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High-resolution inelastic X-ray scattering is an established technique in the synchrotron community, used to investigate collective low-frequency responses of materials. When fielded at hard X-ray free-electron lasers (XFELs) and combined with high-intensity laser drivers, it becomes a promising technique for investigating matter at high temperatures and high pressures. This technique gives access to important thermodynamic properties of matter at extreme conditions, such as temperature, material sound speed, and viscosity. The successful realization of this method requires the acquisition of many identical laser-pump/X-ray-probe shots, allowing the collection of a sufficient number of photons necessary to perform quantitative analyses. Here, a 2.5-fold improvement in the energy resolution of the instrument relative to previous works at the Matter in Extreme Conditions (MEC) endstation, Linac Coherent Light Source (LCLS), and the High Energy Density (HED) instrument, European XFEL, is presented. Some aspects of the experimental design that are essential for improving the number of photons detected in each X-ray shot, making such measurements feasible, are discussed. A careful choice of the energy resolution, the X-ray beam mode provided by the XFEL, and the position of the analysers used in such experiments can provide a more than ten-fold improvement in the photometrics. The discussion is supported by experimental data on 10â µm-thick iron and 50â nm-thick gold samples collected at the MEC endstation at the LCLS, and by complementary ray-tracing simulations coupled with thermal diffuse scattering calculations.
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This corrects the article DOI: 10.1103/PhysRevLett.126.015703.
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We present results from the SPring-8 Angstrom Compact free electron LAser facility, where we used a high intensity (â¼10^{20} W/cm^{2}) x-ray pump x-ray probe scheme to observe changes in the ionic structure of silicon induced by x-ray heating of the electrons. By avoiding Laue spots in the scattering signal from a single crystalline sample, we observe a rapid rise in diffuse scattering and a transition to a disordered, liquidlike state with a structure significantly different from liquid silicon. The disordering occurs within 100 fs of irradiation, a timescale that agrees well with first principles simulations, and is faster than that predicted by purely inertial behavior, suggesting that both the phase change and disordered state reached are dominated by Coulomb forces. This method is capable of observing liquid scattering without masking signal from the ambient solid, allowing the liquid structure to be measured throughout and beyond the phase change.
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We present results for the ionic structure in hydrocarbons (polystyrene, polyethylene) that were shock compressed to pressures of up to 190 GPa, inducing rapid melting of the samples. The structure of the resulting liquid is then probed using in situ diffraction by an x-ray free electron laser beam, demonstrating the capability to obtain reliable diffraction data in a single shot, even for low-Z samples without long range order. The data agree well with ab initio simulations, validating the ability of such approaches to model mixed samples in states where complex interparticle bonds remain, and showing that simpler models are not necessarily valid. While the results clearly exclude the possibility of complete carbon-hydrogen demixing at the conditions probed, they also, in contrast to previous predictions, indicate that diffraction is not always a sufficient diagnostic for this phenomenon.
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Direct metrology of coherent short-wavelength beamlines is important for obtaining operational beam characteristics at the experimental site. However, since beam-time limitation imposes fast metrology procedures, a multi-parametric metrology from as low as a single shot is desirable. Here a two-dimensional (2D) procedure based on high-resolution Fresnel diffraction analysis is discussed and applied, which allowed an efficient and detailed beamline characterization at the SACLA XFEL. So far, the potential of Fresnel diffraction for beamline metrology has not been fully exploited because its high-frequency fringes could be only partly resolved with ordinary pixel-limited detectors. Using the high-spatial-frequency imaging capability of an irradiated LiF crystal, 2D information of the coherence degree, beam divergence and beam quality factor M2 were retrieved from simple diffraction patterns. The developed beam metrology was validated with a laboratory reference laser, and then successfully applied at a beamline facility, in agreement with the source specifications.
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We have employed fast electrons produced by intense laser illumination to isochorically heat thermal electrons in solid density carbon to temperatures of â¼10,000 K. Using time-resolved x-ray diffraction, the temperature evolution of the lattice ions is obtained through the Debye-Waller effect, and this directly relates to the electron-ion equilibration rate. This is shown to be considerably lower than predicted from ideal plasma models. We attribute this to strong ion coupling screening the electron-ion interaction.
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We present structure and equation of state (EOS) measurements of biaxially orientated polyethylene terephthalate (PET, [Formula: see text], also called mylar) shock-compressed to ([Formula: see text]) GPa and ([Formula: see text]) K using in situ X-ray diffraction, Doppler velocimetry, and optical pyrometry. Comparing to density functional theory molecular dynamics (DFT-MD) simulations, we find a highly correlated liquid at conditions differing from predictions by some equations of state tables, which underlines the influence of complex chemical interactions in this regime. EOS calculations from ab initio DFT-MD simulations and shock Hugoniot measurements of density, pressure and temperature confirm the discrepancy to these tables and present an experimentally benchmarked correction to the description of PET as an exemplary material to represent the mixture of light elements at planetary interior conditions.
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The gas and ice giants in our solar system can be seen as a natural laboratory for the physics of highly compressed matter at temperatures up to thousands of kelvins. In turn, our understanding of their structure and evolution depends critically on our ability to model such matter. One key aspect is the miscibility of the elements in their interiors. Here, we demonstrate the feasibility of X-ray Thomson scattering to quantify the degree of species separation in a 1:1 carbon-hydrogen mixture at a pressure of ~150 GPa and a temperature of ~5000 K. Our measurements provide absolute values of the structure factor that encodes the microscopic arrangement of the particles. From these data, we find a lower limit of [Formula: see text]% of the carbon atoms forming isolated carbon clusters. In principle, this procedure can be employed for investigating the miscibility behaviour of any binary mixture at the high-pressure environment of planetary interiors, in particular, for non-crystalline samples where it is difficult to obtain conclusive results from X-ray diffraction. Moreover, this method will enable unprecedented measurements of mixing/demixing kinetics in dense plasma environments, e.g., induced by chemistry or hydrodynamic instabilities.
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We investigated the high-pressure behavior of polyethylene (CH2) by probing dynamically-compressed samples with X-ray diffraction. At pressures up to 200 GPa, comparable to those present inside icy giant planets (Uranus, Neptune), shock-compressed polyethylene retains a polymer crystal structure, from which we infer the presence of significant covalent bonding. The A2/m structure which we observe has previously been seen at significantly lower pressures, and the equation of state measured agrees with our findings. This result appears to contrast with recent data from shock-compressed polystyrene (CH) at higher temperatures, which demonstrated demixing and recrystallization into a diamond lattice, implying the breaking of the original chemical bonds. As such chemical processes have significant implications for the structure and energy transfer within ice giants, our results highlight the need for a deeper understanding of the chemistry of high pressure hydrocarbons, and the importance of better constraining planetary temperature profiles.
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The state and evolution of planets, brown dwarfs and neutron star crusts is determined by the properties of dense and compressed matter. Due to the inherent difficulties in modelling strongly coupled plasmas, however, current predictions of transport coefficients differ by orders of magnitude. Collective modes are a prominent feature, whose spectra may serve as an important tool to validate theoretical predictions for dense matter. With recent advances in free electron laser technology, X-rays with small enough bandwidth have become available, allowing the investigation of the low-frequency ion modes in dense matter. Here, we present numerical predictions for these ion modes and demonstrate significant changes to their strength and dispersion if dissipative processes are included by Langevin dynamics. Notably, a strong diffusive mode around zero frequency arises, which is not present, or much weaker, in standard simulations. Our results have profound consequences in the interpretation of transport coefficients in dense plasmas.
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Impairments in fear extinction are thought to be central to the psychopathology of posttraumatic stress disorder, and endocannabinoid (eCB) signaling has been strongly implicated in extinction learning. Here we utilized the monoacylglycerol lipase inhibitor JZL184 to selectively augment brain 2-AG levels combined with an auditory cue fear-conditioning paradigm to test the hypothesis that 2-AG-mediated eCB signaling modulates short-term fear extinction learning in mice. We show that systemic JZL184 impairs short-term extinction learning in a CB1 receptor-dependent manner without affecting non-specific freezing behavior or the acquisition of conditioned fear. This effect was also observed in over-conditioned mice environmentally manipulated to re-acquire fear extinction. Cumulatively, the effects of JZL184 appear to be partly due to augmentation of 2-AG signaling in the basolateral nucleus of the amygdala (BLA), as direct microinfusion of JZL184 into the BLA produced similar results. Moreover, we elucidate a short ~3-day temporal window during which 2-AG augmentation impairs extinction behavior, suggesting a preferential role for 2-AG-mediated eCB signaling in the modulation of short-term behavioral sequelae to acute traumatic stress exposure.
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Ácidos Araquidônicos/farmacologia , Comportamento Animal/efeitos dos fármacos , Agonistas de Receptores de Canabinoides/farmacologia , Endocanabinoides/farmacologia , Extinção Psicológica/efeitos dos fármacos , Medo/efeitos dos fármacos , Glicerídeos/farmacologia , Transdução de Sinais , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
BACKGROUND: Despite the significant access and cost-saving potential of telehealth, the uptake of telehealth services in Australia has been sporadic. Understanding the factors that drive the uptake of home-telehealth services from the consumer perspective has received scant attention in the literature. AIM: The aim of this study was to explore how a comprehensive set of factors may influence the intention of older Australians to adopt home telehealth services. METHODS: A survey of 306 Australians aged between 50 and 68 years was conducted to examine the influence of six categories of predictors on the intention of older Australians to adopt home telehealth: (a) demographics, (b) health status and usage, (c) mobility and ease of access to healthcare, (d) technology usage and anxiety with technology, (e) telehealth attitudes, and (f) personality traits. RESULTS: Hierarchical regression analysis revealed that significant predictors were: trust in telehealth (ß = 0.35); the technology acceptance model (ß = 0.27); healthcare habits (ß = -0.20); dissatisfaction with traditional healthcare (ß = 0.19) and online behaviors (ß = 0.09). The model explained 63% of the variance in intention to adopt home telehealth. CONCLUSION: This study is the first of its kind in Australia and provides valuable insight into the factors which impact consumer's intention to adopt telehealth services.
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Comportamento do Consumidor/estatística & dados numéricos , Serviços de Assistência Domiciliar/estatística & dados numéricos , Telemedicina/estatística & dados numéricos , Idoso , Austrália , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Acessibilidade aos Serviços de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Fatores de Risco , População Rural/estatística & dados numéricosRESUMO
The temperate phage phi C31 is the most studied bacteriophage infecting Streptomyces spp., and has been used to develop an extensive and widely used series of cloning vectors. The sequence of 10 kb of phi C31 DNA containing most or all of the essential early genes was determined. Among the ORFs, 14 (perhaps 15) appear to be protein-coding, and these have been designated ORF1 to ORF14 and ORFX. Previously mapped transcripts appear to initiate upstream from ORFs 1, 8, 11 and 12, and within ORF3 and ORF12, in each case close to one example of the unusual ('21-mer') sequences that appear to serve as a recognition site for RNA polymerase early in the phi C31 lytic cycle [Ingham et al., Mol. Microbiol. 9 (1993) 1267-1274]. Further copies of the 21-mer are upstream from ORF2 and ORF13. There are four recognisable examples of a conserved inverted repeat sequence motif (CIR) thought to bind phi C31 repressor [Smith and Owen, Mol. Microbiol. 5 (1991) 2833-2844]. Only one CIR is closely associated with a 21-mer sequence, though three are located between known transcription units. Of all 14 ORFs, only one (ORF11) would encode a protein unmistakably resembling other known proteins; its product appears to be a DNA polymerase. Strikingly, two codons, TTA (Leu) and AGG (Arg), are absent from the 14 ORFs.
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Bacteriófagos/genética , Streptomyces , Sequência de Aminoácidos , Sequência de Bases , Códon , DNA Viral/genética , DNA Polimerase Dirigida por DNA/genética , Genes Virais , Lisogenia , Dados de Sequência Molecular , Regiões Operadoras Genéticas , Proteínas Repressoras/genética , Regiões Terminadoras Genéticas , Proteínas Estruturais Virais/genéticaRESUMO
BACKGROUND: In 1989, the gene for cystic fibrosis was cloned and it became possible to detect carriers of the gene among the general population, including pregnant women. AIM: The aim of the pilot study was to assess the acceptability of integrating cystic fibrosis carrier testing into antenatal care by general practitioners at the first booking appointment. METHOD: Between 1 September 1991 and 31 August 1992, inclusive, all patients receiving routine antenatal care in a two-partner training practice in south Manchester were offered carrier testing for cystic fibrosis using a computer protocol for antenatal care developed by the practice. A questionnaire including a Spielberger state-trait anxiety inventory was sent to patients 2 weeks after they received the results of their carrier test, and interviews with the patients in their home were carried out 4 weeks and one year after they received the result. RESULTS: All but one patient (75 out of 76) booking before 14 weeks of pregnancy accepted the offer of cystic fibrosis carrier testing, and 96% (72 out of 75) felt that they had made the right decision and that they had enough time for discussion with their general practitioner before testing. CONCLUSIONS: Cystic fibrosis carrier testing can be successfully integrated into the antenatal booking appointment in general practice and is acceptable to patients. This is a model for other genetic screening opportunities resulting from advances in medical genetics.
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Fibrose Cística/prevenção & controle , Triagem de Portadores Genéticos , Aceitação pelo Paciente de Cuidados de Saúde , Cuidado Pré-Natal/métodos , Inglaterra , Medicina de Família e Comunidade , Feminino , Testes Genéticos , Humanos , Projetos Piloto , GravidezRESUMO
Music therapists are constantly called upon to justify their work through research projects and evaluation processes. Rarely do we get the opportunity to talk personally about our work, the effects it has on us as music therapists, indeed, as human beings. This paper traces my own journey as a music therapist working with the terminally ill. Using audio extracts of music improvised with patients at the end of their lives, the concept of "attention" in music is addressed and explored. The paper will investigate: a) What is the difference between the quality of attention that is available to ourselves and our patients "in" music, as opposed to other ways of being together?; b) What does musical experience, particularly when achieved through improvisation, enable us and our patients to be that we cannot achieve in other ways?; c) Can "being in music" with another person fulfill a sense of longing that is evident in people at the end of their lives? In her book Waiting For God, Simone Weil suggests, "Those who are unhappy have no need for anything else in this world other than people capable of giving them their attention..." (1). Can the improvisation of music offer a unique and uncomplicated medium for being close?
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Musicoterapia , Cuidados Paliativos/métodos , Assistência Terminal/métodos , Adaptação Psicológica , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Relações Profissional-PacienteRESUMO
OBJECTIVE: To assess the feasibility of genetic counselling in general practice by using cystic fibrosis carrier screening at the booking appointment as an integral part of routine antenatal care and as a paradigm for the wider participation of general practitioners in medical genetics. DESIGN: Maternal testing (male partner tested only if woman screens positive) and couple testing for cystic fibrosis carrier status in the antenatal population attending one general practice and, later, in a further six (outreach) practices also. SETTING: Two partner urban training practice (pilot practice) in south Manchester, and six north west practices (two inner city, three urban, one rural dispensing). SUBJECTS: Total practice population of 50,000 (pilot practice plus six outreach practices) with an estimated 500-800 pregnancies per year. MAIN OUTCOME MEASURES: (a) Proportion of carriers of cystic fibrosis identified, counselled, and appropriately managed within the first trimester of pregnancy; (b) questionnaire and interview measures of patient satisfaction and stress. RESULTS: Eleven carriers of cystic fibrosis were detected including one carrier couple. This carrier couple, after extensive counselling, elected to have prenatal diagnosis by chorionic villus biopsy. The fetus was homozygous normal. CONCLUSIONS: General practitioners can successfully integrate genetic counselling and cystic fibrosis carrier screening into the first antenatal booking appointment. When a carrier couple is identified clinical geneticists can help with the discussion of reproductive options, and prenatal diagnosis by chorionic villus biopsy can be completed within the first trimester. The results suggest that general practitioners will have an increasingly important role in medical genetics, subject to continuing evaluation of patient acceptability and stress.
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Fibrose Cística/genética , Medicina de Família e Comunidade , Testes Genéticos/métodos , Ansiedade , Fibrose Cística/prevenção & controle , Inglaterra , Estudos de Viabilidade , Feminino , Triagem de Portadores Genéticos , Aconselhamento Genético , Humanos , Masculino , Prontuários Médicos , Satisfação do Paciente , Gravidez , Primeiro Trimestre da Gravidez , Cuidado Pré-Natal , Diagnóstico Pré-Natal , Inquéritos e QuestionáriosRESUMO
The paper of Seignot in 1961 is the first clinical description of the use of haloperidol to treat the symptoms of Gilles de la Tourette syndrome (GTS). It is widely quoted in literature about GTS. However, it is not widely known that the single case involved had been subject to a frontal lobectomy prior to treatment with haloperidol. We present a translation of that paper and a discussion of its significance.
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Haloperidol/história , Síndrome de Tourette/história , História do Século XX , HumanosRESUMO
Stress is a major risk factor for the development of mood and anxiety disorders; elucidation of novel approaches to mitigate the deleterious effects of stress could have broad clinical applications. Pharmacological augmentation of central endogenous cannabinoid (eCB) signaling may be an effective therapeutic strategy to mitigate the adverse behavioral and physiological consequences of stress. Here we show that acute foot-shock stress induces a transient anxiety state measured 24 h later using the light-dark box assay and novelty-induced hypophagia test. Acute pharmacological inhibition of the anandamide-degrading enzyme, fatty acid amide hydrolase (FAAH), reverses the stress-induced anxiety state in a cannabinoid receptor-dependent manner. FAAH inhibition does not significantly affect anxiety-like behaviors in non-stressed mice. Moreover, whole brain anandamide levels are reduced 24 h after acute foot-shock stress and are negatively correlated with anxiety-like behavioral measures in the light-dark box test. These data indicate that central anandamide levels predict acute stress-induced anxiety, and that reversal of stress-induced anandamide deficiency is a key mechanism subserving the therapeutic effects of FAAH inhibition. These studies provide further support that eCB-augmentation is a viable pharmacological strategy for the treatment of stress-related neuropsychiatric disorders.