Prognostic value of the novel P/FPE index to classify ARDS severity: A cohort study.

OBJECTIVE: To evaluate the impact of the novel P/FPE index to classify ARDS severity on mortality of patients with ARDS. DESIGN: A retrospective cohort study. SETTING: Twelve-bed medical and surgical intensive care unit from January 2018 to December 2020. PATIENTS: A total of 217 ARDS patients managed with invasive mechanical ventilation >48h. INTERVENTIONS: None. VARIABLES: ARDS severity on day 1 and day 3 was measured based on PaO2/FiO2 ratio and P/FPE index [PaO2/(FiO2×PEEP)]. Primary outcome was the hospital mortality. RESULTS: Hospital mortality rate was 59.9%. Relative to PaO2/FiO2 ratio, 31.8% of patients on day 1 and 77.0% on day 3 were reclassified into a different category of ARDS severity by P/FPE index. The level of PEEP was lower by P/FPE index-based ARDS severity classification than by using PaO2/FiO2 ratio. The performance for predicting mortality of P/FPE index was superior to PaO2/FiO2 ratio in term of AROC (day 1: 0.72 vs. 0.62; day 3: 0.87 vs. 0.68) and CORR (day 1: 0.370 vs. 0.213; day 3: 0.634 vs. 0.301). P/FPE index improved prediction of risk of death compared to PaO2/FiO2 ratio as showed by the qNRI (day 1: 72.0%, p<0.0001; day 3: 132.4%, p<0.0001) and IDI (day 1: 0.09, p<0.0001; day 3: 0.31, p<0.0001). CONCLUSIONS: Assessment of ARDS severity based on P/FPE index seems better than PaO2/FiO2 ratio for predicting mortality. The value of P/FPE index for clinical decision-making requires confirmation by randomized controlled trials.

Benralizumab: A New Approach for the Treatment of Severe Eosinophilic Asthma.

Eosinophilic asthma is the most common phenotype of severe asthma. It is characterized by abnormal production and release of type 2 cytokines from T helper type 2 (TH2) lymphocytes and type 2 innate lymphoid cells, such as IL-5. This leads to a persistent increase and activation of eosinophils in blood and the airways despite treatment with high-dose inhaled corticosteroids. Eosinophil differentiation, survival, and activation are preferentially regulated by IL-5, a cytokine that binds to the IL-5 receptor (IL-5R), which is located on the surface of eosinophils or basophils and plays a critical role in the pathogenesis and severity of asthma. Benralizumab is a monoclonal antibody that binds to IL-5R via its Fab domain, blocking the binding of IL-5 to its receptor and resulting in inhibition of eosinophil differentiation and maturation in bone marrow. In addition, this antibody is able to bind through its afucosylated Fc domain to the RIIIa region of the Fcy receptor on NK cells, macrophages, and neutrophils, thus strongly inducing antibody-dependent, cell-mediated cytotoxicity in both circulating and tissue-resident eosinophils. This double function of benralizumab induces almost complete fast and maintained depletion of eosinophils that is much greater than that induced by other monoclonal antibodies targeting the IL-5 pathway, such as mepolizumab and reslizumab. This review focuses on benralizumab as an alternative to other agents targeting the IL-5 pathway in the treatment of eosinophilic asthma.

Benralizumab: a new approach for the treatment of severe eosinophilic asthma

Eosinophilic asthma is the most common phenotype of severe asthma. It is characterized by abnormal production and release of type 2 cytokines from T helper type 2 (TH2) lymphocytes and type 2 innate lymphoid cells, such as IL-5. This leads to a persistent increase and activation of eosinophils in blood and the airways despite treatment with high-dose inhaled corticosteroids. Eosinophil differentiation, survival, and activation are preferentially regulated by IL-5, a cytokine that binds to the IL-5 receptor (IL-5R), which is located on the surface of eosinophils or basophils and plays a critical role in the pathogenesis and severity of asthma. Benralizumab is a monoclonal antibody that binds to IL-5R via its Fab domain, blocking the binding of IL-5 to its receptor and resulting in inhibition of eosinophil differentiation and maturation in bone marrow. In addition, this antibody is able to bind through its afucosylated Fc domain to the RIIIa region of the Fcgamma receptor on NK cells, macrophages, and neutrophils, thus strongly inducing antibody-dependent, cell-mediated cytotoxicity in both circulating and tissue-resident eosinophils. This double function of benralizumab induces almost complete fast and maintained depletion of eosinophils that is much greater than that induced by other monoclonal antibodies targeting the IL-5 pathway, such as mepolizumab and reslizumab. This review focuses on benralizumab as an alternative to other agents targeting the IL-5 pathway in the treatment of eosinophilic asthma

El asma eosinofílica es el fenotipo más común del asma grave. Se caracteriza por una producción y liberación anómala de citocinas de tipo 2, como la IL-5, por los linfocitos T colaboradores de tipo 2 (Th2) y las células linfoides innatas de tipo 2 (ILC-2). Con ello se activan los eosinófilos y se incrementa su número en sangre y vías respiratorias, a pesar del tratamiento con dosis altas de corticosteroides inhalados. La diferenciación, supervivencia y activación de los eosinófilos está regulada principalmente por la IL-5, una citocina que se une a su receptor (IL-5R), situado en la superficie de eosinófilos y basófilos, y que desempeña un papel fundamental en la patogénesis y gravedad del asma. El benralizumab es un anticuerpo monoclonal que se une al IL-5R a través de su dominio Fab, bloqueando la unión de la IL-5 a su receptor, lo que provoca una inhibición de la diferenciación y maduración de los eosinófilos en la médula ósea. Además, este anticuerpo es capaz de unirse a través de su dominio Fc afucosilado a la región RIIIa del receptor Fcgamma situado en células NK, macrófagos y neutrófilos, induciendo así una intensa citotoxicidad mediada por células dependiente de anticuerpos (ADCC), tanto de los eosinófilos circulantes como de los residentes en tejidos. Esta doble función del benralizumab induce una disminución casi completa de los eosinófilos de una forma rápida y mantenida, mucho mayor a la inducida por otros anticuerpos monoclonales dirigidos contra la IL-5, como el mepolizumab o el reslizumab. Esta revisión se centra en describir el uso del benralizumab en el tratamiento del asma eosinofílica como una alternativa a otros agentes que actúan directamente sobre la IL-5

APACHE II score for critically ill patients with a solid tumor: A reclassification study. / Escala APACHE II para pacientes críticos con cáncer sólido. Estudio de reclasificación.

OBJECTIVE: To improve the accuracy of the Acute Physiology and Chronic Health Evaluation (APACHE) II model for predicting hospital mortality in critically ill cancer patients. MATERIALS AND METHODS: This was a prospective cohort study of 522 patients admitted to ICU with a solid tumor. We developed the "APACHE II score for critically ill patients with a solid tumor" (APACHE IICCP score), in which typical variables of critically ill cancer patients were added to general APACHE II score. Calibration and discrimination were evaluated by Hosmer-Lemeshow test (H-L) and area under receiver operating characteristic curve (AROC), respectively. The improvement in predicting hospital mortality with the new model was assessed using a reclassification analysis by integrated discrimination improvement (IDI), net reclassification improvement (NRI; cut-off point of 20% in risk of death) and quantitative NRI (qNRI). RESULTS: The hospital mortality rate was 13%. Discrimination was superior for APACHE IICCP score (AROC=0.91 [95% CI 0.87-0.94; P<.0001]) compared to general APACHE II score (AROC=0.62 [95% CI 0.54-0.70; P=.002]). Calibration was better using APACHE IICCP score (H-L; P=.267 vs. P=.001). In reclassification analysis, an improved mortality prediction was observed with APACHE IICCP score (IDI=0.2994 [P<.0001]; total qNRI=134.3% [95% CI 108.8-159.8%; P<.0001]; total NRI=41.5% [95% CI 23.7-59.3%; P<.0001]). CONCLUSIONS: The performance of APACHE IICCP score was superior to that observed for general APACHE II score in predicting mortality in critically ill patients with a solid tumor. Other studies validating this new predictive model are required.

Risk factors and outcomes of severe acute respiratory failure requiring invasive mechanical ventilation in cancer patients: A retrospective cohort study.

OBJECTIVES: To determine the risk factors for severe acute respiratory failure requiring invasive mechanical ventilation (SARF-MV) and its effect upon clinical outcomes in critically ill cancer patients. DESIGN: A retrospective cohort study was carried out. SETTING: A 12-bed oncological intensive care unit (ICU) from January 2014 to December 2015. PATIENTS: A total of 878 consecutive cancer patients were included. Patients with an ICU stay of ≤1 day were excluded. The final sample size was 691 patients. INTERVENTIONS: None. VARIABLES: Clinical variables at ICU admission were extracted from the medical records. The primary outcome was SARF-MV. We also measured ICU and hospital mortality, as well as length of stay. RESULTS: The SARF-MV rate was 15.8%. The multivariate analysis identified brain tumour (OR 14.54; 95%CI 3.86-54.77; p<0.0001), stage IV cancer (OR 3.47; 95%CI 1.26-9.54; p=0.016), sepsis upon admission (OR 2.28; 95%CI 1.14-4.56; p=0.020) and an APACHE II score≥20 points (OR 5.38; 95%CI 1.92-15.05; p=0.001) as being independently associated to SARF-MV. Compared with the patients without SARF-MV, those with SARF-MV had a prolonged length of ICU stay (p<0.0001), a lower ICU survival rate (p<0.0001) and a lower hospital survival rate (p<0.0001). CONCLUSIONS: A number of clinical factors are related to SARF-MV. In this regard, SARF-MV is a powerful factor independently correlated to poor outcomes. Future studies should investigate means for preventing SARF-MV in critically ill cancer patients, which may have an impact upon outcomes.

Direct and correlated responses to selection in two lines of rabbits selected for feed efficiency under ad libitum and restricted feeding: III. Digestion and excretion of nitrogen and minerals.

Two rabbit lines have been created to result in better feed efficiency: the ConsoResidual line was selected for a lower residual feed intake under ad libitum feeding, and the ADGrestrict line was selected for higher ADG under restricted feeding (-20% of ad libitum). The present study aimed to analyze the digestion and excretion of N and minerals from 29 to 63 d of age of these 2 lines compared with an unselected control line (G0) under 2 feeding levels (ad libitum or restricted). The ADGrestrict line had greater digestibility compared with G0 (+1.3% for OM and N; < 0.05), and the ConsoResidual line had intermediate values. There was no genetic line effect on the digestibility of N and P and on minerals concentrations (P, Zn, and Cu) in the feces and in the urine. The N balance was improved for the 2 selected lines (+5%; < 0.05), leading to a reduced N output through the feces (0.06 g/d compared with G0; < 0.001) and the urine (-0.07 g/d; < 0.05) and to an improved N retention ratio (+3% compared with G0). Over the whole fattening period (d 29-63), significant differences were observed among lines only when fed ad libitum, with 13% greater DM fecal output and 5% greater N fecal output for G0. The N excretion in urine was 2 g less in the 2 selected lines, leading to a reduction of total N release of 4.4 g (compared with G0). The P excretion in feces (12 g) or urine (0.1 g) did not differ among the 3 lines. Over the whole fattening period and for ad libitum-fed rabbits, the 5% improvement in feed efficiency ( < 0.01) for the 2 selected lines corresponded to 400 g less feed intake (-8%) and to 20 g less N intake. The fecal excretion of the ADGrestrict and ConsoResidual lines were reduced by 200 g DM ( < 0.01), corresponding to 417 g fresh matter and 5 g of N. The excretion in minerals (P, Zn, and Cu) was not affected by the line. The feeding level strongly reduced the fecal and urine outputs (-50 and -60%, respectively; < 0.001). Higher digestibility coefficients ( < 0.001) were found in restricted-fed rabbits for OM (+6%), N (+8%), and P (+11%). The N balance was substantially improved by the restriction, with 40% less total (feces + urine) N excretion ( < 0.001). The P balance was improved by the restriction (0.469 vs. 0.360). Over the fattening period, the P fecal output was 37% less (-6 g) with 24% less feed intake and the Zn and Cu outputs were reduced by 27 (-130 mg) and 29% (-30 mg), respectively.

Adsorption of selected emerging contaminants onto PAC and GAC: Equilibrium isotherms, kinetics, and effect of the water matrix.

The removal of three emerging contaminants (ECs) (amitriptyline hydrochloride (AH), methyl salicylate (MS) and 2-phenoxyethanol (PE)) dissolved in several water matrices by means of their adsorption onto powdered activated carbon (PAC) and granular activated carbon (GAC) has been investigated. When dissolved in ultrapure water, adsorption of the ECs followed the trend of AH > MS > PE, with a positive effect of the adsorbent dose. According to the analysis of the adsorption isotherms and adsorption kinetics, PAC showed strongly higher adsorption efficiency in both capacity and velocity of the adsorption, in agreement with its higher mesoporosity. Equilibrium isotherm data were fitted by Langmuir and Freundlich models. Pseudo-second order kinetics modeled very successfully the adsorption process. Finally, the effect of the presence of dissolved organic matter (DOM) in the water matrices (ultrapure water, surface water and two effluents from wastewater treatment plants) on the adsorption of the selected ECs onto PAC was established, as well as its performance on the removal of water quality parameters. Results show a negative effect of the DOM content on the adsorption efficiency. Over 50% of organic matter was removed with high PAC doses, revealing that adsorption onto PAC is an effective technology to remove both micro-pollutants and DOM from water matrices.

Assessment of the UV/Cl2 advanced oxidation process for the degradation of the emerging contaminants amitriptyline hydrochloride, methyl salicylate and 2-phenoxyethanol in water systems.

Three emerging contaminants (amitriptyline hydrochloride (AH), methyl salicylate (MS) and 2-phenoxyethanol (PE)) frequently found in wastewaters were selected to be individually degraded in ultra-pure water by the advanced oxidation process (AOP) constituted by the combination of UV radiation and chlorine. The influence of pH, initial chlorine concentration and nature of the contaminants was firstly explored. The trend for the reactivity of the selected compounds was deduced: AH > MS > PE. A later kinetic study was carried out focused on the evaluation of the first-order rate constants and the determination of the partial contribution to the global reaction of the direct photochemical pathway and the radical pathway. In a second stage, the simultaneous oxidation of mixtures of the selected contaminants in several types of water was also performed by the same combination UV/Cl2. The efficiency of this combined system UV/Cl2 was compared to other oxidants such as the UV/[Formula: see text] and UV/H2O2 AOPs, and the influence of the operating variables was discussed. Results confirmed that the UV/Cl2 system provides higher elimination efficiencies among the AOPs tested. The presence of dissolved organic matter and bicarbonate ions in the water matrix caused a decrease in the treatment efficiency.

Incapacidad laboral permanente en pacientes menores de 62 años sometidos a cardiocirugía abierta. Estudio monocéntrico de un trieno / Permanent incapacity for employment on patients younger than 62 years old underwent cardiac surgery. Single centre 3 years study

Introducción y objetivos: Aunque tras la cirugía cardiaca abierta la calidad de vida mejora, la reinserción laboral no siempre es posible. Nuestro objetivo es identificar cuando es más frecuente la incapacidad laboral permanente tras la cirugía y cuáles son los factores predisponentes. Métodos: Los 204 menores de 62 años intervenidos de cirugía cardiaca entre 2010 y 2012 se estudiaron pre y postoperatoriamente. Resultados: Edad media 51±9 años, 156 (76,5%) varones, Euroscore Logístico 5,1±8,4; fracción de eyección ventricular izquierda 58±11%; 86 (42,2%) coronarios, 79 (38,7%) valvulares, 16 (7,8%) cirugías combinadas y 23 (11,3%) otras. Trabajadores autónomos fueron 28 (13,7%), 176 (86,33%) por cuenta ajena; 90 obtuvieron la incapacidad laboral permanente en 5,8±3,4 meses (15 ya la tenían al operarse). Los pacientes que obtuvieron la incapacidad laboral permanente presentaban, de forma estadísticamente significativa, un Euroscore mayor y mayor edad; sin diferencias en la fracción de eyección. Entre mujeres hubo más incapacidad laboral permanente y estando en incapacidad laboral permanente, más con cirugía valvular 67% que otra cirugía, p=0,013. Mayor número de puentes, ser trabajador autónomo o ser intervenido de alguna válvula, así como el número de válvulas intervenidas, se asoció a más incapacidad laboral permanente. Conclusiones: La edad, comorbilidad, sexo femenino, ser trabajador autónomo y el tipo de intervención fueron predictores para la incapacidad laboral permanente tras la cirugía cardiaca. La cirugía valvular, el número de válvulas y el de puentes coronarios determinan en mayor grado la probabilidad acumulada de incapacidad laboral permanente

Introduction and objectives: Although the quality of life after cardiac-surgery usually improves, the reintegration to work is not always possible. Our target is to identify what patients would have less probability of reintegration to work after open-heart surgery. Methods: We studied 204 patients younger than 62 years who underwent cardiac surgery between 2010 and 2012. Data was recorded and analysed. Results: Average age 51±9 years, 156 (76.5 %) males, Logistic Euroscore 5.1 ±8.4; Left ventricular ejection fraction 58±11 %. 86 (42.2 %) patients underwent coronary surgery, 79 (38.7 %) valve surgery, 16 (7.8 %) combined surgery and 23 (11.3 %) others kinds of cardiac surgery. 28 were self-employed (13.7 %). 90 patients were permanent incapacitation for employment after an average of 5.8 months (15 already had permanent incapacity for employment before surgery). Logistic Euroscore was statistically higher in patients than got a permanent incapacity after surgery and they were older with no difference with left ventricular ejection fraction. Women get more permanent incapacity after cardiac surgery but they had more valve surgery. The coronary grafts number, self-employment, as well as valve surgery or valve number operated, were associated with higher total incapacity for employment. Conclusions: Older age, comorbidity, female, to be self-employed and type of intervention were decisive for permanent incapacity for employment. Valve surgery and the number of valves or coronary grafts determine the cumulative probability of permanent incapacity for employment in such patients

Temperature and rainfall are related to fertility rate after spring artificial insemination in small ruminants.

A total number of 1092 artificial inseminations (AIs) performed from March to May were documented over four consecutive years on 10 Payoya goat farms (36° N) and 19,392 AIs on 102 Rasa Aragonesa sheep farms (41° N) over 10 years. Mean, maximum, and minimum ambient temperatures, mean relative humidity, mean solar radiation, and total rainfall on each insemination day were recorded. Overall, fertility rates were 58 % in goats and 45 % in sheep. The fertility rates of the highest and lowest deciles of each of the meteorological variables indicated that temperature and rainfall had a significant effect on fertility in goats. Specifically, inseminations that were performed when mean (68 %), maximum (68 %), and minimum (66 %) temperatures were in the highest decile, and rainfall was in the lowest decile (59 %), had a significantly (P < 0.0001) higher proportion of does that became pregnant than did the ewes in the lowest decile (56, 54, 58, and 49 %, respectively). In sheep, the fertility rates of the highest decile of mean (62 %), maximum (62 %), and minimum (52 %) temperature, RH (52 %), THI (53 %), and rainfall (45 %) were significantly higher (P < 0.0001) than were the fertility rates among ewes in the lowest decile (46, 45, 45, 45, 46, and 43 %, respectively). In conclusion, weather was related to fertility in small ruminants after AI in spring. It remains to be determined whether scheduling the dates of insemination based on forecasted temperatures can improve the success of AI in goats and sheep.

Variation in allergen content in sublingual allergen immunotherapy with house dust mites.

BACKGROUND: Allergen immunotherapy is a treatment modality which can be applied using different vaccines. The aim of this study was to quantify and compare the allergen content of different house dust mites (HDM)' sublingual treatments and to review the evidence on their efficacy. METHODS: Five sublingual allergen immunotherapy (SLIT) products were ordered and purchased at an ordinary pharmacy and masked for blinding before the study was started. Detection of Dermatophagoides pteronyssinus and Dermatophagoides farinae allergens Der p 1, Der f 1, Der p 2 and Der f 2 was carried out by immunoblotting and fluorescent multiplex. A literature search for meta-analyses and systematic reviews that included SLIT-HDM products was performed. RESULTS: Der p 1 concentrations ranged from 0.6 to 14.5 µg/ml; similar figures were found for Der f 1 that ranged from 0.2 to 12.4 µg/ml. Der p 2+ Der f 2 ranged from 0.2 to 1.5 µg/ml. Data on efficacy are scarce for most of the five products. CONCLUSIONS: Substantial variations regarding allergen content were found among these five SLIT-HDM products. Therefore, it can be necessary to guarantee the quality of the SLIT-HDM products and to demonstrate their effectiveness before they are marketed. It seems necessary, for the moment, to take into account these characteristics of the products before prescribing.

Phase II/III clinical trial to assess the tolerability and immunological effect of a new updosing phase of Dermatophagoides mix-based immunotherapy.

BACKGROUND: Immunologically enhanced subcutaneous specific immunotherapy (SCIT) has been developed with a fast and simplified updosing phase containing equal parts of the house dust mites (HDM) Dermatophagoides pteronyssinus and Dermatophagoides farinae (Dermatophagoides mix) adsorbed on aluminum hydroxide. OBJECTIVE: To evaluate the tolerability and immunological impact of the updosing phase of this new allergen extract formulation. MATERIAL AND METHODS: We performed a multicenter, open-label, single-arm, phase II/III clinical trial. The inclusion criteria were a clinical history of rhinitis/conjunctivitis due to HDM (with/without asthma) and sensitization to HDM (positive specific IgE and skin prick test). Five updosing injections of Dermatophagoides mix (300, 600, 3000, 6000, and 15000 SQ+) were administered at weekly intervals with 1 maintenance injection (15000 SQ+) 2 weeks after the last updosing injection. Two days after each visit, patients were contacted by telephone to follow up on any adverse events. IgE-blocking factor, IgG4, and immediate skin reactivity were evaluated. RESULTS: The sample comprised 102 patients (mean [SD] age, 29.3 [7.7] years; male, 52.9%). There were 117 adverse drug reactions (ADR): 101 were local, regardless of reaction size, in 48 (47.1%) patients and 7 were systemic (all grade I) in 5 (4.9%) patients. All ADRs were mild, except for 1, which was moderate. Six weeks of treatment led to statistically significant increases in IgE-blocking factor and IgG4, as well as a significant reduction in immediate skin reactivity. CONCLUSION: This new updosing phase of Dermatophagoides mix-based immunotherapy had a good tolerability profile and induced a significant immunological effect.

Ozonation of benzotriazole and methylindole: Kinetic modeling, identification of intermediates and reaction mechanisms.

The ozonation of 1H-benzotriazole (BZ) and 3-methylindole (ML), two emerging contaminants that are frequently present in aquatic environments, was investigated. The experiments were performed with the contaminants (1µM) dissolved in ultrapure water. The kinetic study led to the determination of the apparent rate constants for the ozonation reactions. In the case of 1H-benzotriazole, these rate constants varied from 20.1 ± 0.4M(-1)s(-1) at pH=3 to 2143 ± 23 M(-1)s(-1) at pH=10. Due to its acidic nature (pKa=8.2), the degree of dissociation of this pollutant was determined at every pH of work, and the specific rate constants of the un-dissociated and dissociated species were evaluated, being the values of these rate constants 20.1 ± 2.0 and 2.0 ± 0.3 × 10(3)M(-1)s(-1), respectively. On the contrary, 3-methylindole does not present acidic nature, and therefore, it can be proposed an average value for its rate constant of 4.90 ± 0.7 × 10(5)M(-1)s(-1) in the whole pH range 3-10. Further experiments were performed to identify the main degradation byproducts (10 mg L(-1) of contaminants, 0.023 gh(-1) of ozone). Up to 8 intermediates formed in the ozonation of 3-methylindole were identified by LC-TOFMS, while 6 intermediates were identified in the ozonation of 1H-benzotriazole. By considering these intermediate compounds, the reaction mechanisms were proposed and discussed. Finally, evaluated rate constants allowed to predict and modeling the oxidation of these micropollutants in general aquatic systems.

Phase II/III clinical trial to assess the tolerability and immunological effect of a new updosing phase of dermatophagoides mix–based immunotherapy

Background: Immunologically enhanced subcutaneous specific immunotherapy (SCIT) has been developed with a fast and simplified updosing phase containing equal parts of the house dust mites (HDM) Dermatophagoides pteronyssinus and Dermatophagoides farina ( Dermatophagoides mix) adsorbed on aluminum hydroxide. Objective: To evaluate the tolerability and immunological impact of the updosing phase of this new allergen extract formulation. Material and Methods: We performed a multicenter, open-label, single-arm, phase II/III clinical trial. The inclusion criteria were a clinical history of rhinitis/conjunctivitis due to HDM (with/without asthma) and sensitization to HDM (positive specific IgE and skin prick test). Five updosing injections of Dermatophagoides mix (300, 600, 3000, 6000, and 15 000 SQ+) were administered at weekly intervals with 1 maintenance injection (15 000 SQ+) 2 weeks after the last updosing injection. Two days after each visit, patients were contacted by telephone to follow up on any adverse events. IgE-blocking factor, IgG4, and immediate skin reactivity were evaluated. Results: The sample comprised 102 patients (mean [SD] age, 29.3 [7.7] years; male, 52.9%). There were 117 adverse drug reactions (ADR): 101 were local, regardless of reaction size, in 48 (47.1%) patients and 7 were systemic (all grade I) in 5 (4.9%) patients. All ADRs were mild, except for 1, which was moderate. Six weeks of treatment led to statistically significant increases in IgE-blocking factor and IgG4, as well as a significant reduction in immediate skin reactivity. Conclusion: This new updosing phase of Dermatophagoides mix–based immunotherapy had a good tolerability profile and induced a significant immunological effect (AU)

Antecedentes: Se ha desarrollado una mejorada vacuna de inmunoterapia específica (SCIT) adsorbida en hidróxido de aluminio y administración subcutánea con una fase de incremento de dosis más rápida y simplificada que contiene D. pteronyssinus y D. farinae (HDM; Dermatophagoides mezcla) a partes iguales. Objectivo: Evaluar la tolerabilidad de la fase de incremento de dosis de esta nueva formulación de extracto alergénico en SCIT y su impacto inmunológico. Material y Métodos: Ensayo clínico multicéntrico, abierto, de un brazo, fase II/III. Los sujetos que se podían incluir eran pacientes con una historia clínica de rinitis/conjuntivitis a ácaros de polvo doméstico (con/sin asma) y que presentaran sensibilización a HDM (IgE específica y prueba cutánea positiva). Se administraron cinco dosis semanales de Dermatophagoides mezcla en la fase de inicio (300, 600, 3000, 6000 y 15.000 SQ+) y una inyección de mantenimiento (15.000 SQ+) dos semanas tras la última inyección de la fase de incremento de dosis. Dos días tras cada visita se contactó con los pacientes por teléfono para seguir cualquier acontecimiento adverso (AE). Además, se evaluaron la IgG4, factor bloqueante de IgE y la respuesta cutánea inmediata. Resultados: Se incluyeron 102 sujetos en el ensayo (52,9% varones) con una edad media de 29,3±7,7 años. Se notificaron 117 reacciones adversas (RA) relacionadas con el medicamento en investigación: 101 locales, con independencia del tamaño de la reacción, en 48 (47,1%) pacientes y 7 sistémicas, todas grado I, en 5 (4,9%) pacientes. Todas las RA fueron de intensidad leve, excepto una, de intensidad moderada. Tras seis semanas de tratamiento, se obtuvieron incrementos estadísticamente significativos en el factor bloqueante de IgE y en IgG4, así como en la reducción de la respuesta cutánea inmediata. Conclusión: Esta nueva fase de incremento de dosis con inmunoterapia con Dermatophagoides mezcla presenta un buen perfil de tolerabilidad e induce una respuesta inmunológica significativa (AU)

Modeling the photodegradation of emerging contaminants in waters by UV radiation and UV/H2O2 system.

Five emerging contaminants (1-H-Benzotriazole, N,N-diethyl-m-toluamide or DEET, Chlorophene, 3-Methylindole, and Nortriptyline HCl), frequently found in surface waters and wastewaters, were selected to be photooxidized in several water matrices. Previous degradation experiments of these compounds individually dissolved in ultra pure water were performed by using UV radiation at 254 nm and the Fenton's reagent. These oxidation systems allowed the determination of the quantum yields and the rate constants for the radical reaction between each compound and hydroxyl radicals. Later, the simultaneous photodegradation of mixtures of the selected ECs in several types of water (ultrapure water, reservoir water, and two effluents from WWTPs) was carried out and a kinetic study was conducted. A model is proposed for the ECs elimination, and the theoretically calculated concentrations with this model agreed well with the experimental results obtained, which confirmed that it constitutes an excellent tool to predict the elimination of these compounds in waters.

Photolysis of model emerging contaminants in ultra-pure water: kinetics, by-products formation and degradation pathways.

The photolysis of five frequent emerging contaminants (Benzotriazole, Chlorophene, N,N-diethyl-m-toluamide or DEET, Methylindole, and Nortriptyline HCl) was investigated in ultrapure water under monochromatic ultraviolet radiation at 254 nm and by a combination of UV and hydrogen peroxide. The results revealed that the photolysis rates followed first-order kinetics, with rate constant values depending on the nature of the specific compound, the pH, and the presence or absence of the scavenger tert-butanol. Quantum yields were also determined and values in the range of 53.8 × 10⁻³ - 9.4 × 10⁻³ mol E⁻¹ for Benzotriazole, 525 × 10⁻³ - 469 × 10⁻³ mol E⁻¹ for Chlorophene, 2.8 × 10⁻³ - 0.9 × 10⁻³ mol E⁻¹ for DEET, 108 × 10⁻³ - 165 × 10⁻³ mol E⁻¹ for Methylindole, and 13.8 × 10⁻³ - 15.0 × 10⁻³ mol E⁻¹ for Nortriptyline were obtained. The study also found that the UV/H2O2 process enhanced the oxidation rate in comparison to direct photolysis. High-performance liquid chromatography coupled to electrospray ionization quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF-MS) technique was applied to the concentrations evaluation and further identification of the parent compounds and their by-products, which allowed the proposal of the degradation pathways for each compound. Finally, in order to assess the aquatic toxicity in the photodegradation of these compounds, the Vibrio fischeri acute toxicity test was used, and the results indicated an initial increase of this parameter in all cases, followed by a decrease in the specific case of Benzotriazole, DEET, Methylindole, and Chlorophene.

Nonperturbative renormalization group preserving full-momentum dependence: implementation and quantitative evaluation.

We present the implementation of the Blaizot-Méndez-Wschebor approximation scheme of the nonperturbative renormalization group we present in detail, which allows for the computation of the full-momentum dependence of correlation functions. We discuss its significance and its relation with other schemes, in particular, the derivative expansion. Quantitative results are presented for the test ground of scalar O(N) theories. Besides critical exponents, which are zero-momentum quantities, we compute the two-point function at criticality in the whole momentum range in three dimensions and, in the high-temperature phase, the universal structure factor. In all cases, we find very good agreement with the best existing results.

Combined chemical oxidation and membrane filtration techniques applied to the removal of some selected pharmaceuticals from water systems.

The elimination of five selected pharmaceuticals (amoxicillin, hydrochlorothiazide, metoprolol, naproxen and phenacetin) dissolved in different water systems (two natural water matrices and a secondary effluent) was carried out by sequential processes constituted by membrane filtration and chemical oxidation stages. Different configurations of those two stages were applied. In a first group, a pretreatment consisting in a membrane filtration (ultrafiltration or nanofiltration) was conducted; and the permeate and retentate effluents produced were afterwards treated by chemical oxidation, using ozone or chlorine. In a second group, the pretreatment consisted in a chemical oxidation stage (by using ozone, chlorine, O(3)/H(2)O(2), UV or UV/H(2)O(2)) followed by a nanofiltration process. The main objective of this set of experiments was the comparison of the efficiencies reached by using different systems and configurations in order to optimize the elimination of those pollutants from the selected water matrices. Results of removals and rejection coefficients for the five pharmaceuticals showed that the combined treatments involving UV radiation (254 nm monochromatic radiation during 30 min) followed by nanofiltration were very effective, with global removals over 80 % in most of the experiments. Ozonation (initial dose of 2.25 mg L(-1)) followed by nanofiltration also showed high levels of efficiency, with removals over 70 % in the permeate stream generated in experiments carried out with natural waters. The opposite sequence, nanofiltration followed by ozonation, reached removals over 97 % in the natural waters by using an ozone dose of 2.25 mg L(-1); and over 90 % in the secondary effluent with an initial ozone dose of 3.75 mg L(-1).

Bromination of selected pharmaceuticals in water matrices.

The bromination of five selected pharmaceuticals (metoprolol, naproxen, amoxicillin, phenacetin, and hydrochlorothiazide) was studied with these compounds individually dissolved in ultra-pure water. The apparent rate constants for the bromination reaction were determined as a function of the pH, obtaining the sequence amoxicillin>naproxen>>hydrochlorothiazide≈phenacetin≈metoprolol. A kinetic mechanism specifying the dissociation reactions and the species formed for each compound according to its pK(a) value and the pH allowed the intrinsic rate constants to be determined for each elementary reaction. There was fairly good agreement between the experimental and calculated values of the apparent rate constants, confirming the goodness of the proposed reaction mechanism. In a second stage, the bromination of the selected pharmaceuticals simultaneously dissolved in three water matrices (a groundwater, a surface water from a public reservoir, and a secondary effluent from a WWTP) was investigated. The pharmaceutical elimination trend agreed with the previously determined rate constants. The influence of the main operating conditions (pH, initial bromine dose, and characteristics of the water matrix) on the degradation of the pharmaceuticals was established. An elimination concentration profile for each pharmaceutical in the water matrices was proposed based on the use of the previously evaluated apparent rate constants, and the theoretical results agreed satisfactorily with experiment. Finally, chlorination experiments performed in the presence of bromide showed that low bromide concentrations slightly accelerate the oxidation of the selected pharmaceuticals during chlorine disinfection.