Absence of detectable precursory deformation and velocity variation before the large dome collapse of july 2015 at volcan de Colima, Mexico

Improving the ability to foresee volcanic eruption is one of the main objectives of volcanologists. For this purpose, it is essential to better detect eruption forerunners and to understand their relationship with eruptive processes. The evaluation of the performance of the forecasting methods partly relies on the estimation of the frequency of occurrence of the various precursory phenomena. Possible lack of precursor before some events must also be carefully documented and analyzed. In this study, we check for the existence of detectable precursors before the large dome collapse event of Volcan de Colima, which occurred in July 2015, leading to the emplacement of more than 10 km long Pyroclastics Density Currents and the opening of a large breach in the crater. Based on volumes of emitted magma, the 2015 eruption is the largest event recorded at Volcan de Colima since the 1913 Plinian eruption. Surface displacements in the summit cone area are quantified over the period November 2014-June 2015 based on Synthetic Aperture Radar (SAR) images acquired by Sentinel-1 satellite. Velocity variations are investigated by coda wave interferometry. Daily cross-correlation functions of seismic noise recorded at 5 broadband stations are calculated for the period January 2013-April 2017 and apparent velocity variations are obtained by applying the stretching method. We show that no significant surface deformation can be measured by the SAR images over an area reaching 5 km from the summit, such that the volume of emitted magma cannot have been accommodated elastically in the 6 months preceding the eruption at a depth shallower than 5 km. The time series of apparent velocity variations display fluctuations of the order of 0.05% with characteristic time shorter than 1 month. Sharp velocity decreases of up to 0.2% are associated with strong regional tectonic earthquakes. However, no velocity change with amplitude larger than the noise level is observed before the July 2015 eruption. The behavior of the surface deformation and the velocity variation is consistent with the relative quiescence of the volcano-tectonic and low-frequency seismic activities observed before this large eruptive event. This situation could be frequent in case of so called open systems, where additional magma input is directly transferred to the surface, producing dome modification, without significant pressurization of the plumbing system

Long-period seismicity during magma movement at Volcan de Colima

During the period from February to September 2005, Volcan de Colima produced 30 Vulcanian explosions of sufficient magnitude to produce pyroclastic flows of variable size, with a total volume of at least 2.5 x 10(6) m(3). Swarms of long-period events were associated with each event, their duration ranging from about 6 h to 3 days and each swarm containing up to 886 events. The characteristics of the swarms have been studied to understand the source mechanism and their relationship with the Vulcanian explosions. In total, 12,548 long-period events were analysed using various comparative and statistical methods. Patterns were not apparent in the data with no correlation between different properties of the swarms (duration, magnitude or frequency of occurrence of LP events) and the magnitude of the associated Vulcanian explosion, whether recorded by seismicity, volume of pyroclastics or altitude of the eruption column. This, along with other characteristics of the swarms, such as the continuation of the swarm after the explosion, with an increase in long-period event amplitude in some cases, suggests that the mechanism is not merely associated with the pressurization under an impermeable cap and resulting pressure differentials between adjacent volumes within the system. It is more likely that the production of long-period events is dominated by brittle fracturing on the margins of an ascending magma body. A model is proposed whereby the unloading above the ascending magma column produced by a Vulcanian explosion resulted in an increase in ascent rate, reflected in the increasing amplitude of long-period events. The results reflect the complexity of non-linear processes involved during magma ascent, degassing, crystallization and rupture of the impermeable plug during the Vulcanian process. At Volcan de Colima, as at many volcanoes, long-period events represent a useful precursor for eruptive activity. For monitoring, this paper highlights some useful analyses that can be carried out, which could illustrate certain characteristics of an eruptive episode. A preliminary model is presented of the conduit processes at work during the cyclic extrusive and explosive activity during 2005

The anatomy of a pyroclastic density current: the 10 July 2015 event at Volcán de Colima (Mexico)

Pyroclastic density currents (PDCs) represent one of the most dangerous phenomena occurring in explosive volcanic eruptions, and any advance in the physical understanding of their transport and sedimentation processes can contribute to improving their hazard assessment. The 10–11 July 2015 eruption at Volcán de Colima provided a unique opportunity to better understand the internal behaviour of PDCs based on seismic monitoring data. On 10 July 2015, the summit dome collapsed, producing concentrated PDCs that filled the main channel of the Montegrande ravine. A lahar monitoring station installed 6 km from the volcano summit recorded a PDC before being completely destroyed. Real-time data acquisition from a camcorder and a geophone that were part of the station, along with field observations and grain-size data of the pyroclastic deposits, are used here to interpret the internal flow structure and time-variant transport dynamics of low-volume, valley-confined concentrated PDCs. The PDC that reached the monitoring station moved at a velocity of ~ 7 m/s and filled a 12-m-deep channel. The outcrops show massive, block-and-ash flow deposits with trains of coarse clasts in the middle and towards the top of the depositional units. The seismic record gathered with the geophone was analysed for the time window when the flow travelled past the sensor. The geophone record was also compared with the recordings of a broadband seismic station located nearby. Two main frequency ranges were recognised which could be correlated with the basal frictional forces exerted by the flow on the channel bed (10–20 Hz) and a collisional regime (20–40 Hz) interpreted to be associated with a clast segregation process (i.e. kinematic squeezing). This latter regime promoted the upward migration of large blocks, which subsequently deviated towards the margin of the flow where they interacted with the sidewall of the main channel. The energy calculated for both seismic components shows that the collisional regime represents 30% of the total energy including an important sidewall-stress component. These results, gathered directly from a moving flow, contribute to unravelling the internal behaviour of concentrated PDCs providing information on energy partitioning and particle-particle interactions. This confirms previous assumptions inferred from field observations, and tested by analogue or numerical modelling. The nature of the contact between grains is still poorly documented in natural PDCs, and there is still much uncertainty and discussion about dominant forces in such currents. Data reported here may thus be useful to better constrain the physics of low-volume, valley-confined concentrated PDCs and our findings need to be considered in theoretical models. In parallel, this study shows how geophones can provide a cheap alternative for PDC detection. © 2018, Springer-Verlag GmbH Germany, part of Springer Nature.This work was supported by the PAPIIT-DGAPA IN105116 project granted to L. Capra. V. Coviello is grateful for his DGAPA-UNAM postdoctoral fellowship, and D. Doronzo for his Juan de la Cierva contract (JdC 2015) – MINECO. The SPOT image was obtained through a collaborative agreement between the UNAM and the Agrifood-Fishery Mexican Service (SIAP) - ERMEX, under the license of BAirbus Defense & Space^.Peer reviewe

Lipoprotein(a) and Benefit of PCSK9 Inhibition in Patients With Nominally Controlled LDL Cholesterol

Background: Guidelines recommend nonstatin lipid-lowering agents in patients at very high risk for major adverse cardiovascular events (MACE) if low-density lipoprotein cholesterol (LDL-C) remains ≥70 mg/dL on maximum tolerated statin treatment. It is uncertain if this approach benefits patients with LDL-C near 70 mg/dL. Lipoprotein(a) levels may influence residual risk. Objectives: In a post hoc analysis of the ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial, the authors evaluated the benefit of adding the proprotein subtilisin/kexin type 9 inhibitor alirocumab to optimized statin treatment in patients with LDL-C levels near 70 mg/dL. Effects were evaluated according to concurrent lipoprotein(a) levels. Methods: ODYSSEY Outcomes compared alirocumab with placebo in 18,924 patients with recent acute coronary syndromes receiving optimized statin treatment. In 4,351 patients (23.0%), screening or randomization LDL-C was 13.7 mg/dL or ≤13.7 mg/dL; corresponding adjusted treatment hazard ratios were 0.82 (95% CI: 0.72-0.92) and 0.89 (95% CI: 0.75-1.06), with Pinteraction = 0.43. Conclusions: In patients with recent acute coronary syndromes and LDL-C near 70 mg/dL on optimized statin therapy, proprotein subtilisin/kexin type 9 inhibition provides incremental clinical benefit only when lipoprotein(a) concentration is at least mildly elevated. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402

Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients

BACKGROUN

Effects of alirocumab on cardiovascular and metabolic outcomes after acute coronary syndrome in patients with or without diabetes: a prespecified analysis of the ODYSSEY OUTCOMES randomised controlled trial

Background: After acute coronary syndrome, diabetes conveys an excess risk of ischaemic cardiovascular events. A reduction in mean LDL cholesterol to 1·4–1·8 mmol/L with ezetimibe or statins reduces cardiovascular events in patients with an acute coronary syndrome and diabetes. However, the efficacy and safety of further reduction in LDL cholesterol with an inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9) after acute coronary syndrome is unknown. We aimed to explore this issue in a prespecified analysis of the ODYSSEY OUTCOMES trial of the PCSK9 inhibitor alirocumab, assessing its effects on cardiovascular outcomes by baseline glycaemic status, while also assessing its effects on glycaemic measures including risk of new-onset diabetes. Methods: ODYSSEY OUTCOMES was a randomised, double-blind, placebo-controlled trial, done at 1315 sites in 57 countries, that compared alirocumab with placebo in patients who had been admitted to hospital with an acute coronary syndrome (myocardial infarction or unstable angina) 1–12 months before randomisation and who had raised concentrations of atherogenic lipoproteins despite use of high-intensity statins. Patients were randomly assigned (1:1) to receive alirocumab or placebo every 2 weeks; randomisation was stratified by country and was done centrally with an interactive voice-response or web-response system. Alirocumab was titrated to target LDL cholesterol concentrations of 0·65–1·30 mmol/L. In this prespecified analysis, we investigated the effect of alirocumab on cardiovascular events by glycaemic status at baseline (diabetes, prediabetes, or normoglycaemia)—defined on the basis of patient history, review of medical records, or baseline HbA1c or fasting serum glucose—and risk of new-onset diabetes among those without diabetes at baseline. The primary endpoint was a composite of death from coronary heart disease, non-fatal myocardial infarction, fatal or non-fatal ischaemic stroke, or unstable angina requiring hospital admission. ODYSSEY OUTCOMES is registered with ClinicalTrials.gov, number NCT01663402. Findings: At study baseline, 5444 patients (28·8%) had diabetes, 8246 (43·6%) had prediabetes, and 5234 (27·7%) had normoglycaemia. There were no significant differences across glycaemic categories in median LDL cholesterol at baseline (2·20–2·28 mmol/L), after 4 months' treatment with alirocumab (0·80 mmol/L), or after 4 months' treatment with placebo (2·25–2·28 mmol/L). In the placebo group, the incidence of the primary endpoint over a median of 2·8 years was greater in patients with diabetes (16·4%) than in those with prediabetes (9·2%) or normoglycaemia (8·5%); hazard ratio (HR) for diabetes versus normoglycaemia 2·09 (95% CI 1·78–2·46, p<0·0001) and for diabetes versus prediabetes 1·90 (1·65–2·17, p<0·0001). Alirocumab resulted in similar relative reductions in the incidence of the primary endpoint in each glycaemic category, but a greater absolute reduction in the incidence of the primary endpoint in patients with diabetes (2·3%, 95% CI 0·4 to 4·2) than in those with prediabetes (1·2%, 0·0 to 2·4) or normoglycaemia (1·2%, −0·3 to 2·7; absolute risk reduction pinteraction=0·0019). Among patients without diabetes at baseline, 676 (10·1%) developed diabetes in the placebo group, compared with 648 (9·6%) in the alirocumab group; alirocumab did not increase the risk of new-onset diabetes (HR 1·00, 95% CI 0·89–1·11). HRs were 0·97 (95% CI 0·87–1·09) for patients with prediabetes and 1·30 (95% CI 0·93–1·81) for those with normoglycaemia (pinteraction=0·11). Interpretation: After a recent acute coronary syndrome, alirocumab treatment targeting an LDL cholesterol concentration of 0·65–1·30 mmol/L produced about twice the absolute reduction in cardiovascular events among patients with diabetes as in those without diabetes. Alirocumab treatment did not increase the risk of new-onset diabetes. Funding: Sanofi and Regeneron Pharmaceuticals

Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients

Bococizumab is a humanized monoclonal antibody that inhibits proprotein convertase subtilisin- kexin type 9 (PCSK9) and reduces levels of low-density lipoprotein (LDL) cholesterol. We sought to evaluate the efficacy of bococizumab in patients at high cardiovascular risk. METHODS In two parallel, multinational trials with different entry criteria for LDL cholesterol levels, we randomly assigned the 27,438 patients in the combined trials to receive bococizumab (at a dose of 150 mg) subcutaneously every 2 weeks or placebo. The primary end point was nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina requiring urgent revascularization, or cardiovascular death; 93% of the patients were receiving statin therapy at baseline. The trials were stopped early after the sponsor elected to discontinue the development of bococizumab owing in part to the development of high rates of antidrug antibodies, as seen in data from other studies in the program. The median follow-up was 10 months. RESULTS At 14 weeks, patients in the combined trials had a mean change from baseline in LDL cholesterol levels of -56.0% in the bococizumab group and +2.9% in the placebo group, for a between-group difference of -59.0 percentage points (P<0.001) and a median reduction from baseline of 64.2% (P<0.001). In the lower-risk, shorter-duration trial (in which the patients had a baseline LDL cholesterol level of ≥70 mg per deciliter [1.8 mmol per liter] and the median follow-up was 7 months), major cardiovascular events occurred in 173 patients each in the bococizumab group and the placebo group (hazard ratio, 0.99; 95% confidence interval [CI], 0.80 to 1.22; P = 0.94). In the higher-risk, longer-duration trial (in which the patients had a baseline LDL cholesterol level of ≥100 mg per deciliter [2.6 mmol per liter] and the median follow-up was 12 months), major cardiovascular events occurred in 179 and 224 patients, respectively (hazard ratio, 0.79; 95% CI, 0.65 to 0.97; P = 0.02). The hazard ratio for the primary end point in the combined trials was 0.88 (95% CI, 0.76 to 1.02; P = 0.08). Injection-site reactions were more common in the bococizumab group than in the placebo group (10.4% vs. 1.3%, P<0.001). CONCLUSIONS In two randomized trials comparing the PCSK9 inhibitor bococizumab with placebo, bococizumab had no benefit with respect to major adverse cardiovascular events in the trial involving lower-risk patients but did have a significant benefit in the trial involving higher-risk patients

Apolipoprotein B, Residual Cardiovascular Risk After Acute Coronary Syndrome, and Effects of Alirocumab.

Background: Apolipoprotein B (apoB) provides an integrated measure of atherogenic risk. Whether apoB levels and apoB lowering hold incremental predictive information on residual risk after acute coronary syndrome beyond that provided by low-density lipoprotein cholesterol is uncertain. Methods: The ODYSSEY OUTCOMES trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) compared the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome and elevated atherogenic lipoproteins despite optimized statin therapy. Primary outcome was major adverse cardiovascular events (MACE; coronary heart disease death, nonfatal myocardial infarction, fatal/nonfatal ischemic stroke, hospitalization for unstable angina). Associations between baseline apoB or apoB at 4 months and MACE were assessed in adjusted Cox proportional hazards and propensity score–matched models. Results: Median follow-up was 2.8 years. In proportional hazards analysis in the placebo group, MACE incidence increased across increasing baseline apoB strata (3.2 [95% CI, 2.9–3.6], 4.0 [95% CI, 3.6–4.5], and 5.5 [95% CI, 5.0–6.1] events per 100 patient-years in strata 35–<50, and ≤35 mg/dL, respectively). Compared with propensity score–matched patients from the placebo group, treatment hazard ratios for alirocumab also decreased monotonically across achieved apoB strata. Achieved apoB was predictive of MACE after adjustment for achieved low-density lipoprotein cholesterol or non–high-density lipoprotein cholesterol but not vice versa. Conclusions: In patients with recent acute coronary syndrome and elevated atherogenic lipoproteins, MACE increased across baseline apoB strata. Alirocumab reduced MACE across all strata of baseline apoB, with larger absolute reductions in patients with higher baseline levels. Lower achieved apoB was associated with lower risk of MACE, even after accounting for achieved low-density lipoprotein cholesterol or non–high-density lipoprotein cholesterol, indicating that apoB provides incremental information. Achievement of apoB levels as low as ≤35 mg/dL may reduce lipoprotein-attributable residual risk after acute coronary syndrome. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01663402.gov; Unique identifier: NCT01663402.URL: https://www