Metabolomics of fecal samples: a practical consideration

Background Metabolic profiling is becoming increasingly popular to identify subtle metabolic variations induced by diet alterations and to characterize the metabolic impact of variations of the gut microbiota. In this context, fecal samples, that contain unabsorbed metabolites, offer a direct access to the outcome of diet - gut microbiota metabolic interactions. Hence, they are a useful addition to measure the ensemble of endogenous and microbial metabolites, also referred to as the hyperbolome. Scope and Approach Many reviews have focused on the metabolomics analysis of urine, plasma and tissue biopsies; yet the analysis of fecal samples presents some challenges that have received little attention. We propose here a short review of current practices and some practical considerations when analyzing fecal material using metabolic profiling of small polar molecules and lipidomics. Key Findings and Conclusions: To allow for a complete coverage of the fecal metabolome, it is recommended to use a combination of analytical techniques that will measure both hydrophilic and hydrophobic metabolites. A clear set of guidelines to collect, prepare and analyse fecal material is urgently needed

Ældres sikkerhed på Frederikssundsvej: Et trafikpuljeprojekt

Københavns længste vej blev bygget om i 1998 – med midterarealer, ordnede parkeringsforhold , ændrede busstoppesteder og ét kørespor i hver retning. Mange uheld med især ældre fodgængere på tværs af vejen og som buspassagerer samt et uroligt trafikmønster satte fokus på vejen. Overskuelighed, gode krydsningsmuligheder og en rolig afvikling af trafikken var nøgleord for projektet, som blev til i samarbejdet mellem ældreråd, politiet, Vejdirektoratet, Rådet for Større Færdselssikkerhed og Vej & Park. Spørgeskemaundersøgelser, foredrag og informationspjecer til brugerne var vigtige dele af det samlede projekt. I dette paper præsenteres baggrund, projektmål, undersøgelser, projekt, information og evaluering

Trafiksikkerhedsplan for København

Københavns Kommune har i samarbejde med Københavns Politi udarbejdet en Trafiksikkerhedsplan for København for at synliggøre og effektivisere det fremtidige arbejde med trafiksikkerhed. Planen er politisk vedtaget, og der er bevilget 91 mio. kr. til trafiksikkerhedsarbejde over en 12-års periode. Det overordnede mål er at reducere antallet af dræbte og alvorligt tilskadekomne i trafikken i København med 40% inden udgangen af 2012. Dette mål forventes at kunne nås ved at koncentrere indsatsen om uheld med henholdsvis for høj hastighed, med spiritus, i kryds, med cyklister og med fodgængere, der krydser veje uden for vejkryds. For hvert af disse indsatsområder er der opstillet delmål om reduktion af dræbte og alvorligt tilskadekomne samt virkemidler hertil

New insights into the impact of Lactobacillus population on host-bacteria metabolic interplay

We aimed at evaluating the association between intestinal Lactobacillus sp. composition and their metabolic activity with the host metabolism in adult and elderly individuals. Faecal and plasma metabolites were measured and correlated to the Lactobacillus species distribution in healthy Estonian cohorts of adult (n=16; 65 y). Total cholesterol, LDL, C-reactive protein and glycated hemoglobin were statistically higher in elderly, while platelets, white blood cells and urinary creatinine were higher in adults. Aging was associated with the presence of L. paracasei and L. plantarum and the absence of L. salivarius and L. helveticus. High levels of intestinal Lactobacillus sp. were positively associated with increased concentrations of faecal short chain fatty acids, lactate and essential amino acids. In adults, high red blood cell distribution width was positively associated with presence of L. helveticus and absence of L. ruminis. L. helveticus was correlated to lactate and butyrate in faecal waters. This indicates a strong relationship between the composition of the gut Lactobacillus sp. and host metabolism. Our results confirm that aging is associated with modulations of blood biomarkers and intestinal Lactobacillus species composition. We identified specific Lactobacillus contributions to gut metabolic environment and related those to blood biomarkers. Such associations may prove useful to decipher the biological mechanisms underlying host-gut microbial metabolic interactions in an ageing population

A remark on Béjar & Kahnemuyipour 2017:Specificational subjects do have phi-features

In a number of languages, agreement in specificational copular sentences can or must be with the second of the two nominals, even when it is the first that occupies the canonical subject position. Béjar & Kahnemuyipour (2017) show that Persian and Eastern Armenian are two such languages. They then argue that ‘NP2 agreement’ occurs because the nominal in subject position (NP1) is not accessible to an external probe. It follows that actual agreement with NP1 should never be possible: the alternative to NP2 agreement should be ‘default’ agreement. We show that this prediction is false. In addition to showing that English has NP1, not default, agreement, we present new data from Icelandic, a language with rich agreement morphology, including cases that involve ‘plurale tantum’ nominals as NP1. These allow us to control for any confound from the fact that typically in a specificational sentence with two nominals differing in number, it is NP2 that is plural. We show that even in this case, the alternative to agreement with NP2 is agreement with NP1, not a default. Hence, we conclude that whatever the correct analysis of specificational sentences turns out to be, it must not predict obligatory failure of NP1 agreement

Factorized Q-Learning for Large-Scale Multi-Agent Systems

Deep Q-learning has achieved significant success in single-agent decision making tasks. However, it is challenging to extend Q-learning to large-scale multi-agent scenarios, due to the explosion of action space resulting from the complex dynamics between the environment and the agents. In this paper, we propose to make the computation of multi-agent Q-learning tractable by treating the Q-function (w.r.t. state and joint-action) as a high-order high-dimensional tensor and then approximate it with factorized pairwise interactions. Furthermore, we utilize a composite deep neural network architecture for computing the factorized Q-function, share the model parameters among all the agents within the same group, and estimate the agents' optimal joint actions through a coordinate descent type algorithm. All these simplifications greatly reduce the model complexity and accelerate the learning process. Extensive experiments on two different multi-agent problems demonstrate the performance gain of our proposed approach in comparison with strong baselines, particularly when there are a large number of agents.Comment: 7 pages, 5 figures, DAI 201

Metabonomics-based analysis of Brachyspira pilosicoli's response to tiamulin reveals metabolic activity despite significant growth inhibition

Pathogenic anaerobes Brachyspira spp. are responsible for an increasing number of Intestinal Spirochaetosis (IS) cases in livestock against which few approved treatments are available. Tiamulin is used to treat swine dysentery caused by Brachyspira spp. and recently has been used to handle avian intestinal spirochaetosis (AIS). The therapeutic dose used in chickens requires further evaluation since cases of bacterial resistance to tiamulin have been reported. In this study, we evaluated the impact of tiamulin at varying concentrations on the metabolism of B. pilosicoli using a 1H-NMR-based metabonomics approach allowing the capture of the overall bacterial metabolic response to antibiotic treatment. Based on growth curve studies, tiamulin impacted bacterial growth even at very low concentration (0.008 μg/mL) although its metabolic activity was barely affected 72 h post exposure to antibiotic treatment. Only the highest dose of tiamulin tested (0.250 μg/mL) caused a major metabolic shift. Results showed that below this concentration, bacteria could maintain a normal metabolic trajectory despite significant growth inhibition by the antibiotic, which may contribute to disease reemergence post antibiotic treatment. Indeed, we confirmed that B. pilosicoli remained viable even after exposition to the highest antibiotic dose. This paper stresses the need to ensure new evaluation of bacterial viability post bacteriostatic exposure such as tiamulin to guarantee treatment efficacy and decrease antibiotic resistance development

Multidecadal Indian Ocean variability linked to the Pacific and implications for pre-conditioning Indian Ocean Dipole events

The Indian Ocean has sustained robust surface warming in recent decades, but the role of multi-decadal variability remains unclear. Using ocean model hindcasts, characteristics of low-frequency Indian Ocean temperature variations are explored. Simulated upper-ocean temperature changes across the Indian Ocean in the hindcast are consistent with those recorded in observational products and ocean reanalyses. Indian Ocean temperatures exhibit strong warming trends since the 1950s limited to the surface and south of 30°S, while extensive subsurface cooling occurs over much of the tropical Indian Ocean. Previous work focused on diagnosing causes of these long-term trends in the Indian Ocean over the second half of the 20th Century. Instead, the temporal evolution of Indian Ocean subsurface heat content is shown here to reveal distinct multi-decadal variations associated with the Pacific Decadal Oscillation and the long-term trends are thus interpreted to result from aliasing of the low-frequency variability. Transmission of the multi-decadal signal occurs via an oceanic pathway through the Indonesian Throughflow and is manifest across the Indian Ocean centered along 12°S as westward propagating Rossby waves modulating thermocline and subsurface heat content variations. Resulting low-frequency changes in the eastern Indian Ocean thermocline depth are associated with decadal variations in the frequency of Indian Ocean Dipole (IOD) events, with positive IOD events unusually common in the 1960s and 1990s with a relatively shallow thermocline. In contrast, the deeper thermocline depth in the 1970s and 1980s is associated with frequent negative IOD and rare positive IOD events. Changes in Pacific wind forcing in recent decades and associated rapid increases in Indian Ocean subsurface heat content can thus affect the basin’s leading mode of variability, with implications for regional climate and vulnerable societies in surrounding countries

Late 20th Century Indian Ocean Heat Content Gain Masked by Wind Forcing

Rapid increases in upper 700‐m Indian Ocean heat content (IOHC) since the 2000s have focused attention on its role during the recent global surface warming hiatus. Here, we use ocean model simulations to assess distinct multidecadal IOHC variations since the 1960s and explore the relative contributions from wind stress and buoyancy forcing regionally and with depth. Multidecadal wind forcing counteracted IOHC increases due to buoyancy forcing from the 1960s to the 1990s. Wind and buoyancy forcing contribute positively since the mid‐2000s, accounting for the drastic IOHC change. Distinct timing and structure of upper ocean temperature changes in the eastern and western Indian Ocean are linked to the pathway how multidecadal wind forcing associated with the Interdecadal Pacific Oscillation is transmitted and affects IOHC through local and remote winds. Progressive shoaling of the equatorial thermocline—of importance for low‐frequency variations in Indian Ocean Dipole occurrence—appears to be dominated by multidecadal variations in wind forcing