COSMIC-dFBA: A novel multi-scale hybrid framework for bioprocess modeling.

Metabolism governs cell performance in biomanufacturing, as it fuels growth and productivity. However, even in well-controlled culture systems, metabolism is dynamic, with shifting objectives and resources, thus limiting the predictive capability of mechanistic models for process design and optimization. Here, we present Cellular Objectives and State Modulation In bioreaCtors (COSMIC)-dFBA, a hybrid multi-scale modeling paradigm that accurately predicts cell density, antibody titer, and bioreactor metabolite concentration profiles. Using machine-learning, COSMIC-dFBA decomposes the instantaneous metabolite uptake and secretion rates in a bioreactor into weighted contributions from each cell state (growth or antibody-producing state) and integrates these with a genome-scale metabolic model. A major strength of COSMIC-dFBA is that it can be parameterized with only metabolite concentrations from spent media, although constraining the metabolic model with other omics data can further improve its capabilities. Using COSMIC-dFBA, we can predict the final cell density and antibody titer to within 10% of the measured data, and compared to a standard dFBA model, we found the framework showed a 90% and 72% improvement in cell density and antibody titer prediction, respectively. Thus, we demonstrate our hybrid modeling framework effectively captures cellular metabolism and expands the applicability of dFBA to model the dynamic conditions in a bioreactor.

Klotho inversely relates with carotid intima- media thickness in atherosclerotic patients with normal renal function (eGFR ≥60 mL/min/1.73m2): a proof-of-concept study.

Introduction: Klotho protein is predominantly expressed in the kidneys and has also been detected in vascular tissue and peripheral blood circulating cells to a lesser extent. Carotid artery intima-media thickness (CIMT) burden, a marker of subclinical atherosclerosis, has been associated with reductions in circulating Klotho levels in chronic kidney disease patients, who show reduced levels of this protein at all stages of the disease. However, the contribution of serum Klotho and its expression levels in peripheral blood circulating cells and in the carotid artery wall on the CIMT in the absence of kidney impairment has not yet been evaluated. Methods: We conducted a single-center study in 35 atherosclerotic patients with preserved kidney function (eGFR≥60 mL/min/1.73m2) subjected to elective carotid surgery. Serum levels of Klotho and cytokines TNFa, IL6 and IL10 were determined by ELISA and transcripts encoding for Klotho (KL), TNF, IL6 and IL10 from vascular segments were measured by qRT-PCR. Klotho protein expression in the intima-media and adventitia areas was analyzed using immunohistochemistry. Results: APatients with higher values of CIMT showed reduced Klotho levels in serum (430.8 [357.7-592.9] vs. 667.8 [632.5-712.9] pg/mL; p<0.001), mRNA expression in blood circulating cells and carotid artery wall (2.92 [2.06-4.8] vs. 3.69 [2.42-7.13] log.a.u., p=0.015; 0.41 [0.16-0.59] vs. 0.79 [0.37-1.4] log.a.u., p=0.013, respectively) and immunoreactivity in the intimal-medial area of the carotids (4.23 [4.15-4.27] vs. 4.49 [4.28-4.63] log µm2 p=0.008). CIMT was inversely related with Klotho levels in serum (r= -0.717, p<0.001), blood mRNA expression (r=-0.426, p=0.011), and with carotid artery mRNA and immunoreactivity levels (r= -0.45, p=0.07; r= -0.455, p= 0.006, respectively). Multivariate analysis showed that serum Klotho, together with the gene expression levels of tumor necrosis factor TNFa in blood circulating cells, were independent determinants of CIMT values (adjusted R2 = 0.593, p<0.001). Discussion: The results of this study in subjects with eGFR≥60mL/min/1.73m2 show that patients with carotid artery atherosclerosis and higher values of CIMT present reduced soluble Klotho levels, as well as decreased KL mRNA expression in peripheral blood circulating cells and Klotho protein levels in the intima-media of the carotid artery wall.

Guidelines for extracting biologically relevant context-specific metabolic models using gene expression data.

Genome-scale metabolic models comprehensively describe an organism's metabolism and can be tailored using omics data to model condition-specific physiology. The quality of context-specific models is impacted by (i) choice of algorithm and parameters and (ii) alternate context-specific models that equally explain the -omics data. Here we quantify the influence of alternate optima on microbial and mammalian model extraction using GIMME, iMAT, MBA, and mCADRE. We find that metabolic tasks defining an organism's phenotype must be explicitly and quantitatively protected. The scope of alternate models is strongly influenced by algorithm choice and the topological properties of the parent genome-scale model with fatty acid metabolism and intracellular metabolite transport contributing much to alternate solutions in all models. mCADRE extracted the most reproducible context-specific models and models generated using MBA had the most alternate solutions. There were fewer qualitatively different solutions generated by GIMME in E. coli, but these increased substantially in the mammalian models. Screening ensembles using a receiver operating characteristic plot identified the best-performing models. A comprehensive evaluation of models extracted using combinations of extraction methods and expression thresholds revealed that GIMME generated the best-performing models in E. coli, whereas mCADRE is better suited for complex mammalian models. These findings suggest guidelines for benchmarking -omics integration algorithms and motivate the development of a systematic workflow to enumerate alternate models and extract biologically relevant context-specific models.

Phenotype-centric modeling for rational metabolic engineering.

Phenotype-centric modeling enables a paradigm shift in the analysis of mechanistic models. It brings the focus to a network's biochemical phenotypes and their relationship with measurable traits (e.g., product yields, system dynamics, signal amplification factors, etc.) and away from computationally intensive simulation-centric modeling. Here, we explore applications of this new modeling strategy in the field of rational metabolic engineering using the amorphadiene biosynthetic network as a case study. This network has previously been studied using a mechanistic model and the simulation-centric strategy, and thus provides an excellent means to compare and contrast results obtained from these two very different strategies. We show that the phenotype-centric strategy, without values for the parameters, not only identifies beneficial intervention strategies obtained with the simulation-centric strategy, but it also provides an understanding of the mechanistic context for the validity of these predictions. Additionally, we propose a set of hypothetical strains with the potential to outperform reported production strains and to enhance the mechanistic understanding of the amorphadiene biosynthetic network. Further, we identify the landscape of possible intervention strategies for the given model. We believe that phenotype-centric modeling can advance the field of rational metabolic engineering by enabling the development of next generation kinetics-based algorithms and methods that do not rely on a priori knowledge of kinetic parameters but allow a structured, global analysis of system design in the parameter space.

Klotho expression in peripheral blood circulating cells is associated with vascular and systemic inflammation in atherosclerotic vascular disease.

Cardiovascular disease is the leading cause of death worldwide. New therapeutic strategies are aimed to modulate the athero-inflammatory process that partially orchestrates underlying vascular damage. Peripheral blood circulating cells include different immune cells with a central role in the development of the atherogenic inflammatory response. The anti-aging protein α-Klotho has been related to protective effects against CVD. KL is expressed in monocytes, macrophages, and lymphocytes where it exerts anti-inflammatory effects. In this work, we analyse the relationships of the levels of inflammatory markers with the expression of the KL gene in PBCCs and with the serum levels of soluble KL in atherosclerotic vascular disease. For this, we conducted a cross-sectional single-center case-control study including a study group of 76 CVD patients and a control group of 16 cadaveric organ donors without medical antecedent or study indicating CVD. Vascular artery fragments and whole blood and serum samples were obtained during elective or organ retrieval surgery. Serum levels of sKL, TNFα and IL10, and gene expression levels of KL, TNF, IL10, NFKB1, DNMT1, and DNMT3A in PBCCs were measured. In these cells, we also determined KL promoter methylation percentage. Histological and immunohistochemical analyses were employed to visualize atherosclerotic lesions and to measure IL10 and TNFα levels in vascular fragments. Patients with CVD presented higher values of proinflammatory markers both at systemic and in the vasculature and in the PBCCs, compared to the control group. In PBCCs, CVD patients also presented lower gene expression levels of KL gene (56.4% difference, P < 0.001), higher gene expression levels of DNMT1 and DNMT3A (P < 0.0001, for both) and a higher methylation status of in the promoter region of KL (34.1 ± 4.1% vs. 14.6 ± 3.4%, P < 0.01). In PBCCs and vasculature, KL gene expression correlated inversely with pro-inflammatory markers and directly with anti-inflammatory markers. sKL serum levels presented similar associations with the expression levels of pro- and anti-inflammatory markers in PBCCs. The differences in KL expression levels in PBCCs and in serum sKL levels with respect to control group was even greater in those CVD patients with macroscopically observable atheromatous plaques. We conclude that promoter methylation-mediated downregulation of KL gene expression in PBCCs is associated with the pro-inflammatory status in atherosclerotic vascular disease.

Individualization of Pinus radiata Canopy from 3D UAV Dense Point Clouds Using Color Vegetation Indices.

The location of trees and the individualization of their canopies are important parameters to estimate diameter, height, and biomass, among other variables. The very high spatial resolution of UAV imagery supports these processes. A dense 3D point cloud is generated from RGB UAV images, which is used to obtain a digital elevation model (DEM). From this DEM, a canopy height model (CHM) is derived for individual tree identification. Although the results are satisfactory, the quality of this detection is reduced if the working area has a high density of vegetation. The objective of this study was to evaluate the use of color vegetation indices (CVI) in canopy individualization processes of Pinus radiata. UAV flights were carried out, and a 3D dense point cloud and an orthomosaic were obtained. Then, a CVI was applied to 3D point cloud to differentiate between vegetation and nonvegetation classes to obtain a DEM and a CHM. Subsequently, an automatic crown identification procedure was applied to the CHM. The results were evaluated by contrasting them with results of manual individual tree identification on the UAV orthomosaic and those obtained by applying a progressive triangulated irregular network to the 3D point cloud. The results obtained indicate that the color information of 3D point clouds is an alternative to support individualizing trees under conditions of high-density vegetation.

Impact of elite soccer coaching change on team performance according to coach- and club-related variables.

A coaching change is an extreme, but frequently occurring phenomenon in elite soccer with its impact on team success debatable. The aim of the current study was twofold: (i) to compare team's performance when coached by new and old coaches; and (ii) to investigate the impact of a coaching change on team's performance according to coach- and club-related factors. All in-season coaching changes from the 2010-11 to 2017-18 seasons within the Spanish, French, English, German and Italian professional leagues were examined. Team performance was assessed as points awarded from match outcome over 1-20 matches prior to and following the coaching change. Four independent variables (coach's experience, team's budget, whether the coach had been an elite former player or not, and whether the coach was a novice or not) were included into linear regression modelling. The main results showed that team's short-term performance was improved significantly with a change to a new coach with this impact declining in the longer term (> 10 matches). Specifically, the number of points (1.15-1.32 vs. 0.37-1.03, p < 0.05) and the moving average of points (1.19-1.31 vs. 0.37-1.04, p < 0.05) awarded per match were significantly greater after the coaching change. Further, the winning effect due to the new coach was independent of coach-related factors such as coaching experience or the new coach being a former elite player. A critical organisational decision to change coaches may provide an essential stimulus for future team success in elite soccer.

Impact of Match Type on Exercise Volume and Intensity of Semi-Professional Basketball Referees During a Competitive Season.

Identification of the exercise volume and intensity of basketball referees, across competitive match types based on competition sex and level, would assist in developing appropriate training regimes. Purpose: The aims of this study were to quantify and compare the exercise volume and intensity encountered by semiprofessional basketball referees during different match types across a competitive season. Method: Sixteen referees participated and were monitored for absolute and relative PlayerLoad (PL) using microsensors during 25 semiprofessional matches (12 men's, 13 women's, 17 regular season, eight playoff). Comparisons between match types (men's vs. women's; regular season vs. playoff) were examined via independent t-tests or Mann-Whitney U tests, and repeated measures ANOVA with the magnitude of differences calculated via effect size. Results: Referees experienced an absolute PL of ~365 arbitrary units (AU) per match that was similar for men's, women's, regular season, and playoff matches during a competitive season. Relative PL was significantly greater (5.35 ± 0.82 vs. 4.26 ± 0.59 AU.min-1, p < .001, effect size = 1.57) during women's matches with a greater proportion of each quarter and match spent within PL band 2 compared to men's matches (11.6 ± 2.2 vs. 8.8 ± 1.4%, p < .001, effect size = 1.53), likely due to a reduced number of referees officiating. Minimal differences existed between the regular season and playoff matches for absolute PL, relative PL, and proportion of quarter/match time within PL bands. Conclusion: The current study confirmed that referees experienced considerable exercise volume and intensity per match during a competitive season with these influenced primarily by referee configuration. The current results provide crucial information to develop effective training regimes for referees during a competitive season.

TaxisPy: A Python-based software for the quantitative analysis of bacterial chemotaxis.

Several species of bacteria are able to modify their swimming behavior in response to chemical attractants or repellents. Methods for the quantitative analysis of bacterial chemotaxis such as quantitative capillary assays are tedious and time-consuming. Computer-based video analysis of swimming bacteria represents a valuable method to directly assess their chemotactic response. Even though multiple studies have used this approach to elucidate various aspects of bacterial chemotaxis, to date, no computer software for such analyses is freely available. Here, we introduce TaxisPy, a Python-based software for the quantitative analysis of bacterial chemotaxis. The software comes with an intuitive graphical user interface and can be accessed easily through Docker on any operating system. Using a video of freely swimming cells as input, TaxisPy estimates the culture's average tumbling frequency over time. We demonstrate the utility of the software by assessing the effect of different concentrations of the attractant shikimate on the swimming behavior of Pseudomonas putida F1 and by capturing the adaptation process that Escherichia coli undergoes after being exposed to l-aspartate.

Mechanistic Modeling of Biochemical Systems without A Priori Parameter Values Using the Design Space Toolbox v.3.0.

Mechanistic models of biochemical systems provide a rigorous description of biological phenomena. They are indispensable for making predictions and elucidating biological design principles. To date, mathematical analysis and characterization of these models encounter a bottleneck consisting of large numbers of unknown parameter values. Here, we introduce the Design Space Toolbox v.3.0 (DST3), a software implementation of the Design Space formalism enabling mechanistic modeling without requiring previous knowledge of parameter values. This is achieved by using a phenotype-centric modeling approach, in which the system is first decomposed into a series of biochemical phenotypes. Parameter values realizing phenotypes of interest are subsequently predicted. DST3 represents the most generally applicable implementation of the Design Space formalism and offers unique advantages over earlier versions. By expanding the Design Space formalism and streamlining its distribution, DST3 represents a valuable tool for elucidating biological design principles and designing novel synthetic circuits.

Long rallies and next rally performances in elite men's and women's badminton.

The aim of the present study was twofold: (i) to identify contextual variables associated with the occurrence of long rallies while investigating time-related and technical parameters; and (ii) to identify performance differences between long rallies and the subsequent rally when accounting for match-context and the players' sex. The sample included 60 men's (n = 4,475 rallies) and 60 women's (n = 4,490 rallies) matches randomly selected from the 2015 World Badminton Super Series and World Championship (the final sample included long rallies that had an immediate next point played: n = 1,734 and n = 1,644 rallies for male and female players, respectively). The long rallies represented 19.4% (n = 867) and 16.5% (n = 822) of total rallies for male and female players, respectively. Long rallies were established using a two-step cluster model based on rally time and number of strokes for male (13-79s, 14-72 strokes) and female players (11-56s, 11-52 strokes). The variables collected were point outcome (when serving and receiving, winner, forced-error and unforced-error), number of strokes per rally, rally time, rest time, density, and time between strokes. The rallies were classified into different contexts (clusters) according to influencing factors with eight clusters for male players and three clusters for female players identified. Comparisons among clusters were conducted using Kruskal Wallis and one-way ANOVAs. Comparisons between long and immediate next points were conducted using the Wilcoxon tests for most variables and Crosstabs Command for point outcome and rallies (long and immediate next). Statistically significant differences were identified for both sexes among clusters only for time-related variables (i.e., rally time, rest time, density and time between strokes). In addition, a greater number of strokes, longer rally, rest time, and higher density were identified during long rallies compared with the immediate next rally for both men's and women's matches (p<0.05). The time between strokes during long rallies was significantly greater for male players during clusters 3, 5, 6, and 7 (p<0.05) and significantly lower for female players during all clusters (p<0.05). Significant relationships were identified between winning point outcome, and more unforced errors when serving during the immediate next rally (men's cluster 5 and women's cluster 2), and more winners when serving during the immediate next rally (men's cluster 6). The current study identified and characterised long rallies in elite men´s and women´s badminton matches highlighting the importance of sex and contextual factors on time-related and technical demands. Information obtained from these unique sequences of play (i.e., long and immediate next rallies) will assist coaches when modelling and simulating players' performances (i.e., physiologically and cognitively) during athlete preparation/competition.

Ibuprofen removal by a microfiltration membrane bioreactor during the startup phase.

The behavior of ibuprofen (IBU) during the startup phase of a microfiltration membrane bioreactor (MBR) was determined. A full-scale experimental installation treating real urban wastewater was used for the study. The MBR was composed of an anoxic and an aerobic bioreactors working in pre-denitrification configuration, followed of a membrane reactor. A full mass balance was carried out to estimate the contribution of biotransformation and sorption to biomass to the overall removal of the IBU. During the startup phase of the MBR system there were significant oscillations of the operational variables, mainly of the sludge retention time (SRT); nevertheless, the capacity of the system for IBU removal was very high, with yields of over 94%, despite reaching minimum SRT values of 4.15 d. The main IBU removal occurs in the aerobic reactor, both in the liquid phase and the one associated with the sludge, while in the anoxic bioreactor the removal was scarce, although a certain transfer of IBU from the liquid phase to the sludge took place under anoxic conditions. Despite the high IBU removal yields during startup, the SRT was the most influential variable in IBU removal, an effect observed in all bioreactors, particularly in the anoxic one.

Physical Performance Differences Between Starter and Non-Starter Players During Professional Soccer Friendly Matches.

The aim of this study was to investigate the physical performance differences between players that started (i.e. starters, ≥65 minutes played) and those that were substituted into (i.e. non-starter) soccer friendly matches. Fourteen professional players (age: 23.2 ± 2.7 years, body height: 178 ± 6 cm, body mass: 73.2 ± 6.9 kg) took part in this study. Twenty, physical performance-related match variables (e.g. distance covered at different intensities, accelerations and decelerations, player load, maximal running speed, exertion index, work-to-rest ratio and rating of perceived exertion) were collected during two matches. Results were analysed using effect sizes (ES) and magnitude based inferences. Compared to starters, non-starters covered greater match distance within the following intensity categories: >3.3≤4.2m/s (very likely), >4.2≤5 m/s (likely) and >5≤6.9 m/s (likely). In contrast, similar match average acceleration and deceleration values were identified for starters and non-starters (trivial). Indicators of workloads including player loads (very likely), the exertion index (very likely), and the work-to-rest ratio (very likely) were greater, while self- reported ratings of perceived exertion were lower (likely) for non-starters compared to starters. The current study demonstrates that substantial physical performance differences during friendly soccer matches exist between starters and non-starters. Identification of these differences enables coaches and analysts to potentially prescribe optimal training loads and microcycles based upon player's match starting status.

Fibroblast growth factor 23 expression in human calcified vascular tissues.

Vascular calcification is a major risk for cardiovascular disease and implies the transformation of smooth muscle cells to an osteoblastic phenotype as a consequence of dysregulation of calcium and phosphate metabolism. Fibroblast growth factor (FGF) 23 is the most potent phosphate regulator. Observational studies suggest that high levels of FGF23 are related to cardiovascular morbidity and mortality. In this work, we determined the levels of both the intact and the carboxi-terminal fragments of circulating FGF23 in 133 patients with established cardiovascular disease, the expression of FGF23, its receptors 1 and 3, and its co-receptor Klotho in vascular fragments of aorta, carotid and femoral in 43 out of this group of patients, and in a control group of 20 organ donors. Patients with atherosclerosis and vascular calcification presented increased levels of FGF23 respect to the control group. Vascular immunoreactivity for FGF23 was also significantly increased in patients with vascular calcification as compared to patients without calcification and to controls. Finally, gene expression of FGF23 and RUNX2 were also higher and directly related in vascular samples with calcification. Conversely, expression of Klotho was reduced in patients with cardiovascular disease when comparing to controls. In conclusion, our findings link the calcification of the vascular tissue with the expression of FGF23 in the vessels and with the elevation of circulating levels this hormone.

Molecular Mechanisms Driving Switch Behavior in Xylem Cell Differentiation.

Plant xylem cells conduct water and mineral nutrients. Although most plant cells are totipotent, xylem cells are unusual and undergo terminal differentiation. Many genes regulating this process are well characterized, including the Vascular-related NAC Domain 7 (VND7), MYB46, and MYB83 transcription factors, which are proposed to act in interconnected feedforward loops (FFLs). Less is known regarding the molecular mechanisms underlying the terminal transition to xylem cell differentiation. Here, we generate whole-root and single-cell data, which demonstrate that VND7 initiates sharp switching of root cells to xylem cell identity. Based on these data, we identified 4 candidate VND7 downstream target genes capable of generating this switch. Although MYB46 responds to VND7 induction, it is not among these targets. This system provides an important model to study the emergent properties that may give rise to totipotency relative to terminal differentiation and reveals xylem cell subtypes.

Technical and physical match performance of teams in the 2018 FIFA World Cup: Effects of two different playing styles.

In order to investigate the effect of playing styles on the match performance of football teams, data were analysed on 18 technical performance-related variables and 8 physical performance-related variables from 59 matches in the 2018 FIFA World Cup. A k-means cluster analysis was conducted to classify all match observations into two clusters of tactical approach in order to identify the playing styles of teams (characterised as direct-play, possession-play and mixed-play). Separate Poisson regression models were run in the generalised mixed linear modelling to examine the differences in technical and physical performance between teams classified as using different playing styles when facing different opponents. Results showed that possession-play characterised teams achieved higher values in all the variables related to goal scoring, attacking and passing (ES: 0.32 ~ 1.27) and covered more distance in sprints and high-intensity running (ES: 0.33 ~ 0.47) than direct-play characterised teams. Both possession- and direct-play characterised teams achieved higher values in passing, pass accuracy and delivery into the attacking third playing against direct-play characterised teams than playing against possession-play characterised sides (ES: 0.22 ~ 0.98). These findings may provide insights into the establishment of performance profiles of teams with different tactical styles and the development of specific training drills to optimise playing style.

Relationships Among Circuit Training, Small-Sided and Mini Goal Games, and Competition in Professional Soccer Players: A Comparison of On-Field Integrated Training Routines.

Giménez, JV and Gomez, MA. Relationships among circuit training, small-sided and mini goal games, and competition in professional soccer players: A comparison of on-field integrated training routines. J Strength Cond Res 33(7): 1887-1896, 2019-The aim of this study was to investigate and compare different physical variables and load indicators of 2 small-sided game (SSG) formats and ball circuit training (CT). Fourteen professional players participated in 3 training routines using a similar occupied area per player (90 m). The CT, SSGs, and mini goal games (MGs) consisted of 8 repetitions of 4-minute game play, interspersed by 2 minutes of active recovery, and data were compared with the first 32 minutes of 2 competitive match simulations (MS). All movement patterns from walking to sprinting were recorded using 10-Hz global positioning system devices, whereas player perception of exertion was recorded after trial using a visual analogue scale. Practical differences among the 3 drills and MS were analyzed using magnitude-based inferences. The results suggested that the training routines did not exactly replicate the movement patterns of a competitive match. Furthermore, this study provides evidence that if high-intensity play is preferred, then SSGs should be emphasized (because they provide more total accelerations compared with the other drills; most likely effects). Moreover, the CT showed lower load and distance covered (m) than the MGs and SSGs. In conclusion, these drills may be useful for competition and impact microcycles (i.e., intermittent efforts with accelerations, decelerations, and walking actions) to achieve the specific adaptations of high-intensity efforts.

Effects of water re-allocation in the Ebro river basin: A multiregional input-output and geographical analysis.

The quality and availability of water are affected by numerous variables, through which the evaluation of water uses from different perspectives, and policy proposals to save water have now become essential. This paper aims to study water use and the water footprint from a river basin perspective, taking into account regions, sectors, and municipalities, while considering the physical frontier along with the administrative sectors. To this end, we have constructed a multi-regional input-output table for the Ebro river basin, disaggregating the primary sector into 18 different crops and 6 livestock groups. We pay special attention to crop production because it is the most water-consuming industry. The construction of the multi-regional input-output model represents an important contribution to the literature, in itself, since, to the best of our knowledge, it is the first to be built for this large basin. We extend this multi-regional input-output model to assess the water footprint by sectors and regions within the basin. We use these data to propose two scenarios: reallocating final demand to reduce the blue water footprint (scenario 1), and increasing value added (scenario 2). These scenarios outline the opportunity costs of saving water in socioeconomic terms in the basin. In another application, we downscale the multi-regional input-output model results at the municipal level and depict them using a geographical information system, identifying the hotspots and the areas that would pay for the socioeconomic opportunity costs of saving water. Our results suggest that saving 1 hm3 of blue water could cost around €41,500 of value added if we consider the entire basin. However, this water re-allocation implies losses and gains at the municipal level: some municipalities would reduce value added by more than €30,000, while others would gain more than €85,000 of value added. These tools and results can be useful for policy makers when considering re-allocating water. The contribution and the novelty of this paper is the construction of the multiregional input-output model for the Ebro river basin, and its link with geographical systems analysis at the municipal level.

Skin temperature response to a liquid meal intake is different in men than in women.

BACKGROUND & AIM: The thermic effect of food (TEF) refers to the increase of the metabolic rate and body temperature in response to a single meal. To date, most of the studies have focused to determine the TEF in terms of energy expenditure, but little is known about which is the response in terms of skin temperature. The aim of this study was to analyze whether the thermic effect of food (TEF) on the skin temperature with a standardized and individualized liquid meal test is different in young adult men than in young adult women. METHODS: A total of 104 young adults (36 men and 68 women, age: 18-25 years old) consumed a standardized and individualized liquid meal (energy intake: 50% of measured basal metabolic rate, 50% carbohydrates, 35% fat, 15% protein). The skin temperature was measured by means of 17 iButtons during 3 h and 20 min. The mean, proximal, distal, and supraclavicular skin temperature, as well as the peripheral gradient, were determined as a proxy of a peripheral vasoconstriction. The participants reported the thermal sensation of the whole body, clavicular, feet, and hands zones. The body composition was measured by dual X-ray absorptiometry. RESULTS: The overall, mean, proximal, and supraclavicular skin temperature significantly increased after the meal intake (all P < 0.05 vs. the baseline temperature). There was a postprandial peripheral vasoconstriction right after the meal intake and over the first hour and a peripheral vasodilatation during the second and third hour. Women had a higher increase in all skin temperature parameters in comparison to men (all, P < 0.05), whereas there were no sex differences in the proximal skin temperature (P = 0.279). The pattern of thermal sensation was similar between sexes, but women always felt colder than men. All of the results persisted after adjusting the analyses for body composition or menstrual cycle. CONCLUSION: A standardized and individualized liquid meal test increases the skin temperature in young adults, being the thermic effect higher in women than in men.

Association of Objectively Measured Physical Activity With Brown Adipose Tissue Volume and Activity in Young Adults.

Purpose: Human brown adipose tissue (BAT) has gained considerable attention as a potential therapeutic target for obesity and type 2 diabetes; however, whether physical activity (PA) might be an efficient stimulus to activate and recruit BAT remains to be ascertained. We aimed to examine whether objectively measured PA levels were associated with BAT volume and activity in young sedentary adults. We additionally examined the association of PA levels with the skeletal muscles activity. Methods: A total of 130 young healthy and sedentary adults (67% women; age, 21.9 ± 2.1 years old; body mass index, 25 ± 4.8 kg/m2) participated in this cross-sectional study. PA was objectively measured with a wrist-worn accelerometer for 7 consecutive days. Age-specific cut points were applied to classify wrist accelerations into sedentary time and different PA intensities (i.e., light, moderate, vigorous, moderate-vigorous). The participants underwent 2 hours of a personalized cold exposure to determine the cold-induced BAT volume and activity and the skeletal muscles activity by means of an 18F-fluorodeoxyglucose positron emission tomography combined with a CT scan. Results: Objectively measured PA intensity levels were neither associated with BAT volume and activity nor with the skeletal muscles activity (all P > 0.05). The results remained after adjusting for sex, waking time, and environmental temperature. Conclusions: Although PA plays an important role in the prevention of obesity and related comorbidities, it seems that other physiological mechanisms rather than brown adipocyte activation or recruitment might moderate its beneficial metabolic effects in young sedentary adults.