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Unobserved individual heterogeneity is a common challenge in population cancer survival studies. This heterogeneity is usually associated with the combination of model misspecification and the failure to record truly relevant variables. We investigate the effects of unobserved individual heterogeneity in the context of excess hazard models, one of the main tools in cancer epidemiology. We propose an individual excess hazard frailty model to account for individual heterogeneity. This represents an extension of frailty modelling to the relative survival framework. In order to facilitate the inference on the parameters of the proposed model, we select frailty distributions which produce closed-form expressions of the marginal hazard and survival functions. The resulting model allows for an intuitive interpretation, in which the frailties induce a selection of the healthier individuals among survivors. We model the excess hazard using a flexible parametric model with a general hazard structure which facilitates the inclusion of time-dependent effects. We illustrate the performance of the proposed methodology through a simulation study. We present a real-data example using data from lung cancer patients diagnosed in England, and discuss the impact of not accounting for unobserved heterogeneity on the estimation of net survival. The methodology is implemented in the R package IFNS., Accepted for publication in Statistics in Medicine. Codes and Examples can be found at: https://github.com/FJRubio67/IFNS

Rates of antimicrobial resistance are increasing globally while the pipeline of new antibiotics is drying up, putting patients with disease caused by drug-resistant bacteria at increased risk of complications and death. The growing costs for diagnosis and management of drug resistance threaten tuberculosis control where the disease is endemic and resources limited. Bacteriophages are viruses that attack bacteria. Phage preparations served as anti-infective agents long before antibiotics were discovered. Though small in size, phages are the most abundant and diverse biological entity on earth. Phages have co-evolved with their hosts and possess all the tools needed to infect and kill bacteria, independent of drug resistance. Modern biotechnology has improved our understanding of the biology of phages and their possible uses. Phage preparations are available to treat meat, fruit, vegetables, and dairy products against parasites or to prevent contamination with human pathogens, such as Listeria monocytogenes, Escherichia coli, or Staphylococcus aureus. Such phage-treated products are considered fit for human consumption. A number of recent case reports describe in great detail the successful treatment of highly drug-resistant infections with individualized phage preparations. Formal clinical trials with standardized products are slowly emerging. With its highly conserved genome and relative paucity of natural phage defence mechanisms Mycobacterium tuberculosis appears to be a suitable target for phage treatment. A phage cocktail with diverse and strictly lytic phages that kill all lineages of M. tuberculosis, and can be propagated on Mycobacterium smegmatis, has been assembled and is available for the evaluation of optimal dosage and suitable routes of administration for tuberculosis in humans. Phage treatment can be expected to be safe and active on extracellular organisms, but phage penetration to intracellular and granulomatous environments as well as synergistic effects with antibiotics are important questions to address during further evaluation.

Ca. Accumulibacter was the predominant microorganism (relative FISH bio-abundance of 67 ± 5%) in a lab-scale sequential batch reactor that accomplished enhanced biological phosphorus removal (EBPR) while using glucose and acetate as the carbon sources (1:1 COD-based ratio). Both organic compounds were completely anaerobically consumed. The reactor's performance in terms of P/C ratio, phosphorous release and uptake, and overall kinetic and stoichiometric parameters were on the high end of the reported spectrum for EBPR systems (100:9.3 net mg phosphate removal per mg COD consumed when using glucose and acetate in a 1:1 ratio). The batch tests showed that, to the best of our knowledge, this is the first time a reactor enriched with Ca. Accumulibacter can putatively utilize glucose as the sole carbon source to biologically remove phosphate (COD:P (mg/mg) removal ratio of 100:6.3 when using only glucose). Thus, this research proposes that Ca. Accumulibacter directly anaerobically stored the fed glucose primarily as glycogen by utilizing the ATP provided via the hydrolysis of poly-P and secondarily as PHA by balancing its ATP utilization (glycogen generation) and formation (PHA storage). Alternative hypotheses are also discussed. The reported findings could challenge the conventional theories of glucose assimilation by Ca. Accumulibacter, and can be of significance for the biological removal of phosphorus from wastewaters with high contents of fermentable compounds or low VFAs.

We propose two classes of nonparametric point estimators of = P (X < Y ) in the case where (X;Y ) are paired, possibly dependent, absolutely continuous random variables. The proposed estimators are based on nonparametric estimators of the joint density of (X;Y ) and the distri- bution function of Z = Y X. We explore the use of several density and distribution function estimators and characterise the convergence of the re- sulting estimators of . We consider the use of bootstrap methods to obtain condence intervals. The performance of these estimators is illustrated us- ing simulated and real data. These examples show that not accounting for pairing and dependence may lead to erroneous conclusions about the rela- tionship between X and Y.

Miguel Angel Luque-Fernandez is supported by a Miguel Servet I Investigator award (Grant CP17/00206) and a project grant EU-FEDER-FIS PI-18/01593 from the Instituto de Salud Carlos III, Madrid, Spain. Danilo Alvares is supported by the National Fund for Scientific and Technological Development (FONDECYT, Chile) grant number 11190018., Cancer survival represents one of the main indicators of interest in cancer epidemiology. However, the survival of cancer patients can be affected by several factors, such as comorbidities, that may interact with the cancer biology. Moreover, it is interesting to understand how different cancer sites and tumour stages are affected by different comorbidities. Identifying the comorbidities that affect cancer survival is thus of interest as it can be used to identify factors driving the survival of cancer patients. This information can also be used to identify vulnerable groups of patients with comorbidities that may lead to worst prognosis of cancer. We address these questions and propose a principled selection and evaluation of the effect of comorbidities on the overall survival of cancer patients. In the first step, we apply a Bayesian variable selection method that can be used to identify the comorbidities that predict overall survival. In the second step, we build a general Bayesian survival model that accounts for time-varying effects. In the third step, we derive several posterior predictive measures to quantify the effect of individual comorbidities on the population overall survival. We present applications to data on lung and colorectal cancers from two Spanish population-based cancer registries. The proposed methodology is implemented with a combination of the R-packages mombf and rstan. We provide the code for reproducibility at https://github.com/migariane/ BayesVarImpComorbiCancer., Miguel Servet I Investigator award CP17/00206 EU-FEDER-FIS PI-18/01593, Instituto de Salud Carlos III, Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT) CONICYT FONDECYT 11190018

Summary Background Despite the improvement in the prognosis of acute coronary syndrome (ACS), substantial morbidity and mortality remain. We aimed to evaluate the effect of obstructive sleep apnoea (OSA) and its treatment with continuous positive airway pressure (CPAP) on the clinical evolution of patients with ACS. Methods We designed a multicentre, open-label, parallel-group, randomised controlled trial of patients with ACS at 15 hospitals in Spain. Eligible non-sleepy patients were men and women aged 18 years and older, admitted to hospital for documented symptoms of ACS. All patients underwent respiratory polygraphy during the first 24–72 h after admission. OSA patients were randomly assigned (1:1) to CPAP treatment plus usual care (CPAP group) or usual care alone (UC group) by a computerised system available 24 h a day. A group of patients with ACS but without OSA was also included as a reference group. Because of the nature of the intervention, the trial intervention could not be masked to either investigators or patients. Patients were monitored and followed for a minimum of 1 year. Patients were examined at the time of inclusion; after 1 month, 3 months, 6 months, 12 months, 18 months, 24 months, 30 months, and 36 months; and every 12 months thereafter, if applicable, during the follow-up period. The primary endpoint was the prevalence of a composite of cardiovascular events (cardiovascular death or non-fatal events [Acute myocardial infarction, non-fatal stroke, hospital admission for heart failure, and new hospitalisations for unstable angina or transient ischaemic attack]) in patients followed up for a minimum of 1 year. The primary analysis was done according to the intention-to-treat principle. This study is registered with Clinicaltrials.gov , NCT01335087 and is now closed. Findings Between April 25, 2011, and Feb 2, 2018, a total of 2834 patients with ACS had respiratory polygraphy, of whom 2551 (90·01%) were recruited. 1264 (49·55%) patients had OSA and were randomly assigned to the CPAP group (n=633) or the UC group (n=631). 1287 (50·45%) patients did not have OSA, of whom 603 (46·85%) were randomly assigned to the reference group. Patients were followed up for a median of 3·35 years (IQR 1·50–5·31). The prevalence of cardiovascular events was similar in the CPAP and UC groups (98 events [16%] vs 108 events [17%]; hazard ratio [HR] 0·89 [95% CI 0·68–1·17]; p=0·40) during follow-up. Mean time of adherence to CPAP treatment was 2·78 h/night (SD 2·73). The prevalence of cardiovascular events was similar between patients in the reference group (90 [15%] events) and those in the UC group (102 (17%) events) during follow-up (1·01 [0·76–1·35]; p=0·93). The prevalence of cardiovascular events seem not to be related to CPAP compliance or OSA severity. 464 (74%) of 629 patients in the CPAP group had 1538 serious adverse events and 406 (65%) of 626 patients in the UC group had 1764 serious adverse events. Interpretation Among non-sleepy patients with ACS, the presence of OSA was not associated with an increased prevalence of cardiovascular events and treatment with CPAP did not significantly reduce this prevalence. Funding ResMed (Australia), Fondo de Investigacion Sanitaria (Fondo Europeo de Desarrollo Regional), the Spanish Respiratory Society, the Catalonian Cardiology Society, Esteve-Teijin, Oxigen Salud, and ALLER.

Background Large and complex population-based cancer data are becoming broadly available, thanks to purposeful linkage between cancer registry data and health electronic records. Aiming at understanding the explanatory power of factors on cancer survival, the modelling and selection of variables need to be understood and exploited properly for improving model-based estimates of cancer survival. Method We assess the performances of well-known model selection strategies developed by Royston and Sauerbrei and Wynant and Abrahamowicz that we adapt to the relative survival data setting and to test for interaction terms. Results We apply these to all male patients diagnosed with lung cancer in England in 2012 (N = 15,688), and followed-up until 31/12/2015. We model the effects of age at diagnosis, tumour stage, deprivation, comorbidity and emergency presentation, as well as interactions between age and all of the above. Given the size of the dataset, all model selection strategies favoured virtually the same model, except for a non-linear effect of age at diagnosis selected by the backward-based selection strategies (versus a linear effect selected otherwise). Conclusion The results from extensive simulations evaluating varying model complexity and sample sizes provide guidelines on a model selection strategy in the context of excess hazard modelling.

In cancer epidemiology using population-based data, regression models for the excess mortality hazard is a useful method to estimate cancer survival and to describe the association between prognosis factors and excess mortality. This method requires expected mortality rates from general population life tables: each cancer patient is assigned an expected (background) mortality rate obtained from the life tables, typically at least according to their age and sex, from the population they belong to. However, those life tables may be insufficiently stratified, as some characteristics such as deprivation, ethnicity, and comorbidities, are not available in the life tables for a number of countries. This may affect the background mortality rate allocated to each patient, and it has been shown that not including relevant information for assigning an expected mortality rate to each patient induces a bias in the estimation of the regression parameters of the excess hazard model. We propose two parametric corrections in excess hazard regression models, including a single-parameter or a random effect (frailty), to account for possible mismatches in the life table and thus misspecification of the background mortality rate. In an extensive simulation study, the good statistical performance of the proposed approach is demonstrated, and we illustrate their use on real population-based data of lung cancer patients. We present conditions and limitations of these methods, and provide some recommendations for their use in practice., to appear in Biostatistics

This contribution discusses about the rheological, kinematic and dynamic frameworks necessary to produce recumbent and upright folds from syn-orogenic granitic massifs that were formed during an early stage of magma genesis related to the onset of a migmatitic dome. Syn-kinematic granitoids occurring within the high-grade infrastructure of the Padrón migmatitic dome (NW Iberia) are deformed into large-scale recumbent folds (D2) that are later affected by upright folds (D3). Petrostructural analysis of a selected area of this dome reveals that after a period of crustal thickening (D1), NNW-directed extensional flow gave way to recumbent folds and penetrative axial plane foliation (S2). Superimposed subhorizontal compression resulted in upright folds (D3). A closer view into the dynamics of the dome allows exploring the factors that may condition the nucleation of folds with contrasting geometries during progressive deformation of molten continental crust. The formation of folds affecting syn-kinematic granitoids suggests a cooling metamorphic path in migmatitic domes. Active and passive folding mechanisms require a crystallizing (cooling) magma to nucleate folds. A more competent metamorphic host inhibits fold nucleation from much less competent magmas. As it crystallizes, magma becomes more rigid (competent), and approaches viscosity values of its host. Passive folding is favored when no significant competence contrast exists between magma and host, so this folding mechanism is more likely shortly after magma genesis and emplacement. In such conditions, and under dominant subhorizontal flow accompanied by flattening (D2), passive folding would produce isoclinal recumbent geometries. Further magma cooling introduces a shift into the rheological behavior of partially molten crust. Thereon, crystallizing magma bodies would represent significant competence contrasts relative to their host. At this point, buckling is a more likely folding mechanism, and more regular, buckle folds re-fold previous structures after significant cooling. The geometry of resulting folds is upright due to dominant subhorizontal compression (D3) at this stage. Keywords: Recumbent folds, Migmatitic domes, Partial melting, Crustal-derived granitoids, Orogenic collapse, Variscan orogen

We introduce a numerically tractable formulation of Bayesian joint models for longitudinal and survival data. The longitudinal process is modeled using generalized linear mixed models, while the survival process is modeled using a parametric general hazard structure. The two processes are linked by sharing fixed and random effects, separating the effects that play a role at the time scale from those that affect the hazard scale. This strategy allows for the inclusion of nonlinear and time-dependent effects while avoiding the need for numerical integration, which facilitates the implementation of the proposed joint model. We explore the use of flexible parametric distributions for modeling the baseline hazard function which can capture the basic shapes of interest in practice. We discuss prior elicitation based on the interpretation of the parameters. We present an extensive simulation study, where we analyze the inferential properties of the proposed models, and illustrate the trade-off between flexibility, sample size, and censoring. We also apply our proposal to two real data applications in order to demonstrate the adaptability of our formulation both in univariate time-to-event data and in a competing risks framework. The methodology is implemented in rstan.

A kind of energy storage proceeding from renewable sources is presented. It has been studied the storage, in the form of Compressed Air Energy Storage Systems (CAES) or Liquefied Air Energy Storage Systems (LAES) of the renewable electricity that, at the time it is generated, it is not delivered to the network because of technical or economic reasons, or saturation. The possibility of using an artificial storage system allows the installation not to be conditioned by the availability of a natural reservoir. This article focuses on the use of artificial storage systems, mainly for small power wind farms (about 30 kW), so storage systems will alternatively be called CAES or SCAES and LAES or SLAES (S from “small”) CAES systems advantages and disadvantages of each different thermodynamic cycle are studied. One of CAES systems higher limitations is the huge volume needed to store air mass enough. Instead of storing gaseous phase air, much more energy density can be accumulated by storing air in liquid phase (LAES). LAES system functioning is similar to CAES one. Liquid air is produced in an air liquefying plant when there is an excess of energy or it is not interesting to drop it into the network Some LAES systems advantages are storage volume reduction for the same energy density and the possibility of storing at about atmospheric pressure.

A stacking of nappes forms the Parautochthonous Domain located beneath the Allochthonous Complexes of the NW Iberian Massif. Lower Paleozoic metasedimentary and felsic metavolcanic rocks, including some riebeckite gneiss, form the uppermost nappe of the Parautochthon. Micaschists of this nappe may contain albite porphyroblasts with aligned mineral microinclusions defining a relic internal schistosity. Thermobarometric estimates on the relic mineral assemblage suggest an early M1 stage of High-Pressure, Low-Temperature (HP-LT) metamorphism (11–14 kbar; 450–500 °C), probably related to the same continental subduction process that affected the overlying Lower Allochthon nappes or Basal Units. This uppermost nappe was emplaced onto its relative autochthon by a broad, ductile shear zone that shows top-to-the-E/ENE shear-sense and whose exposure has lateral continuity through to the basal thrust of the Lower Allochthons in the Bragança Complex. The HP-LT metamorphism and its hanging wall position relative to the basal thrust of the Allochthonous Complexes, suggest a re-interpretation of this uppermost parautochthonous nappe as another nappe of the Lower Allochthon. In turn, the other parautochthonous nappes comprise both, Lower Paleozoic pre-orogenic rocks, with no M1 relics, and Upper Paleozoic syn-orogenic rocks. Shear-sense criteria related to the current juxtaposition of the Parautochthon Domain onto the Central Iberian autochthon show contrasting top-to-the-S/SE kinematics. The whole orogenic section was affected by an M2 episode of recrystallization under intermediate P/T conditions during the first stages of collision. P-T estimates on kyanite-bearing schists from the upper sections of the autochthon (9.0 kbar; 425–450 °C) are consistent with a geothermal gradient somewhat lower than the classical Barrovian one at the beginning of collision. Thermobarometric calculations on schists from the lower parautochthonous nappes yield peak metamorphic conditions around 7.5 Kbar and 600–700 °C, constraining the original thickness of the allochthonous/parautochthonous pile to about 22.5–27.0 km. Schists sampled from deeper sections of the autochthon yield M2 conditions around 11–12 kbar and 700–725 °C, matching those registered by correlative regions from Central Iberia. Subsequent M3 syn-collisional recrystallization under High-Temperature and Low-Pressure conditions is associated with top-to-the-N/NW and top-to-the-S/SE extensional flow. The early metamorphic evolution of the autochthons, Parautochthon and Allochthonous Complexes of NW Iberia recorded a transition in P/T regimes and appears as a model case of a change from subduction to collision.

Bayesian variable selection often assumes normality, but the effects of model misspecification are not sufficiently understood. There are sound reasons behind this assumption, particularly for large $p$: ease of interpretation, analytical and computational convenience. More flexible frameworks exist, including semi- or non-parametric models, often at the cost of some tractability. We propose a simple extension of the Normal model that allows for skewness and thicker-than-normal tails but preserves tractability. It leads to easy interpretation and a log-concave likelihood that facilitates optimization and integration. We characterize asymptotically parameter estimation and Bayes factor rates, in particular studying the effects of model misspecification. Under suitable conditions misspecified Bayes factors are consistent and induce sparsity at the same asymptotic rates than under the correct model. However, the rates to detect signal are altered by an exponential factor, often resulting in a loss of sensitivity. These deficiencies can be ameliorated by inferring the error distribution from the data, a simple strategy that can improve inference substantially. Our work focuses on the likelihood and can thus be combined with any likelihood penalty or prior, but here we focus on non-local priors to induce extra sparsity and ameliorate finite-sample effects caused by misspecification. Our results highlight the practical importance of focusing on the likelihood rather than solely on the prior, when it comes to Bayesian variable selection. The methodology is available in R package `mombf'.

This article focuses on the advantages found by incorporating Hygroscopic Cycle Technology into the 12.5-MWe “Vetejar” biomass power plant operating in the province of Cordoba (Spain) since 1996. The power plant required upgrades to increase its availability, net electrical performance and to extend the service life span of refrigeration equipment. The incorporation of the new Hygroscopic Cycle Technology has allowed not only to alleviate the shortcomings of the power station in a simple way, but also to make the most of the existing equipment, despite the adverse environmental conditions. The scarcity of water in the area is one of the greatest difficulties the plant has met since its start-up. It significantly diminishes the operation hours of the plant, reducing the electrical power generated, electrical performance and availability. The incorporation of this novel technology to the existing plant has allowed the cooling temperature to increase by 13 °C while maintaining the same condensing pressure. As a result, significant net increase in electrical efficiency, reduction of auto-consumption and cut down on annual cooling water consumption were obtained.

This contribution provides a case example on the generation of large-scale recumbent folds in syn-orogenic granitoids. We analyze the progressive reworking of extension-related structures into later ones after a period of crustal thickening. The Padrón migmatitic dome formed after the climax of the Gondwana-Laurussia collision in the late Paleozoic. Petrostructural analysis carried out in the eastern flank of this dome reveals that extensional flow resulted in progressive exhumation of mainland Gondwana, which rested under peri-gondwanan allochthonous terranes and a suture zone during maximum crustal thickening. Exhumation proceeded up to upper crust levels (andalusite stability field) along with partial melting of the middle-lower crust and with the generation of granitoid laccoliths during an early extensional stage. Newly-formed lithological andmechanical anisotropies, such as the presence of variably-sized sheet-shaped bodies of syn-orogenic granitoids, provided a favorable rheological setting for fold nucleation during the intermediate stages of extension. In extending orogenic crust, whether recumbent folds occur after significant melt production depends on the lateral/vertical flow ratio, and on the orientation of deforming bodies with regard to kinematic/strain axes. We suggest that subhorizontal extensional flow dominated over vertical flow during the early and intermediate stages of the evolution of the Padrón dome. A component of vertical (diapiric) flow caused progressive tilting of the sheet-like bodies and obliquity respect to strain axes. This resulted in the development of regional-scale folds at the expense of syn-orogenic granitoids, such as in the case of the Portomouro recumbent synform. Extensional ductile flow was oblique to the trend of the orogen during the whole process, and directed to the NNWduring the formation of recumbent folds. Non-coaxial shearing favored an (NNW-SSE) elongate shape for the syn-kinematic granitic massifs as well as the subsequent nucleation of recumbent folds. Deformation concentrated along discrete detachments during the late stages of extension., Departamento de Geodinámica, Universidad Complutense de Madrid, España, Instituto Geológico y Minero de España, España

An integrated interpretation of the late Paleozoic structural and geochronological record of the Iberian Massif is presented and discussed under the perspective of a Gondwana-Laurussia collision giving way to the Variscan orogen. Compressional and extensional structures developed during the building of the Variscan orogenic crust of Iberia are linked together into major tectonic events operating at lithosphere scale. A review of the tectonometamorphic and magmatic evolution of the Iberian Massif reveals backs and forths in the overall convergence between Gondwana and Laurussia during the amalgamation of Pangea in late Paleozoic times. Stages dominated by lithosphere compression are characterized by subduction, both oceanic and continental, development of magmatic arcs, (over- and under-) thrusting of continental lithosphere, and folding. Variscan convergence resulted in the eventual transference of a large allochthonous set of peri-Gondwanan terranes, the Iberian Allochthon, onto the Gondwana mainland. The Iberian Allochthon bears the imprint of previous interaction between Gondwana and Laurussia, including their juxtaposition after the closure of the Rheic Ocean in Lower Devonian times. Stages governed by lithosphere extension are featured by the opening of two short-lived oceanic basins that dissected previous Variscan orogenic crust, first in the Lower-Middle Devonian, following the closure of the Rheic Ocean, and then in the early Carboniferous, following the emplacement of the peri-Gondwanan allochthon. An additional, major intra-orogenic extensional event in the early-middle Carboniferous dismembered the Iberian Allochthon into individual thrust stacks separated by extensional faults and domes. Lateral tectonics played an important role through the Variscan orogenesis, especially during the creation of new tectonic blocks separated by intracontinental strike-slip shear zones in the late stages of continental convergence., Financial support has been provided by the Spanish project CGL2012-34618, funded by Ministerio de Economía y Competitividad (Spain).

NW Iberia includes a rather complete section of a Variscan suture, where different terranes with continental or oceanic affinities appear with clear structural relationships. Three groups of terranes, namely Upper, Ophiolitic and Basal units and a frontal tectonic mélange appear in Galicia, in Cabo Ortegal, Órdenes and Malpica-Tui complexes. They constitute a huge allochthonous pile thrust over the Iberian parautochthonous and autochthonous domains, which represent the section of the Gondwanan margin that escaped continental subduction during the Variscan cycle. Considering the allochthonous character of the nappe pile and the strong deformation associated to the Variscan collision, there are problems to identify the original tectonic setting of the terranes and thence, it is difficult to reconstruct the paleogeographic context during the Variscan and pre-Variscan times in detail. Key features to perform any model for the Variscan convergence should consider the existence of two different high-P metamorphic events (dated at c. 400 and 370 Ma, respectively), separated in time for the generation of mafic-ultramafic sequences at c. 395 Ma which constitute the most common ophiolites described in the Variscan suture. Some dynamic models developed in NW Iberia have important problems to explain the observed tectonothermal evolution, especially the older high-P metamorphic event and the exhumation of deeply subducted transitional-type sections. On the other hand, the recently discovered participation of an older continental crust in the generation of different protoliths of the Middle Devonian ophiolites, makes difficult the interpretation of these ophiolites in relation to open wide oceanic domains. This paper describes the distribution, structure, lithologies, geochronology and chemical composition of the terranes involved in the Variscan suture of NW Spain. The scope of this description ranges from detailed regional aspects to the discussion of the development of the Variscan Orogen in the context of the assembly of Pangea. A two-stage collisional model affecting a wide Gondwanan platform may explain most of the evidences in NW Iberia. The generation of a long pull-apart basin probably occurred after the first collision, where the Devonian ophiolites were formed. These ophiolites have been in general described in the context of the Rheic Ocean, but according to the new existing data they do not seem related to this ocean, but rather they were formed after its closure., Financial support has been provided by the Spanish project CGL2012-34618 (Ministerio de Economía y Competitividad).

We study Bayesian linear regression models with skew-symmetric scale mixtures of normal error distributions. These kinds of models can be used to capture departures from the usual assumption of normality of the errors in terms of heavy tails and asymmetry. We propose a general noninformative prior structure for these regression models and show that the corresponding posterior distribution is proper under mild conditions. We extend these propriety results to cases where the response variables are censored. The latter scenario is of interest in the context of accelerated failure time models, which are relevant in survival analysis. We present a simulation study that demonstrates good frequentist properties of the posterior credible intervals associated with the proposed priors. This study also sheds some light on the trade-off between increased model flexibility and the risk of over-fitting. We illustrate the performance of the proposed models with real data. Although we focus on models with univariate response variables, we also present some extensions to the multivariate case in the Supporting Information. Copyright © 2016 John Wiley & Sons, Ltd.

We introduce a general class of continuous univariate distributions with positive support obtained by transforming the class of two-piece distributions. We show that this class of distributions is very flexible, easy to implement, and contains members that can capture different tail behaviours and shapes, producing also a variety of hazard functions. The proposed distributions represent a flexible alternative to the classical choices such as the log-normal, Gamma, and Weibull distributions. We investigate empirically the inferential properties of the proposed models through an extensive simulation study. We present some applications using real data in the contexts of time-to-event and accelerated failure time models. In the second kind of applications, we explore the use of these models in the estimation of the distribution of the individual remaining life.

The Hygroscopic cycle is a novel proprietary power cycle characterized by working with hygroscopic compounds which optimize the condensation of the turbine output steam in a steam absorber. This technology can be incorporated in any power plant that uses a Rankine cycle, obtaining higher electrical efficiency without limiting the cold sink temperature and without cooling water consumption. The novelty of this article is that Hygroscopic cycle is experimentally investigated in a test power plant with high concentrations of lithium bromide solution in water in the cooling reflux to analyze the effect on condensing temperature, condensing pressure, power output and efficiency. Mass concentration of lithium bromide in the cooling reflux stream ranges from 45 to 65%. The increase in salt concentration at the cooling reflux stream allows the condensing temperatures to be significantly increased by more than 15 °C in a Hygroscopic cycle with respect to a Rankine cycle. Results also show that it is possible to decrease the turbine outlet condensing pressures for the same condensing temperature. Thereby, as mass concentration of lithium bromide is increased the gross electric power output increases with reference to a Rankine cycle for the same condensing temperature. The minimum increments in net electric power output and electrical efficiency are 7.6% and 2.6% respectively.

Many preclinical studies examined cue-induced relapse to heroin and cocaine seeking in animal models, but most of these studies examined only one drug at a time. In human addicts, however, polydrug use of cocaine and heroin is common. We used a polydrug self-administration relapse model in rats to determine similarities and differences in brain areas activated during cue-induced reinstatement of heroin and cocaine seeking. We trained rats to lever press for cocaine (1.0 mg/kg/infusion, 3-h/d, 18 d) or heroin (0.03 mg/kg/infusion) on alternating days (9 d for each drug); drug infusions were paired with either intermittent or continuous light cue. Next, the rats underwent extinction training followed by tests for cue-induced reinstatement where they were exposed to either heroin- or cocaine-associated cues. We observed cue-selective reinstatement of drug seeking: the heroin cue selectively reinstated heroin seeking and the cocaine cue selectively reinstated cocaine seeking. We used Fos immunohistochemistry to assess cue-induced neuronal activation in different subregions of the medial prefrontal cortex (mPFC), dorsal striatum (DS), nucleus accumbens (NAc), and amygdala. Fos expression results indicated that only the prelimbic cortex (PL) was activated by both heroin and cocaine cues; in contrast, no significant cue-induced neuronal activation was observed in other brain areas. RNA in situ hybridization indicated that the proportion of glutamatergic and GABAergic markers in PL Fos-expressing cells were similar for the heroin and cocaine cue-activated neurons. Overall the results indicate that PL may be a common brain area involved in both heroin and cocaine seeking during polydrug use.

BackgroundReducing hospital emergency admissions is a key target for all modern health systems.MethodsWe analysed colon cancer patients diagnosed in 2011–13 in England. We screened their individual Hospital Episode Statistics records in the 90 days pre-diagnosis, the 90 days post-diagnosis, and the 90 days pre-death (in the year following diagnosis), for the occurrence of hospital emergency admissions (HEAs).ResultsBetween a quarter and two thirds of patients experience HEA in the three 90-day periods examined: pre-diagnosis, post-diagnosis and before death. Patients with tumour stage I-III from more deprived backgrounds had higher proportions of HEAs than less deprived patients during all studied periods. This remains even after adjusting for differing distributions of risk factors such as age, sex, comorbidity and stage at diagnosis.CONCLUSIONSAlthough in some cases HEAs might be unavoidable or even appropriate, the proportion of HEAs varies by socioeconomic status, even after controlling for the usual patient factors, suggestive of remediable causes of excess emergency healthcare utilisation in patients belonging to higher deprivation groups. Future inquiries should address the potential role of clinical complications, sub-optimal healthcare administration, premature discharge or a lack of social support as potential explanations for these patterns of inequality.

The proportional hazards model represents the most commonly assumed hazard structure when analysing time to event data using regression models. We study a general hazard structure which contains, as particular cases, proportional hazards, accelerated hazards, and accelerated failure time structures, as well as combinations of these. We propose an approach to apply these different hazard structures, based on a flexible parametric distribution (Exponentiated Weibull) for the baseline hazard. This distribution allows us to cover the basic hazard shapes of interest in practice: constant, bathtub, increasing, decreasing, and unimodal. In an extensive simulation study, we evaluate our approach in the context of excess hazard modelling, which is the main quantity of interest in descriptive cancer epidemiology. This study exhibits good inferential properties of the proposed model, as well as good performance when using the Akaike Information Criterion for selecting the hazard structure. An application on lung cancer data illustrates the usefulness of the proposed model., Comment: To appear in Statistical Methods in Medical Research. Supplementary material and software available here: https://sites.google.com/site/fjavierrubio67/home/papers

In the Ossa Morena Domain of SW Iberia, the Calzadilla Ophiolite is formed by an ensemble of ultramafic and mafic rocks that seem to represent a fragment of an oceanic Moho transition zone. The ophiolite consists of a main sheet with a minimum thickness of c. 1000 m and several ultramafic slices that appear imbricated with Ediacaran siliciclastic rocks of the so called Serie Negra. The mafic rocks of the Calzadilla Ophiolite show an extreme depletion in some HFSE such as Nb, Zr, Th, Hf and Ta, low TiO2 contents and high MgO, which allow identifying them as magmatic types of boninitic affinity, such as those frequently associated with fore-arc settings. U-Pb zircon dating of the gabbroic rocks suggests that the igneous protoliths crystallised at c. 600 Ma and were extracted directly from the mantle, according to the juvenile isotopic sources revealed by the Hf isotopic composition of the dated zircons. At c. 540 Ma the U-Pb isotopic system was affected by a partial resetting event with moderate generation of new zircon. According to these data, it is considered that the Calzadilla Ophiolite was formed in a supra-subduction zone setting, very likely in a fore-arc domain, during a roll-back episode affecting the peri-Gondwanan subductive slab. The fore-arc domain was probably proximal to the West Africa Craton. It is very likely that the ductile deformation, metamorphism and tectonic imbrication of the Calzadilla Ophiolite and the Serie Negra occurred at c. 540 Ma, during an increase in the subduction rate and a significant decrease of the subduction angle of the oceanic slab. The information provided by the Calzadilla Ophiolite allows to better constrain the geodynamic evolution of the African margin of Gondwana., Financial support has been provided by the Spanish project CGL2016-76438-P (Ministerio de Economía, Industria y Competitividad).

Background Emergency presentations (EP) represent over a third of all lung cancer admissions in England. Such presentations usually reflect late stage disease and are associated with poor survival. General practitioners (GPs) act as gate-keepers to secondary care and so we sought to understand the association between GP practice characteristics and lung cancer EP. Methods Data on general practice characteristics were extracted for all practices in England from the Quality Outcomes Framework, the Health and Social Care Information Centre, the GP Patient Survey, the Cancer Commissioning Toolkit and the area deprivation score for each practice. After linking these data to lung cancer patient registrations in 2006–2013, we explored trends in three types of EP, patient-led, GP-led and ‘other’, by general practice characteristics and by socio-demographic characteristics of patients. Results Overall proportions of lung cancer EP decreased from 37.9% in 2006 to 34.3% in 2013. Proportions of GP-led EP nearly halved during this period, from 28.3 to 16.3%, whilst patient-led emergency presentations rose from 62.1 to 66.7%. When focusing on practice-specific levels of EP, 14% of general practices had higher than expected proportions of EP at least once in 2006–13, but there was no evidence of clustering of patients within practice, meaning that none of the practice characteristics examined explained differing proportions of EP by practice. Conclusion We found that the high proportion of lung cancer EP is not the result of a few practices with very abnormal patterns of EP, but of a large number of practices susceptible to reaching high proportions of EP. This suggests a system-wide issue, rather than problems with specific practices. High proportions of lung cancer EP are mainly the result of patient-initiated attendances in A&E. Our results demonstrate that interventions to encourage patients not to bypass primary care must be system wide rather than targeted at specific practices. Electronic supplementary material The online version of this article (10.1186/s12885-018-4476-5) contains supplementary material, which is available to authorized users.

We propose a Bayesian approach using improper priors for hierarchical linear mixed models with flexible random effects and residual error distributions. The error distribution is modelled using scale mixtures of normals, which can capture tails heavier than those of the normal distribution. This generalisation is useful to produce models that are robust to the presence of outliers. The case of asymmetric residual errors is also studied. We present general results for the propriety of the posterior that also cover cases with censored observations, allowing for the use of these models in the contexts of popular longitudinal and survival analyses. We consider the use of copulas with flexible marginals for modelling the dependence between the random effects, but our results cover the use of any random effects distribution. Thus, our paper provides a formal justification for Bayesian inference in a very wide class of models (covering virtually all of the literature) under attractive prior structures that limit the amount of required user elicitation., Comment: To appear in the Electronic Journal of Statistics. Additional R codes can be found at: http://rpubs.com/FJRubio

A model for the P–T–t evolution of NW and Central Iberia is presented to better understand its metamorphic evolution from initial Barrovian stage through HT–LP conditions. The model is constrained by the well-known succession of structural events and geochronology of the Variscan deformation, standard physical parameters, and conservative values for the surface heat flow and radiogenic heat production. The goals are to test an orogenic model derived from observations against a physical reality constrained by the thermal properties of the lithosphere, and to explore the implications for Variscan orogenic evolution. A600 km section, parallel to the axial surface of the Central Iberian arc is modeled to the scale of the continental lithosphere. The model outcomes are presented as sections showing the evolution of isotherms over 65 Ma, as the variation of the lithospheric geotherm and as P–T–t paths for significant parts of the model section and for points originating at different depths. Profiles of lithosphere strength have been constructed combining the maximum shear stress for brittle fracture with published flow–stress–depth profiles of characteristic rocks and temperatures obtained for the different depths in the model. Quantitative constraints from 2-D thermal models suggest that the metamorphic and magmatic evolution can be explained by the succession of three orogenic stages, namely crustal thickening, a period of thermal relaxation, and subsequent extensional collapse, providing that the first stage doubles the thickness of the continental crust. Thrusting of a thick nappe stack, well preserved in NW Iberia, seems to be the likely cause of the high temperatures reached later during the HT–LP event that occurred during late orogenic extension. The late addition of heat from asthenospheric upwelling remains a possibility, but the model results suggest that it is not necessary to explain the Variscan P–T–t paths.

The incidence of an accessory soleus muscle, according to autopsy studies, ranged from 0.5 to 6.0% of the population. The typical presentation is a soft mass in the posteromedial distal third of the leg, which increases in size with physical activity, especially plantar flexion. It is accompanied by pain with exercise in 67% of reported cases. The treatment of choice is conservative, but when it causes compartment syndrome, fasciotomy should be performed. If a patient has symptoms of claudication or nerve compression, a complete excision of the muscle is required. We report the case of an athlete who had a symptomatic accessory soleus muscle, which was studied by standard X-ray, ultrasound and magnetic resonance imaging (MRI).

The use of improper priors in the context of Bayesian hierarchical linear mixed models has been studied under the assumption of normality of the random effects. We study the propriety of the posterior under more flexible distributional assumptions and general improper prior structures.

An objective Bayesian approach to estimate the number of degrees of freedom $(\nu)$ for the multivariate $t$ distribution and for the $t$-copula, when the parameter is considered discrete, is proposed. Inference on this parameter has been problematic for the multivariate $t$ and, for the absence of any method, for the $t$-copula. An objective criterion based on loss functions which allows to overcome the issue of defining objective probabilities directly is employed. The support of the prior for $\nu$ is truncated, which derives from the property of both the multivariate $t$ and the $t$-copula of convergence to normality for a sufficiently large number of degrees of freedom. The performance of the priors is tested on simulated scenarios. The R codes and the replication material are available as a supplementary material of the electronic version of the paper and on real data: daily logarithmic returns of IBM and of the Center for Research in Security Prices Database., Comment: To appear in Computational Statistics and Data Analysis

In this note, I address the use of improper priors on the shape parameters of some asymmetric exponential power models. It is shown that the use of certain prior structures, with improper priors on the shape parameters, lead to improper posteriors. These results imply that the posteriors associated to some of the asymmetric exponential power models studied in Naranjo et al. (2014) are improper. Alternative improper priors, inspired by the structure of the independence Jeffreys prior, as well as vague proper priors are pointed out.

Power output of power plant is substantially reduced when cooling is conducted at high ambient temperatures. The problem is also intensified at locations with water scarcity. Hygroscopic cycle is a novel technology that improves Rankine cycle and solve those problems in an effective way. Hygroscopic Cycle Technology works with hygroscopic compounds that increase the cooling temperature for each output pressure of the steam turbine and uses dry coolers for refrigeration. As a result, much better cooling conditions are obtained and water consumption is avoided. Higher electrical performance is obtained without the limitation of high ambient temperatures. In this paper, Hygroscopic Cycle is experimentally studied. Results have been obtained in a test plant with a live steam generation capacity of 110 kg/h. This article shows cooling temperatures increase obtained for high mass concentrations from 45 to 65% of lithium bromide solution in water at the cooling reflux stream. The increase of the saline concentration in the cooling reflux significantly increase the cooling temperatures by more than 15 °C in a Hygroscopic cycle with respect to a Rankine cycle, for the same condensing pressure. Consequently, it reduces the electrical power required by the chosen cooling system, as well as to save all the cooling water consumption needed for cooling towers in other installations. Hygroscopic Cycle with high concentrations is able to increase up to 17.41% the net electrical power output respect to Rankine cycle.

Several units exposed in the boundary area of the Ossa Morena Zone (OMZ) and the South Portuguese Zone (SPZ) preserve petrographic and thermobarometric evidence for an early metamorphic episode (M1), developed under a high- P , low to intermediate- T gradient, related to Early Variscan subduction in the SW Iberian Massif. In the OMZ, these are the Cubito–Moura Unit ( P min ~ 9.2 kbar and T = 395 ± 45 °C), blueschists from its basal melange ( P min ~ 12.4 kbar and T = 310 ± 11 °C), and the underlying Fuenteheridos Group ( P = 10.9 ± 0.4 kbar and T = 449 ± 31 °C). The equivalent units in the SPZ are the La Minilla Formation ( P = 8.7 ± 0.4 kbar and T = 388 ± 16 °C) and the lawsonite pseudomorphs-bearing Pulo do Lobo Formation. All these units formed part of an approximately NE verging orogenic wedge (present coordinates) developed by the accretion of subducted slabs of the outermost margin of Gondwana and other elements of the Rheic Ocean realm, from at least the Middle Devonian to the lowermost Tournaisian. High-pressure rocks were subsequently emplaced on more internal zones of the OMZ that only experienced a younger high- T , low to intermediate- P metamorphism (M2). This high- T event was coeval with magmatic activity from the uppermost Devonian to the Middle Mississippian, probably as a consequence of transtensional lithospheric thinning and/or delamination of the lower crust and mantle lithosphere of the Gondwana margin. Pre-Late Devonian synorogenic sedimentation in forearc and back-arc basins of the subduction complex evolved to a Late Devonian–Middle Mississippian foreland basin system in early collisional stages. Finally, a new Middle–Late Mississippian fold-and-thrust belt with opposite (SW) vergence and new foreland basins developed during late collisional stages.

Correlation of a group of allochthonous terranes (referred to as basal, ophiolitic and upper units) exposed in the NW and SW of the Iberian Massif, is used to propose a new geotectonic zone in the southern branch of the Variscan Orogen: the Galicia–Ossa-Morena Zone. Recent advances in SW Iberia identify most of the former Ossa-Morena Zone as another allochthonous complex of the Iberian Massif, the Ossa-Morena Complex, equivalent to the Cabo Ortegal, Órdenes, Malpica-Tui, Bragança and Morais complexes described in NW Iberia. The new geotectonic zone and its counterparts along the rest of the Variscan Orogen constitute an Internal Variscan Zone with ophiolites and units affected by high-P metamorphism. The Galicia–Ossa-Morena Zone includes a Variscan suture and pieces of continental crust bearing the imprint of Ediacaran–Cambrian events related to the activity of peri-Gondwanan magmatic arcs (Cadomian orogenesis). In the Iberian Massif, the general structure of this geotectonic zone represents a duplication of the Gondwanan platform, the outboard sections being juxtaposed on top of domains located closer to the mainland before amalgamation. This interpretation offers an explanation that overcomes some issues regarding the differences between the stratigraphic and paleontological record of the central and southern sections of the Iberian Massif. Also, equivalent structural relationships between other major geotectonic domains of the rest of the Variscan Orogen are consistent with our interpretation and allow suspecting similar configurations along strike of the orogen. A number of issues may be put forward in this respect that potentially open new lines of thinking about the architecture of the Variscan Orogen., Financial support has been provided by the Spanish project CGL2012-34618 (Ministerio de Economía y Competitividad).

The Variscan tectonothermal structure of the NW and Central Iberian Massif shows an important thickening during the Early Carboniferous, prior to its thermal weakening and gravitational collapse in the Middle Carboniferous, triggering the uplift of its orogenic roots. Pseudosections modelling of selected samples from Somosierra, in the Barrovian metamorphic area of Central Iberia, yield P–T conditions of at least 6 kbar and 500–540 °C for a micaschist of the garnet zone, 5.0–9.7 kbar and 580–620 °C for a psammitic schist of the staurolite zone, above 9.0 kbar and 680 °C for a kyanite micaschist of the sillimanite zone, and 4.0–9.0 kbar and 750–800 °C for a migmatitic paragneiss structurally beneath the Barrovian sequence. These data, together with previous metamorphic and structural data, imply the near-parallel emplacement of a > 9 km-thick allochthonous nappe over the Central Iberian foreland during the Early Carboniferous. Emplacement was probably related to the lateral extension of a mid-European orogenic plateau in the form of a channel between opposite-verging collisional wedges. This orogen-parallel extension flow can be traced from the Bohemian Massif through the French Massif Central, South Domain of the Armorican Massif and NW of the Iberian Massif, to the Central Iberian area. The highly oblique emplacement of the thick allochthonous nappe explains the orogen-parallel stretching lineations, the development of Barrovian and subsequent low-pressure metamorphisms, and it could also explain the massive granitic magmatism located in the NW and central areas of the Central Iberian Zone., This work was financially supported by the Spanish Government project CGL2012-34618 and the Spanish Geological Survey (IGME) project no. 2281.