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This study's objective was to compare the effect of two therapies for lowering the vocal fundamental frequency on two adolescent girls, aged 15 and 17, who have profound hearing losses. One of the therapies used the SpeechViewer system; the other used no computer support. The treatments were applied in alternating order for a period of 5 weeks using an ABACA/ACABA (i.e., 'crossover') design. The results reveal that one subject obtained an appropriate fundamental frequency during the treatment with SpeechViewer and maintained the new fundamental frequency to the end of the experiment. The second subject did not obtain an appropriate fundamental frequency. The reasons for these different results are discussed. Finally, SpeechViewer's use as a tool in clinical intervention is analyzed. [ABSTRACT FROM AUTHOR]

Heterogeneous visible light photocatalysis is a compelling approach to address sustainability in synthetic photochemistry. However, the use of solid-state photocatalysts remains very unpopular in organic synthesis because of their limited accessibility and the black-box effect associated to the lack of rational between their molecular structure and their photochemical properties. Herein, we disclose the synthesis, characterization, photocatalytic properties and synthetic applications of a simple and readily available solid-state conjugated organic polymer, poly-(para-phenylene ethynylene) 1, which exhibits a strong oxidative power upon irradiation with visible light (E(1*/1⋅ - )=+1.67 V vs SCE). Comparisons with structural analogues highlighted the superior photocatalytic activity of this linear semiconductor, on account of its fully conjugated architecture. The associated excited-state reactivity enabled the transformation of various amines into imines in batch and continuous flow reactors together with straightforward photocatalyst recycling. Mechanistic investigations revealed concomitant photoredox and energy transfer pathways, that led to the formation of the desired products. Ultimately, the inline generation of imines was exploited in telescoped three-component Ugi reactions (3CR) in batch and flow toward biologically relevant α-acylaminoamides., (© 2024 The Author(s). Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

The article provides extensive data on the diversity of bacterial communities collected on 480 conventional broiler carcasses from a French slaughterhouse between October 2022 and January 2023. Half of the carcasses were collected from the first slaughter batches and the other half from the later batches to highlight possible microbial cross-contamination between carcasses along the slaughter chain. Campylobacter and the Total Viable Count were quantified on agar plates before and after 7 days of refrigerated storage to estimate the contamination level of broiler carcasses. These data on Campylobacter quantification allow us to assess the prevalence and concentration of this pathogen on chicken meat in France. Broiler bacterial communities were sequenced and characterized before and after storage, offering an understanding of broiler carcass microbial diversity and ecology on large-scale data along the food chain. Amplicons from the region V3-V4 of 16S rRNA were sequenced with Illumina MiSeq technology. Raw sequencing data were deposited in the ANR-21-CE21-0008 ESCAPE project, and the sample accession numbers for the rRNA 16S sequencing range from J017_lib692622_cleaned_R1 to J0176_lib692782_cleaned_R2 for the samples before storage and from J717_lib692783_cleaned_R1 to J7176_lib692988_cleaned_R2 for the samples after storage., (© 2024 The Author(s).)

The health and well-being of a host are deeply influenced by the interactions with its gut microbiota. Contrasted environmental conditions, such as diseases or dietary habits, play a pivotal role in modulating these interactions, impacting microbiota composition and functionality. Such conditions can also lead to transitions from beneficial to detrimental symbiosis, viewed as alternative stable states of the host-microbiota dialogue. This article introduces a novel mathematical model exploring host-microbiota interactions, integrating dynamics of the colonic epithelial crypt, microbial metabolic functions, inflammation sensitivity and colon flows in a transverse section. The model considers metabolic shifts in epithelial cells based on butyrate and hydrogen sulfide concentrations, innate immune pattern recognition receptor activation, microbial oxygen tolerance and the impact of antimicrobial peptides on the microbiota. Using the model, we demonstrated that a high-protein, low-fibre diet exacerbates detrimental interactions and compromises beneficial symbiotic resilience, underscoring a destabilizing effect towards an unhealthy state. Moreover, the proposed model provides essential insights into oxygen levels, fibre and protein breakdown, and basic mechanisms of innate immunity in the colon and offers a crucial understanding of factors influencing the colon environment.

The gut microbiota plays a crucial role in health and is significantly modulated by human diets. In addition to Western diets which are rich in proteins, high-protein diets are used for specific populations or indications, mainly weight loss. In this study, we investigated the effect of protein supplementation on Bacteroides caccae , a Gram-negative gut symbiont. The supplementation with whey proteins led to a significant increase in growth rate, final biomass, and short-chain fatty acids production. A comprehensive genomic analysis revealed that B. caccae possesses a set of 156 proteases with putative intracellular and extracellular localization and allowed to identify amino acid transporters and metabolic pathways. We developed a fully curated genome-scale metabolic model of B. caccae that incorporated its proteolytic activity and simulated its growth and production of fermentation-related metabolites in response to the different growth media. We validated the model by comparing the predicted phenotype to experimental data. The model accurately predicted B. caccae 's growth and metabolite production ( R 2 = 0.92 for the training set and R 2 = 0.89 for the validation set). We found that accounting for both ATP consumption related to proteolysis, and whey protein accessibility is necessary for accurate predictions of metabolites production. These results provide insights into B. caccae 's adaptation to a high-protein diet and its ability to utilize proteins as a source of nutrition. The proposed model provides a useful tool for understanding the feeding mechanism of B. caccae in the gut microbiome.IMPORTANCEMicrobial proteolysis is understudied despite the availability of dietary proteins for the gut microbiota. Here, the proteolytic potential of the gut symbiont Bacteroides caccae was analyzed for the first time using pan-genomics. This sketches a well-equipped bacteria for protein breakdown, capable of producing 156 different proteases with a broad spectrum of cleavage targets. This functional potential was confirmed by the enhancement of growth and metabolic activities at high protein levels. Proteolysis was included in a B. caccae metabolic model which was fitted with the experiments and validated on external data. This model pinpoints the links between protein availability and short-chain fatty acids production, and the importance for B. caccae to gain access to glutamate and asparagine to promote growth. This integrated approach can be generalized to other symbionts and upscaled to complex microbiota to get insights into the ecological impact of proteins on the gut microbiota., Competing Interests: The authors declare no conflict of interest.

Background: With the emergence of metagenomic data, multiple links between the gut microbiome and the host health have been shown. Deciphering these complex interactions require evolved analysis methods focusing on the microbial ecosystem functions. Despite the fact that host or diet-derived fibres are the most abundant nutrients available in the gut, the presence of distinct functional traits regarding fibre and mucin hydrolysis, fermentation and hydrogenotrophic processes has never been investigated., Results: After manually selecting 91 KEGG orthologies and 33 glycoside hydrolases further aggregated in 101 functional descriptors representative of fibre and mucin degradation pathways in the gut microbiome, we used nonnegative matrix factorization to mine metagenomic datasets. Four distinct metabolic profiles were further identified on a training set of 1153 samples, thoroughly validated on a large database of 2571 unseen samples from 5 external metagenomic cohorts and confirmed with metatranscriptomic data. Profiles 1 and 2 are the main contributors to the fibre-degradation-related metagenome: they present contrasted involvement in fibre degradation and sugar metabolism and are differentially linked to dysbiosis, metabolic disease and inflammation. Profile 1 takes over Profile 2 in healthy samples, and unbalance of these profiles characterize dysbiotic samples. Furthermore, high fibre diet favours a healthy balance between profiles 1 and profile 2. Profile 3 takes over profile 2 during Crohn's disease, inducing functional reorientations towards unusual metabolism such as fucose and H2S degradation or propionate, acetone and butanediol production. Profile 4 gathers under-represented functions, like methanogenesis. Two taxonomic makes up of the profiles were investigated, using either the covariation of 203 prevalent genomes or metagenomic species, both providing consistent results in line with their functional characteristics. This taxonomic characterization showed that profiles 1 and 2 were respectively mainly composed of bacteria from the phyla Bacteroidetes and Firmicutes while profile 3 is representative of Proteobacteria and profile 4 of methanogens., Conclusions: Integrating anaerobic microbiology knowledge with statistical learning can narrow down the metagenomic analysis to investigate functional profiles. Applying this approach to fibre degradation in the gut ended with 4 distinct functional profiles that can be easily monitored as markers of diet, dysbiosis, inflammation and disease. Video Abstract., (© 2023. BioMed Central Ltd., part of Springer Nature.)

While wetland ecosystem services are widely recognized, the lack of fine-scale national inventories prevents successful implementation of conservation policies. Wetlands are difficult to map due to their complex fine-grained spatial pattern and fuzzy boundaries. However, the increasing amount of open high-spatial-resolution remote sensing data and accurately georeferenced field data archives, as well as progress in artificial intelligence (AI), provide opportunities for fine-scale national wetland mapping. The objective of this study was to map wetlands over mainland France (ca. 550,000 km 2 ) by applying AI to environmental variables derived from remote sensing and archive field data. A random forest model was calibrated using spatial cross-validation according to the precision-recall area under the curve (PR-AUC) index using ca. 135,000 soil or flora plots from archive databases, as well as 5 m topographical variables derived from an airborne DTM and a geological map. The model was validated using an experimentally designed sampling strategy with ca. 3000 plots collected during a ground survey in 2021 along non-wetland/wetland transects. Map accuracy was then compared to those of nine existing wetland maps with global, European, or national coverage. The model-derived suitability map (PR-AUC 0.76) highlights the gradual boundaries and fine-grained pattern of wetlands. The binary map is significantly more accurate (F1-score 0.75, overall accuracy 0.67) than existing wetland maps. The approach and end-results are of important value for spatial planning and environmental management since the high-resolution suitability and binary maps enable more targeted conservation measures to support biodiversity conservation, water resources maintenance, and carbon storage., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors.)

The seed acts as the primary inoculum source for the plant microbiota. Understanding the processes involved in its assembly and dynamics during germination and seedling emergence has the potential to allow for the improvement of crop establishment. Changes in the bacterial community structure were tracked in 1,000 individual seeds that were collected throughout seed developments of beans and radishes. Seeds were associated with a dominant bacterial taxon that represented more than 75% of all reads. The identity of this taxon was highly variable between the plants and within the seeds of the same plant. We identified selection as the main ecological process governing the succession of dominant taxa during seed filling and maturation. In a second step, we evaluated the seedling transmission of seed-borne taxa in 160 individual plants. While the initial bacterial abundance on seeds was not a good predictor of seedling transmission, the identities of the seed-borne taxa modified the phenotypes of seedlings. Overall, this work revealed that individual seeds are colonized by a few bacterial taxa of highly variable identity, which appears to be important for the early stages of plant development. IMPORTANCE Seeds are key components of plant fitness and are central to the sustainability of the agri-food system. Both the seed quality for food consumption and the seed vigor in agricultural settings can be influenced by the seed microbiota. Understanding the ecological processes involved in seed microbiota assembly will inform future practices for promoting the presence of important seed microorganisms for plant health and productivity. Our results highlighted that seeds were associated with one dominant bacterial taxon of variable taxonomic identity. This variety of dominant taxa was due to (i) spatial heterogeneity between and within plants and (ii) primary succession during seed development. According to neutral models, selection was the main driver of microbial community assembly for both plant species.

Human health and physiology is strongly influenced by interactions between human cells and intestinal microbiota in the gut. In mammals, the host-microbiota crosstalk is mainly mediated by regulations at the intestinal crypt level: the epithelial cell turnover in crypts is directly influenced by metabolites produced by the microbiota. Conversely, enterocytes maintain hypoxia in the gut, favorable to anaerobic bacteria which dominate the gut microbiota. We constructed an individual-based model of epithelial cells interacting with the microbiota-derived chemicals diffusing in the crypt lumen. This model is formalized as a piecewise deterministic Markov process (PDMP). It accounts for local interactions due to cell contact (among which are mechanical interactions), for cell proliferation, differentiation and extrusion which are regulated spatially or by chemicals concentrations. It also includes chemicals diffusing and reacting with cells. A deterministic approximated model is also introduced for a large population of small cells, expressed as a system of porous media type equations. Both models are extensively studied through numerical exploration. Their biological relevance is thoroughly assessed by recovering bio-markers of an healthy crypt, such as cell population distribution along the crypt or population turn-over rates. Simulation results from the deterministic model are compared to the PMDP model and we take advantage of its lower computational cost to perform a sensitivity analysis by Morris method. We finally use the crypt model to explore butyrate supplementation to enhance recovery after infections by enteric pathogens., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

We describe the continuous-flow synthesis of (R)-tamsulosin, a blockbuster therapeutic drug employed for dysuria associated with urinary stones and benign prostatic hyperplasia, by utilizing sequential heterogeneous catalysis. Two heterogeneous catalysts have been developed for the synthesis, and the key step involves reductive amination of nitriles using dimethylpolysilane-modified Pd on activated carbon/calcium phosphate. Overall, (R)-tamsulosin was obtained in 60 % yield and 64 % ee (99 % ee after recrystallization) in a flow stream through four catalytic transformations without the need for the isolation or purification of any intermediates or byproduct., (© 2022 Wiley-VCH GmbH.)

Compounds are morphologically complex words made of different linguistic parts. They are very prevalent in a number of languages such as French. Different psycholinguistic characteristics of compounds have been used in certain studies to investigate the mechanisms involved in compound processing (see Table 7). We provide psycholinguistic norms for a set of 506 French compound words. The words were normed on seven characteristics: lexeme meaning dominance, semantic transparency, sensory experience, conceptual familiarity, imageability, age of acquisition (AoA) and subjective frequency. Reliability measures were computed for the collected norms. Descriptive statistical analyses, and correlational and multiple regression analyses were performed. We also report some comparisons made between our normative data and certain norms obtained in other similar studies. The entire set of norms, which will be very useful to researchers investigating the processing of compounds, is available as Supplemental Material., (© 2021. The Psychonomic Society, Inc.)

In this study, we developed predictive models describing the growth of Staphylococcus aureus on cooked broccoli florets. A pool of 3.5 log CFU/g of five S. aureus strains were inoculated on 10 g broccoli portions. The samples were then stored at 10, 20, 30 and 37 °C, and colonies were enumerated at different time intervals. Baranyi and Roberts model was fitted to the data using a Bayesian Adaptive Markov Chain Monte Carlo for estimation of the growth parameters. S. aureus showed low growth at 10 °C on broccoli samples and at 20-37 °C interval, Baranyi and Roberts model fitted well to the experimental data (R 2 >0.97). Estimated growth parameters were correlated with the possibility of toxin production and indicate the potential presence of these biological hazards on contaminated broccoli after heat treatment. Additionally, linear regression was performed for growth rate as storage temperature function. This secondary model followed a linear tendency with R 2 =0.997 and was compared with two tertiary models (ComBase Predictor and Pathogen Modeling Program) and literature data, demonstrating similar growth rate values of both. These results can be helpful for food services and managers to establish food safety standards for S. aureus growth on cooked broccoli., (© 2021. Sociedade Brasileira de Microbiologia.)

Aspochalasins are leucine-derived cytochalasins. Their complexity is associated with a high degree of biosynthetic oxidation, herein inspiring a two-phase strategy in total synthesis. We thus describe the synthesis of a putative biomimetic tetracyclic intermediate. The constructive steps are an intramolecular Diels-Alder reaction to install the isoindolone core of cytochalasins, whose branched precursor was obtained from a stereoselective Ireland-Claisen rearrangement performed from a highly unsaturated substrate. This also constitutes a formal synthesis of trichoderone A.

This review focuses on modeling methodologies of the gastrointestinal tract during digestion that have adopted a systems-view approach and, more particularly, on physiologically based compartmental models of food digestion and host-diet-microbiota interactions. This type of modeling appears very promising for integrating the complex stream of mechanisms that must be considered and retrieving a full picture of the digestion process from mouth to colon. We may expect these approaches to become more and more accurate in the future and to serve as a useful means of understanding the physicochemical processes occurring in the gastrointestinaltract, interpreting postprandial in vivo data, making relevant predictions, and designing healthier foods. This review intends to provide a scientific and historical background of this field of research, before discussing the future challenges and potential benefits of the establishment of such a model to study and predict food digestion and absorption in humans.

We report a photochemical method for the chemoselective radical functionalization of tryptophan (Trp)-containing peptides. The method exploits the photoactivity of an electron donor-acceptor complex generated between the tryptophan unit and pyridinium salts. Irradiation with weak light (390 nm) generates radical intermediates right next to the targeted Trp amino acid, facilitating a proximity-driven radical functionalization. This protocol exhibits high chemoselectivity for Trp residues over other amino acids and tolerates biocompatible conditions.

High blood cholesterol levels are often associated with cardiovascular diseases. Therapeutic strategies, targeting different functions involved in cholesterol transport or synthesis, were developed to control cholesterolemia in human. However, the gut microbiota is also involved in cholesterol regulation by direct biotransformation of luminal cholesterol or conversion of bile salts, opening the way to the design of new strategies to manage cholesterol level. In this report, we developed for the first time a whole-body human model of cholesterol metabolism including the gut microbiota in order to investigate the relative impact of host and microbial pathways. We first used an animal model to investigate the ingested cholesterol distribution in vivo . Then, using in vitro bacterial growth experiments and metabolite measurements, we modeled the population dynamics of bacterial strains in the presence of cholesterol or bile salts, together with their bioconversion function. Next, after correct rescaling to mimic the activity of a complex microbiota, we developed a whole body model of cholesterol metabolism integrating host and microbiota mechanisms. This global model was validated with the animal experiments. Finally, the model was numerically explored to give a further insight into the different flux involved in cholesterol turn-over. According to this model, bacterial pathways appear as an important driver of cholesterol regulation, reinforcing the need for development of novel "bacteria-based" strategies for cholesterol management., (Copyright © 2020 Bourgin, Labarthe, Kriaa, Lhomme, Gérard, Lesnik, Laroche, Maguin and Rhimi.)

A diversity-oriented synthesis (DOS) approach has been used to functionalize 17-ethynyl-17-hydroxysteroids through a one-pot procedure involving a ring-closing enyne metathesis (RCEYM) and a Diels-Alder reaction on the resulting diene, under microwave irradiations. Taking advantage of the propargyl alcohol moiety present on commercially available steroids, this classical strategy was applied to mestranol and lynestrenol, giving a collection of new complex 17-spirosteroids., (Copyright © 2020, Laroche et al.; licensee Beilstein-Institut.)

While organic synthesis carried out in most laboratories uses batch methods, there is growing interest in modernizing fine chemical synthesis through continuous-flow processes. As a synthetic method, flow processes have several advantages over batch systems in terms of environmental compatibility, efficiency, and safety, and recent advances have allowed for the synthesis of several complex molecules, including active pharmaceutical ingredients (APIs). Nevertheless, due to several reasons related to the difficulties arising from byproduct formation during the flow process, such as lower yields, poor selectivities, clogging of columns due to poor solubility, catalyst poisoning, etc., successful examples of continuous-flow synthesis of complex organic molecules are still limited. In order to solve this bottleneck, the development of selective and atom-economical continuous-flow organic transformations are needed. This perspective highlights examples of atom-economical addition and condensation reactions with heterogeneous catalysts under continuous-flow conditions and their applications for the synthesis of complex organic molecules such as natural products and APIs. In order to realize new continuous-flow methodologies, based on addition and condensation reactions, in place of substitution reactions, the development of novel reactions and heterogeneous catalysts is required.

The aim of the present study was to investigate how the context in which an action is presented could modulate the effect of action observation on language processing, an effect that is classically observed in the literature. To address this question, we recorded both behavioral (reaction times) and electrophysiological measures (event-related potentials) of participants performing a semantic decision task involving a verb describing an action that was congruent or incongruent with the action presented in a prime picture that had been observed. The prime picture presented an action performed in a usual or an unusual context. The results revealed different behavioral and topographical pattern responses according to the context in which an action is presented. Importantly, only in the usual context, the congruency between the prime picture and the verb stimulus facilitated the semantic processes, leading to shorter response times in this condition compared to the others. Moreover, the topographic analysis revealed that this facilitation was related to reduced processing times for the semantic access to the verb and for the motor preparation for the answer. Taken together, these findings demonstrate that the context of an action is crucial in the link between action and language.

In this work, we study a multiscale inverse problem associated with a multi-type model for age structured cell populations. In the single type case, the model is a McKendrick-VonFoerster like equation with a mitosis-dependent death rate and potential migration at birth. In the multi-type case, the migration term results in an unidirectional motion from one type to the next, so that the boundary condition at age 0 contains an additional extrinsic contribution from the previous type. We consider the inverse problem of retrieving microscopic information (the division rates and migration proportions) from the knowledge of macroscopic information (total number of cells per layer), given the initial condition. We first show the well-posedness of the inverse problem in the single type case using a Fredholm integral equation derived from the characteristic curves, and we use a constructive approach to obtain the lattice division rate, considering either a synchronized or non-synchronized initial condition. We take advantage of the unidirectional motion to decompose the whole model into nested submodels corresponding to self-renewal equations with an additional extrinstic contribution. We again derive a Fredholm integral equation for each submodel and deduce the well-posedness of the multi-type inverse problem. In each situation, we illustrate numerically our theoretical results.

The gut microbiota, mainly located in the colon, is engaged in a complex dialogue with the large intestinal epithelium through which important regulatory processes for the health and well-being of the host take place. Imbalances of the microbial populations, called dysbiosis, are related to several pathological status, emphasizing the importance of understanding the gut bacterial ecology. Among the ecological drivers of the microbiota, the spatial structure of the colon is of special interest: spatio-temporal mechanisms can lead to the constitution of spatial interactions among the bacterial populations and of environmental niches that impact the overall colonization of the colon. In the present study, we introduce a mathematical model of the colon microbiota in its fluid environment, based on the explicit coupling of a population dynamics model of microbial populations involved in fibre degradation with a fluid dynamics model of the luminal content. This modeling framework is used to study the main drivers of the spatial structure of the microbiota, specially focusing on the dietary fibre inflow, the epithelial motility, the microbial active swimming and viscosity gradients in the digestive track. We found 1) that the viscosity gradients allow the creation of favorable niches in the vicinity of the mucus layer; 2) that very low microbial active swimming in the radial direction is enough to promote bacterial growth, which sheds a new light on microbial motility in the colon and 3) that dietary fibres are the main driver of the spatial structure of the microbiota in the distal bowel whereas epithelial motility is preponderant for the colonization of the proximal colon; in the transverse colon, fibre levels and chemotaxis have the strongest impact on the distribution of the microbial communities., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Growth rates, interactions between community members, stochasticity, and immigration are important drivers of microbial community dynamics. In sequencing data analysis, such as network construction and community model parameterization, we make implicit assumptions about the nature of these drivers and thereby restrict model outcome. Despite apparent risk of methodological bias, the validity of the assumptions is rarely tested, as comprehensive procedures are lacking. Here, we propose a classification scheme to determine the processes that gave rise to the observed time series and to enable better model selection., Results: We implemented a three-step classification scheme in R that first determines whether dependence between successive time steps (temporal structure) is present in the time series and then assesses with a recently developed neutrality test whether interactions between species are required for the dynamics. If the first and second tests confirm the presence of temporal structure and interactions, then parameters for interaction models are estimated. To quantify the importance of temporal structure, we compute the noise-type profile of the community, which ranges from black in case of strong dependency to white in the absence of any dependency. We applied this scheme to simulated time series generated with the Dirichlet-multinomial (DM) distribution, Hubbell's neutral model, the generalized Lotka-Volterra model and its discrete variant (the Ricker model), and a self-organized instability model, as well as to human stool microbiota time series. The noise-type profiles for all but DM data clearly indicated distinctive structures. The neutrality test correctly classified all but DM and neutral time series as non-neutral. The procedure reliably identified time series for which interaction inference was suitable. Both tests were required, as we demonstrated that all structured time series, including those generated with the neutral model, achieved a moderate to high goodness of fit to the Ricker model., Conclusions: We present a fast and robust scheme to classify community structure and to assess the prevalence of interactions directly from microbial time series data. The procedure not only serves to determine ecological drivers of microbial dynamics, but also to guide selection of appropriate community models for prediction and follow-up analysis.

Whole Genome Shotgun (WGS) metagenomics is increasingly used to study the structure and functions of complex microbial ecosystems, both from the taxonomic and functional point of view. Gene inventories of otherwise uncultured microbial communities make the direct functional profiling of microbial communities possible. The concept of community aggregated trait has been adapted from environmental and plant functional ecology to the framework of microbial ecology. Community aggregated traits are quantified from WGS data by computing the abundance of relevant marker genes. They can be used to study key processes at the ecosystem level and correlate environmental factors and ecosystem functions. In this paper we propose a novel model based approach to infer combinations of aggregated traits characterizing specific ecosystemic metabolic processes. We formulate a model of these Combined Aggregated Functional Traits (CAFTs) accounting for a hierarchical structure of genes, which are associated on microbial genomes, further linked at the ecosystem level by complex co-occurrences or interactions. The model is completed with constraints specifically designed to exploit available genomic information, in order to favor biologically relevant CAFTs. The CAFTs structure, as well as their intensity in the ecosystem, is obtained by solving a constrained Non-negative Matrix Factorization (NMF) problem. We developed a multicriteria selection procedure for the number of CAFTs. We illustrated our method on the modelling of ecosystemic functional traits of fiber degradation by the human gut microbiota. We used 1408 samples of gene abundances from several high-throughput sequencing projects and found that four CAFTs only were needed to represent the fiber degradation potential. This data reduction highlighted biologically consistent functional patterns while providing a high quality preservation of the original data. Our method is generic and can be applied to other metabolic processes in the gut or in other ecosystems., Competing Interests: The authors have declared that no competing interests exist.

The present study was aimed at testing the locus of word frequency effects in spelling to dictation: Are they located at the level of spoken word recognition (Chua & Rickard Liow, 2014) or at the level of the orthographic output lexicon (Delattre, Bonin, & Barry, 2006)? Words that varied on objective word frequency and on phonological neighborhood density were orally presented to adults who had to write them down. Following the additive factors logic (Sternberg, 1969, 2001), if word frequency in spelling to dictation influences a processing level, that is, the orthographic output level, different from that influenced by phonological neighborhood density, that is, spoken word recognition, the impact of the 2 factors should be additive. In contrast, their influence should be overadditive if they act at the same processing level in spelling to dictation, namely the spoken word recognition level. We found that both factors had a reliable influence on the spelling latencies but did not interact. This finding is in line with an orthographic output locus hypothesis of word frequency effects in spelling to dictation. (PsycINFO Database Record, ((c) 2016 APA, all rights reserved).)

The ring closing enyne metathesis of substrates with propargylic hindrance was investigated, revealing the successful combination of the Stewart-Grubbs catalysts and microwave heating sometimes up to 170 °C for oxacycles. Medium-sized rings were obtained from terminal alkynes previously reputed as reluctant substrates. This unmatched combination was applied to the synthesis of carbocycles and oxacycles. In addition, this is the first report on the use of the Stewart Grubbs catalyst in ring closing enyne metatheses.

Animates are better remembered than inanimates. According to the adaptive view of human memory ( Nairne, 2010 ; Nairne & Pandeirada, 2010a , 2010b ), this observation results from the fact that animates are more important for survival than inanimates. This ultimate explanation of animacy effects has to be complemented by proximate explanations. Moreover, animacy currently represents an uncontrolled word characteristic in most cognitive research ( VanArsdall, Nairne, Pandeirada, & Cogdill, 2015 ). In four studies, we therefore investigated the "how" of animacy effects. Study 1 revealed that words denoting animates were recalled better than those referring to inanimates in an intentional memory task. Study 2 revealed that adding a concurrent memory load when processing words for the animacy dimension did not impede the animacy effect on recall rates. Study 3A was an exact replication of Study 2 and Study 3B used a higher concurrent memory load. In these two follow-up studies, animacy effects on recall performance were again not altered by a concurrent memory load. Finally, Study 4 showed that using interactive imagery to encode animate and inanimate words did not alter the recall rate of animate words but did increase the recall of inanimate words. Taken together, the findings suggest that imagery processes contribute to these effects.

This study aimed at determining the kinetics of milk protein digestion and amino acid absorption after ingestion by six multi-canulated mini-pigs of two gelled dairy matrices having the same composition, similar rheological and structural properties, but differing by their mode of coagulation (acidification/renneting). Duodenal, mid-jejunal effluents and plasma samples were collected at different times during 7h after meal ingestion. Ingestion of the acid gel induced a peak of caseins and β-lactoglobulin in duodenal effluents after 20min of digestion and a peak of amino acids in the plasma after 60min. The rennet gel induced lower levels of both proteins in the duodenum (with no defined peak) as well as much lower levels of amino acids in the plasma than the acid gel. Plasma ghrelin concentrations suggested a potentially more satiating effect of the rennet gel compared to the acid gel. This study clearly evidences that the gelation process can significantly impact on the nutritive value of dairy products., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Introduction: We estimate the lifetime cost of treatment for moderate/severe symptoms associated with benign prostatic hyperplasia (BPH) in a cohort of Canadian men aged 50 to 59, and we evaluate the costs of 2 daily bioequivalent treatment options: fixed-dose combination (FDC) of dutasteride (0.5 mg) and tamsulosin (0.4 mg), or concomitant administration of dutasteride (0.5 mg) and tamsulosin (0.4 mg) monotherapies., Methods: The expected lifetime costs were estimated by modelling the incidence of acute urinary retention (AUR), BPH-related surgery and clinical progression over a patient's lifetime (up to 25 years). A model was developed to simulate clinical events over time, based on a discrete Markov process with 6 mutually exclusive health states and annual cycle length., Results: The estimated lifetime budget cost for the cohort of 374 110 men aged 50 to 59 in Canada is between $6.35 billion and $7.60 billion, equivalent to between $16 979 and $20 315 per patient with moderate/severe symptoms associated with BPH. Costs are lower for FDC treatment, with the net difference in lifetime budget impact between the 2 treatment regimens at $1.25 billion. In this analysis, the true costs of BPH in Canada are underestimated for 2 main reasons: (1) to make the analysis tractable, it is restricted to a cohort aged 50 to 59, whereas BPH can affect all men; and (2) a closed cohort approach does not include the costs of new (incident) cases., Conclusion: Canadian clinical guidelines recommend the use of the combination of tamsulosin and dutasteride for men with moderate/severe symptoms associated with BPH and enlarged prostate volume. This analysis, using a representational patient group, suggests that the FDC is a more cost-effective treatment option for BPH.

Introduction: Benign prostatic hyperplasia (BPH) is common in men 50 years old and older. The main treatment options are alpha-blockers (such as tamsulosin), which reduce symptoms, and 5-alpha reductase inhibitors (such as dutasteride), which reduce symptoms and slow disease progression. Clinical studies have demonstrated that dutasteride-tamsulosin combination therapy is more effective than either monotherapy to treat symptomatic BPH. We studied the cost-effectiveness in Canada of the dutasteride (0.5 mg/day) and tamsulosin (0.4 mg/day) combination compared with tamsulosin or dutasteride monotherapy., Methods: A Markov model was developed which follows a cohort of male BPH patients ≥50 with moderate to severe lower urinary tract symptoms (LUTS). The model estimates costs to the Canadian health care system and outcomes (in terms of quality adjusted life years [QALYs]) at 10 years and over a patient's lifetime. The dutasteride-tamsulosin combination was compared to each of tamsulosin monotherapy and dutasteride monotherapy., Results: Compared with tamsulosin, the combination was more costly and produced better patient outcomes. Over a lifetime, the incremental cost-effectiveness ratio was CAN$25 437 per QALY gained. At a willingness to pay CAN$50 000 per QALY, the probability of combination therapy being cost-effective was 99.6%. Compared with dutasteride, the combination therapy was the dominant option from year 2, offering improved patient outcomes at lower cost. The probability that combination therapy is more cost-effective than dutasteride was 99.8%., Conclusion: Combination therapy offers important clinical benefits for patients with symptomatic BPH, and there is a high probability that it is cost-effective in the Canadian health care system relative to either monotherapy.

This study aimed to determine the kinetics of milk protein digestion and amino acid absorption after ingestion of four dairy matrices by six minipigs: unheated or heated skim milk and corresponding rennet gels. Digestive contents and plasma samples were collected over a 7 h-period after meal ingestion. Gelation of milk slowed down the outflow of the meal from the stomach and the subsequent absorption of amino acids, and decreased their bioavailability in peripheral blood. The gelled rennet matrices also led to low levels of milk proteins at the duodenum. Caseins and β-lactoglobulin, respectively, were sensitive and resistant to hydrolysis in the stomach with the unheated matrices, but showed similar digestion with the heated matrices, with a heat-induced susceptibility to hydrolysis for β-lactoglobulin. These results suggest a significant influence of the meal microstructure (resulting from heat treatment) and macrostructure (resulting from gelation process) on the different steps of milk proteins digestion., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Butyrate is the preferred energy source for colonocytes and has an important role in gut health; in contrast, accumulation of high concentrations of lactate is detrimental to gut health. The major butyrate-producing bacterial species in the human colon belong to the Firmicutes. Eubacterium hallii and a new species, Anaerostipes coli SS2/1, members of clostridial cluster XIVa, are able to utilize lactate and acetate via the butyryl CoA : acetate CoA transferase route, the main metabolic pathway for butyrate synthesis in the human colon. Here we provide a mathematical model to analyse the production of butyrate by lactate-utilizing bacteria from the human colon. The model is an aggregated representation of the fermentation pathway. The parameters of the model were estimated using total least squares and maximum likelihood, based on in vitro experimental data with E. hallii L2-7 and A. coli SS2/1. The findings of the mathematical model adequately match those from the bacterial batch culture experiments. Such an in silico approach should provide insight into carbohydrate fermentation and short-chain fatty acid cross-feeding by dominant species of the human colonic microbiota., (© 2011 INRA. FEMS Microbiology Ecology © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd.)

The human colon is an anaerobic ecosystem that remains largely unexplored as a result of its limited accessibility and its complexity. Mathematical models can play a central role for a better insight into its dynamics. In this context, this paper presents the development of a mathematical model of carbohydrate degradation. Our aim was to provide an in silico approach to contribute to a better understanding of the fermentation patterns in such an ecosystem. Our mathematical model is knowledge-based, derived by writing down mass-balance equations. It incorporates physiology of the intestine, metabolic reactions and transport phenomena. The model was used to study various nutritional scenarios and to assess the role of the mucus on the system behavior. Model simulations provided an adequate qualitative representation of the human colon. Our model is complementary to experimental studies on human colonic fermentation, which, of course, is not meant to replace. It may be helpful to gain insight on questions that are still difficult to elucidate by experimentation and suggest future experiments., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Studying the spread of a pathogen in a managed metapopulation such as cattle herds in a geographical region often requires to take into account both the within- and between-herd transmission dynamics. This can lead to high-dimensional metapopulation systems resulting from the coupling of several within-herd transmission models. To tackle this problem, we aim in this paper at reducing the dimension of a tractable but realistic dynamical system reproducing the within-herd spread. The context chosen to illustrate our purpose is bovine viral diarrhoea virus (BVDV) transmission in a cattle herd structured in two age classes and several epidemiological states, including two infectious states (transiently and persistently infected). Different time scales, corresponding to the epidemiological and demographic processes, are identified which allow to build a reduced model. Singular perturbation technique is used to prove that, under some non-restrictive conditions on parameter values, the behaviour of the original system is quite accurately approximated by that of the reduced system. Simulations are also performed to corroborate the approximation quality. Our study illustrates the methodological interest of using singular perturbations to reduce model complexity. It also rigorously proves the biologically intuitive assumption that transiently infected individuals can be neglected in a homogeneous population, when capturing the global dynamics of BVDV spread.

Objective: To develop the first Canadian guidelines for the management of lower urinary tract symptoms in men with benign prostatic hyperplasia (BPH)., Methods: These guidelines, developed under a mandate provided by the Canadian Urological Association (CUA), were a collaborative effort between the CUA guidelines committee and the Canadian Prostate Health Council. BPH guidelines developed by the American Urological Association, the European Association of Urology, the World Health Organization International Consultation on BPH, and similar committees from Germany, Sweden and Australia were reviewed. The committee further reviewed a systematic literature search, updated to May 2004, and systematically derived Canadian urological opinion data., Results: The subsequent Canadian BPH guidelines were developed as an evidence based consensus among the committee members. Mandatory evaluation includes history, physical examination and urinalysis, while a symptom inventory and PSA in selected patients are recommended. Serum creatinine, uroflow, voiding diary, post void residual and sexual function questionnaire are optional. Unless there is an indication, other related tests are not recommended. Treatment choices should be governed by the severity of the symptoms, bother and patient preference. Guidelines for medical, surgical and minimally invasive treatment as well as special considerations are described in terms of guideline, option and recommendation., Conclusions: Diagnostic and treatment guidelines for BPH reflect the Canadian social priorities, economics, socialized medical practice, manpower issues, and medicolegal considerations.

Hydronephrosis early after aorto-bifemoral bypass grafting is probably an underestimated complication. We describe early and transient hydronephrosis that developed in two patients after totally laparoscopic aorto-bifemoral bypass surgery to treat aortoiliac occlusive disease. A conservative approach to treatment was adopted, and both patients recovered. We review the literature and discuss the pathophysiology, diagnosis, and treatment of this unusual form of hydronephrosis.

The pathogenesis of septic shock is mainly due to unregulated tumour necrosis factor-alpha (TNF-alpha) production. Procalcitonin (PCT) and calcitonin gene-related peptide (CGRP) are alternative transcription products of the calcitonin gene. Since high PCT levels have been described in human sepsis, and since CGRP inhibits TNF synthesis in rats, we examined the role of these peptides in the regulation of the inflammatory response during septic shock. LPS-induced TNF production was assessed using a human whole blood model. In this model, PCT (10(-7) M) and CGRP (10(-6) M) significantly inhibit TNF production by 27 and 24 % respectively. The effect of CGRP was reversed by CGRP 8-37 (10 microM), an antagonist of CGRP receptor. No effect on interleukin (IL)-1, IL-6 and IL-8 was found. This is the first description of an anti-inflammatory role for PCT and CGRP in humans., (Copyright 2000 Academic Press.)

A multicenter randomized, double-blind trial comparing total androgen blockade obtained by the use of castration with a pure anti-androgen (nilutamide) with simple castration was begun. One hundred and five patients received the combined treatment and 103 the orchiectomy plus placebo. Several features were used to evaluate the efficacy. Bone pain responded better to combined treatment at 6 months (P = 0.042). The number of favorable responses, as evaluated by the NPCP criteria, was 61% with simple castration and 78% with the combined treatment (P = 0.013). There was no statistically significant difference between the two groups in time to progression (logrank test P = 0.462) or survival (logrank test P = 0.137) despite an increase in median survival of 5.4 months. All other measures showed no difference between the two treatments. With total androgen blockade, 50% of the patients had disease progression at 1 year, and 45% were dead at 2 years. A review of the results of similar reported studies suggests no improvement or very modest improvement with total androgen blockade over testicular androgen ablation alone.

A randomized double-blind trial in patients with disseminated, previously untreated prostate cancer (Stage D2) was conducted in eight Canadian centers. All 203 patients enrolled in this study underwent bilateral orchiectomy and were randomized to receive either the nonsteroidal anti-androgen nilutamide or a placebo. Patient responses were graded according to the criteria of the National Prostatic Cancer Project (NPCP). Patients treated with nilutamide had a significantly greater number of positive objective responses (partial and complete regression) than did the patients treated with castration alone (46% versus 20%, P = 0.001). Progression-free survival was improved initially in the nilutamide group, but the median time to progression was 12 months for both groups. Despite an increase in the median length of survival from 18.9 to 24.3 months with the nilutamide, the survival time was not significantly longer in the nilutamide group (log = rank test, P = 0.048). Although minor side effects were frequent, adverse effects related to the medication and leading to discontinuation of treatment were observed in 9% of cases. These results suggest some benefit of the combined treatment (orchiectomy + nilutamide) over orchiectomy alone in the treatment of metastatic prostatic carcinoma.

We evaluated renal function within 48 hours after extracorporeal shock-wave lithotripsy (ESWL) as well as 1 month and up to 6 months later employing technetium-99m dimercaptosuccinic acid and iodine-131-labelled ortho-iodohippurate. All 17 patients displayed abnormal renal function immediately after ESWL. The abnormalities identified included focal cortical lesions, diffuse reduction of renal function, increased kidney volume, and diffusely and focally increased parenchymal transit times. The follow-up scintigraphic studies indicated that the great majority of the lesions had been temporary.

The effect of chronic treatment with the luteinizing hormone-releasing hormone (LH-RH) agonist Buserelin (Hoechst AG, Frankfurt/Main, West Germany) ([D-Ser(TBU)6,des-Gly-NH2(10)]LH-RH ethylamide) administrered by nasal spray (200 or 500 micrograms, twice daily) or subcutaneously (50 micrograms daily) for periods of 1 to 8 months was studied on serum sex steroids and LH levels in 18 patients with cancer of the prostate. Basal serum testosterone concentration decreases to 71.1 +/- 18.3 (NS) and 28.6 +/- 9.3%, (P less than 0.01) of control in patients receiving the 200-micrograms and 500-micrograms dose by nasal spray, respectively. In patients treated subcutaneously, a more rapid inhibition of serum testosterone levels to 19.6 +/- 6.4% of control (P less than 0.01) is observed. The finding of decreased levels of 17-OH-progesterone, testosterone, and dihydrotestosterone in the presence of unchanged pregnenolone concentration indicates that the decrease in androgen biosynthesis induced by Buserelin treatment is due to a blockage at the level of 17-hydroxylase and 17,20-desmolase activities. The present data indicate that chronic administration of Buserelin could be a safe and effective means of reducing serum androgens in patients with cancer of the prostate.

A comparative study was done in 59 recently diagnosed Stage D2 prostatic cancer patients treated with either long-term GnRH-A (Buserelin) (N = 42) or with orchiectomy (N = 17) and followed up for three years. The suppressed limits of plasma testosterone and estradiol levels after eight-week follow-up as well as the objective clinical response and disease outcome were found to be similar with either treatment. Hot flushes and loss of libido were noticed in both groups throughout the follow-up period; however, there were no other side effects. Analysis of Stage D2 patients based on their time of death enables us to identify nonhormonal variables which, in the form of an aggressiveness score, correlated well with both clinical response and disease outcome. These data confirm that (1) Buserelin is an effective and safe alternative to orchiectomy in advanced prostatic cancer, and (2) in clinical studies a multifactor aggressiveness score is useful for analyzing clinical efficacy data. Prospective application of that score may enable predictability of patient response and influence patient management.