The term Alcohol Use Disorder (AUD) incorporates different states of disease related to the recurrent use of alcohol and linked to the relevant impairment, disability and failure to perform major ...responsibilities in different realms. Many neurotransmitter systems are involved in the phases or states of alcoholism from reward mechanisms, associated to binge intoxication, to stress and anxiety linked to relapse and withdrawal. Some neuropeptides play a key function in the control of anxiety and stress, and establish a close relationship with the pathological mechanisms underlying alcohol addiction. Among them, Neuropeptide Y (NPY), Corticotropin-releasing factor (CRF)/Urocortins and Neuropeptide S (NPS) cross-talk, and are responsible for some of the maladaptation processes that the brain exhibits during the progression of the disease.
In this study, we review the literature mainly focused on the participation of these neuropeptides in the pathophysiology of AUD, as well as on the use of antagonists designed to investigate signaling mechanisms initiated after ligand binding and their connection to biochemical adaptation events coupled to alcohol addiction. The possibility that these systems may serve as therapeutic objectives to mitigate or eliminate the harm that drinking ethanol generates, is also discussed.
The peptide systems reviewed here, together with other neurotransmitter systems and their mutual relationships, are firm candidates to be targeted to treat AUD.
This paper assesses the mechanical and durability performance of concretes produced using alkali silicate-activated ground granulated blast furnace slag as sole binder. Alkali-activated concretes are ...formulated with 300, 400 and 500
kg slag per m
3 of fresh concrete, and their performance is compared with reference concretes produced using Portland cement (OPCC). Regardless of the binder content, the alkali-activated slag concretes (AASC) develop higher compressive strength than the comparable reference concretes. A higher binder content leads to increased strength in both AASC and OPCC at 28
days. However, at 90
days, the performance penalty for low binder content is more significant in the OPCC than AASC samples. Permeability, water sorption and carbonation resistance properties are also improved at higher binder contents. By controlling mix design parameters, it is possible to produce AASC with mechanical strength and durability comparable to conventional Portland cement concretes.
•A conceptual framework for assessing level and sub-level of protection is presented.•Management effort in 153 multiple-use MPAs in the English Channel was assessed.•83.70% of the MPAs assessed were ...assigned medium management effort.•No correlation was found between management effort and conservation status.•Low consistency in the ratings by different management bodies in England was found.
A conceptual framework was developed for assessing the sub-level of protection in 185 multiple-use marine protected areas (MPAs) in the English Channel through a survey on management effort. Data were retrieved from 153 MPAs: 4.56% were assigned low management effort, 83.70% were assigned medium management effort, and 11.76% were assigned high management effort. Overall, French MPAs performed better in terms of management effort than English MPAs and lack of consistency in ratings by different management bodies in England was found. Lack of correlation between management effort and conservation status within an available subset of 13 MPAs suggests that management may not be as influential a factor for the effective conservation of MPAs, especially in marine environments under heavy human pressure such as the English Channel. It is suggested that MPAs in such areas may therefore require an upgrade of their legal level of protection to be effective.
Although whole‐exome sequencing (WES) is the gold standard for the diagnosis of neurodevelopmental disorders (NDDs), it remains expensive for some genetic centers. Commercialized panels comprising ...all OMIM‐referenced genes called “medical exome” (ME) constitute an alternative strategy to WES, but its efficiency is poorly known. In this study, we report the experience of 2 clinical genetic centers using ME for diagnosis of NDDs. We recruited 216 consecutive index patients with NDDs in 2 French genetic centers, corresponded to the daily practice of the units and included non‐syndromic intellectual disability (NSID, n = 33), syndromic ID (NSID = 122), pediatric neurodegenerative disorders (n = 7) and autism spectrum disorder (ASD, n = 54). We sequenced samples from probands and their parents (when available) with the Illumina TruSight One sequencing kit. We found pathogenic or likely pathogenic variants in 56 index patients, for a global diagnostic yield of 25.9%. The diagnosis yield was higher in patients with ID as the main diagnosis (32%) than in patients with ASD (3.7%). Our results suggest that the use of ME is a valuable strategy for patients with ID when WES cannot be used as a routine diagnosis tool.
TruSight One global diagnostic yield in 216 consecutive patients with neurodevelopmental disorder, negative for X fragile and chromosomal microarray from 2 French clinical genetic centers (25.9%).
Present approaches to assess cancer treatments are often inaccurate, costly, and/or cumbersome. Functional testing platforms that use live tumor cells are a promising tool both for drug development ...and for identifying the optimal therapy for a given patient, i.e. precision oncology. However, current methods that utilize patient-derived cells from dissociated tissue typically lack the microenvironment of the tumor tissue and/or cannot inform on a timescale rapid enough to guide decisions for patient-specific therapy. We have developed a microfluidic platform that allows for multiplexed drug testing of intact tumor slices cultured on a porous membrane. The device is digitally-manufactured in a biocompatible thermoplastic by laser-cutting and solvent bonding. Here we describe the fabrication process in detail, we characterize the fluidic performance of the device, and demonstrate on-device drug-response testing with tumor slices from xenografts and from a patient colorectal tumor.
Dynamic Estimation of Electrical Demand in Hot Rolling Mills Alonso Orcajo, Gonzalo; Rodriguez D, Josue; Ardura G, Pablo ...
IEEE transactions on industry applications,
2016-May-June, 2016-5-00, 20160501, Letnik:
52, Številka:
3
Journal Article
Recenzirano
Odprti dostop
This paper proposes a method capable of reproducing the particular operating conditions of a hot strip mill and predicting the evolution of the main electrical variables from both the characteristics ...of the steel to be milled and the specific features of the rolling mill. The method analyzes the load torque and the motor-speed evolution in the stands of the roughing and finishing mill drives, according to the steel to be milled. In this study, three types of carbon alloy steel are considered, thus involving dissimilar hardness characteristics. The main stands of the mill, the power network, and the filter banks have been modeled. The relationship between the grade of steel and both the electrical demand and various power quality parameters is discussed. The results can be used as a part of an expert system for the automatic estimation of the electrical demand in a hot rolling mill.
End-expiratory lung volume (EELV) is reduced in mechanically ventilated patients, especially in pathologic conditions. The resulting heterogeneous distribution of ventilation increases the risk for ...ventilation induced lung injury. Clinical measurement of EELV however, remains difficult.
Validation of a novel continuous capnodynamic method based on expired carbon dioxide (CO
) kinetics for measuring EELV in mechanically ventilated critically-ill patients.
Prospective study of mechanically ventilated patients scheduled for a diagnostic computed tomography exploration. Comparisons were made between absolute and corrected EELVCO
values, the latter accounting for the amount of CO
dissolved in lung tissue, with the reference EELV measured by computed tomography (EELVCT). Uncorrected and corrected EELVCO
was compared with total CT volume (density compartments between - 1000 and 0 Hounsfield units (HU) and functional CT volume, including density compartments of - 1000 to - 200HU eliminating regions of increased shunt. We used comparative statistics including correlations and measurement of accuracy and precision by the Bland Altman method.
Of the 46 patients included in the final analysis, 25 had a diagnosis of ARDS (24 of which COVID-19). Both EELVCT and EELVCO
were significantly reduced (39 and 40% respectively) when compared with theoretical values of functional residual capacity (p < 0.0001). Uncorrected EELVCO
tended to overestimate EELVCT with a correlation r
0.58; Bias - 285 and limits of agreement (LoA) (+ 513 to - 1083; 95% CI) ml. Agreement improved for the corrected EELVCO
to a Bias of - 23 and LoA of (+ 763 to - 716; 95% CI) ml. The best agreement of the method was obtained by comparison of corrected EELVCO
with functional EELVCT with a r
of 0.59; Bias - 2.75 (+ 755 to - 761; 95% CI) ml. We did not observe major differences in the performance of the method between ARDS (most of them COVID related) and non-ARDS patients.
In this first validation in critically ill patients, the capnodynamic method provided good estimates of both total and functional EELV. Bias improved after correcting EELVCO
for extra-alveolar CO
content when compared with CT estimated volume. If confirmed in further validations EELVCO
may become an attractive monitoring option for continuously monitor EELV in critically ill mechanically ventilated patients.
clinicaltrials.gov (NCT04045262).
Spain has undergone rapid socioeconomic development in the past three decades. This has been linked to massive residential and infrastructural development based on a short-term, profitable and ...resource-intensive consuming model. As a result, large amounts of agricultural, natural and semi-natural soils have been lost to artificial areas, especially around main cities and on the coast. In this study, we assessed the effectiveness of the Spanish Shores Act at preventing land development in two biogeographical regions and three administrative scales between 1988 and 2020 using a BACI design and remote sensing data. We also analysed the combined effect of other regulations to prevent land development on the coast. The Shores Act was effective in reducing land development although moderate to substantial land development occurred in the zones affected by the Law, especially in the Mediterranean region. Adding other sectoral regulations to the Shores Act notably and consistently reduced land development across regions. Among them, cumulative protected area (PA) regulations were most effective in reducing coastal land development. The use of satellite images, especially Sentinel 2A MSI data within a BACI design, proved a useful method for assessing the effectiveness of fine-scale objectives of environmental policies such as the Shores Act.
•The effectiveness of the Spanish Shores Act was assessed at multiple scales.•Landsat 5 and Sentinel 2 data were used to ascertain coastal land development.•A BACI research design using two case zones and one control zone was applied.•The Shores Act reduced land development, especially on the Mediterranean coast.•Additional sectoral regulations further reduced land development substantially.
This study aimed to compare the effect on neuromuscular performance of 2 isoinertial resistance training programs that differed only in actual repetition velocity: maximal intended (MaxV) vs. ...half-maximal (HalfV) concentric velocity. 21 resistance-trained young men were randomly assigned to a MaxV (n=10) or HalfV (n=11) group and trained for 6 weeks using the full squat exercise. A complementary study (n=8) described the acute metabolic and mechanical response to the protocols used. MaxV training resulted in a likely more beneficial effect than HalfV on squat performance: maximum strength (ES: 0.94 vs. 0.54), velocity developed against all (ES: 1.76 vs. 0.88), light (ES: 1.76 vs. 0.75) and heavy (ES: 2.03 vs. 1.64) loads common to pre- and post-tests, and CMJ height (ES: 0.63 vs. 0.15). The effect on 20-m sprint was unclear, however. Both groups attained the greatest improvements in squat performance at their training velocities. Movement velocity seemed to be of greater importance than time under tension for inducing strength adaptations. Slightly higher metabolic stress (blood lactate and ammonia) and CMJ height loss were found for MaxV vs. HalfV, while metabolite levels were low to moderate for both conditions. MaxV may provide a superior stimulus for inducing adaptations directed towards improving athletic performance.
Water stress triggers acclimation responses and can damage plants, which varies by species and stress levels. Ongoing climate change is projected to result in longer and more intense water stress ...conditions leading to an alarming increase in drought-induced forest decline. The aim of this study was to evaluate the physiological responses of leaves and stem wood anatomy from Araucaria araucana pot-grown three-year old seedlings, a conifer tree from northwestern Patagonia. Plants were subjected to moderate and severe water restriction regimes and compared to well-watered controls. Severe water stress reduced relative leaf water content and triggered an accumulation of free proline in leaves, regardless of age. Epicuticular wax extrusions increased in apical leaf stomata while photosynthetic pigments decreased, resulting in differential oxidative damage. The concentration of phenolic compounds was not affected by water restrictions. Plants exposed to restricted water regimes showed diminished middle leaf biomass and expansion (~60% of total leaves), increased stem wood density, and experienced 7% and 30% mortality rates under moderate and severe water stress, respectively. Our findings suggest that under moderate water stress, analogous to short-term droughts, A. araucana seedlings activate physiological mechanisms that allow them to withstand short periods of drought, while more severe water stress and longer droughts can be severely harmful.
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In a controlled experiment, water stress triggered these physiological reactions in A. araucana seedlings:•A reduction in leaf area, leaf dry weight, and relative water content.•An increase in free proline and a decrease in chlorophyll a, b.•The development of thick layers of epicuticular waxes on stomata antechambers.•Intra-annual wood density fluctuations (IADFs).
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