Transient Cenozoic tectonic stages in the southern margin of the Caribbean plate : U-Th/He thermochronological constraints from Eocene plutonic rocks in the Santa Marta massif and Serranía de Jarara, northern Colombia

We use U-Th/(He) zircon and apatite thermochronology and Al in hornblende geobarometry from Eocene granitoids of the Sierra Nevada de Santa Marta and Guajira uplifted massifs in northern Colombia to elucidate the exhumation history of the northern South America continental margin and its bearing to Cenozoic Caribbean- South American plate interactions. Aluminium in hornblende geobarometry from the Eocene Santa Marta batholith yields pressures between 4.9±0.6kbar and 6.4±0.6kbar, which indicate that at least, 14.7-19.2km of unroofing took place since 56-50Ma in the northwestern Sierra Nevada de Santa Marta. In the Guajira Peninsula, calculated pressures for the Eocene Parashi stock are 2.3±0.6kbar and 3±0.6kbar. Stratigraphic considerations pertaining to Oligocene conglomerates from the Guajira area suggest that 6.9-9km of crust was lost between 50Ma and ca. 26Ma. U-Th/He zircon and apatite thermochronology from granitoids in the Sierra Nevada de Santa Marta shows the existence of major exhumation events in the Late Eocene (ca. 45-40Ma), Late Oligocene (ca. 25Ma) and Miocene (ca. 15Ma). The Guajira region records the Late Eocene to Early Oligocene (35-25Ma) event, but it lacks evidence for the Miocene exhumation phase. These differences reflect isolation of the Guajira region from the Sierra Nevada de Santa Marta and the Andean chain due to extensive block rotation and transtensional tectonics that affected the region during post-Eocene times. The post-Eocene events correlate in time with an increased convergence rate and the frontal approach of North and South America. It is suggested that the two major tectonic mechanisms that govern exhumation in these Caribbean massifs are: 1) subduction of the Caribbean plate, and 2) post Eocene changes in plate convergence obliquity and rates that caused the South American continental margin blocks to override the Caribbean plate. Temporal correlation with other Caribbean and Northern Andean events allows to resolve the regional Cenozoic plate tectonic reorganizations experienced by the South American, Caribbean and Pacific plates at a regional scale

Casting Fe-Al-based intermetallics microalloyed with Li and Ag

The effect on the mechanical properties at room temperature of Li and Ag additions to the Fe–Al (40 at.%)-based alloy produced by conventional casting were evaluated in this work. Alloying elements were added into a previously molted Fe–(40 at.%) aluminum-based alloy, stirred, and then cast into sand molds to directly produce tensile specimens. To determine the mechanical properties, tensile tests and hardness measurements were performed. The additions of both Ag and Li showed an increase in ductility and tensile strength of the intermetallic alloys. In addition, hardness was substantially increased with the Li addition. Lithium additions promoted a solid solution hardening, whereas 3 at.% of Ag additions promoted ductility due to a microstructural modification and to the formation of a soft Ag 3 Al phase. Characterization by both optical and electronic microscopy, energy dispersive spectroscopy microanalysis, and x-ray diffraction supported the mechanical characterization.Peer ReviewedPostprint (author's final draft

Multiple Anticancer Effects of Damsin and Coronopilin Isolated from Ambrosia arborescens on Cell Cultures

Terpenoids in plants are important sources for drug discovery. In this study, we extracted damsin and coronopilin, two sesquiterpene lactones, from Ambrosia arborescens and examined their anticancer effects on cell cultures. Damsin and coronopilin inhibited cell proliferation, DNA biosynthesis and formation of cytoplasmic DNA histone complexes in Caco-2 cells, with damsin being more potent than coronopilin. Further studies using the luciferase reporter system showed that damsin and coronopilin also inhibited expressions of nuclear factor-κB (NF-κB) and signal transducer and activator of transcription-3 (STAT3), indicating that these sesquiterpenes can interfere with NF- κB and STAT3 pathways. Finally, we examined the effects of two synthetic dibrominated derivatives of damsin, 11α,13- dibromodamsin and 11β,13-dibromodamsin. While bromination appeared to weaken the antiproliferative effects of damsin, the β epimer had strong inhibitory effects on STAT3 activation. In conclusion, the sesquiterpene lactones damsin and coronopilin have inhibitory effects on cell proliferation, DNA biosynthesis and NF-κB and STAT3 pathways, thus being potentially important for discovery of drugs against cancer

Association Between Ventilatory Settings and Development of Acute Respiratory Distress Syndrome in Mechanically Ventilated Patients Due to Brain Injury

PURPOSE: In neurologically critically ill patients with mechanical ventilation (MV), the development of acute respiratory distress syndrome (ARDS) is a major contributor to morbidity and mortality, but the role of ventilatory management has been scarcely evaluated. We evaluate the association of tidal volume, level of PEEP and driving pressure with the development of ARDS in a population of patients with brain injury. MATERIALS AND METHODS: We performed a secondary analysis of a prospective, observational study on mechanical ventilation. RESULTS: We included 986 patients mechanically ventilated due to an acute brain injury (hemorrhagic stroke, ischemic stroke or brain trauma). Incidence of ARDS in this cohort was 3%. Multivariate analysis suggested that driving pressure could be associated with the development of ARDS (odds ratio for unit increment of driving pressure 1.12; confidence interval for 95%: 1.01 to 1.23) whereas we did not observe association for tidal volume (in ml per kg of predicted body weight) or level of PEEP. ARDS was associated with an increase in mortality, longer duration of mechanical ventilation, and longer ICU length of stay. CONCLUSIONS: In a cohort of brain-injured patients the development of ARDS was not common. Driving pressure was associated with the development of this disease.info:eu-repo/semantics/publishedVersio

Severe Hypercapnia and Outcome of Mechanically Ventilated Patients with Moderate or Severe Acute Respiratory Distress Syndrome

PURPOSE: To analyze the relationship between hypercapnia developing within the first 48 h after the start of mechanical ventilation and outcome in patients with acute respiratory distress syndrome (ARDS). PATIENTS AND METHODS: We performed a secondary analysis of three prospective non-interventional cohort studies focusing on ARDS patients from 927 intensive care units (ICUs) in 40 countries. These patients received mechanical ventilation for more than 12 h during 1-month periods in 1998, 2004, and 2010. We used multivariable logistic regression and a propensity score analysis to examine the association between hypercapnia and ICU mortality. MAIN OUTCOMES: We included 1899 patients with ARDS in this study. The relationship between maximum PaCO2 in the first 48 h and mortality suggests higher mortality at or above PaCO2 of ≥50 mmHg. Patients with severe hypercapnia (PaCO2 ≥50 mmHg) had higher complication rates, more organ failures, and worse outcomes. After adjusting for age, SAPS II score, respiratory rate, positive end-expiratory pressure, PaO2/FiO2 ratio, driving pressure, pressure/volume limitation strategy (PLS), corrected minute ventilation, and presence of acidosis, severe hypercapnia was associated with increased risk of ICU mortality [odds ratio (OR) 1.93, 95% confidence interval (CI) 1.32 to 2.81; p = 0.001]. In patients with severe hypercapnia matched for all other variables, ventilation with PLS was associated with higher ICU mortality (OR 1.58, CI 95% 1.04-2.41; p = 0.032). CONCLUSIONS: Severe hypercapnia appears to be independently associated with higher ICU mortality in patients with ARDS.info:eu-repo/semantics/publishedVersio

Validation of the diabetes, hypertension and hyperlipidemia (DHL) knowledge instrument in Malaysia

BACKGROUND: Patient's knowledge on diabetes, hypertension and hyperlipidaemia and its medications can be used as one of the outcome measures to assess the effectiveness of educational intervention. To date, no such instrument has been validated in Malaysia. Therefore, the aim of this study was to evaluate the validity and reliability of the Diabetes, Hypertension and Hyperlipidemia (DHL) knowledge instrument for assessing the knowledge of patients with type 2 diabetes in Malaysia. METHODS: A 28-item instrument which comprised of 5 domains: diabetes, hypertension, hyperlipidemia, medications and general issues was designed and tested. One point was given for every correct answer, whilst zero was given for incorrect answers. Scores ranged from 0 to 28, which were then converted into percentage. This was administered to 77 patients with type 2 diabetes in a tertiary hospital, who were on medication(s) for diabetes and who could understand English (patient group), and to 40 pharmacists (professional group). The DHL knowledge instrument was administered again to the patient group after one month. Excluded were patients less than 18 years old. RESULTS: Flesch reading ease was 60, which is satisfactory, while the mean difficulty factor(SD) was 0.74(0.21), indicating that DHL knowledge instrument was moderately easy. Internal consistency of the instrument was good, with Cronbach's alpha = 0.791. The test-retest scores showed no significant difference for 26 out of the 28 items, indicating that the questionnaire has achieved stable reliability. The overall mean(SD) knowledge scores was significantly different between the patient and professional groups 74.35(14.88) versus 93.84(6.47), p < 0.001. This means that the DHL knowledge instrument could differentiate the knowledge levels of participants. The DHL knowledge instrument shows similar psychometric properties as other validated questionnaires. CONCLUSIONS: The DHL knowledge instrument shows good promise to be adopted as an instrument for assessing diabetic patients' knowledge concerning their disease conditions and medications in Malaysia