Interest Rate Determination in the Interbank Market

The purpose of this paper is to study the determinants of equilibrium in the market for daily funds. We use the EONIA panel database which includes daily information on the lending rates applied by contributing commercial banks. The data clearly shows an increase in both the time series volatility and the cross section dispersion of rates towards the end of the reserve maintenance period. These increases are highly correlated. With respect to quantities, we find that the volume of trade as well as the use of the standing facilities are also larger at the end of the maintenance period. Our theoretical model shows how the operational framework of monetary policy causes a reduction in the elasticity of the supply of funds by banks throughout the reserve maintenance period. This reduction in the elasticity together with market segmentation and heterogeneity are able to generate distributions for the interest rates and quantities traded with the same properties as in the data.Overnight interest rate; Monetary policy instruments; Eonia panel

Quality of life analyses in patients with multiple myeloma: Results from the Selinexor (KPT-330) Treatment of Refractory Myeloma (STORM) phase 2b study

BACKGROUND: Selinexor is an oral, selective nuclear export inhibitor. STORM was a phase 2b, single-arm, open-label, multicenter trial of selinexor with low dose dexamethasone in patients with penta-exposed relapsed/refractory multiple myeloma (RRMM) that met its primary endpoint, with overall response of 26% (95% confidence interval [CI], 19 to 35%). Health-related quality of life (HRQoL) was a secondary endpoint measured using the Functional Assessment of Cancer Therapy - Multiple Myeloma (FACT-MM). This study examines impact of selinexor treatment on HRQoL of patients treated in STORM and reports two approaches to calculate minimal clinically important differences for the FACT-MM. METHODS: FACT-MM data were collected at baseline, on day 1 of each 4-week treatment cycle, and at end of treatment (EOT). Changes from baseline were analyzed for the FACT-MM total score, FACT-trial outcome index (TOI), FACT-General (FACT-G), and the MM-specific domain using mixed-effects regression models. Two approaches for evaluating minimal clinically important differences were explored: the first defined as 10% of the instrument range, and the second based on estimated mean baseline differences between Eastern Cooperative Oncology Group performance status (ECOG PS) scores. Post-hoc difference analysis compared change in scores from baseline to EOT for treatment responders and non-responders. RESULTS: Eighty patients were included in the analysis; the mean number of prior therapies was 7.9 (standard deviation [SD] 3.1), and mean duration of myeloma was 7.6 years (SD 3.4). Each exploratory minimal clinically important difference threshold yielded consistent results whereby most patients did not experience HRQoL decline during the first six cycles of treatment (range: 53.9 to 75.7% for the first approach; range: 52.6 to 72.9% for the second). Treatment responders experienced less decline in HRQoL from baseline to EOT than non-responders, which was significant for the FACT-G, but not for other scores. CONCLUSION: The majority of patients did not experience decline in HRQoL based on minimal clinically important differences during early cycles of treatment with selinexor and dexamethasone in the STORM trial. An anchor-based approach utilizing patient-level data (ECOG PS score) to define minimal clinically important differences for the FACT-MM gave consistent results with a distribution-based approach. TRIAL REGISTRATION: This trial was registered on ClinicalTrials.gov under the trial-ID NCT02336815 on January 8, 2015

Membrane glucocorticoid receptors are localised in the extracellular matrix and signal through the MAPK pathway in mammalian skeletal muscle fibres

A number of studies have previously proposed the existence of glucocorticoid receptors on the plasma membrane of many cell types including skeletal muscle fibres. However, their exact localisation and the cellular signalling pathway(s) they utilise to communicate with the rest of the cell are still poorly understood. In this study, we investigated the localisation and the mechanism(s) underlying the non-genomic physiological functions of these receptors in mouse skeletal muscle cells. The results show that the receptors were localised in the cytoplasm in myoblasts, in the nucleus in myotubes and in the extracellular matrix, in satellite cells and in the proximity of mitochondria in adult muscle fibres. Also, they bound laminin in a glucocorticoid-dependent manner. Treating small skeletal muscle fibre bundles with the synthetic glucocorticoid, beclomethasone dipropionate, increased the phosphorylation (=activation) of extracellular-signal regulated kinase 1&2, c-Jun N-terminal kinase and p38 mitogen-activated protein kinase. This occurred within 5min and depended on the fibre-type and the duration of the treatment. It was also abolished by the glucocorticoid receptor inhibitor, mifepristone, and a monoclonal antibody against the receptor. From these results we conclude that the non-genomic/non-canonical physiological functions of glucocorticoids, in adult skeletal muscle fibres are mediated by a glucocorticoid receptor localised in the extracellular matrix, in satellite cells and close to mitochondria and involve activation of the MAPK pathway

H55N polymorphism is associated with low citrate synthase activity which regulates lipid metabolism in mouse muscle cells

Funding: This work was supported, in whole or in part, by European Social Fund under the Global Grant measure Grant VP1-3.1-ŠMM-07-K-02-057 (to A.L.), European Foundation for the Study of Diabetes grant (to T.V.), NHS Grampian Endowment grant (to A.R. and S.R.G.), Kuwait Ministry of Health grant (to M.A.), Saudi Ministry of Higher Education grant (to Y.A.,) as well as Saltire scholarship, Wenner-Gren Foundation Postdoctoral Fellowship, Albert Renold Travel Fellowship and a Novo Nordisk Foundation Challenge Grant (to B.G.).Peer reviewedPublisher PD

Alteraciones a los Entornos de Permafrost Inducidas por el Cambio Climático

Permafrost environments currently cover approximately twenty-five percent of the Northern Hemisphere. However current empirical and theoretical evidence indicates that much of the existing permafrost is in thermal imbalance to the warming that has occurred over the last 150 years. Long-term increases of temperature in the polar regions has already led to a thickening of the active layer and the gaseous release of the once sequestered carbon and methane tundra stores; an event which is likely to amplify the changes foreseen and experienced in natural and human environments. Permafrost degradation has resulted in the complete restructuring of ecosystems and geomorphological and hydrological patterns and processes. Such changes have led to extensive thawing, removal of discontinuous permafrost and the growth of thermokarst. Collectively, all these climatic-induced alterations in the structure of permafrost environments has had a detrimental effect on wildlife populations, human settlement and infrastructure. The former has seen a transition from terrestrial to aquatic ecosystems whilst damage to the latter has led to some areas being officially classed as natural hazard zones. Therefore research and corresponding action must be undertaken at those locations where sequestered carbon is being released in sufficient quantities to be of concern to the wellbeing of the entire planet. Resumen Los entornos de permafrost actualmente cubren aproximadamente el veinticinco por ciento del hemisferio norte. Sin embargo, la evidencia empírica y teórica actual indica que gran parte del permafrost existente está en desequilibrio térmico por el calentamiento que se ha producido en los últimos 150 años. Los aumentos de la temperatura a largo plazo en las regiones polares ya han dado lugar a un engrosamiento de la capa activa y a la liberación gaseosa de los depósitos de carbono y el metano alguna vez secuestrados en la tundra; un evento que es probable que amplifique los cambios previstos y experimentados por los entornos naturales y humanos. La degradación del permafrost se ha traducido en la reestructuración completa de los ecosistemas y de los patrones y procesos geomorfológicos e hidrológicos. Tales cambios han conducido a un extenso descongelamiento, la eliminación del permafrost discontinuo y al crecimiento de termokarst. En conjunto, todas estas alteraciones climáticamente inducidas en la estructura de los ambientes de permafrost han tenido un efecto perjudicial sobre las poblaciones de la vida silvestre, los asentamientos humanos y la infraestructura. Las primeras formaciones han visto una transición de ecosistemas terrestre a acuáticos, mientras que el daño a estos últimos ha dado lugar a que algunas áreas sean clasificadas oficialmente como zonas de peligros naturales. Por lo tanto, la investigación y las acciones correspondientes deben llevarse a cabo en los lugares donde se está liberando el carbono secuestrado en cantidades suficientes como para ser motivo de preocupación para el bienestar de todo el planeta

Carrier relaxation mechanisms in self-assembled (In,Ga)As/GaAs quantum dots: Efficient P -> S Auger relaxation of electrons

We calculate the P-shell--to-S-shell decay lifetime \tau(P->S) of electrons in lens-shaped self-assembled (In,Ga)As/GaAs dots due to Auger electron-hole scattering within an atomistic pseudopotential-based approach. We find that this relaxation mechanism leads to fast decay of \tau(P->S)~1-7 ps for dots of different sizes. Our calculated Auger-type P-shell--to-S-shell decay lifetimes \tau(P->S) compare well to data in (In,Ga)As/GaAs dots, showing that as long as holes are present there is no need for an alternative polaron mechanism.Comment: Version published in Phys. Rev.

Mechanisms Involving Sensory Pathway Steps Inform Impacts of Global Climate Change on Ecological Processes

Human-caused environmental change will have significant non-lethal and indirect impacts on organisms due to altered sensory pathways, with consequences for ecological interactions. While a growing body of work addresses how global ocean change can impair the way organisms obtain and use information to direct their behavior, these efforts have typically focused on one step of the pathway (e.g., reception of a cue/signal), one sensory modality (e.g., visual), or one environmental factor (e.g., temperature). An integrated view of how aspects of environmental change will impact multiple sensory pathways and related ecological processes is needed to better anticipate broader consequences for marine ecosystems. Here, we present a conceptual synthesis of effects of global change on marine sensory ecology, based on a literature review. Our review supports several predictions for how particular sensory pathway steps – production, transmission, and reception/processing of cues/signals – are affected by environmental change. First, the production and reception/processing of multiple modalities of cues/signals are vulnerable to multiple global change stressors, indicating that there are generalizable mechanisms by which environmental change impairs these pathways steps, leading to altered sensory pathway outcomes. Factors that enhance organismal stress as a whole may amplify impacts to these sensory pathways. Second, global change factors tend to affect specific modalities of cue/signal transmission. Consequently, local impacts on ecological processes linked with cue/signal transmission will vary depending on environmental stressor(s) present and the corresponding sensory modality. Finally, because many ecological and evolutionary interactions rely on sensory processing, impairment of sensory pathways may frequently underpin impacts of global ocean change on marine ecosystems. Effects on individual sensory processes will integrate to shape processes like mating, predation, and habitat selection, and we highlight new insights on impacts to ecological interactions by employing our mechanistic conceptual framework