Granger causality and systemic risk

Building on the concept of Granger causality in risk in Hong et al. (2009), and focusing on an international sample of large-capitalization banks, we test for predictability in comovements in the left tails of returns of individual banks and the global system. The main results show that large individual shocks (defined as balance-sheet contractions exceeding the 1% VaR level) are a strong predictor of subsequent shocks in the global system. This evidence is particularly strong for US banks with large desks of proprietary trading. Similarly, we document strong evidence of financial vulnerabilities (exposures) to systemic shocks in US subprime creditors.

Modulation allostérique du récepteur FP dans le cancer colorectal

Les prostaglandines modulent d’importants rôles physiologiques. Elles sont aussi impliquées dans le développement d’une variété de conditions pathologiques telles l’inflammation, la douleur et le cancer. La prostaglandine PGF2α et son récepteur (récepteur FP) se trouvent impliqué dans la modulation de nombreuses pathologies tels lors de l’accouchement préterme et le cancer colorectal. Récemment, nous avons fait partie d’un groupe de recherche ayant développé des modulateurs allostériques du récepteur FP. Dans une première étude, l’action du PGF2α sur le déclenchement des contractions myométriales a été évaluée, car peu d’information est connue sur la signalisation de cette prostaglandine lors de l’accouchement. Ainsi, nous avons utilisé un peptidomimétique de la deuxième boucle extracellulaire, dénommée PDC113.824. Nos résultats ont démontré que le PDC113.824 permettait de retarder la mise bas chez des souris gestantes, mais agissait de manière différente sur les multiples voies de signalisation de la PGF2α. Ainsi, le PDC113.824 inhibait la voie RhoA-ROCK, dépendante de l’activation de la protéine Gα12 par le. Les protéines RhoA-ROCK sont des acteurs clés dans le remodelage du cytosquelette d’actine et des contractions myométriales lors de l’accouchement. De plus, le PDC113.824 en présence de PGF2α agit comme un modulateur positif sur la voie dépendante de l’activation de la protéine Gαq. Le PDC113.824 serait donc un modulateur allostérique non compétitif possédant des actions à la fois de modulateurs positifs et négatifs sur la signalisation du récepteur FP Dans une seconde étude, des analogues du PDC113.824 ont été conçus et analysés dans un second modèle pathologique, le cancer colorectal. Ce cancer possède de hauts niveaux de récepteur FP. Nous avons donc étudié le rôle du récepteur FP dans le développement et la progression du cancer colorectal et l’effet de modulateurs allostériques. Il est généralement accepté que dans le cancer colorectal, la prostaglandine PGE2 permet la croissance et l’invasion tumorale, ainsi que l’angiogenèse. Toutefois, peu d’informations sont connues sur le rôle du PGF2α dans le cancer colorectal. C’est dans ce contexte que nous avons décidé d’examiner la contribution de ce récepteur dans la progression du cancer colorectal et cherché à déterminer si la modulation des fonctions du récepteur FP a un impact sur la croissance de tumeurs colorectales. Nos recherches ont révélé que l’activation du récepteur FP permet la migration et la prolifération de plusieurs lignées cellulaires humaines et murines d’adénocarcinomes colorectaux. Dans ce contexte, nos expériences ont démontré que la migration des cellules cancéreuses était dépendante de l’activation de la voie Rho. Nos résultats démontrent qu’en effet, l’activation de RhoA, une petite GTPase clé de la voie Gα12, est inhibée de façon sélective par nos composés. De plus, nos molécules allostériques sont également efficaces pour inhiber la voie de signalisation de la ß-caténine, une protéine impliquée dans la genèse du cancer colorectal. In vivo, le traitement de souris avec un des ces modulateurs a permis une inhibition effective de la croissance tumorale. Dans l’ensemble, nos résultats suggèrent donc que les modulateurs allostériques des récepteurs FP pourraient constituer une nouvelle classe de médicaments utilisés pour le traitement du cancer colorectal.

Tropically-driven climate shifts in southwestern Europe during MIS 19, a low eccentricity interglacial

The relative roles of high- versus low-latitude forcing of millennial-scale climate variability are still not well understood. Here we present terrestrial–marine climate profiles from the southwestern Iberian margin, a region particularly affected by precession, that show millennial climate oscillations related to a nonlinear response to the Earth's precession cycle during Marine Isotope Stage (MIS) 19. MIS 19 has been considered the best analogue to our present interglacial from an astronomical point of view due to the reduced eccentricity centred at 785 ka. In our records, seven millennial-scale forest contractions punctuated MIS 19 superimposed to two orbitally-driven Mediterranean forest expansions. In contrast to our present interglacial, we evidence for the first time low latitude-driven 5000-yr cycles of drying and cooling in the western Mediterranean region, along with warmth in the subtropical gyre related to the fourth harmonic of precession. These cycles indicate repeated intensification of North Atlantic meridional moisture transport that along with decrease in boreal summer insolation triggered ice growth and may have contributed to the glacial inception, at ∼774 ka. The freshwater fluxes during MIS 19ab amplified the cooling events in the North Atlantic promoting further cooling and leading to MIS 18 glaciation. The discrepancy between the dominant cyclicity observed during MIS 1, 2500-yr, and that of MIS 19, 5000-yr, challenges the similar duration of the Holocene and MIS 19c interglacials under natural boundary conditions.

Better outcome of ablation for sustained outflow-tract ventricular tachycardia when tachycardia is inducible.

AIMS In patients presenting with spontaneous sustained ventricular tachycardia (VT) from the outflow-tract region without overt structural heart disease ablation may target premature ventricular contractions (PVCs) when VT is not inducible. We aimed to determine whether inducibility of VT affects ablation outcome. METHODS AND RESULTS Data from 54 patients (31 men; age, 52 ± 13 years) without overt structural heart disease who underwent catheter ablation for symptomatic sustained VT originating from the right- or left-ventricular outflow region, including the great vessels. A single morphology of sustained VT was inducible in 18 (33%, SM group) patients, and 11 (20%) had multiple VT morphologies (MM group). VT was not inducible in 25 (46%) patients (VTni group). After ablation, VT was inducible in none of the SM group and in two (17%) patients in the MM group. In the VTni group, ablation targeted PVCs and 12 (48%) patients had some remaining PVCs after ablation. During follow-up (21 ± 19 months), VT recurred in 46% of VTni group, 40% of MM inducible group, and 6% of the SM inducible group (P = 0.004). Analysis of PVC morphology in the VTi group further supported the limitations of targeting PVCs in this population. CONCLUSION Absence of inducible VT and multiple VT morphologies are not uncommon in patients with documented sustained outflow-tract VT without overt structural heart disease. Inducible VT is associated with better outcomes, suggesting that attempts to induce VT to guide ablation are important in this population.

Towards Batteryless Cardiac Implantable Electronic Devices – The Swiss Way

Energy harvesting devices are widely discussed as an alternative power source for todays active implantable medical devices. Repeated battery replacement procedures can be avoided by extending the implants life span, which is the goal of energy harvesting concepts. This reduces the risk of complications for the patient and may even reduce device size. The continuous and powerful contractions of a human heart ideally qualify as a battery substitute. In particular, devices in close proximity to the heart such as pacemakers, defibrillators or bio signal (ECG) recorders would benefit from this alternative energy source. The clockwork of an automatic wristwatch was used to transform the hearts kinetic energy into electrical energy. In order to qualify as a continuous energy supply for the consuming device, the mechanism needs to demonstrate its harvesting capability under various conditions. Several in-vivo recorded heart motions were used as input of a mathematical model to optimize the clockworks original conversion efficiency with respect to myocardial contractions. The resulting design was implemented and tested during in-vitro and in-vivo experiments, which demonstrated the superior sensitivity of the new design for all tested heart motions.

Changes in the vegetation and trade winds in equatorial Northwest Africa 140,000-70,000 yr B.P., as deduced from two marine pollen records

The deep-sea cores M 16415-2 and M 16416-2 at about 9°N off Sierra Leone were analysed palynologically for the time interval 140,000-70,000 yr B.P. Results were presented in absolute (pollen concentration and pollen influx) and relative diagrams (pollen percentage). In a previous study it was evidenced that in northwest Africa pollen is mainly transported to the Atlantic by wind, so that the efficiency of aeolian pollen transport (pollen flux) could be used to evaluate changes in the intensity of the northeast trade winds. The glacial episodes (represented by the oxygen isotope stages 6 and 4) are characterized by strong northeast trade winds, whereas the last interglacial (stage 5) is characterized by weak trade winds. The pollen influx diagram shows that the intensity of the trade winds increased slightly during the relatively cool intervals of stage 5 (viz. 5.4 and 5.2). Tropical forest had maximally expanded around 124,000 yr B.P. (stage 5.5), around 98,000 yr B.P. (transition of stage 5.3 to 5.2), and around 70,000 yr B.P. (first part of stage 4): an increasing delay of the response of tropical forest to global intervals with maximum temperature is apparent during the last interglacial. As tropical forests need continuous humidity, the record of tropical forest monitors changes in climatic humidity south of the Sahara. During the last interglacial, the southern boundary of the Sahara shifted only little: expansions and contractions of the tropical forest area are correlated with contra-oscillations of the grass-dominated savanna zone. Great latitudinal shifts of the desert savanna boundary, on the contrary, occurred during the penultimate glacial interglacial transition (around 128,000 yr B.P.) to the north, and during the last interglacial-glacial transition (around 65,000 yr B.P.) to the south.

(Table 1) Abundances of Discoaster species in ODP Hole 130-806C

Members of the calcareous nannofossil genus Discoaster have been used extensively to subdivide Tertiary deep-sea sediments into biostratigraphic zones or subzones (e.g., Martini, 1971; Bukry, 1973). Haq and Lohmann (1976) mapped biogeographic migrations of this group through time and over latitude. They suggested that expansions and contractions of Discoaster-dominated assemblages across latitudes reflect sea-surface temperature changes. Subsequently, late Pliocene Discoaster species were counted at closely spaced sample intervals from various Atlantic sites (Backman et al., 1986; Backman and Pestiaux, 1987; Chepstow-Lusty et al., 1989, 1991), and Indian Ocean as well as Pacific Ocean sites (Chepstow-Lusty, 1990). In addition to the biostratigraphic information revealing positions and the precision by which the different late Pliocene Discoaster species can be determined, these studies also demonstrated that discoasters strongly fluctuate in abundance as a function of time. These abundance variations occur in equatorial as well as temperate temperature regimes, and show periodicities that reflect orbital frequencies. Chepstow-Lusty et al. (1989, 1991) also suggested that the oscillating abundances partly represent productivity pressure, because discoasters tend to show low abundances under high productivity conditions and vice versa. In the Pacific Ocean, counts showing late Pliocene Discoaster abundances exist from three sites, namely Ocean Drilling Program (ODP) Site 677 in the eastern equatorial upwelling region, Core V28-179 from the central equatorial region, and Core V32-127 from the mid-latitude Hess Rise. The two Vema cores are condensed and show sedimentation rates below 0.5 cm/1000 yr, thus offering a poorly resolved stratigraphy. Hole 806C from the Ontong Java Plateau provided an opportunity to establish a highly resolved Discoaster record from the western extreme of the equatorial Pacific under an environmental setting that differed from ODP Site 677 by being less influenced by intense upwelling. The Discoaster counting technique is described by Backman and Shackleton (1983).

Dynamic Management of Loyalty Program Strategies

Thesis (Ph.D.)--University of Washington, 2016-06

S-Nitrosocaptopril: In vitro characterization of pulmonary vascular effects in rats

1 On rat isolated pulmonary arteries, vasorelaxation by S-nitrosocaptopril (SNOcap) was compared with S-nitrosoglutathione (GSNO) and nitroprusside, and inhibition by SNOcap of contractions to angiotensin I was compared with the angiotensin converting enzyme (ACE) inhibitor, captopril. 2 SNOcap was equipotent as a vasorelaxant on main (i.d. 2-3 mm) and intralobar (i.d. 600 mum)pulmonary arteries (pIC(50) values: 5.00 and 4.85, respectively). Vasorelaxant responses reached equilibrium rapidly (2-3 min). 3 Pulmonary vasorelaxant responses to SNOcap, like GSNO, were (i) partially inhibited by the soluble guanylate cyclase inhibitor, ODQ (1H-(1,2,4) oxadiazolo(4,3-a)-quinoxalin-1-one; 3 muM) whereas responses to nitroprusside were abolished and (ii) potentiated by hydroxocobalamin (HCOB; NO. free radical scavenger; 100 muM) whereas responses to nitroprusside were inhibited. 4 The relative potencies for pulmonary vasorelaxation compared with inhibition of platelet aggregation were: SNOcap 7: 1; GSNO 25: 1; nitroprusside > 2000:1. 5 SNOcap, like captopril, concentration-dependently and time-dependently increased the EC50 for angiotensin I but not angiotensin II. The dependence on incubation time was independent of the presence of tissue but differed for SNOcap and captopril. This difference reflected the slow dissociation of SNOcap and instability of captopril, and precluded a valid comparison of the potency of the two drugs. After prolonged incubation (greater than or equal to 5.6 h) SNOcap was more effective than captopril. 6 Thus, in pulmonary arteries SNOcap (i) possesses NO donor properties characteristic of S-nitrosothiols but different from nitroprusside and (ii) inhibits ACE at least as effectively as captopril. These properties suggest that SNOcap could be valuable in the treatment of pulmonary hypertension.

Neuromuscular efficiency of the sternocleidomastoid and anterior scalene muscles in patients with chronic neck pain

Purpose: This study compared the neuromuscular efficiency (NME) of the sternocleidomastoid (SCM) and anterior scalene (AS) muscles between 20 chronic neck pain patients and 20 asymptomatic controls. Method: Myoelectric signals were recorded from the sternal head of SCM and the AS muscles as subjects performed sub-maximal isometric cervical flexion contractions at 25 and 50% of the maximum voluntary contraction (MVC). The NME was calculated as the ratio between MVC and the corresponding average rectified value of the EMG signal. Ultrasonography was used to measure subcutaneous tissue thickness over the SCM and AS to ensure that differences did not exist between groups. Results: For both the SCM and AS muscles, NME was shown to be significantly reduced in patients with neck pain at 25% MVC (p < 0.05). Subcutaneous tissue thickness over the SCM and AS muscles was not different between groups. Conclusions: Reduced NME in the superficial cervical flexor muscles in patients with neck pain may be a measurable altered muscle strategy for dysfunction in other muscles. This aberrant pattern of muscle activation appears to be most evident under conditions of low load. NME, when measured at 25% MVC, may be a useful objective measure for future investigation of muscle dysfunction in patients with neck pain.

Neck flexor muscle fatigue is side specific in patients with unilateral neck pain

Despite the evidence of greater fatigability of the cervical flexor muscles in neck pain patients, the effect of unilaterality of neck pain on muscle fatigue has not been investigated. This study compared myoelectric manifestations of sternocleidomastoid (SCM) and anterior scalene (AS) muscle fatigue between the painful and non-painful sides in patients with chronic unilateral neck pain. Myoelectric signals were recorded from the sternal head of SCM and the AS muscles bilaterally during sub-maximal isometric cervical flexion contractions at 25% and 50% of the maximum voluntary contraction (MVC). The time course of the mean power frequency, average rectified value and conduction velocity of the electromyographic signals were calculated to quantify myoelectric manifestations of muscle fatigue. Results revealed greater estimates of the initial value and slope of the mean frequency for both the SCM and AS muscles on the side of the patient's neck pain at 25% and 50% of MVC. These results indicate greater myoelectric manifestations of muscle fatigue of the superficial cervical flexor muscles ipsilateral to the side of pain. This suggests a specificity of the effect of pain on muscle function and hence the need for specificity of therapeutic exercise in the management of neck pain patients. (C) 2003 European Federation of Chapters of the International Association for the Study of Pain. Published by Elsevier Ltd. All rights reserved.

Transfer of resistance training to enhance rapid coordinated force production by older adults

The purpose of this study was to examine the capacity of resistance training to enhance the rapid and coordinated production of force by older people. Thirty adults (greater than or equal to 60 years) completed a visually guided aiming task that required the generation of isometric torque in 2 df about the elbow prior to and following a 4-week training period. Groups of six participants were allocated to two progressive ( 40 - 100% maximal voluntary contraction (MVC)) resistance-training (PRT) groups, to two constant low-load (10% MVC) training groups (CLO) and to one no-training control group. Training movements required the generation of either combined flexion and supination (FLESUP), or combined extension and supination (EXTSUP). In response to training, target acquisition times in the aiming task decreased for all groups; however, both the nature of the training load and the training movement influenced the pattern and magnitude of improvements (EXTSUP_ CLO: 36%, FLESUP_ PRT 26%, EXTSUP_ PRT 22%, FLESUP_ CLO 20%, CONTROL 15%). For one group that trained with progressively increasing loads, there arose a subsequent decrease in performance in one condition of the transfer task. For each group, these adaptations were accompanied by systematic changes in the coordination of muscles about the elbow joint, particularly the biceps brachii.

Postural and respiratory activation of the trunk muscles changes with mode and speed of locomotion

Despite the importance of the deep intrinsic spinal muscles for trunk control, few studies have investigated their activity during human locomotion or how this may change with speed and mode of locomotion. Furthermore, it has not been determined whether the postural and respiratory functions, of which these muscles take part, can be coordinated when locomotor demands are increased. EMG recordings of abdominal and paraspinal muscles were made in seven healthy subjects using fine-wire and surface electrodes. Measurements were also made of respiration and gait parameters. Recordings were made for 10s as subjects walked on a treadmill at 1 and 2 ms(-1) and ran at 2, 3, 4 and 5 ms(-1). Unlike the superficial muscles, transversus abdominis was active tonically throughout the gait cycle with all tasks, except running at speeds of 3 ms(-1) and greater. All other muscles were recruited in a phasic manner. The relative duration of these bursts of activity was influenced by speed and/or mode of locomotion. Activity of all abdominal muscles, except rectus abdominis (RA), was modulated both for respiration and locomotor-related functions but this activity was affected by the speed and mode of locomotion. This study provides evidence that the deep abdominal muscles are controlled independently of the other trunk muscles. Furthermore, the pattern of recruitment of the trunk muscles and their respiratory and postural coordination is dependent on the speed and mode of locomotion. (C) 2003 Published by Elsevier B.V.

The Randomized Nitric Oxide Tocolysis Trial (RNOTT) for the treatment of preterm labor

Objective: This study was undertaken to assess the effectiveness of glyceryl trinitrate (GTN) patches in comparison with beta2 sympathornimetics (beta2) for the treatment of preterm labor. Study design: A multicenter, multinational, randomized controlled trial was conducted in tertiary referral teaching hospitals. Women in threatened preterm labor with positive fetal fibronectin or ruptured membranes between 24 and 35 weeks' gestation were recruited and randomly assigned to either beta2 or GTN with rescue beta2 tocolysis if moderate-to-strong contractions persisted at 2 hours. Obstetric and neonatal outcomes were assessed. Results: Two hundred thity-eight women were recruited and randomly assigned, 117 to beta2 and 121 to GTN. On a strict intention-to-treat basis, there was no significant difference in the time to delivery using Kaplan-Meier curves (P = .451). At 2 hours, 27% of women receiving beta2 had moderate or stronger contractions compared with 53% in the GTN group (P < .001). This led to 35% of women in the GTN group receiving rescue treatment. If delivery or requirement for beta2 rescue are regarded as treatment failure, then a significant difference was observed between the 2 arms (P = .0032). There were no significant differences in neonatal outcomes. Conclusion: GTN is a less efficacious tocolytic compared with beta2 sympathomimetics. (C) 2004 Elsevier Inc. All rights reserved.