacterial and Archaeal Viruses Subcommittee for the years 2018 and 2019. Highlights include the creation of a new order, 10 families, 22 subfamilies, 424 genera and 964 species. Some of our concerns about the ICTV’s ability to adjust to and incorporate new DNA- and protein-based taxonomic tools are discussed.