QuantiFERON-TB reversion in children and adolescents with tuberculosis.

We analyzed 136 children with tuberculosis disease or infection and a positive QuantiFERON-TB (QFT) assay, followed-up for a median of 21 months (0.4-11years). QFT reversed in 16.9% of cases, with significant decreases in TB1 (-1.72 vs. -0.03 IU/ml, p=0.001) and TB2 (-1.65 vs. -0.43 IU/ml, p=0.005) levels compared to non-reverters. We found a higher QFT reversion rate among children under 5 years (25.0% vs 11.9%, p=0.042), and those with TST induration <15mm (29% vs 13.3%, p=0.055). Our data reveal that, although QFT test remained positive in the majority of children, reversion occurred in 16% of cases in a progressive and stable pattern. Younger age and reduced TST induration were associated with QFT reversion.

Toward the autonomous flushing of building plumbing: Characterizing oxidation-reduction potential and temperature sensor dynamics.

Manual flushing of building plumbing is commonly used to address water quality issues that arise from water stagnation. Autonomous flushing informed by sensors has the potential to aid in the management of building plumbing, but a number of knowledge gaps hinder its application. This study evaluates autonomous flushing of building plumbing with online sensor and actuator nodes deployed under kitchen sinks in five residential houses. Online oxidation-reduction potential (ORP) and temperature data were collected for nine weeks during the winter and summer in houses with both free chlorine and chloramine. ORP levels in houses with free chlorine residuals decreased after overnight stagnation. The overnight decrease in ORP was not observed when tap water was automatically flushed for five minutes at 6:00 h every morning. ORP levels in houses with chloramine residuals did not decrease consistently after overnight stagnation, and daily automated flushes did not have an observable effect on the ORP signals. Additional laboratory experiments were carried out to evaluate ORP signals during chlorine decay and after incremental changes in chlorine, as would be expected in building plumbing conditions. Results from the lab and field deployments suggest on-line ORP sensors may be used to detect free chlorine decay due to stagnating water, but are not as effective in detecting chloramine decay. However, field results also suggest ORP may not respond as expected on a timely manner after free chlorine or chloramine have been restored, hindering their applicability in developing control algorithms. In this paper we tested twice-daily five-minute automatic flushing and found that it counteracts water quality degradation associated with overnight stagnation in free chlorine systems. An automatic sensor-based flushing is proposed using online temperature sensor data to determine when flushing has reached water from the main. The results suggest that flushing informed by temperature sensors can reduce the flushing time by 46 % compared to the preset five-minute static flush.

Asymptomatic bacteriuria in critical-access hospitals: Prevalence and patient characteristics driving treatment.

We evaluated the prevalence and treatment of asymptomatic bacteriuria (ASB) in 17 critical-access hospitals. Among 891 patients with urine cultures from September 2021 to June 2022, 170 (35%) had ASB. Also, 76% of patients with ASB received antibiotics for a median duration of 7 days, demonstrating opportunities for antimicrobial stewardship.

Cost benefit analysis of diversified farming systems across Europe: Incorporating non-market benefits of ecosystem services.

Crop diversification can enhance farm economic sustainability while reducing the negative impact on the environment and ecosystem services related. Despite the market and non-market benefits of crop diversification, monocropping is a widely used dominant practice in Europe. In this context, this works aims to assess the overall economic impact of several crop diversification systems across Europe and compared it to the monocropping system. For this purpose, an economic valuation by integrating market and non-market values for eight case studies distributed across three different European pedoclimatic regions (Southern Mediterranean, Northern Mediterranean and Boreal) is proposed. The economic valuation was conducted both in the short and medium-long term. For the short-term we conducted a social gross margin analysis, while for the medium-long term a cost-benefit analysis is developed. The results show an improvement in social gross margins for most of the diversification scenarios assessed when environmental and socio-cultural benefits are considered in the short-term. In the medium and long-term the transformation of cropping towards a more diversified agriculture is encouraged by greater economic benefits. These results provide a first insight in global economic performance of diversified cropping systems, whose main contribution relies on the integration of market and non-market values of ecosystem services from crop diversification. They are expected to be useful for guiding policy makers to promote crop diversification practices as a key instrument for building resilience in farming systems for an adaptive management to climate change.

[Influencia de la pandemia de la COVID-19 en la distribución de la bronquiolitis aguda en España.] / Influencia de la pandemia de la COVID-19 en la distribución de la bronquiolitis aguda en España.

OBJECTIVE: Bronchiolitis is the leading cause of hospitalization in children under one year of age, with annual epidemics. Since the onset of the SARS-CoV-2 coronavirus disease pandemic (COVID-19), there has been a change in the transmission of other respiratory viruses. Our aim in this paper was to describe how COVID-19 had affected the distribution of acute bronchiolitis in our country. METHODS: We conducted a retrospective descriptive study of the cases of bronchiolitis treated in a sample of Spanish hospitals belonging to four autonomous communities. A chi-square test and Student's t- test were used to compare epidemiological and demographic variables between patients attending the hospital with bronchiolitis during January 2021-June 2021 with patients attending the hospital in the previous three years (2018-2020). RESULTS: We analyzed 6,124 cases of bronchiolitis (58.8% males and 41.2% females). The mean age was 0.5 years (SD: 0.4). In 2020, we observed a decrease of bronchiolitis cases compared to 2019 of 67%. During 2020 and 2021, the epidemic season started in January-February and peaked in June. During the first half of 2021, the highest percentage of admissions for bronchiolitis associated with RSV infection was observed in hospitals in central Spain corresponding to the Autonomous Community of Madrid (78.5% of admissions). CONCLUSIONS: The COVID-19 pandemic significantly modifies the seasonality of bronchiolitis. In our country, the flow and distribution of the disease are not uniform. It starts in the center of Spain and ends on the coast.

OBJETIVO: La bronquiolitis es la primera causa de hospitalización en menores de un año, presentándose en forma de epidemias anuales. Desde el inicio de la pandemia por la enfermedad causada por el coronavirus SARS-CoV-2 (COVID-19) se ha producido un cambio en la transmisión de otros virus respiratorios. Nuestro objetivo en este trabajo fue describir cómo había afectado la pandemia de la COVID-19 a la distribución de la bronquiolitis aguda en nuestro país. METODOS: Realizamos un estudio descriptivo retrospectivo de los casos de bronquiolitis atendidos en una muestra de hospitales españoles que pertenecían a cuatro comunidades autónomas. Empleado el test chi-cuadrado y la prueba t de Student comparamos variables epidemiológicas y demográficas de los casos de bronquiolitis atendidos durante enero de 2021 y junio 2021, con los tres años anteriores (2018-2020). RESULTADOS: Analizamos 6.124 casos de bronquiolitis (58,8% varones y 41,2% mujeres). La media de edad fue de 0,5 años (DE: 0,4). En 2020 observamos un descenso de casos de bronquiolitis con respecto a 2019 del 67%. Durante 2020 y 2021 la temporada epidémica empezó en enero-febrero y alcanzó su pico máximo en junio. Durante el primer semestre de 2021, el porcentaje más elevado de ingresos por bronquiolitis asociados a infección VRS fue observado en hospitales del centro de España correspondientes a la Comunidad Autónoma de Madrid (78,5% de los ingresos). CONCLUSIONES: La pandemia por la COVID-19 modifica de manera significativa la estacionalidad de la bronquiolitis. En nuestro país, el flujo y distribución de la enfermedad no es uniforme, comenzado por el centro peninsular y, por último, la zona litoral.

Influencia de la pandemia dela COVID-19 en la distribución de la bronquiolitis aguda en España / Influence of the pandemic of COVID-19 in distribution of acute bronchiolitis in Spain

Fundamentos: La bronquiolitis es la primera causa de hospitalización en menores de un año, presentándose en forma de epidemias anuales. Desde el inicio de la pandemia por la enfermedad causada por el coronavirus SARS-CoV-2 (COVID-19) se ha producido un cambio en la transmisión de otros virus respiratorios. Nuestro objetivo en este trabajo fue describir cómo había afectado la pandemia de la COVID-19 a la distribución de la bronquiolitis aguda en nuestro país. Métodos: Realizamos un estudio descriptivo retrospectivo de los casos de bronquiolitis atendidos en una muestra de hospitales españoles que pertenecían a cuatro comunidades autónomas. Empleado el test chi-cuadrado y la pruebat de Student comparamos variables epidemiológicas y demográficas de los casos de bronquiolitis atendidos durante enero de 2021 y junio 2021, con los tres años anteriores (2018-2020). Resultados: Analizamos 6.124 casos de bronquiolitis (58,8% varones y 41,2% mujeres). La media de edad fue de 0,5 años (DE: 0,4). En 2020 observamos un descenso de casos de bronquiolitis con respecto a 2019 del 67%. Durante 2020 y 2021 la temporada epidémica empezó en enero-febrero y alcanzó su pico máximo en junio. Durante el primer semestre de 2021, el porcentaje más elevado de ingresos por bronquiolitis asociados a infección VRS fue observado en hospitales del centro de España correspondientes a la Comunidad Autónoma de Madrid (78,5% de los ingresos). Conclusiones: La pandemia por la COVID-19 modifica de manera significativa la estacionalidad de la bronquiolitis. En nuestro país, el flujo y distribución de la enfermedad no es uniforme, comenzado por el centro peninsular y, por último, la zona litoral.(AU)

Background: Bronchiolitis is the leading cause of hospitalization in children under one year of age, with annual epidemics. Sincethe onset of the SARS-CoV-2 coronavirus disease pandemic (COVID-19), there has been a change in the transmission of other respiratory viruses. Our aim in this paper was to describe how COVID-19 had affected the distribution of acute bronchiolitis in our country. Methods: We conducted a retrospective descriptive study of the cases of bronchiolitis treated in a sample of Spanish hospitals belonging to four autonomous communities. A chi-square test and Student’s t- test were used to compare epidemiological and demographicvariables between patients attending the hospital with bronchiolitis during January 2021-June 2021 with patients attending the hospital in the previous three years (2018-2020). Results: We analyzed 6,124 cases of bronchiolitis (58.8% males and 41.2% females). The mean age was 0.5 years (SD: 0.4). In 2020, weobserved a decrease of bronchiolitis cases compared to 2019 of 67%. During 2020 and 2021, the epidemic season started in January-February and peaked in June. During the first half of 2021, the highest percentage of admissions for bronchiolitis associated with RSVinfection was observed in hospitals in central Spain corresponding to the Autonomous Community of Madrid (78.5% of admissions).Conclusions: The COVID-19 pandemic significantly modifies the seasonality of bronchiolitis. In our country, the flow and distri-bution of the disease are not uniform. It starts in the center of Spain and ends on the coast.(AU)

Adenomatoid odontogenic tumor associated to reactive fibro-osseous lesion: A case report.

An adenomatoid odontogenic tumor (AOT) is a benign epithelial lesion, being the fourth most common among all odontogenic tumors. Usually presents as slow painless growth that sometimes leads to facial asymmetry. Many cases are detected by radiographic studies, and the indication for biopsy and surgery is secondary to this finding. We report a case of a 17-year-old man with a history of left mandibular painless swelling since 4 months ago, associated with facial asymmetry and hard consistency. An imaging study showed an extensive unilocular radiolucent lesion to the basilar arch, with defined limits and with peripheral hyperdense areas located only vestibular to the lesion. The histopathology was composed of odontogenic epithelial cell proliferation, with epithelial nodular and duct-like structures, rosettes of spindled epithelial cells with eosinophilic material, calcifications, and fibro-osseous reaction. Surgical conservative excision including the affected tooth is the treatment of choice and recurrence is rare. The histologic findings of reactive fibro-osseous proliferation in AOT should be interpreted as a reactive change in the tumor capsule and not as an adnexal lesion. We present an atypical case of AOT with reactive fibro-osseous reaction. Despite clinical aggressive behavior, conservative surgical treatment could be the treatment of choice. Additionally, we emphasize the importance of histopathological examination together with the imaging study of radiolucent lesions of the maxillary bones. Key words:Adenomatoid Odontogenic Tumor, Odontogenic tumor, fibro-osseous lesion.

Gene Co-Expression Networks Offer New Perspectives on Sepsis Pathophysiology.

Sepsis is among the most common causes of death in intensive care units. Septic shock is a type of circulatory shock that shows signs and symptoms that are similar to non-septic shock. Despite the impact of shock on patients and the economic burden, knowledge of the pathophysiology of septic shock is scarce. In this context, weighted gene co-expression network analysis can help to elucidate the molecular mechanisms of this condition. The gene expression dataset used in this study was downloaded from the Gene Expression Omnibus, which contains 80 patients with septic shock, 33 patients with non-septic shock, and 15 healthy controls. Our novel analysis revealed five gene modules specific for patients with septic shock and three specific gene modules for patients with non-septic shock. Interestingly, genes related to septic shock were mainly involved in the immune system and endothelial cells, while genes related to non-septic shock were primarily associated with endothelial cells. Together, the results revealed the specificity of the genes related to the immune system in septic shock. The novel approach developed here showed its potential to identify critical pathways for the occurrence and progression of these conditions while offering new treatment strategies and effective therapies.

Effectiveness and Safety of Cannabinoids as an Add-On Therapy in the Treatment of Resistant Spasticity in Multiple Sclerosis: A Systematic Review.

Background: Spasticity continues to be a very prevalent, highly invalidating, and difficult-to-manage symptom in patients with multiple sclerosis (MS). The aim of this systematic review is to evaluate the effectiveness of the use of cannabis and cannabinoids in these patients, evaluating its use as an additional therapy. Methods: We performed a systematic review of the literature searching in the major scientific databases (PubMed, Scopus, EMBASE, WOS, and Cochrane Library) for articles from January 2017 to May 2022 containing information about the effectiveness of cannabis and cannabinoids in patients with insufficient response to first-line oral antispastic treatment. Results: A total of five medium high-quality articles were selected to be part of the study and all evaluated the effectiveness of the tetrahydrocannabinol (THC) and cannabidiol (CBD) spray. The effectiveness of this drug and the significant improvements are produced on the patient-related spasticity assessment scales, obtaining improvement up to 45%; and on quality of life, producing a decrease in the appearance of symptoms related to spasticity, as well as an increase in the development of basic activities of daily living. The average dose is 5-7 sprays/day. The discontinuation rate for these treatments is around 40% due to lack of effectiveness and adverse events. All reported adverse effects are mild to moderate in severity and their incidence is ∼17%, although this figure tends to decrease with drug use. Conclusions: Adding the THC:CBD sprays have been shown to be more effective in treating MS spasticity than optimizing the dose of first-line antispastic drugs in selected responders patients. The safety and tolerability profiles remain in line with those obtained in other trials. More patients would benefit from treatment if the initial response search period was extended.

Prevalence and treatment of asymptomatic bacteriuria at academic and critical-access hospitals-Opportunities for stewardship efforts.

Asymptomatic bacteriuria (ASB) is common among hospitalized patients and often leads to inappropriate antimicrobial use. Data from critical-access hospitals are underrepresented. To target antimicrobial stewardship efforts, we measured the point prevalence of ASB and detected a high frequency of ASB overtreatment across academic, community, and critical-access hospitals.

Dyslipidemia and Inflammation as Hallmarks of Oxidative Stress in COVID-19: A Follow-Up Study.

Recent works have demonstrated a significant reduction in cholesterol levels and increased oxidative stress in patients with coronavirus disease 2019 (COVID-19). The cause of this alteration is not well known. This study aimed to comprehensively evaluate their possible association during the evolution of COVID-19. This is an observational prospective study. The primary endpoint was to analyze the association between lipid peroxidation, lipid, and inflammatory profiles in COVID-19 patients. A multivariate regression analysis was employed. The secondary endpoint included the long-term follow-up of lipid profiles. COVID-19 patients presented significantly lower values in their lipid profile (total, low, and high-density lipoprotein cholesterol) with greater oxidative stress and inflammatory response compared to the healthy controls. Lipid peroxidation was the unique oxidative parameter with a significant association with the total cholesterol (OR: 0.982; 95% CI: 0.969-0.996; p = 0.012), IL1-RA (OR: 0.999; 95% CI: 0.998-0.999; p = 0.021) IL-6 (OR: 1.062; 95% CI: 1.017-1.110; p = 0.007), IL-7 (OR: 0.653; 95% CI: 0.433-0.986; p = 0.042) and IL-17 (OR: 1.098; 95% CI: 1.010-1.193; p = 0.028). Lipid abnormalities recovered after the initial insult during long-term follow-up (IQR 514 days); however, those with high LPO levels at hospital admission had, during long-term follow-up, an atherogenic lipid profile. Our study suggests that oxidative stress in COVID-19 is associated with derangements of the lipid profile and inflammation. Survivors experienced a recovery in their lipid profiles during long-term follow-up, but those with stronger oxidative responses had an atherogenic lipid profile.

PCR-based diagnosis of respiratory virus in postsurgical septic patients: A preliminary study before SARS-CoV-2 pandemic.

Respiratory viruses are part of the normal microbiota of the respiratory tract, which sometimes cause infection with/without respiratory insufficiency and the need for hospital or ICU admission. The aim of this study is to determine the prevalence of respiratory viruses in nontransplanted postoperative septic patients as well as lymphocyte count influence in their presence and its relationship to mortality. 223 nontransplanted postsurgical septic patients were recruited on the Intensive Care Unit (ICU) at Hospital Clínico Universitario de Valladolid prior to the SARS-COV-2 pandemic. Patients were split into 2 groups according to the presence/absence of respiratory viruses. Multivariate logistic regression analysis was used to identify independent factors related to positive respiratory virus PCR test. Respiratory viruses were isolated in 28.7% of patients. 28-day mortality was not significantly different between virus-positive and virus-negative groups. Logistic regression analysis revealed that lymphocyte count ≤ 928/µl is independently associated with a positive PCR result [OR 3.76, 95% CI (1.71-8.26), P = .001] adjusted by platelet count over 128,500/µL [OR 4.27, 95% CI (1.92-9.50) P < .001] and the presence of hypertension [OR 2.69, 95% CI (1.13-6.36) P = .025] as confounding variables. Respiratory viruses' detection by using PCR in respiratory samples of nontransplanted postoperative septic patients is frequent. These preliminary results revealed that the presence of lymphopenia on sepsis diagnosis is independently associated to a positive virus result, which is not related to a higher 28-day mortality.

CEACAM7 polymorphisms predict genetic predisposition to mortality in post-surgical septic shock patients.

We carried out a retrospective exploratory study on 173 patients who underwent major surgery and developed septic shock after surgery. Our findings suggest that CEACAM7 rs1001578, rs10409040, and rs889365 polymorphisms could influence septic shock-related death in individuals who underwent major surgery.

Effect of environmental stressors on the mRNA expression of ecdysone cascade genes in Chironomus riparius.

Chemical compounds produced by humans are continuously reaching the environment. In this work, we characterised the expression patterns of important endocrine-related genes involved in the ecdysone pathway in the fourth larval instar of the model species Chironomus riparius after exposure to three chemicals: ethinyl oestradiol (EE), nonylphenol (NP) and bis(tributyltin) oxide (TBTO). We used real-time PCR to analyse the gene expression levels of ecdysone receptor (EcR) and ultraspiracle (usp), two genes that encode the dimerising partners of the functional ecdysone receptor; the orphan receptor ERR (oestrogen-related receptor), with an unknown function in invertebrates; and E74, an early response gene induced by ecdysteroids. We estimated the bioaccumulation potential, bioavailability and physicochemical properties of these chemicals, together with a number of other exogenous agents known to interfere with the hormonal system. We also provide a review of previous transcriptional studies showing the effect of all these chemicals on ecdysone cascade genes. This analysis provides useful data for future ecotoxicological studies involving invertebrate species. CAPSULE: Changes in transcriptional activities of EcR, E74, usp and ERR genes after exposure to endocrine-disrupting chemicals would be useful as molecular bioindicators of endocrine disruption in Chironomus riparius.

Predictive Modeling of Poor Outcome in Severe COVID-19: A Single-Center Observational Study Based on Clinical, Cytokine and Laboratory Profiles.

Pneumonia is the main cause of hospital admission in COVID-19 patients. We aimed to perform an extensive characterization of clinical, laboratory, and cytokine profiles in order to identify poor outcomes in COVID-19 patients. METHODS: A prospective and consecutive study involving 108 COVID-19 patients was conducted between March and April 2020 at Hospital Clínico Universitario de Valladolid (Spain). Plasma samples from each patient were collected after emergency room admission. Forty-five serum cytokines were measured in duplicate, and clinical data were analyzed using SPPS version 25.0. RESULTS: A multivariate predictive model showed high hepatocyte growth factor (HGF) plasma levels as the only cytokine related to intubation or death risk at hospital admission (OR = 7.38, 95%CI-(1.28-42.4), p = 0.025). There were no comorbidities included in the model except for the ABO blood group, in which the O blood group was associated with a 14-fold lower risk of a poor outcome. Other clinical variables were also included in the predictive model. The predictive model was internally validated by the receiver operating characteristic (ROC) curve with an area under the curve (AUC) of 0.94, a sensitivity of 91.7% and a specificity of 95%. The use of a bootstrapping method confirmed these results. CONCLUSIONS: A simple, robust, and quick predictive model, based on the ABO blood group, four common laboratory values, and one specific cytokine (HGF), could be used in order to predict poor outcomes in COVID-19 patients.

Can the Cytokine Profile According to ABO Blood Groups Be Related to Worse Outcome in COVID-19 Patients? Yes, They Can.

Severe status of coronavirus disease 2019 (COVID-19) is extremely associated to cytokine release. Moreover, it has been suggested that blood group is also associated with the prevalence and severity of this disease. However, the relationship between the cytokine profile and blood group remains unclear in COVID-19 patients. In this sense, we prospectively recruited 108 COVID-19 patients between March and April 2020 and divided according to ABO blood group. For the analysis of 45 cytokines, plasma samples were collected in the time of admission to hospital ward or intensive care unit and at the sixth day after hospital admission. The results show that there was a risk of more than two times lower of mechanical ventilation or death in patients with blood group O (log rank: p = 0.042). At first time, all statistically significant cytokine levels, except from hepatocyte growth factor, were higher in O blood group patients meanwhile the second time showed a significant drop, between 20% and 40%. In contrast, A/B/AB group presented a maintenance of cytokine levels during time. Hepatocyte growth factor showed a significant association with intubation or mortality risk in non-O blood group patients (OR: 4.229, 95% CI (2.064-8.665), p < 0.001) and also was the only one bad prognosis biomarker in O blood group patients (OR: 8.852, 95% CI (1.540-50.878), p = 0.015). Therefore, higher cytokine levels in O blood group are associated with a better outcome than A/B/AB group in COVID-19 patients.

Lipid peroxidation as a hallmark of severity in COVID-19 patients.

BACKGROUND: Oxidative stress may be a key player in COVID-19 pathogenesis due to its significant role in response to infections. A defective redox balance has been related to viral pathogenesis developing a massive induction of cell death provoked by oxidative stress. The aim of this study is to perform a complete oxidative stress profile evaluation regarding antioxidant enzymes, total antioxidant capacity and oxidative cell damage in order to characterize its role in diagnosis and severity of this disease. METHODS: Blood samples were obtained from 108 COVID-19 patients and 28 controls and metabolites representative of oxidative stress were assessed. The association between lipid peroxidation and 28-day intubation/death risk was evaluated by multivariable regression analysis. Probability of intubation/death to day-28 was analyzed by using Kaplan-Meier curves and tested with the log-rank test. RESULTS: Antioxidant enzymes (Superoxide dismutase (SOD) and Catalase) and oxidative cell damage (Carbonyl and Lipid peroxidation (LPO)) levels were significantly higher in COVID-19 patients while total antioxidant capacity (ABTS and FRAP) levels were lower in these patients. The comparison of oxidative stress molecules' levels across COVID-19 severity revealed that only LPO was statistically different between mild and intubated/death COVID-19 patients. COX multivariate regression analysis identified LPO levels over the OOP (LPO>1948.17 µM) as an independent risk factor for 28-day intubation/death in COVID-19 patients [OR: 2.57; 95% CI: 1.10-5.99; p = 0.029]. Furthermore, Kaplan-Meier curve analysis revealed that COVID-19 patients showing LPO levels above 1948.17 µM were intubated or died 8.4 days earlier on average (mean survival time 15.4 vs 23.8 days) when assessing 28-day intubation/death risk (p < 0.001). CONCLUSION: These findings deepen our knowledge of oxidative stress status in SARS-CoV-2 infection, supporting its important role in COVID-19. In fact, higher lipid peroxidation levels are independently associated to a higher risk of intubation or death at 28 days in COVID-19 patients.

Modulation of the goodness of fit in hydrological modelling based on inner balance errors.

In hydrological modelling, a good result for the criterion of goodness of fit does not always imply that the hypothesis of mass conservation is fulfilled, and models can lose their essential physical soundness. We propose a way for detecting this anomaly by accounting the resulting water balance during model simulation and use it to modulate the obtained goodness of fit. We call this anomaly in water balance as "inner balance error of the model". To modulate the goodness of fit values, a penalty function that depends on this error is proposed. In addition, this penalty function is introduced into a multi-criteria objective function, which is also tested. This procedure was followed in modelling the Headwater of the Tagus River (Spain), applying the monthly abcd water balance model. Modulation of the goodness of fit allowed for detecting balance errors in the modelling, revealing that in the simulation of some catchments the model tends to accumulate water in, or release water from, the reservoir that simulates groundwater storage. Although the proposed multi-criteria objective function solves the inner balance error for most catchments, in some cases the error cannot be corrected, indicating that any error in the input and output data is probably related to groundwater flows.

Evaluation of Cytokines as Robust Diagnostic Biomarkers for COVID-19 Detection.

Antigen tests or polymerase chain reaction (PCR) amplification are currently COVID-19 diagnostic tools. However, developing complementary diagnosis tools is mandatory. Thus, we performed a plasma cytokine array in COVID-19 patients to identify novel diagnostic biomarkers. A discovery-validation study in two independent prospective cohorts was performed. The discovery cohort included 136 COVID-19 and non-COVID-19 patients recruited consecutively from 24 March to 11 April 2020. Forty-five cytokines' quantification by the MAGPIX system (Luminex Corp., Austin, TX, USA) was performed in plasma samples. The validation cohort included 117 patients recruited consecutively from 15 to 25 April 2020 for validating results by ELISA. COVID-19 patients showed different levels of multiple cytokines compared to non-COVID-19 patients. A single chemokine, IP-10, accurately identified COVID-19 patients who required hospital admission (AUC: 0.962; 95%CI (0.933-0.992); p < 0.001)). The results were validated in an independent cohort by multivariable analysis (OR: 25.573; 95%CI (8.127-80.469); p < 0.001) and AUROC (AUC: 0.900; 95%CI (0.846-0.954); p < 0.001). Moreover, showing IP-10 plasma levels over 173.35 pg/mL identified COVID-19 with higher sensitivity (86.20%) than the first SARS-CoV-2 PCR. Our discover-validation study identified IP-10 as a robust biomarker in clinical practice for COVID-19 diagnosis at hospital. Therefore, IP-10 could be used as a complementary tool in clinical practice, especially in emergency departments.