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Ketamine therapy for treatment-resistant depression in European national health systems may only be considered after attempting all evidence-based antidepressant strategies outlined in clinical guidelines. This paper seeks to explain the ethical, regulatory and procedural framework for the off-label use of ketamine for treatment-resistant depression within a public healthcare system.
After five positive randomized controlled trials showed benefit of mechanical thrombectomy in the management of acute ischemic stroke with emergent large-vessel occlusion, a multi-society meeting was organized during the 17th Congress of the World Federation of Interventional and Therapeutic Neuroradiology in October 2017 in Budapest, Hungary. This multi-society meeting was dedicated to establish standards of practice in acute ischemic stroke intervention aiming for a consensus on the minimum requirements for centers providing such treatment. In an ideal situation, all patients would be treated at a center offering a full spectrum of neuroendovascular care (a level 1 center). However, for geographical reasons, some patients are unable to reach such a center in a reasonable period of time. With this in mind, the group paid special attention to define recommendations on the prerequisites of organizing stroke centers providing medical thrombectomy for acute ischemic stroke, but not for other neurovascular diseases (level 2 centers). Finally, some centers will have a stroke unit and offer intravenous thrombolysis, but not any endovascular stroke therapy (level 3 centers). Together, these level 1, 2, and 3 centers form a complete stroke system of care. The multi-society group provides recommendations and a framework for the development of medical thrombectomy services worldwide.
Polyurethanes (PUs) were synthesized with polyols derived from castor oil and isophorone diisocyanate. The materials were evaluated for their mechanical properties using stress–strain curves, thermogravimetric analysis, differential scanning calorimetry, and contact angle analysis. The biological response of the materials was evaluated by determining their cell viability in vitro, antimicrobial activity against Escherichia coli and Pseudomonas aeruginosa, and biological response in vivo of PUs by means of implanting them in Wistar rats. The cell proliferation on the materials was analyzed using mouse fibroblast L929, human fibroblast MRC-5, and adult human dermal fibroblast (HDFa) cells by the ISO 10993-5 method. The materials showed no toxic effects and promoted cell proliferation. Experiments performed in vivo for 30 days in mice showed that the materials neither affected the wound healing process nor caused adverse effects or severe injuries in the dorsal mid-cervical tissue or organs on histological evaluation. PUs synthesized can be used in biomedical devices.
Polyurethane/cellulose composites were synthesized from castor-oil-derived polyols and isophorone diisocyanate using dibutyltin dilaurate (DBTDL) as the catalyst. Materials were obtained by adding 2% cellulose in the form of either microcrystals (20 μm) or nanocrystals obtained by acid hydrolysis. The aim was to assess the effects of filler particle size and the use of a catalyst on the physicochemical properties and biological response of these composites. The addition of the catalyst was found to be essential to prevent filler aggregations and to enhance the tensile strength and elongation at break. The cellulose particle size influenced the composite properties, as its nanocrystals heighten hydrogen bond interactions between the filler surface and polyurethane domains, improving resistance to hydrolytic degradation. All hybrids retained cell viability, and the addition of DBTDL did not impair their biocompatibility. The samples were prone to calcification, which suggests that they could find application in the development of bioactive materials.
Cognitive deficits are a core feature of early stages in schizophrenia. However, the extent to which antipsychotic (AP) have a deleterious effect on cognitive performance remains under debate. We aim to investigate whether anticholinergic loadings and dose of AP drugs in first episode of psychosis (FEP) in advanced phase of remission are associated with cognitive impairment and the differences between premorbid intellectual quotient (IQ) subgroups.
Two hundred and sixty-six patients participated. The primary outcomes were cognitive dimensions, dopaminergic/anticholinergic load of AP [in chlorpromazine equivalents (Eq-CPZ) and the Anticholinergic Risk Scale (ARS), respectively].
Impairments in processing speed, verbal memory and global cognition were significantly associated with high Eq-CPZ and verbal impairment with high ARS score. Moreover, this effect was higher in the low IQ subgroup.
Clinicians should be aware of the potential cognitive impairment associated with AP in advanced remission FEP, particularly in lower premorbid IQ patients.
Polyurethane-based bioadhesive was synthesized with polyols derived from castor oil (chemically modified and unmodified) and hexamethylene diisocyanate with chitosan addition as a bioactive filler. The objective was to evaluate the effect of type of polyols with the incorporation of low-concentrations of chitosan on the mechanical and biological properties of the polymer to obtain suitable materials in the design of biomaterials. The results showed that increasing physical crosslinking increased the mechanical and adhesive properties. An in vitro cytotoxic test of polyurethanes showed cellular viability. The biocompatibility of the polyurethanes favors the adhesion of L929 cells at 6, 24, and 48 h. The polyurethanes showed bacterial inhibition depending on the polyol and percentage of chitosan. The antibacterial effect of the polyurethanes for Escherichia coli decreased 60–90% after 24 h. The mechanical and adhesive properties together with biological response in this research suggested these polyurethanes as external application tissue bioadhesives.
A remarkable stela from Montoro, southern Spain, is unique in its morphology, epigraphic traits and landscape context. A programme of chemical characterisation, digital imaging, and geo-lithological and epigraphic analyses were conducted to determine its age and significance, and the results were integrated with data from archaeological investigations of the surrounding area. This multi-faceted approach allowed the stela to be interpreted within the context of early interactions between literate Mediterranean societies of the Late Bronze Age and Iron Age and non-literate Iberian societies. A key outcome of this research is a wider understanding of the complex patterns in the use and perception of early scripts.
Since work organizations became the subject of scientific research, how to operationalize and measure dimensions of work design has been an issue, mainly due to concerns about internal consistency and factor structure. In response, Morgeson and Humphrey (2006) built the Work Design Questionnaire –WDQ–, an instrument that identifies and measures these dimensions in different work and organizational contexts. This paper presents the instruent’s adaptation into Spanish using reliability and validity analysis and drawing on a sample of 1035 Spanish workers who hold various jobs in an array of occupational categories. The total instrument’s internal consistency was Cronbach’s alpha of .92 and the various scales’ reliability ranged from .70 to .96, except for three dimensions. There was initially a difference in the comparative fit of the two versions’ factor structures, but the model with 21 work characteristics (motivational -task and knowledge-, social, and work context) showed the highest goodness of fit of the various models tested, confirming previous results from the U.S. version as well as adaptations into other languages and contexts. CFA results indicated goodness of fit of factor configurations corresponding to each of the four major categories of work characteristics, with CFI and TLI around .90, as well as SRMR and RMSEA below .08. Thus it brings to the table a reliable, valid measure of work design with clear potential applications in research as well as professional practice, applications that could improve working conditions, boost productivity, and generate more personal and professional development opportunities for workers.
The Endangered Cuvier's gazelle Gazella cuvieri is an endemic ungulate of north-western Africa. Information on the species has been based primarily on non-systematic surveys, and the corresponding status estimates are of unknown quality. We evaluate the effectiveness and efficiency of two field methods for systematic surveys of populations of Cuvier's gazelle in arid environments: distance sampling (based on sightings) and sampling indirect sign (tracks and scats). The work was carried out in the north-western Sahara Desert, in Morocco, where what is possibly the largest population of Cuvier's gazelle persists. A logistically viable survey was conducted over a total area of c. 20.000 km2 in 10 expeditions during 2011–2014. A total of 67 sites were surveyed, with 194 walking surveys (2,169 km in total). Gazelle signs were detected at 50 sites, and gazelles were sighted at 21 sites (61 individuals). We found a relationship between sightings and abundance indices based on indirect sign, which could be useful for population monitoring or ecological studies. Additionally, the data could be used in occupancy modelling. Density estimates based on distance sampling required considerable effort; however, it is possible to survey large areas during relatively short campaigns, and this proved to be the most useful approach to obtain data on the demographic structure of the population.
High-order and conservative phase space direct solvers that preserve the Euler asymptotic limit of the Boltzmann-BGK equation for modelling rarefied gas flows are explored and studied. The approach is based on the conservative discrete ordinate method for velocity space by using Gauss Hermite or Simpsons quadrature rule and conservation of macroscopic properties are enforced on the BGK collision operator. High-order asymptotic-preserving time integration is adopted and the spatial evolution is performed by high-order schemes including a finite difference weighted essentially non-oscillatory method and correction procedure via reconstruction schemes. An artificial viscosity dissipative model is introduced into the Boltzmann-BGK equation when the correction procedure via reconstruction scheme is used. The effects of the discrete velocity conservative property and accuracy of high-order formulations of kinetic schemes based on BGK model methods are provided. Extensive comparative tests with one-dimensional and two-dimensional problems in rarefied gas flows have been carried out to validate and illustrate the schemes presented. Potentially advantageous schemes in terms of stable large time step allowed and higher-order of accuracy are suggested.
Transiting candidate validation is essentially a Bayesian model comparison problem: different models, all explaining the observations comparably well, compete for the support of the available data. The basic characteristics of the planet validation problem are discussed and the different approaches taken to tackle its difficulties are reviewed.
Taking as a point of departure the in-depth analysis and description of an exceptional discovery, consisting of a large hammered gold sheet decorated with embossed motifs from the well-known Chalcolithic settlement of Valencina de la Concepción (Seville, Spain), this article presents a general appraisal of the social and ideological role of gold in Copper Age Iberia. The information available for this find, including both its context and its inherent characteristics, opens up new perspectives for research into the technology, use, sociology and symbolism of gold during this time period. We describe and analyse this unique item in detail, including the characterization of the raw material used and the manufacturing process (via SEM-BSE and LA-ICP-MS), as well as an extensive reconstruction of the graphic motifs that are represented, by using digital imaging processing techniques (RTI). We compare this find with the data currently available for the (approximately) 100 Chalcolithic golden artefacts (or fragments of artefacts) found in Iberia to date. Finally, we present an appraisal of the social and ideological framework in which gold was used in Copper Age Iberia, discussing its relevance in aspects such as the dynamics of social complexity, worldviews or artistic creations.
In this paper, we develop and study numerical methods for the two-mode shallow water equations recently proposed in [S. STECHMANN, A. MAJDA, and B. KHOUIDER, Theor. Comput. Fluid Dynamics, 22 (2008), pp. 407-432]. Designing a reliable numerical method for this system is a challenging task due to its conditional hyperbolicity and the presence of nonconservative terms. We present several numerical approaches—two operator splitting methods (based on either Roe-type upwind or central-upwind scheme), a central-upwind scheme and a path-conservative central-upwind scheme—and test their performance in a number of numerical experiments. The obtained results demonstrate that a careful numerical treatment of nonconservative terms is crucial for designing a robust and highly accurate numerical method.
The aim of this work was to study how machine milking (MM) carried out in suitable conditions affects teat wall thickness and teat canal length and their return after milking to pre-milking conditions, in comparison with other milk extraction methods considered biological referents: lamb suckling (LS), milk removal by catheter (RC) and hand milking (HM). Three Latin square experiments were designed, using 11 ewes in the first experiment (LS), 13 in the second (RC) and 12 in the third (HM). Each of the Latin squares was divided into two periods: in the first, the left gland of each animal was machine milked and the corresponding treatment (LS, RC and HM) was applied to the right gland. Subsequently, in the second period the extraction methods were interchanged. During the experimental period, 4 sampling days were carried out (2 in each experimental period), where ultrasound scans were taken before (B) and immediately after milking (A) and at 1 (1 h), 2 (2 h), 3 (3 h), 4 (4 h), 6 (6 h), 8 (8 h) and 10 (10 h) hours after milking finished. Teat wall thickness (TWT), teat wall area (TWA), teat end area (TEWA) and teat canal length (TCL) were measured in all the ultrasound images. MM increased TWT after milking compared with RC. TWT, TWA, TEWA and TCL were lower (P<0·05) in HM than in MM. No significant differences (P>0·05) were found between LS and MM for any variable. The extraction method affected the recovery time of the variables, with total teat recovery at 6 h after RC and 4 h after HM. In the case of LS, the TEWA and TCL values were recovered sooner, as of 3 h. Teat recovery time after MM was similar to the extraction method with which it was compared in each experiment. Thus, considering the similar increase in wall thickness and their recovery time compared with the reference methods, it was concluded that machine milking, carried out in optimum conditions and respecting the time interval between milkings usually applied on sheep farms (8–12 h), would not affect teat integrity. Moreover, given the variability observed in teat thickness recovery time between the different experiments, further research should be carried out to study which factors intrinsic and extrinsic to the animal may affect the teat wall thickness and recovery time after machine milking.
The aim of this work was to study the effect on teat wall thickness and canal length in sheep and goats of overmilking for 2 min (OM+2) and of milking with used (AL; +3000 milkings) and twisted (TL; 45°) liners in sheep and goats, as well as the effect of milking goats with liners designed for sheep (SL, shorter length and diameter than liners for goats). To this end, we performed four experiments in goats and three in sheep, in a Latin square design with two experimental periods. During the experimental period 4 controls were carried out, performing ultrasound scans before and immediately after milking to determine the teat wall thickness (TWT), teat wall area (TWA), teat end area (TEWA) and teat canal length (TCL). OM+2 caused a significant increase in TWT, TWA, TEWA and TCL in goats and in TWA, TEWA and TCL in sheep. Liner features had a strong influence on the variables studied; aged liners caused significant changes in TWT and TCL in goats and in TWT in sheep; twisted liners produced a significant effect on the increase of TWT and TCL in goats, without reaching significance level in sheep; and milking goats with sheep liners led to a significant increase in TWT, TWA, TEWA and TCL. In practice, it is therefore important to avoid overmilking and the use of worn-out liners. It is also necessary to use liners designed for the morphological features of each species, taking special care to carry out periodic liner positioning revisions to ensure the benefits of pulsation on the teat end. Finally, it would be necessary to carry out long-term experiments to study whether the increase in thickness observed in some experiments is sufficient to affect milking efficiency and mammary gland health status.
Citral is a monoterpene commonly found as volatile component in many different aromatic plants. Although many studies have identified the presence of citral in phytotoxic essential oils, this work determines for the first time the potential herbicidal effect of citral on weeds. The use of citral against weeds and crops resulted in the potential for the management of barnyardgrass, redroot pigweed, and ribwort. Clear morphological differences were observed between adult thale cress plants exposed to citral in two different application methods: spraying and watering. Citral-sprayed and citral-watered thale cress plants showed completely different effects after treatment, suggesting that foliar or root absorption can determine the effectiveness of this compound. This work demonstrates that citral is effective not only on seedling metabolism but also on adult plants by inhibiting growth and development altering the plant oxidative status.