Fast parallel kriging-based stepwise uncertainty reduction with application to the identification of an excursion set

Stepwise uncertainty reduction (SUR) strategies aim at constructing a sequence of points for evaluating a function  f in such a way that the residual uncertainty about a quantity of interest progressively decreases to zero. Using such strategies in the framework of Gaussian process modeling has been shown to be efficient for estimating the volume of excursion of f above a fixed threshold. However, SUR strategies remain cumbersome to use in practice because of their high computational complexity, and the fact that they deliver a single point at each iteration. In this article we introduce several multipoint sampling criteria, allowing the selection of batches of points at which f can be evaluated in parallel. Such criteria are of particular interest when f is costly to evaluate and several CPUs are simultaneously available. We also manage to drastically reduce the computational cost of these strategies through the use of closed form formulas. We illustrate their performances in various numerical experiments, including a nuclear safety test case. Basic notions about kriging, auxiliary problems, complexity calculations, R code, and data are available online as supplementary materials.

Plasma PCSK9 concentrations during an oral fat load and after short term high-fat, high-fat high-protein and high-fructose diets

Background PCSK9 (Proprotein Convertase Subtilisin Kexin type 9) is a circulating protein that promotes hypercholesterolemia by decreasing hepatic LDL receptor protein. Under non interventional conditions, its expression is driven by sterol response element binding protein 2 (SREBP2) and follows a diurnal rhythm synchronous with cholesterol synthesis. Plasma PCSK9 is associated to LDL-C and to a lesser extent plasma triglycerides and insulin resistance. We aimed to verify the effect on plasma PCSK9 concentrations of dietary interventions that affect these parameters. Methods We performed nutritional interventions in young healthy male volunteers and offspring of type 2 diabetic (OffT2D) patients that are more prone to develop insulin resistance, including: i) acute post-prandial hyperlipidemic challenge (n=10), ii) 4 days of high-fat (HF) or high-fat/high-protein (HFHP) (n=10), iii) 7 (HFruc1, n=16) or 6 (HFruc2, n=9) days of hypercaloric high-fructose diets. An acute oral fat load was also performed in two patients bearing the R104C-V114A loss-of-function (LOF) PCSK9 mutation. Plasma PCSK9 concentrations were measured by ELISA. For the HFruc1 study, intrahepatocellular (IHCL) and intramyocellular lipids were measured by 1H magnetic resonance spectroscopy. Hepatic and whole-body insulin sensitivity was assessed with a two-step hyperinsulinemic-euglycemic clamp (0.3 and 1.0 mU.kg-1.min-1). Findings HF and HFHP short-term diets, as well as an acute hyperlipidemic oral load, did not significantly change PCSK9 concentrations. In addition, post-prandial plasma triglyceride excursion was not altered in two carriers of PCSK9 LOF mutation compared with non carriers. In contrast, hypercaloric 7-day HFruc1 diet increased plasma PCSK9 concentrations by 28% (p=0.05) in healthy volunteers and by 34% (p=0.001) in OffT2D patients. In another independent study, 6-day HFruc2 diet increased plasma PCSK9 levels by 93% (p<0.0001) in young healthy male volunteers. Spearman’s correlations revealed that plasma PCSK9 concentrations upon 7-day HFruc1 diet were positively associated with plasma triglycerides (r=0.54, p=0.01) and IHCL (r=0.56, p=0.001), and inversely correlated with hepatic (r=0.54, p=0.014) and whole-body (r=−0.59, p=0.0065) insulin sensitivity. Conclusions Plasma PCSK9 concentrations vary minimally in response to a short term high-fat diet and they are not accompanied with changes in cholesterolemia upon high-fructose diet. Short-term high-fructose intake increased plasma PCSK9 levels, independent on cholesterol synthesis, suggesting a regulation independent of SREBP-2. Upon this diet, PCSK9 is associated with insulin resistance, hepatic steatosis and plasma triglycerides.

Echocardiogram versus cardiac magnetic resonance imaging for assessing systolic function of subaortic right ventricle in adults with complete transposition of great arteries and previous atrial switch operation

In adults with congenital heart disease and a systemic right ventricle, subaortic ventricular systolic dysfunction is common. Echocardiographic assessment of systolic right ventricular (RV) function in these patients is important but challenging. The aim of the present study was to assess the reliability of conventional echocardiographic RV functional parameters to quantify the systolic performance of a subaortic right ventricle. We compared 56 contemporary echocardiograms and cardiac magnetic resonance studies in 37 adults, aged 26.9 ± 7.4 years, with complete transposition and a subaortic right ventricle. The fractional area change (FAC), lateral tricuspid annular plane systolic excursion, lateral RV systolic motion velocities by tissue Doppler, RV myocardial performance index, and the rate of systolic RV pressure increase (dp/dt) measured across the tricuspid regurgitant jet were assessed by echocardiography and correlated with the cardiac magnetic resonance-derived RV ejection fraction (EF). The mean RVEF was 48.0 ± 7.8%. FAC (r(2) = 0.206, p = 0.001) and dp/dt (r(2) = 0.173, p = 0.009) significantly correlated with RVEF, and the other nongeometric echocardiographic parameters failed to show a significant correlation with RVEF by linear regression analysis. FAC <33% and dp/dt <1,000 mm Hg/s identified a RVEF of <50% with a sensitivity of 77% and 69% and a specificity of 58% and 87%, respectively. In conclusion, in patients with a systemic right ventricle, routine nongeometric echocardiographic parameters of RV function correlated weakly with cardiac magnetic resonance-derived EF. RV FAC and the measurement of the rate of systolic RV pressure increase (dp/dt) should be preferentially used to assess systemic systolic function in adult patients with a subaortic right ventricle.

Functions and effects of creatine in the central nervous system

Creatine kinase catalyses the reversible transphosphorylation of creatine by ATP. In the cell, creatine kinase isoenzymes are specifically localized at strategic sites of ATP consumption to efficiently regenerate ATP in situ via phosphocreatine or at sites of ATP generation to build-up a phosphocreatine pool. Accordingly, the creatine kinase/phosphocreatine system plays a key role in cellular energy buffering and energy transport, particularly in cells with high and fluctuating energy requirements like neurons. Creatine kinases are expressed in the adult and developing human brain and spinal cord, suggesting that the creatine kinase/phosphocreatine system plays a significant role in the central nervous system. Functional impairment of this system leads to a deterioration in energy metabolism, which is phenotypic for many neurodegenerative and age-related diseases. Exogenous creatine supplementation has been shown to reduce neuronal cell loss in experimental paradigms of acute and chronic neurological diseases. In line with these findings, first clinical trials have shown beneficial effects of therapeutic creatine supplementation. Furthermore, creatine was reported to promote differentiation of neuronal precursor cells that might be of importance for improving neuronal cell replacement strategies. Based on these observations there is growing interest on the effects and functions of this compound in the central nervous system. This review gives a short excursion into the basics of the creatine kinase/phosphocreatine system and aims at summarizing findings and concepts on the role of creatine kinase and creatine in the central nervous system with special emphasis on pathological conditions and the positive effects of creatine supplementation.

Swimming as a model of task-specific locomotor retraining after spinal cord injury in the rat

BACKGROUND: The authors have shown that rats can be retrained to swim after a moderately severe thoracic spinal cord contusion. They also found that improvements in body position and hindlimb activity occurred rapidly over the first 2 weeks of training, reaching a plateau by week 4. Overground walking was not influenced by swim training, suggesting that swimming may be a task-specific model of locomotor retraining. OBJECTIVE: To provide a quantitative description of hindlimb movements of uninjured adult rats during swimming, and then after injury and retraining. METHODS: The authors used a novel and streamlined kinematic assessment of swimming in which each limb is described in 2 dimensions, as 3 segments and 2 angles. RESULTS: The kinematics of uninjured rats do not change over 4 weeks of daily swimming, suggesting that acclimatization does not involve refinements in hindlimb movement. After spinal cord injury, retraining involved increases in hindlimb excursion and improved limb position, but the velocity of the movements remained slow. CONCLUSION: These data suggest that the activity pattern of swimming is hardwired in the rat spinal cord. After spinal cord injury, repetition is sufficient to bring about significant improvements in the pattern of hindlimb movement but does not improve the forces generated, leaving the animals with persistent deficits. These data support the concept that force (load) and pattern generation (recruitment) are independent and may have to be managed together with respect to postinjury rehabilitation.

KrigInv: An efficient and user-friendly implementation of batch-sequential inversion strategies based on kriging

Several strategies relying on kriging have recently been proposed for adaptively estimating contour lines and excursion sets of functions under severely limited evaluation budget. The recently released R package KrigInv 3 is presented and offers a sound implementation of various sampling criteria for those kinds of inverse problems. KrigInv is based on the DiceKriging package, and thus benefits from a number of options concerning the underlying kriging models. Six implemented sampling criteria are detailed in a tutorial and illustrated with graphical examples. Different functionalities of KrigInv are gradually explained. Additionally, two recently proposed criteria for batch-sequential inversion are presented, enabling advanced users to distribute function evaluations in parallel on clusters or clouds of machines. Finally, auxiliary problems are discussed. These include the fine tuning of numerical integration and optimization procedures used within the computation and the optimization of the considered criteria.

Different Prognostic Value of Functional Right Ventricular Parameters in Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia

BACKGROUND -The value of standard two-dimensional transthoracic echocardiographic (TTE) parameters for risk stratification in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is controversial. METHODS AND RESULTS -We investigated the impact of right ventricular fractional area change (FAC) and tricuspid annulus plane systolic excursion (TAPSE) for prediction of major adverse cardiovascular events (MACE) defined as the occurrence of cardiac death, heart transplantation, survived sudden cardiac death, ventricular fibrillation, sustained ventricular tachycardia or arrhythmogenic syncope. Among 70 patients who fulfilled the 2010 ARVC/D Task Force Criteria and underwent baseline TTE, 37 (53%) patients experienced a MACE during a median follow-up period of 5.3 (IQR 1.8-9.8) years. Average values for FAC, TAPSE, and TAPSE indexed to body surface area (BSA) decreased over time (p=0.03 for FAC, p=0.03 for TAPSE and p=0.01 for TAPSE/BSA, each vs. baseline). In contrast, median right ventricular end-diastolic area (RVEDA) increased (p=0.001 vs. baseline). Based on the results of Kaplan-Meier estimates, the time between baseline TTE and experiencing MACE was significantly shorter for patients with FAC <23% (p<0.001), TAPSE <17mm (p=0.02) or right atrial (RA) short axis/BSA ≥25mm/m(2) (p=0.04) at baseline. A reduced FAC constituted the strongest predictor of MACE (hazard ratio 1.08 per 1% decrease; 95% confidence interval 1.04-1.12; p<0.001) on bivariable analysis. CONCLUSIONS -This long-term observational study indicates that TAPSE and dilation of right-sided cardiac chambers are associated with an increased risk for MACE in ARVC/D patients with advanced disease and a high risk for adverse events. However, FAC is the strongest echocardiographic predictor of adverse outcome in these patients. Our data advocate a role for TTE in risk stratification in patients with ARVC/D, although our results may not be generalizable to lower risk ARVC/D cohorts.

"Fascinating Voids: Alexander von Humboldt and the Myth of Chimborazo"

When Alexander von Humboldt reached the village of Calpi in the Andes on 22 June 1802, he was greeted with reverence and enthusiasm. Triumphal arches adorned with cotton, cloth, and silver decorated his path. The natives performed a dance in festive dress. A singer praised the explorer's expedition, which had departed three years earlier from the Spanish port of La Coruña. Like Odysseus on the isle of the Phaeacians, the traveler listened to a local rhapsodist singing about his heroic deeds. Before his adventure ended, it had already spun a popular myth. This episode, which Humboldt recorded in his diary, occurred at a significant moment. One day later, the “Second Discoverer of America” rose to even greater fame on an excursion marking in more ways than one the climax of his enterprise. Humboldt set out to climb Chimborazo (6,310 m/20,702 ft.), the mountain then thought to be the highest in the world. He was accompanied by the French botanist Aimé Bonpland (1773–1858) and the Creole nobleman and future activist Carlos Montúfar (1780–1816), as well as native guides and assistants. They climbed to heights never reached before, setting a new record and catapulting Humboldt to fame on both continents.

In situ dehydration behavior of zeolite-like pentagonite: A single-crystal X-ray study

The structural modifications upon heating of pentagonite, Ca(VO)(Si4O10)·4H2O (space group Ccm21, a=10.3708(2), b=14.0643(2), c=8.97810(10) Å, V=1309.53(3) Å3) were investigated by in situ temperature dependent single-crystal X-ray structure refinements. Diffraction data of a sample from Poona district (India) have been measured in steps of 25 up to 250 °C and in steps of 50 °C between 250 and 400 °C. Pentagonite has a porous framework structure made up by layers of silicate tetrahedra connected by V4+O5 square pyramids. Ca and H2O molecules are extraframework occupants. Room temperature diffraction data allowed refinement of H positions. The hydrogen-bond system links the extraframework occupants to the silicate layers and also interconnects the H2O molecules located inside the channels. Ca is seven-fold coordinated forming four bonds to O of the tetrahedral framework and three bonds to extraframework H2O. The H2O molecule at O9 showing a high displacement parameter is not bonded to Ca. The dehydration in pentagonite proceeds in three steps. At 100 °C the H2O molecule at O8 was released while O9 moved towards Ca. As a consequence the displacement parameter of H2O at O9 halved compared to that at room temperature. The unit-cell volume decreased to 1287.33(3) Å3 leading to a formula with 3H2O per formula unit (pfu). Ca remained seven-fold coordinated. At 175 °C Ca(VO)(Si4O10)·3H2O transformed into a new phase with 1H2O molecule pfu characterized by doubling of the c axis and the monoclinic space group Pn. Severe bending of specific TOT angles led to contraction of the porous three-dimensional framework. In addition, H2O at O9 was expelled while H2O at O7 approached a position in the center of the channel. The normalized volume decreased to 1069.44(9) Å3. The Ca coordination reduced from seven- to six-fold. At 225 °C a new anhydrous phase with space group Pna21 but without doubling of c had formed. Release of H2O at O7 caused additional contraction of TOT angles and volume reduction (V=1036.31(9) Å3). Ca adopted five-fold coordination. During heating excursion up to 400 °C this anhydrous phase remained preserved. Between room temperature and 225 °C the unit-cell volume decreased by 21% due to dehydration. The dehydration steps compare well with the thermo-gravimetric data reported in the literature.

Direct linking of Greenland and Antarctic ice cores at the Toba eruption (74 ka BP)

The Toba eruption that occurred some 74 ka ago in Sumatra, Indonesia, is among the largest volcanic events on Earth over the last 2 million years. Tephra from this eruption has been spread over vast areas in Asia, where it constitutes a major time marker close to the Marine Isotope Stage 4/5 boundary. As yet, no tephra associated with Toba has been identified in Greenland or Antarctic ice cores. Based on new accurate dating of Toba tephra and on accurately dated European stalagmites, the Toba event is known to occur between the onsets of Greenland interstadials (GI) 19 and 20. Furthermore, the existing linking of Greenland and Antarctic ice cores by gas records and by the bipolar seesaw hypothesis suggests that the Antarctic counterpart is situated between Antarctic Isotope Maxima (AIM) 19 and 20. In this work we suggest a direct synchronization of Greenland (NGRIP) and Antarctic (EDML) ice cores at the Toba eruption based on matching of a pattern of bipolar volcanic spikes. Annual layer counting between volcanic spikes in both cores allows for a unique match. We first demonstrate this bipolar matching technique at the already synchronized Laschamp geomagnetic excursion (41 ka BP) before we apply it to the suggested Toba interval. The Toba synchronization pattern covers some 2000 yr in GI-20 and AIM-19/20 and includes nine acidity peaks that are recognized in both ice cores. The suggested bipolar Toba synchronization has decadal precision. It thus allows a determination of the exact phasing of inter-hemispheric climate in a time interval of poorly constrained ice core records, and it allows for a discussion of the climatic impact of the Toba eruption in a global perspective. The bipolar linking gives no support for a long-term global cooling caused by the Toba eruption as Antarctica experiences a major warming shortly after the event. Furthermore, our bipolar match provides a way to place palaeo-environmental records other than ice cores into a precise climatic context.

Ayamama, retour sur un bassin-versant après l’inondation de septembre 2009. Compte-rendu de l’excursion urbaine du 25 novembre 2009

Report of an urban excursion organized in Istanbul by Jean-François Pérouse (Observatoire Urbain d'Istanbul - Institut Français d'Etudes Anatoliennes)