Eficacia y seguridad de la melatonina para el manejo de los trastornos del sueño en el autismo: meta-análisis

INTRODUCCIÓN: El 80% de los niños y adolescentes con trastornos del espectro autista (TEA) presenta algún trastorno del sueño, en cuya génesis al parecer intervienen alteraciones en la regulación de la melatonina. El objetivo de este metaanálisis fue determinar la eficacia y seguridad de la melatonina para el manejo de ciertos trastornos del sueño en niños con TEA. MÉTODOS: Tres revisores extrajeron los datos relevantes de los ensayos clínicos aleatorizados doble ciego de alta calidad publicados en bases de datos primarias, de ensayos clínicos, de revisiones sistemáticas y de literatura gris; además se realizó búsqueda en bola de nieve. Se analizaron los datos con RevMan 5.3. Se realizó un análisis del inverso de la varianza por un modelo de efectos aleatorios para las diferencias de medias de los desenlaces propuestos: duración del tiempo total, latencia de sueño y número de despertares nocturnos. Se evaluó la heterogeneidad interestudios con el parámetro I2 RESULTADOS: La búsqueda inicial arrojó 355 resultados, de los cuales tres cumplieron los criterios de selección. La melatonina resultó ser un medicamento seguro y eficaz para aumentar la duración total del sueño y disminuir la latencia de sueño en niños y adolescentes con TEA; hasta el momento la evidencia sobre el número de despertares nocturnos no es estadísticamente significativa. DISCUSIÓN: A la luz de la evidencia disponible, la melatonina es una elección segura y eficaz para el manejo de ciertos problemas del sueño en niños y adolescentes con TEA. Es necesario realizar estudios con mayores tamaños muestrales y comparados con otros medicamentos disponibles en el mercado.

Avaluació del procés de desintegració de papers recuperats

La desintegració és una etapa important en la recuperació de paper vell, ja que té importants conseqüències en consum d'energia i en el comportament de les etapes posteriors. Per això els objectius es centren en analitzar la desintegració des del punt de vista del temps de desintegració, els aspectes energètics, modelització de la màquina de desintegració utilitzada i anàlisi dels factors de cisallament calculats com a mesura global de les forces implicades en la desintegració. Els autors que hi han treballat donen diferents explicacions a aquestes forces. Fins avui només s'ha pogut avaluar qualitativament la influència que tenen cada un dels mecanismes en el temps necessari per a desintegrar i en el consum energètic. Les característiques reològiques de les suspensions papereres, i el seu comportament no newtonià tenen una clara influència en el consum energètic i les forces de desfibrat en el desintegrador. Els experiments de desintegració s'han realitzat en un púlper convencional, amb tres tipus de paper recuperat: paper estucat d'alta qualitat imprès offset (PQ), paper revista estucat imprès en color (PR), paper blanc imprès en impresora làsser (PF). Anàlisi del temps de desintegració Per cada un del papers estudiats (PQ, PR i PF), les fraccions màssiques des de 0.06 fins a la màxima que estat possible per cada paper (de 0.14 a 0.18), i a dues velocitats d'agitació diferents, s'ha determinat el temps de desintegració (tD) fins a aconseguir un índex de Sommerville de 0.01%. S'obté que en augmentar la fracció màssica disminueix potencialment el temps de desintegració. S'ha estudiat la velocitat de desintegració, la producció teòrica del púlper en cada cas, i la seva relació amb les forces d'impacte i de fregament que produeixen la desintegració. Aspectes energètics El consum específic d'energia (SEC), definit com l'energia consumida per a desintegrar 1 kg de paper recuperat, disminueix molt en augmentar Xm, ja que a més de disminuir l'energia consumida en cada desintegració, el contingut en paper és més elevat. Pel disseny de desintegradors, cal tenir en compte que en augmentar Xm i en augmentar la velocitat, sempre augmenta la potència consumida. Però així com els beneficis de treballar a Xm alt són de 10 vegades en termes de SEC i de producció, l'augment de potència és només de l'ordre de 2 vegades la necessària respecte de la Xm baixa. Viscositat aparent i energia de fluidització S'estudia la relació entre el temps de desintegració, les forces de fregament i els valors de viscositat aparent de la bibliografia. Per cada paper i velocitat s'ha observat que el consum específic d'energia disminueix en funció de la viscositat aparent. Reologia del púlper Utilitzant el mètode de Metzner i Otto (1957) per determinar la viscositat aparent mitjana de les suspensions papereres, modificat per Roustan, s'ha caracteritzat el pulper mitjançant el model: Np= K· Rex·Fry S'han utilitzat dissolucions de glicerina com a fluid newtonià per a calcular les constants d'ajust, i a partir d'aquí, aïllar la viscositat aparent en funció de la potència neta i els paràmetres d'agitació. La viscositat aparent, d'acord amb Fabry (1999) es substitueix pel concepte de factor de cisallament. Factor de cisallament Calculat el factor de cisallament per a cada paperot i condicions d'agitació, s'ha relacionat amb Xm, SEC, tD, consum de potència, potència instal·lada i fracció cel·lulòsica. El factor de cisallament és un paràmetre útil per a quantificar les forces globals implicades en la desintegració.

Procés de destintatge del paper per flotació. Avaluació de l'eficàcia de l'eliminació de tinta

La tesi doctoral presentada té com a objectius principals l'estudi de les etapes fonamentals de desintegració i flotació en un procés de destintatge de papers vell de qualitats elevades per a poder millorar l'eficàcia d'aquestes etapes clau. Conté una revisió teòrica completa i molt actualitzada del procés de desintegració i flotació tant a nivell macroscòpic com microscòpic. La metodologia de treball en el laboratori, la posada a punt dels aparells, així com les anàlisis efectuades per a valorar la resposta del procés (anàlisi de blancor, anàlisi d'imatge i anàlisi de la concentració efectiva de tinta residual) estan descrites en el capítol de material i mètodes. La posada en marxa permet obtenir unes primeres conclusions respecte la necessitat de treballar amb una matèria primera homogènia i respecte la no significació de la temperatura de desintegració dins l'interval de treball permès al laboratori (20-50°C). L'anàlisi de les variables mecàniques de desintegració: consistència de desintegració (c), velocitat d'agitació en la desintegració (N) i temps de desintegració (t), permet de discernir que la consistència de desintegració és una variable fonamental. El valor de consistència igual al 10% marca el límit d'existència de les forces d'impacte mecànic en la suspensió fibrosa. A consistències superiors, les forces viscoses i d'acceleració dominen l'etapa de desintegració. Existeix una interacció entre la consistència i el temps de desintegració, optimitzant-se aquesta darrera variable en funció del valor de la consistència. La velocitat d'agitació és significativa només per a valors de consistència de desintegració inferiors al 10%. En aquests casos, incrementar el valor de N de 800 a 1400 rpm representa una disminució de 14 punts en el factor de destintabilitat. L'anàlisi de les variables químiques de desintegració: concentració de silicat sòdic (% Na2SiO3), peròxid d'hidrogen (% H2O2) i hidròxid sòdic (% Na2OH), proporciona resultats força significatius. El silicat sòdic presenta un efecte altament dispersant corroborat per les corbes de distribució dels diàmetres de partícula de tinta obtingudes mitjançant anàlisi d'imatges. L'hidròxid sòdic també presenta un efecte dispersant tot i que no és tant important com el del silicat sòdic. Aquests efectes dispersants són deguts principalment a l'increment de les repulsions electrostàtiques que aporten a la suspensió fibrosa aquests reactius químics fent disminuir l'eficàcia d'eliminació de l'etapa de flotació. El peròxid d'hidrogen utilitzat generalment com agent blanquejant, actua en aquests casos com a neutralitzador dels grups hidroxil provinents tant del silicat sòdic com de l'hidròxid sòdic, disminuint la repulsió electrostàtica dins la suspensió. Amb l'anàlisi de les variables hidrodinàmiques de flotació: consistència de flotació (c), velocitat d'agitació durant la flotació (N) i cabal d'aire aplicat (q), s'aconsegueix la seva optimització dins el rang de treball permès al laboratori. Valors elevats tant de la velocitat d'agitació com del cabal d'aire aplicat durant la flotació permeten eliminar majors quantitats de tinta. La consistència de flotació assoleix valors òptims depenent de les condicions de flux dins la cel·la de flotació. Les metodologies d'anàlisi emprades permeten obtenir diferents factors de destintabilitat. Entre aquests factors existeix una correlació important (determinada pels coeficients de correlació de Pearson) que permet assegurar la utilització de la blancor com a paràmetre fonamental en l'anàlisi del destintatge de papers vells, sempre i quan es complementi amb anàlisis d'imatge o bé amb anàlisi de la concentració efectiva de tinta residual. S'aconsegueixen expressions empíriques tipus exponencial que relacionen aquests factors de destintabilitat amb les variables experimentals. L' estudi de les cinètiques de flotació permet calcular les constants cinètiques (kBlancor, kERIC, kSupimp) en funció de les variables experimentals, obtenint un model empíric de flotació que relacionant-lo amb els paràmetres microscòpics que afecten realment l'eliminació de partícules de tinta, deriva en un model fonamental molt més difícil d'interpretar. Mitjançant l'estudi d'aquestes cinètiques separades per classes, també s'aconsegueix determinar que l'eficàcia d'eliminació de partícules de tinta és màxima si el seu diàmetre equivalent és superior a 50 μm. Les partícules amb diàmetres equivalents inferiors a 15 μm no són eliminades en les condicions de flotació analitzades. Es pot dir que és físicament impossible eliminar partícules de tinta de diàmetres molt diferents amb la mateixa eficiència i sota les mateixes condicions de treball. El rendiment del procés analitzat en funció de l'eliminació de sòlids per l'etapa de flotació no ha presentat relacions significatives amb cap de les variables experimentals analitzades. Únicament es pot concloure que addicionar quantitats elevades de silicat sòdic provoca una disminució tant de sòlids com de matèria inorgànica presents en les escumes de flotació.

Parameter sensitivity and predictive uncertainty in a new water quality model, Q(2)

A new dynamic model of water quality, Q(2), has recently been developed, capable of simulating large branched river systems. This paper describes the application of a generalized sensitivity analysis (GSA) to Q(2) for single reaches of the River Thames in southern England. Focusing on the simulation of dissolved oxygen (DO) (since this may be regarded as a proxy for the overall health of a river); the GSA is used to identify key parameters controlling model behavior and provide a probabilistic procedure for model calibration. It is shown that, in the River Thames at least, it is more important to obtain high quality forcing functions than to obtain improved parameter estimates once approximate values have been estimated. Furthermore, there is a need to ensure reasonable simulation of a range of water quality determinands, since a focus only on DO increases predictive uncertainty in the DO simulations. The Q(2) model has been applied here to the River Thames, but it has a broad utility for evaluating other systems in Europe and around the world.

Acoustic and petrophysical relationships in low-shale sandstone reservoir rocks

This paper describes the measurements of the acoustic and petrophysical properties of two suites of low-shale sandstone samples from North Sea hydrocarbon reservoirs, under simulated reservoir conditions. The acoustic velocities and quality factors of the samples, saturated with different pore fluids (brine, dead oil and kerosene), were measured at a frequency of about 0.8 MHz and over a range of pressures from 5 MPa to 40 MPa. The compressional-wave velocity is strongly correlated with the shear-wave velocity in this suite of rocks. The ratio V-P/V-S varies significantly with change of both pore-fluid type and differential pressure, confirming the usefulness of this parameter for seismic monitoring of producing reservoirs. The results of quality factor measurements were compared with predictions from Biot-flow and squirt-flow loss mechanisms. The results suggested that the dominating loss in these samples is due to squirt-flow of fluid between the pores of various geometries. The contribution of the Biot-flow loss mechanism to the total loss is negligible. The compressional-wave quality factor was shown to be inversely correlated with rock permeability, suggesting the possibility of using attenuation as a permeability indicator tool in low-shale, high-porosity sandstone reservoirs.

Sonic to ultrasonic Q of sandstones and limestones: Laboratory measurements at in situ pressures

Laboratory measurements of the attenuation and velocity dispersion of compressional and shear waves at appropriate frequencies, pressures, and temperatures can aid interpretation of seismic and well-log surveys as well as indicate absorption mechanisms in rocks. Construction and calibration of resonant-bar equipment was used to measure velocities and attenuations of standing shear and extensional waves in copper-jacketed right cylinders of rocks (30 cm in length, 2.54 cm in diameter) in the sonic frequency range and at differential pressures up to 65 MPa. We also measured ultrasonic velocities and attenuations of compressional and shear waves in 50-mm-diameter samples of the rocks at identical pressures. Extensional-mode velocities determined from the resonant bar are systematically too low, yielding unreliable Poisson's ratios. Poisson's ratios determined from the ultrasonic data are frequency corrected and used to calculate the sonic-frequency compressional-wave velocities and attenuations from the shear- and extensional-mode data. We calculate the bulk-modulus loss. The accuracies of attenuation data (expressed as 1000/Q, where Q is the quality factor) are +/- 1 for compressional and shear waves at ultrasonic frequency, +/- 1 for shear waves, and +/- 3 for compressional waves at sonic frequency. Example sonic-frequency data show that the energy absorption in a limestone is small (Q(P) greater than 200 and stress independent) and is primarily due to poroelasticity, whereas that in the two sandstones is variable in magnitude (Q(P) ranges from less than 50 to greater than 300, at reservoir pressures) and arises from a combination of poroelasticity and viscoelasticity. A graph of compressional-wave attenuation versus compressional-wave velocity at reservoir pressures differentiates high-permeability (> 100 mD, 9.87 X 10(-14) m(2)) brine-saturated sandstones from low-permeability (< 100 mD, 9.87 X 10 (14) m(2)) sandstones and shales.

Distribution of nutrients in the root zone affects yield, quality and blossom end rot of tomato fruits

Tomato plants (Lycopersicon esculentum Mill. 'DRK') were grown hydroponically in two experiments to determine the effects of nutrient concentration and distribution in the root zone on yield, quality and blossom end rot (BER). The plants were grown in rockwool with their root systems divided into two portions. Each portion was irrigated with nutrient solutions with either the same or different electrical conductivity (EC) in the range 0 to 6 dS m(-1). In both experiments, fruit yields decreased as EC increased from moderate to high when solutions of equal concentration were applied to both portions of the root system. However, higher yields were obtained when a solution with high EC was applied to one portion of the root system and a solution of low EC to the other portion. For example, the fresh weight of mature fruits in the 6/6 treatment was only 20% that of the 3/3 treatment but the 6/0 treatment had a yield that was 40% higher. The reduction in yield in the high EC treatments was due to an increase in the number of fruits with BER and smaller fruit size. BER increased from 12% to 88% of total fruits as EC increased from 6/0 to 6/6 and fruit length decreased from 67 mm to 52 mm. Fruit quality (expressed as titratable acidity and soluble solids) increased as EC increased. In summary, high yields of high quality tomatoes with minimal incidence of BER were obtained when one portion of the root system was supplied with a solution of high EC and the other portion with a solution of moderate or zero EC.

High throughput profile-profile based fold recognition for the entire human proteome

BACKGROUND: In order to maintain the most comprehensive structural annotation databases we must carry out regular updates for each proteome using the latest profile-profile fold recognition methods. The ability to carry out these updates on demand is necessary to keep pace with the regular updates of sequence and structure databases. Providing the highest quality structural models requires the most intensive profile-profile fold recognition methods running with the very latest available sequence databases and fold libraries. However, running these methods on such a regular basis for every sequenced proteome requires large amounts of processing power.In this paper we describe and benchmark the JYDE (Job Yield Distribution Environment) system, which is a meta-scheduler designed to work above cluster schedulers, such as Sun Grid Engine (SGE) or Condor. We demonstrate the ability of JYDE to distribute the load of genomic-scale fold recognition across multiple independent Grid domains. We use the most recent profile-profile version of our mGenTHREADER software in order to annotate the latest version of the Human proteome against the latest sequence and structure databases in as short a time as possible. RESULTS: We show that our JYDE system is able to scale to large numbers of intensive fold recognition jobs running across several independent computer clusters. Using our JYDE system we have been able to annotate 99.9% of the protein sequences within the Human proteome in less than 24 hours, by harnessing over 500 CPUs from 3 independent Grid domains. CONCLUSION: This study clearly demonstrates the feasibility of carrying out on demand high quality structural annotations for the proteomes of major eukaryotic organisms. Specifically, we have shown that it is now possible to provide complete regular updates of profile-profile based fold recognition models for entire eukaryotic proteomes, through the use of Grid middleware such as JYDE.

Distribution of nutrients in the root zone affects yield, quality and blossom end rot of tomato fruits

Tomato plants (Lycopersicon esculentum Mill. 'DRK') were grown hydroponically in two experiments to determine the effects of nutrient concentration and distribution in the root zone on yield, quality and blossom end rot (BER). The plants were grown in rockwool with their root systems divided into two portions. Each portion was irrigated with nutrient solutions with either the same or different electrical conductivity (EC) in the range 0 to 6 dS m(-1). In both experiments, fruit yields decreased as EC increased from moderate to high when solutions of equal concentration were applied to both portions of the root system. However, higher yields were obtained when a solution with high EC was applied to one portion of the root system and a solution of low EC to the other portion. For example, the fresh weight of mature fruits in the 6/6 treatment was only 20% that of the 3/3 treatment but the 6/0 treatment had a yield that was 40% higher. The reduction in yield in the high EC treatments was due to an increase in the number of fruits with BER and smaller fruit size. BER increased from 12% to 88% of total fruits as EC increased from 6/0 to 6/6 and fruit length decreased from 67 mm to 52 mm. Fruit quality (expressed as titratable acidity and soluble solids) increased as EC increased. In summary, high yields of high quality tomatoes with minimal incidence of BER were obtained when one portion of the root system was supplied with a solution of high EC and the other portion with a solution of moderate or zero EC.

The graduate teacher programme in England: mentor training, quality assurance and the findings of inspection

In its recent report on the Graduate Teacher Programme (GTP), an employment-based route to Qualified Teacher Status (QTS) in England, the Government's Office for Standards in Education found that, although almost all trainees meet the standards required to qualify, too often they do so at an adequate level, rather than achieving the high levels of which they should be capable. The underlying reason for this is the quality of mentoring provided in the schools. The inspectors concluded that schoolbased trainers are often not adequately prepared for their role in implementing wide-ranging training programmes for trainee teachers. Despite this generally bleak picture, Ofsted concluded that 'the minority of cases of good practice in the training programmes and of high quality teaching by trainees indicate that the GTP can be an effective alternative route for training teachers'™. This article considers the strengths and weaknesses of the Graduate Teacher Programme, introduced in January 1998, and also reports on a small-scale project, funded by the Teacher Training Agency (TTA), the key objective of which was to strengthen the existing partnerships by improving the quality of school-based tutor training and continuous professional development of staff.

Automated tertiary structure prediction with accurate local model quality assessment using the IntFOLD-TS method

The IntFOLD-TS method was developed according to the guiding principle that the model quality assessment would be the most critical stage for our template based modelling pipeline. Thus, the IntFOLD-TS method firstly generates numerous alternative models, using in-house versions of several different sequence-structure alignment methods, which are then ranked in terms of global quality using our top performing quality assessment method – ModFOLDclust2. In addition to the predicted global quality scores, the predictions of local errors are also provided in the resulting coordinate files, using scores that represent the predicted deviation of each residue in the model from the equivalent residue in the native structure. The IntFOLD-TS method was found to generate high quality 3D models for many of the CASP9 targets, whilst also providing highly accurate predictions of their per-residue errors. This important information may help to make the 3D models that are produced by the IntFOLD-TS method more useful for guiding future experimental work

Provider diversity in the NHS: impact on quality and innovation

The overall objective of the research project has been to assess the impact of provider diversity on quality and innovation in the NHS. The specific research aims were to identify the differences in performance between non-profit Third Sector organisations, for-profit private enterprises, and incumbent public sector institutions within the NHS as providers of health care services, as well as the factors that affect the entry and growth of new private and Third Sector providers. The study used both qualitative and quantitative methods based on case studies of four Local Health Economies (LHEs). Qualitative methods included documentary analysis and interviews with key informants and managers of both commissioning and provider organisations. To provide a focus to the study, two tracer conditions were followed: orthopaedic surgery and home health care for frail older people. In the case of hospital inpatient care, data on patient characteristics were also collected from the HES database. The analysis of this data provided preliminary estimates of the effects of provider type on quality, controlling for client characteristics and case mix. In addition, a survey of patient experience in diverse provider organisations was analysed to compare the different dimensions of quality of provision of acute services between incumbent NHS organisations and new independent sector treatment centres. The research has shown that, in respect of inpatient hospital services, diverse providers supply health services of at least as good quality as traditional NHS providers, and that there is ample opportunity to expand their scale and scope as providers of services commissioned by the NHS. The research used patient experience survey data to investigate whether hospital ownership affects the quality of services reported by NHS patients in areas other than clinical quality. The raw survey data appear to show that private hospitals provide higher quality services than the public hospitals. However, further empirical analysis leads to a more nuanced understanding of the performance differences. Firstly, the analysis shows that each sector offers greater quality in certain specialties. Secondly, the analysis shows that differences in the quality of patients’ reported experience are mainly attributable to patient characteristics, the selection of patients into each type of hospital, and the characteristics of individual hospitals, rather than to hospital ownership as such. Controlling for such differences, NHS patients are on average likely to experience a similar quality of care in a public or privately-run hospital. Nevertheless, for specific groups of patients and for specific types of treatments, especially the more straightforward ones, the private sector provides an improved patient experience compared to the public sector. Elsewhere, the NHS continues to provide a high quality service and outperforms the private sector in a range of services and for a range of clients.

Quantifying the impact and relevance of scientific research

Qualitative and quantitative methods are being developed to measure the impacts of research on society, but they suffer from serious drawbacks associated with linking a piece of research to its subsequent impacts. We have developed a method to derive impact scores for individual research publications according to their contribution to answering questions of quantified importance to end users of research. To demonstrate the approach, here we evaluate the impacts of research into means of conserving wild bee populations in the UK. For published papers, there is a weak positive correlation between our impact score and the impact factor of the journal. The process identifies publications that provide high quality evidence relating to issues of strong concern. It can also be used to set future research agendas.

Global retrieval of ATSR cloud parameters and evaluation (GRAPE): dataset assessment

The Along-Track Scanning Radiometers (ATSRs) provide a long time-series of measurements suitable for the retrieval of cloud properties. This work evaluates the freely-available Global Retrieval of ATSR Cloud Parameters and Evaluation (GRAPE) dataset (version 3) created from the ATSR-2 (1995�2003) and Advanced ATSR (AATSR; 2002 onwards) records. Users are recommended to consider only retrievals flagged as high-quality, where there is a good consistency between the measurements and the retrieved state (corresponding to about 60% of converged retrievals over sea, and more than 80% over land). Cloud properties are found to be generally free of any significant spurious trends relating to satellite zenith angle. Estimates of the random error on retrieved cloud properties are suggested to be generally appropriate for optically-thick clouds, and up to a factor of two too small for optically-thin cases. The correspondence between ATSR-2 and AATSR cloud properties is high, but a relative calibration difference between the sensors of order 5�10% at 660 nm and 870 nm limits the potential of the current version of the dataset for trend analysis. As ATSR-2 is thought to have the better absolute calibration, the discussion focusses on this portion of the record. Cloud-top heights from GRAPE compare well to ground-based data at four sites, particularly for shallow clouds. Clouds forming in boundary-layer inversions are typically around 1 km too high in GRAPE due to poorly-resolved inversions in the modelled temperature profiles used. Global cloud fields are compared to satellite products derived from the Moderate Resolution Imaging Spectroradiometer (MODIS), Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP) measurements, and a climatology of liquid water content derived from satellite microwave radiometers. In all cases the main reasons for differences are linked to differing sensitivity to, and treatment of, multi-layer cloud systems. The correlation coefficient between GRAPE and the two MODIS products considered is generally high (greater than 0.7 for most cloud properties), except for liquid and ice cloud effective radius, which also show biases between the datasets. For liquid clouds, part of the difference is linked to choice of wavelengths used in the retrieval. Total cloud cover is slightly lower in GRAPE (0.64) than the CALIOP dataset (0.66). GRAPE underestimates liquid cloud water path relative to microwave radiometers by up to 100 g m�2 near the Equator and overestimates by around 50 g m�2 in the storm tracks. Finally, potential future improvements to the algorithm are outlined.

Credit risk in covered bonds

Covered bonds are a promising alternative for prime mortgage securitization. In this paper, we explore risk premia in the covered bond market and particularly investigate whether and how credit risk is priced. In extant literature, yield spreads between high-quality covered bonds and government bonds are often interpreted as pure liquidity premia. In contrast, we show that although liquidity is important, it is not the exclusive risk factor. Using a hand-collected data set of cover pool information, we find that the credit quality of the cover assets is an important determinant of covered bond yield spreads. This effect is particularly strong in times of financial turmoil and has a significant influence on the issuer's refinancing cost.