The Initial Slope of the Variogram, Foundation of the Trabecular Bone Score, Is Not or Poorly Associated With Vertebral Strength

Trabecular bone score (TBS) rests on the textural analysis of DXA to reflect the decay in trabecular structure characterising osteoporosis. Yet, its discriminative power in fracture studies remains incomprehensible as prior biomechanical tests found no correlation with vertebral strength. To verify this result possibly due to an unrealistic set-up and to cover a wide range of loading scenarios, the data from three previous biomechanical studies using different experimental settings was used. They involved the compressive failure of 62 human lumbar vertebrae loaded 1) via intervertebral discs to mimic the in vivo situation (“full vertebra”), 2) via the classical endplate embedding (“vertebral body”) or 3) via a ball joint to induce anterior wedge failure (“vertebral section”). HR-pQCT scans acquired prior testing were used to simulate anterior-posterior DXA from which areal bone mineral density (aBMD) and the initial slope of the variogram (ISV), the early definition of TBS, were evaluated. Finally, the relation of aBMD and ISV with failure load (Fexp) and apparent failure stress (σexp) was assessed and their relative contribution to a multi-linear model was quantified via ANOVA. We found that, unlike aBMD, ISV did not significantly correlate with Fexp and σexp, except for the “vertebral body” case (r2 = 0.396, p = 0.028). Aside from the “vertebra section” set-up where it explained only 6.4% of σexp (p = 0.037), it brought no significant improvement to aBMD. These results indicate that ISV, a replica of TBS, is a poor surrogate for vertebral strength no matter the testing set-up, which supports the prior observations and raises a fortiori the question of the deterministic factors underlying the statistical relationship between TBS and vertebral fracture risk.

Fast Update of Conditional Simulation Ensembles

Gaussian random field (GRF) conditional simulation is a key ingredient in many spatial statistics problems for computing Monte-Carlo estimators and quantifying uncertainties on non-linear functionals of GRFs conditional on data. Conditional simulations are known to often be computer intensive, especially when appealing to matrix decomposition approaches with a large number of simulation points. This work studies settings where conditioning observations are assimilated batch sequentially, with one point or a batch of points at each stage. Assuming that conditional simulations have been performed at a previous stage, the goal is to take advantage of already available sample paths and by-products to produce updated conditional simulations at mini- mal cost. Explicit formulae are provided, which allow updating an ensemble of sample paths conditioned on n ≥ 0 observations to an ensemble conditioned on n + q observations, for arbitrary q ≥ 1. Compared to direct approaches, the proposed formulae proveto substantially reduce computational complexity. Moreover, these formulae explicitly exhibit how the q new observations are updating the old sample paths. Detailed complexity calculations highlighting the benefits of this approach with respect to state-of-the-art algorithms are provided and are complemented by numerical experiments.

Flood triggering in Switzerland: the role of daily to monthly preceding precipitation

Determining the role of different precipitation periods for peak discharge generation is crucial for both projecting future changes in flood probability and for short- and medium-range flood forecasting. In this study, catchment-averaged daily precipitation time series are analyzed prior to annual peak discharge events (floods) in Switzerland. The high number of floods considered – more than 4000 events from 101 catchments have been analyzed – allows to derive significant information about the role of antecedent precipitation for peak discharge generation. Based on the analysis of precipitation times series, a new separation of flood-related precipitation periods is proposed: (i) the period 0 to 1 day before flood days, when the maximum flood-triggering precipitation rates are generally observed, (ii) the period 2 to 3 days before flood days, when longer-lasting synoptic situations generate "significantly higher than normal" precipitation amounts, and (iii) the period from 4 days to 1 month before flood days when previous wet episodes may have already preconditioned the catchment. The novelty of this study lies in the separation of antecedent precipitation into the precursor antecedent precipitation (4 days before floods or earlier, called PRE-AP) and the short range precipitation (0 to 3 days before floods, a period when precipitation is often driven by one persistent weather situation like e.g., a stationary low-pressure system). A precise separation of "antecedent" and "peak-triggering" precipitation is not attempted. Instead, the strict definition of antecedent precipitation periods permits a direct comparison of all catchments. The precipitation accumulating 0 to 3 days before an event is the most relevant for floods in Switzerland. PRE-AP precipitation has only a weak and region-specific influence on flood probability. Floods were significantly more frequent after wet PRE-AP periods only in the Jura Mountains, in the western and eastern Swiss plateau, and at the outlet of large lakes. As a general rule, wet PRE-AP periods enhance the flood probability in catchments with gentle topography, high infiltration rates, and large storage capacity (karstic cavities, deep soils, large reservoirs). In contrast, floods were significantly less frequent after wet PRE-AP periods in glacial catchments because of reduced melt. For the majority of catchments however, no significant correlation between precipitation amounts and flood occurrences is found when the last 3 days before floods are omitted in the precipitation amounts. Moreover, the PRE-AP was not higher for extreme floods than for annual floods with a high frequency and was very close to climatology for all floods. The fact that floods are not significantly more frequent nor more intense after wet PRE-AP is a clear indicator of a short discharge memory of Pre-Alpine, Alpine and South Alpine Swiss catchments. Our study poses the question whether the impact of long-term precursory precipitation for floods in such catchments is not overestimated in the general perception. The results suggest that the consideration of a 3–4 days precipitation period should be sufficient to represent (understand, reconstruct, model, project) Swiss Alpine floods.

Differentiating the Multipoint Expected Improvement for Optimal Batch Design

This work deals with parallel optimization of expensive objective functions which are modelled as sample realizations of Gaussian processes. The study is formalized as a Bayesian optimization problem, or continuous multi-armed bandit problem, where a batch of q > 0 arms is pulled in parallel at each iteration. Several algorithms have been developed for choosing batches by trading off exploitation and exploration. As of today, the maximum Expected Improvement (EI) and Upper Confidence Bound (UCB) selection rules appear as the most prominent approaches for batch selection. Here, we build upon recent work on the multipoint Expected Improvement criterion, for which an analytic expansion relying on Tallis’ formula was recently established. The computational burden of this selection rule being still an issue in application, we derive a closed-form expression for the gradient of the multipoint Expected Improvement, which aims at facilitating its maximization using gradient-based ascent algorithms. Substantial computational savings are shown in application. In addition, our algorithms are tested numerically and compared to state-of-the-art UCB-based batchsequential algorithms. Combining starting designs relying on UCB with gradient-based EI local optimization finally appears as a sound option for batch design in distributed Gaussian Process optimization.

Microbiota depletion promotes browning of white adipose tissue and reduces obesity.

Brown adipose tissue (BAT) promotes a lean and healthy phenotype and improves insulin sensitivity. In response to cold or exercise, brown fat cells also emerge in the white adipose tissue (WAT; also known as beige cells), a process known as browning. Here we show that the development of functional beige fat in the inguinal subcutaneous adipose tissue (ingSAT) and perigonadal visceral adipose tissue (pgVAT) is promoted by the depletion of microbiota either by means of antibiotic treatment or in germ-free mice. This leads to improved glucose tolerance and insulin sensitivity and decreased white fat and adipocyte size in lean mice, obese leptin-deficient (ob/ob) mice and high-fat diet (HFD)-fed mice. Such metabolic improvements are mediated by eosinophil infiltration, enhanced type 2 cytokine signaling and M2 macrophage polarization in the subcutaneous white fat depots of microbiota-depleted animals. The metabolic phenotype and the browning of the subcutaneous fat are impaired by the suppression of type 2 cytokine signaling, and they are reversed by recolonization of the antibiotic-treated or germ-free mice with microbes. These results provide insight into the microbiota-fat signaling axis and beige-fat development in health and metabolic disease.

Gut Microbiota Orchestrates Energy Homeostasis during Cold.

Microbial functions in the host physiology are a result of the microbiota-host co-evolution. We show that cold exposure leads to marked shift of the microbiota composition, referred to as cold microbiota. Transplantation of the cold microbiota to germ-free mice is sufficient to increase insulin sensitivity of the host and enable tolerance to cold partly by promoting the white fat browning, leading to increased energy expenditure and fat loss. During prolonged cold, however, the body weight loss is attenuated, caused by adaptive mechanisms maximizing caloric uptake and increasing intestinal, villi, and microvilli lengths. This increased absorptive surface is transferable with the cold microbiota, leading to altered intestinal gene expression promoting tissue remodeling and suppression of apoptosis-the effect diminished by co-transplanting the most cold-downregulated strain Akkermansia muciniphila during the cold microbiota transfer. Our results demonstrate the microbiota as a key factor orchestrating the overall energy homeostasis during increased demand.

El episodio de la Carreta : Un viaje discursivo de Lanzarote entre Francia y España

En este trabajo se intentará demostrar la importancia del episodio de la carreta en el proceso de constitución y fijación del ciclo artúrico en Francia y en España. Con ese propósito serán considerados Le chevalier de la Charrette de Chrétien de Troyes, dos versiones diferentes del Lancelot du Lac y el pasaje correspondiente del Libro de Lanzarote del Lago (ms. 9611 de la Biblioteca Nacional de Madrid). Las cuatro redacciones son consideradas como diferentes estadios textuales que demuestran los cambios literarios y culturales producidos en ellos. En función de la compleja tradición textual, no es posible postular una derivación directa entre dichas versiones, sino que proponemos calas puntuales que contribuyan a caracterizar las construcciones literarias de ese período.

El episodio de la Carreta : Un viaje discursivo de Lanzarote entre Francia y España

En este trabajo se intentará demostrar la importancia del episodio de la carreta en el proceso de constitución y fijación del ciclo artúrico en Francia y en España. Con ese propósito serán considerados Le chevalier de la Charrette de Chrétien de Troyes, dos versiones diferentes del Lancelot du Lac y el pasaje correspondiente del Libro de Lanzarote del Lago (ms. 9611 de la Biblioteca Nacional de Madrid). Las cuatro redacciones son consideradas como diferentes estadios textuales que demuestran los cambios literarios y culturales producidos en ellos. En función de la compleja tradición textual, no es posible postular una derivación directa entre dichas versiones, sino que proponemos calas puntuales que contribuyan a caracterizar las construcciones literarias de ese período.

El episodio de la Carreta : Un viaje discursivo de Lanzarote entre Francia y España

En este trabajo se intentará demostrar la importancia del episodio de la carreta en el proceso de constitución y fijación del ciclo artúrico en Francia y en España. Con ese propósito serán considerados Le chevalier de la Charrette de Chrétien de Troyes, dos versiones diferentes del Lancelot du Lac y el pasaje correspondiente del Libro de Lanzarote del Lago (ms. 9611 de la Biblioteca Nacional de Madrid). Las cuatro redacciones son consideradas como diferentes estadios textuales que demuestran los cambios literarios y culturales producidos en ellos. En función de la compleja tradición textual, no es posible postular una derivación directa entre dichas versiones, sino que proponemos calas puntuales que contribuyan a caracterizar las construcciones literarias de ese período.

Alacant. Planos de población. 1708

Cuadro explicativo de lo representado en parte sup. derecha

Molecular Cloning and Characterization of Apricot Fruit Polyphenol Oxidase

A reverse transcriptase-polymerase chain reaction experiment was done to synthesize a homologous polyphenol oxidase (PPO) probe from apricot (Prunus armeniaca var Bergeron) fruit. This probe was further used to isolate a full-length PPO cDNA, PA-PPO (accession no. AF020786), from an immature-green fruit cDNA library. PA-PPO is 2070 bp long and contains a single open reading frame encoding a PPO precursor peptide of 597 amino acids with a calculated molecular mass of 67.1 kD and an isoelectric point of 6.84. The mature protein has a predicted molecular mass of 56.2 kD and an isoelectric point of 5.84. PA-PPO belongs to a multigene family. The gene is highly expressed in young, immature-green fruit and is turned off early in the ripening process. The ratio of PPO protein to total proteins per fruit apparently remains stable regardless of the stage of development, whereas PPO specific activity peaks at the breaker stage. These results suggest that, in addition to a transcriptional control of PPO expression, other regulation factors such as translational and posttranslational controls also occur.