Structure, biomass, and secondary production of benthic macroinvertebrates in subtropical Andean rivers.

Secondary production is the formation of heterotrophic biomass across time, which integrates several important ecological processes that affect the life of organisms, populations, communities and ecosystems, but its study has poor developed in South America. The objectives of this work were to describe the diversity of benthic macroinvertebrate assemblages in terms of abundance and biomass, and to quantify their secondary production for the first time in Andean rivers. A quantitative sampling scheme was implemented, using a Surber sampler, in three forested streams. Physical-chemical variables, nutrients, organic matter and chlorophyll were measured also. The macroinvertebrates were separated and identified mostly at the species level. Each taxon was assigned to a functional feeding group. Secondary production was estimated for 38 taxa, mostly Diptera, Trichoptera, Coleoptera, and Ephemeroptera. The annual production varied from 3769 to 13916 mg dry mass m-2 y-1. Most abundant taxa were also those with higher production, dominated by Ephemeroptera (Baetidae), Trichoptera (Hydropsychidae) and Diptera (Chironomidae and Simuliidae). Density, biomass, and production of collectors and predators were much higher than the other feeding groups. We expect that our results will be useful to evaluate the effects on stream functioning produced by global warming and other anthropogenic disturbances in our region.

Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC.

BACKGROUND: An earlier analysis in this phase 3 trial showed that durvalumab significantly prolonged progression-free survival, as compared with placebo, among patients with stage III, unresectable non-small-cell lung cancer (NSCLC) who did not have disease progression after concurrent chemoradiotherapy. Here we report the results for the second primary end point of overall survival. METHODS: We randomly assigned patients, in a 2:1 ratio, to receive durvalumab intravenously, at a dose of 10 mg per kilogram of body weight, or matching placebo every 2 weeks for up to 12 months. Randomization occurred 1 to 42 days after the patients had received chemoradiotherapy and was stratified according to age, sex, and smoking history. The primary end points were progression-free survival (as assessed by blinded independent central review) and overall survival. Secondary end points included the time to death or distant metastasis, the time to second progression, and safety. RESULTS: Of the 713 patients who underwent randomization, 709 received the assigned intervention (473 patients received durvalumab and 236 received placebo). As of March 22, 2018, the median follow-up was 25.2 months. The 24-month overall survival rate was 66.3% (95% confidence interval [CI], 61.7 to 70.4) in the durvalumab group, as compared with 55.6% (95% CI, 48.9 to 61.8) in the placebo group (two-sided P=0.005). Durvalumab significantly prolonged overall survival, as compared with placebo (stratified hazard ratio for death, 0.68; 99.73% CI, 0.47 to 0.997; P=0.0025). Updated analyses regarding progression-free survival were similar to those previously reported, with a median duration of 17.2 months in the durvalumab group and 5.6 months in the placebo group (stratified hazard ratio for disease progression or death, 0.51; 95% CI, 0.41 to 0.63). The median time to death or distant metastasis was 28.3 months in the durvalumab group and 16.2 months in the placebo group (stratified hazard ratio, 0.53; 95% CI, 0.41 to 0.68). A total of 30.5% of the patients in the durvalumab group and 26.1% of those in the placebo group had grade 3 or 4 adverse events of any cause; 15.4% and 9.8% of the patients, respectively, discontinued the trial regimen because of adverse events. CONCLUSIONS: Durvalumab therapy resulted in significantly longer overall survival than placebo. No new safety signals were identified. (Funded by AstraZeneca; PACIFIC ClinicalTrials.gov number, NCT02125461 .).

Influence of organic matter and CO2 supply on bioremediation of heavy metals by Chlorella vulgaris and Scenedesmus almeriensis in a multimetallic matrix.

This research evaluated the influence of organic matter (OM) and CO2 addition on the bioremediation potential of two microalgae typically used for wastewater treatment: Chlorella vulgaris (CV) and Scenedesmus almeriensis (SA). The heavy metal (HM) removal efficiencies and biosorption capacities of both microalgae were determined in multimetallic solutions (As, B, Cu, Mn, and Zn) mimicking the highest pollutant conditions found in the Loa river (Northern Chile). The presence of OM decreased the total biosorption capacity, specially in As (from 2.2 to 0.0 mg/g for CV and from 2.3 to 1.7 mg/g for SA) and Cu (from 3.2 to 2.3 mg/g for CV and from 2.1 to 1.6 mg/g for SA), but its influence declined over time. CO2 addition decreased the total HM biosorption capacity for both microalgae species and inhibited CV growth. Finally, metal recovery using different eluents (HCl, NaOH, and CaCl2) was evaluated at two different concentrations. HCl 0.1 M provided the highest recovery efficiencies, which supported values over 85% of As, 92% of Cu, and ≈100% of Mn and Zn from SA. The presence of OM during the loaded stage resulted in a complete recovery of As, Cu, Mn, and Zn when using HCl 0.1 M as eluent.

Tremelimumab as second-line or third-line treatment in relapsed malignant mesothelioma (DETERMINE): a multicentre, international, randomised, double-blind, placebo-controlled phase 2b trial.

BACKGROUND: New therapeutic strategies for malignant mesothelioma are urgently needed. In the DETERMINE study, we investigated the effects of the cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4) monoclonal antibody tremelimumab in patients with previously treated advanced malignant mesothelioma. METHODS: DETERMINE was a double-blind, placebo-controlled, phase 2b trial done at 105 study centres across 19 countries in patients with unresectable pleural or peritoneal malignant mesothelioma who had progressed after one or two previous systemic treatments for advanced disease. Eligible patients were aged 18 years or older with Eastern Cooperative Oncology Group performance status of 0 or 1 and measurable disease as defined in the modified Response Evaluation Criteria In Solid Tumors (RECIST) version 1.0 for pleural mesothelioma or RECIST version 1.1 for peritoneal mesothelioma. Patients were randomly assigned (2:1) in blocks of three, stratified by European Organisation for Research and Treatment of Cancer status (low risk vs high risk), line of therapy (second line vs third line), and anatomic site (pleural vs peritoneal), by use of an interactive voice or web system, to receive intravenous tremelimumab (10 mg/kg) or placebo every 4 weeks for 7 doses and every 12 weeks thereafter until a treatment discontinuation criterion was met. The primary endpoint was overall survival in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study drug. The trial is ongoing but no longer recruiting participants, and is registered with ClinicalTrials.gov, number NCT01843374. FINDINGS: Between May 17, 2013, and Dec 4, 2014, 571 patients were randomly assigned to receive tremelimumab (n=382) or placebo (n=189), of whom 569 patients received treatment (two patients in the tremelimumab group were excluded from the safety population because they did not receive treatment). At the data cutoff date (Jan 24, 2016), 307 (80%) of 382 patients had died in the tremelimumab group and 154 (81%) of 189 patients had died in the placebo group. Median overall survival in the intention-to-treat population did not differ between the treatment groups: 7·7 months (95% CI 6·8-8·9) in the tremelimumab group and 7·3 months (5·9-8·7) in the placebo group (hazard ratio 0·92 [95% CI 0·76-1·12], p=0·41). Treatment-emergent adverse events of grade 3 or worse occurred in 246 (65%) of 380 patients in the tremelimumab group and 91 (48%) of 189 patients in the placebo group; the most common were dyspnoea (34 [9%] patients in the tremelimumab group vs 27 [14%] patients in the placebo group), diarrhoea (58 [15%] vs one [<1%]), and colitis (26 [7%] vs none). The most common serious adverse events were diarrhoea (69 [18%] patients in the tremelimumab group vs one [<1%] patient in the placebo group), dyspnoea (29 [8%] vs 24 [13%]), and colitis (24 [6%] vs none). Treatment-emergent events leading to death occurred in 36 (9%) of 380 patients in the tremelimumab group and 12 (6%) of 189 in the placebo group; those leading to the death of more than one patient were mesothelioma (three [1%] patients in the tremelimumab group vs two [1%] in the placebo group), dyspnoea (three [1%] vs two [1%]); respiratory failure (one [<1%] vs three [2%]), myocardial infarction (three [1%] vs none), lung infection (three [1%] patients vs none), cardiac failure (one [<1%] vs one [<1%]), and colitis (two [<1%] vs none). Treatment-related adverse events leading to death occurred in five (1%) patients in the tremelimumab group and none in the placebo group. The causes of death were lung infection in one patient, intestinal perforation and small intestinal obstruction in one patient; colitis in two patients, and neuritis and skin ulcer in one patient. INTERPRETATION: Tremelimumab did not significantly prolong overall survival compared with placebo in patients with previously treated malignant mesothelioma. The safety profile of tremelimumab was consistent with the known safety profile of CTLA-4 inhibitors. Investigations into whether immunotherapy combination regimens can provide greater efficacy than monotherapies in malignant mesothelioma are ongoing. FUNDING: AstraZeneca.

A new synonym-substitution method to enrich the human phenotype ontology.

BACKGROUND: Named entity recognition is critical for biomedical text mining, where it is not unusual to find entities labeled by a wide range of different terms. Nowadays, ontologies are one of the crucial enabling technologies in bioinformatics, providing resources for improved natural language processing tasks. However, biomedical ontology-based named entity recognition continues to be a major research problem. RESULTS: This paper presents an automated synonym-substitution method to enrich the Human Phenotype Ontology (HPO) with new synonyms. The approach is mainly based on both the lexical properties of the terms and the hierarchical structure of the ontology. By scanning the lexical difference between a term and its descendant terms, the method can learn new names and modifiers in order to generate synonyms for the descendant terms. By searching for the exact phrases in MEDLINE, the method can automatically rule out illogical candidate synonyms. In total, 745 new terms were identified. These terms were indirectly evaluated through the concept annotations on a gold standard corpus and also by document retrieval on a collection of abstracts on hereditary diseases. A moderate improvement in the F-measure performance on the gold standard corpus was observed. Additionally, 6% more abstracts on hereditary diseases were retrieved, and this percentage was 33% higher if only the highly informative concepts were considered. CONCLUSIONS: A synonym-substitution procedure that leverages the HPO hierarchical structure works well for a reliable and automatic extension of the terminology. The results show that the generated synonyms have a positive impact on concept recognition, mainly those synonyms corresponding to highly informative HPO terms.

An ontology-aware integration of clinical models, terminologies and guidelines: an exploratory study of the Scale for the Assessment and Rating of Ataxia (SARA).

BACKGROUND: Electronic rating scales represent an important resource for standardized data collection. However, the ability to exploit reasoning on rating scale data is still limited. The objective of this work is to facilitate the integration of the semantics required to automatically interpret collections of standardized clinical data. We developed an electronic prototype for the Scale of the Assessment and Rating of Ataxia (SARA), broadly used in neurology. In order to address the modeling challenges of the SARA, we propose to combine the best performances from OpenEHR clinical archetypes, guidelines and ontologies. METHODS: A scaled-down version of the Human Phenotype Ontology (HPO) was built, extracting the terms that describe the SARA tests from free-text sources. This version of the HPO was then used as backbone to normalize the content of the SARA through clinical archetypes. The knowledge required to exploit reasoning on the SARA data was modeled as separate information-processing units interconnected via the defined archetypes. Each unit used the most appropriate technology to formally represent the required knowledge. RESULTS: Based on this approach, we implemented a prototype named SARA Management System, to be used for both the assessment of cerebellar syndrome and the production of a clinical synopsis. For validation purposes, we used recorded SARA data from 28 anonymous subjects affected by Spinocerebellar Ataxia Type 36 (SCA36). When comparing the performance of our prototype with that of two independent experts, weighted kappa scores ranged from 0.62 to 0.86. CONCLUSIONS: The combination of archetypes, phenotype ontologies and electronic information-processing rules can be used to automate the extraction of relevant clinical knowledge from plain scores of rating scales. Our results reveal a substantial degree of agreement between the results achieved by an ontology-aware system and the human experts.

The Brazilian Cardioprotective Nutritional Program to reduce events and risk factors in secondary prevention for cardiovascular disease: study protocol (The BALANCE Program Trial).

This article reports the rationale for the Brazilian Cardioprotective Nutritional Program (BALANCE Program) Trial. This pragmatic, multicenter, nationwide, randomized, concealed, controlled trial was designed to investigate the effects of the BALANCE Program in reducing cardiovascular events. The BALANCE Program consists of a prescribed diet guided by nutritional content recommendations from Brazilian national guidelines using a unique nutritional education strategy, which includes suggestions of affordable foods. In addition, the Program focuses on intensive follow-up through one-on-one visits, group sessions, and phone calls. In this trial, participants 45 years or older with any evidence of established cardiovascular disease will be randomized to the BALANCE or control groups. Those in the BALANCE group will receive the afore mentioned program interventions, while controls will be given generic advice on how to follow a low-fat, low-energy, low-sodium, and low-cholesterol diet, with a view to achieving Brazilian nutritional guideline recommendations. The primary outcome is a composite of death (any cause), cardiac arrest, acute myocardial infarction, stroke, myocardial revascularization, amputation for peripheral arterial disease, or hospitalization for unstable angina. A total of 2468 patients will be enrolled in 34 sites and followed up for up to 48 months. If the BALANCE Program is found to decrease cardiovascular events and reduce risk factors, this may represent an advance in the care of patients with cardiovascular disease.

Ceftaroline fosamil versus ceftriaxone for the treatment of community-acquired pneumonia: individual patient data meta-analysis of randomized controlled trials.

BACKGROUND: We conducted a meta-analysis of clinical trials of adults hospitalized with pneumonia outcomes research team (PORT) risk class 3-4 community-acquired pneumonia (CAP) receiving ceftaroline fosamil versus ceftriaxone. METHODS: Three Phase III trials (clinicaltrials.gov registration numbers NCT00621504, NCT00509106 and NCT01371838) including 1916 hospitalized patients with CAP randomized 1:1 to empirical ceftaroline fosamil (600 mg every 12 h) or ceftriaxone (1-2 g every 24 h) for 5-7 days were included in the meta-analysis. Primary outcome was clinical response at the test-of-cure visit (8-15 days after end of treatment) in the PORT risk class 3-4 modified ITT (MITT) and clinically evaluable (CE) populations. Data were tested for heterogeneity (χ(2) test) and, if not significant, results were pooled and OR and 95% CI constructed. A logistic regression analysis assessed factors impacting cure rate and treatment interactions. RESULTS: Clinical cure rates in each trial consistently favoured ceftaroline fosamil versus ceftriaxone, with no evidence of heterogeneity. In the meta-analysis, ceftaroline fosamil was superior to ceftriaxone in the MITT (OR: 1.66; 95% CI 1.34, 2.06; P < 0.001) and CE (OR: 1.65; 95% CI 1.26, 2.16; P < 0.001) populations. Results were consistent across various patient- and disease-related factors including patients' age and PORT score. Prior antimicrobial use within 96 h of starting study treatment was associated with diminished differences in cure rates between treatments. CONCLUSIONS: Ceftaroline fosamil was superior to ceftriaxone for empirical treatment of adults hospitalized with CAP. Receipt of prior antimicrobial therapy appeared to diminish the observed treatment effect.

Leaching of Copper Concentrates with Iodized Salts in a Saline Acid Medium: Part 2-Effect on Chloride Concentration and an Aerated System.

To enhance the leaching of chalcopyrite concentrates, this study evaluated a new process for extracting copper using iodized solutions and sulfuric acid diluted in seawater without pressure or high temperatures. The work involved a leaching test carried out under various conditions by varying the concentrations of chloride ions, H2SO4, and an evenly distributed oxygen supply in an aeration system. It was demonstrated that Cl- ion addition could promote the chalcopyrite-leaching process. The leaching efficiency of copper reached 70% after 96 h. However, a chloride ion dosage excess can have the opposite effect on extraction, reducing copper recovery. XRD and SEM-EDS results showed that cuprous chloride (CuCl) was formed at high dosages (>0.5 M); meanwhile, at a lower dosage, elemental sulfur (S) was formed in the presence of sulfuric acid solution and seawater medium. In contrast, in an aerated system, surface roughness markedly increased due to continuous oxidation on the surface of the ore. This change in morphology and the high value of the redox potential, given by the aerated system and the acidic environment, allowed copper recovery of up to 70% after 96 h. The results showed that an aerated system is the most effective factor in chalcopyrite concentrate leaching.

Leaching of Copper Concentrate with Iodized Salts in a Saline Acid Medium: Part 1-Effect of Concentrations.

One of the main problems in processing chalcopyrite ore with hydrometallurgical methods is its refractoriness, which is due to the formation of a layer that inhibits the contact of the ore with the leaching solution, thus reducing the dissolution rate. The main objective of this paper is to evaluate the leaching potential of iodide ions in copper extraction from chalcopyrite concentrate in an acidic seawater medium. Leaching tests were carried out in glass reactors stirred at 45 °C. Parameters such as iodide salt concentration and acidity were evaluated in ranges of 0-5000 ppm and 0-1.0 M, respectively. According to the results obtained, adding iodide ions to a medium acid enhances the leaching kinetics in the chalcopyrite concentrate, observing that it improves copper extraction at low concentrations of 100 ppm KI compared to high concentrations of 5000 ppm KI. As a result, part of the iodide required to oxidize copper tends to sublimate or is associated with other ions producing iodinated compounds such as CuI. Copper extraction reached 45% within the first 96 h, while at 216 h, it reached an extraction of close to 70% copper. The recovery rate improves at potentials between 600 and 650 mV, while at lower potentials, the copper extraction decreases. The mineral surface was analyzed using SEM/EDS and XRD analyses for the identification of precipitates on the surface, finding porous elemental sulfur and precipitated jarosite. An increase in iodide ions improves the leaching kinetics in the chalcopyrite concentrate, observing that it improves copper extraction at low concentrations of 100 ppm KI compared to high concentrations of 5000 ppm KI. As a result, part of the iodide required to oxidize copper tends to sublimate or is associated with other ions producing iodinated compounds such as CuI. Copper extraction reached 45% within the first 96 h, while at 216 h, it reached an extraction of close to 70% copper. The recovery rate improves at potentials between 600 and 650 mV, while at lower potentials, the copper extraction decreases. The mineral surface was analyzed using SEM/EDS and XRD analyses for the identification of precipitates on the surface, finding porous elemental sulfur and precipitated jarosite.

Querying phenotype-genotype relationships on patient datasets using semantic web technology: the example of Cerebrotendinous xanthomatosis.

BACKGROUND: Semantic Web technology can considerably catalyze translational genetics and genomics research in medicine, where the interchange of information between basic research and clinical levels becomes crucial. This exchange involves mapping abstract phenotype descriptions from research resources, such as knowledge databases and catalogs, to unstructured datasets produced through experimental methods and clinical practice. This is especially true for the construction of mutation databases. This paper presents a way of harmonizing abstract phenotype descriptions with patient data from clinical practice, and querying this dataset about relationships between phenotypes and genetic variants, at different levels of abstraction. METHODS: Due to the current availability of ontological and terminological resources that have already reached some consensus in biomedicine, a reuse-based ontology engineering approach was followed. The proposed approach uses the Ontology Web Language (OWL) to represent the phenotype ontology and the patient model, the Semantic Web Rule Language (SWRL) to bridge the gap between phenotype descriptions and clinical data, and the Semantic Query Web Rule Language (SQWRL) to query relevant phenotype-genotype bidirectional relationships. The work tests the use of semantic web technology in the biomedical research domain named cerebrotendinous xanthomatosis (CTX), using a real dataset and ontologies. RESULTS: A framework to query relevant phenotype-genotype bidirectional relationships is provided. Phenotype descriptions and patient data were harmonized by defining 28 Horn-like rules in terms of the OWL concepts. In total, 24 patterns of SWQRL queries were designed following the initial list of competency questions. As the approach is based on OWL, the semantic of the framework adapts the standard logical model of an open world assumption. CONCLUSIONS: This work demonstrates how semantic web technologies can be used to support flexible representation and computational inference mechanisms required to query patient datasets at different levels of abstraction. The open world assumption is especially good for describing only partially known phenotype-genotype relationships, in a way that is easily extensible. In future, this type of approach could offer researchers a valuable resource to infer new data from patient data for statistical analysis in translational research. In conclusion, phenotype description formalization and mapping to clinical data are two key elements for interchanging knowledge between basic and clinical research.

Preliminary study of the specific endothelin a receptor antagonist zibotentan in combination with docetaxel in patients with metastatic castration-resistant prostate cancer.

BACKGROUND: This two-part study assessed the safety and tolerability of combined treatment with zibotentan (ZD4054), a specific endothelin A receptor antagonist, plus docetaxel in patients with metastatic castration-resistant prostate cancer. METHODS: Part A was an open-label, dose-finding phase to determine the safety and toxicity profile of zibotentan in combination with docetaxel. Patients received once-daily oral zibotentan 10 mg (initial cohort) or 15 mg in combination with docetaxel 75 mg/m(2) (administered on day 1 of each 21-day cycle) for up to 10 cycles. Part B was a double-blind phase which evaluated the safety and preliminary activity of zibotentan plus docetaxel. Patients were randomized 2:1 to receive zibotentan (at the highest tolerated dose identified in part A) plus docetaxel or placebo plus docetaxel. RESULTS: Six patients were enrolled in part A (n = 3, zibotentan 10 mg; n = 3, zibotentan 15 mg). No dose-limiting toxicity was observed, thus zibotentan 15 mg in combination with docetaxel was evaluated in part B (n = 20, zibotentan plus docetaxel; n = 11, placebo plus docetaxel). CTCAE grade ≥3, most commonly neutropenia or leucopenia, were reported in 10 (50%) and nine (82%) patients in the zibotentan and placebo groups, respectively. One (17%) patient receiving placebo achieved complete response, two (22%) patients receiving zibotentan achieved partial response and stable disease occurred in six (67%) and three (50%) patients receiving zibotentan and placebo, respectively. CONCLUSIONS: The tolerability of zibotentan plus docetaxel was consistent with the known profiles of each drug. Sufficient preliminary activity was seen with this combination to merit continued development.

Pharmacokinetics and tolerability of zibotentan (ZD4054) in subjects with hepatic or renal impairment: two open-label comparative studies.

BACKGROUND: Zibotentan (ZD4054) is a specific endothelin A (ETA) receptor antagonist being investigated for the treatment of prostate cancer. As zibotentan is eliminated by renal and metabolic routes, clearance may be reduced in patients with hepatic or renal impairment, leading to greater drug exposure. METHODS: Open-label studies investigated the PK and tolerability of zibotentan in subjects with hepatic or renal impairment, compared with those with normal organ function. In the hepatic and renal studies, respectively, subjects were divided into categories using Child-Pugh classification or 24-hour urine creatinine clearance (mild, moderate, or severe impairment and normal function). Each subject received a single oral dose of zibotentan 10 mg and PK sampling was undertaken. Within the hepatic study, AUC and Cmax were expressed as the ratio of geometric means and 90% CI for each impairment group compared with the normal function group. The possibility that hepatic impairment had a clinically relevant effect on exposure was considered if the upper 90% CI for the ratio exceeded 2. In the renal study, AUC, Cmax and t1/2 were analyzed using linear regression fitting effects for creatinine clearance and age. RESULTS: In the hepatic and renal studies respectively, 32 subjects (eight per group) and 48 subjects received treatment (n = 18 normal, n = 12 mild, n = 9 moderate, n = 9 severe). Zibotentan Cmax was not significantly affected by hepatic or renal impairment. Compared with the normal function group, zibotentan AUC was 40% (1.40; 90% CI 0.91-2.17), 45% (1.45; 90% CI 0.94-2.24) and 190% (2.90; 90% CI 1.88-4.49) higher in subjects with mild, moderate and severe hepatic impairment, respectively, and 66% (1.66; 90% CI 1.38-1.99), 89% (1.89; 90% CI 1.50-2.39) and 117% (2.17; 90% CI 1.64-2.86) higher in subjects with mild, moderate and severe renal impairment, respectively. In both studies mean t1/2 increased and zibotentan clearance decreased with the degree of impairment. Headache was the most common AE in all groups. CONCLUSIONS: Zibotentan absorption was unchanged, however, exposure was higher in subjects with hepatic or renal impairment due to slower clearance. This increased exposure did not result in differences in the range or severity of AEs observed. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00672581 and AstraZeneca study number D4320C00016 (renal trial; conducted in Germany).

Executive Functioning: A Mediator Between Sensory Processing and Behaviour in Autism Spectrum Disorder.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interaction, executive functioning, sensory-perceptual abilities and behaviour, such as anxious/depressed states, attention problems, aggression, or somatic complains. However, the dynamic relationship between these dimensions remains to be addressed. Therefore, we explored the link between executive functions, sensory processing and behaviour in 79 children and adolescents with ASD. Results showed significant associations between all dimensions-executive functions, sensory processing and behaviour. Furthermore, using structural equation modelling methods, we observed a mediation effect of executive functioning, specifically the domain pertaining to emotion regulation and control, and in the relationship between sensory processing abnormalities and behavioural problems. We discuss the importance of emotion regulation as a mediator between sensory processing and behavioural impairments and its impact in social competence in ASD.

Geometric stability and lens decentering in compact digital cameras.

A study on the geometric stability and decentering present in sensor-lens systems of six identical compact digital cameras has been conducted. With regard to geometrical stability, the variation of internal geometry parameters (principal distance, principal point position and distortion parameters) was considered. With regard to lens decentering, the amount of radial and tangential displacement resulting from decentering distortion was related with the precision of the camera and with the offset of the principal point from the geometric center of the sensor. The study was conducted with data obtained after 372 calibration processes (62 per camera). The tests were performed for each camera in three situations: during continuous use of the cameras, after camera power off/on and after the full extension and retraction of the zoom-lens. Additionally, 360 new calibrations were performed in order to study the variation of the internal geometry when the camera is rotated. The aim of this study was to relate the level of stability and decentering in a camera with the precision and quality that can be obtained. An additional goal was to provide practical recommendations about photogrammetric use of such cameras.

Thermodynamic Model for the Design of a Process of Production of Copper Sulfate Pentahydrate from Copper Ores.

In Chile, one of the ways in which small-scale mining industries sustain themselves is through the sale of copper ores to the state company ENAMI, which monetizes this product depending on the copper's mineral grade. To sell this mineral, small mining companies must transport the product to ENAMI, which means a high monetary cost, added to the fact that there are large amounts of waste minerals that cannot be sold because of their low grade. The present work aims that small miners can process these copper ores in situ to commercialize a more valuable product, such as copper salts. Considering the high solar radiation and the scarce superficial water resources found in the north side of the country, a possible process alternative is the leaching of the ores using acid seawater solutions followed by crystallization by solar evaporation. As a necessary tool for this process design, the present work has developed a model able to predict the copper sulfate pentahydrate crystallization from multicomponent solutions, preventing the co-precipitation of undesired compounds (such as iron salts, sodium chloride, and sodium sulphate among others) that contaminate the final product. The Pitzer thermodynamic model was successfully applied to predict the crystallization process of copper sulfate pentahydrate from synthetic leaching solutions. These results were validated through experimental tests.

Three-Year Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC-Update from PACIFIC.

INTRODUCTION: In the phase 3 PACIFIC study of patients with unresectable stage III NSCLC without progression after chemoradiotherapy, durvalumab demonstrated significant improvements versus placebo in the primary end points of progression-free survival (hazard ratio [HR] = 0.52, 95% confidence interval [CI]: 0.42-65, p < 0.0001) and overall survival (OS) (HR = 0.68, 95% CI: 0.53-0.87, p = 0.00251), with manageable safety and no detrimental effect on patient-reported outcomes. Here, we report 3-year OS rates for all patients randomized in the PACIFIC study. METHODS: Patients, stratified by age, sex, and smoking history, were randomized (2:1) to receive durvalumab, 10 mg/kg intravenously every 2 weeks, or placebo for up to 12 months. OS was analyzed by using a stratified log-rank test in the intention-to-treat population. Medians and rates at 12, 24, and 36 months were estimated by the Kaplan-Meier method. RESULTS: As of January 31, 2019, 48.2% of patients had died (44.1% and 56.5% in the durvalumab and placebo groups, respectively). The median duration of follow-up was 33.3 months. The updated OS remained consistent with that previously reported (stratified HR = 0.69 [95% CI: 0.55-0.86]); the median OS was not reached with durvalumab but was 29.1 months with placebo. The 12-, 24- and 36-month OS rates with durvalumab and placebo were 83.1% versus 74.6%, 66.3% versus 55.3%, and 57.0% versus 43.5%, respectively. All secondary outcomes examined showed improvements consistent with previous analyses. CONCLUSIONS: Updated OS data from PACIFIC, including 3-year survival rates, demonstrate the long-term clinical benefit with durvalumab after chemoradiotherapy and further establish the PACIFIC regimen as the standard of care in this population.

[Erectile dysfunction as a marker of silent cardiovascular disease in type-2 diabetic patients in Spain. The DIVA (DIabetes and VAscular disease) study]. / Disfunción eréctil como marcador de vasculopatía en la diabetes mellitus tipo 2 en España. Estudio DIVA.

BACKGROUND AND OBJECTIVES: Erectile dysfunction (ED) is a sign of vascular disease in type 2 diabetic patients. The present subanalysis of the DIVA Registry, whose main objective was to estimate the prevalence of clinical vascular disorder and silent vascular disorder, as well as risk factors in type 2 diabetic patients treated in Spain, aims to analyze the relationship between those data and the prevalence of ED in these patients. PATIENTS AND METHODS: A total of 2444 type 2 diabetic patients (56% male; mean age 65.2 years) attended by 387 cardiologists and endocrinologists at ambulatory care were included. RESULTS: Coronary heart disease was present in 37% of the patients, cerebrovascular disease in 12%, and peripheral arterial disease in 13%. Forty percent of male patients had ED (according to the IIEF criteria), although in this group, as compared to those patients without ED, the prevalence of cardiovascular disease and signs of subclinical vascular disorder (microalbuminuria and abnormal ankle/brachial index (ABI)) was higher. The only independent predictor of ED was left ventricular hypertrophy (OR 5.2; 95% CI: 1.1-24.1; P=.03), with the ABI <0,9 being of borderline significance (OR 5.9; 95% CI: 0.9-39.9; P=.06). Poor glycemic and lipemic control (P<.05 in both cases) as well as cerebrovascular and peripheral arterial disease (P<.01 in both cases) and renal dysfunction (P<.001) were all more frequent among patients with severe ED. CONCLUSIONS: Forty percent of diabetic patients suffer from ED. The results of this study suggest that ED may be considered as an atherosclerosis marker and could be included in algorithms for risk stratification and subclinical vascular disorder detection.