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Water features prominently in discussions on sustainability. The recent Cape Town 'Day Zero' drought heightened fears about global cities running dry as the climate changes. During that crisis a campaign was launched to save water at schools, consisting of a basic maintenance campaign and a behavioural campaign. The former was limited to easy fixes, and the latter comprised an information campaign and an information and competition campaign. The impacts of these were assessed immediately after the interventions. This paper revisits the maintenance results by assessing the difference in responses according to affluence levels of the schools, and by evaluating the impacts one year after the campaigns. We find that the poorer schools were not able to sustain the maintenance gains, especially at the primary schools.
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Instituciones Académicas , Inseguridad Hídrica , Ciudades , Pobreza , SudáfricaRESUMEN
We report the cases of 2 patients hospitalized in our intensive care unit with confirmed coronavirus disease 2019 infection in whom brain MR imaging showed an unusual DWI pattern with nodular and ring-shaped lesions involving the periventricular and deep white matter. We discuss the possible reasons for these findings and their relationship to the infection.
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Encéfalo/diagnóstico por imagen , Encéfalo/patología , COVID-19/complicaciones , Adulto , Encéfalo/virología , Humanos , Leucoencefalopatías/diagnóstico por imagen , Leucoencefalopatías/patología , Leucoencefalopatías/virología , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Neuroimagen/métodos , Síndrome de Dificultad Respiratoria/virología , SARS-CoV-2RESUMEN
Chronic social defeat (CSD) can lead to impairments in social interaction and other behaviors that are supposed to model features of major depressive disorder (MDD). Not all animals subjected to CSD, however, develop these impairments, and maintained social interaction in some animals is widely used as a model for resilience to stress-induced mental dysfunctions. So far, animals have mainly been studied shortly (24 hours and 7 days) after CSD exposure and longitudinal development of behavioral phenotypes in individual animals has been mostly neglected. We have analyzed social interaction and novel object recognition behavior of stressed mice at different time points after CSD and have found very dynamic courses of behavior of individual animals. Instead of the two groups, resilient or susceptible, that are found at early time points our data suggest four groups with (i, ii) animals behaving resilient or susceptible at early and late time points, respectively (iii) animals that start susceptible and recover with time or (iv) animals that are resilient at early time points but develop vulnerability later on.
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Trastorno Depresivo Mayor/psicología , Susceptibilidad a Enfermedades/psicología , Relaciones Interpersonales , Resiliencia Psicológica , Estrés Psicológico/complicaciones , Agresión/psicología , Animales , Técnicas de Observación Conductual , Conducta Animal , Enfermedad Crónica/psicología , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/etiología , Modelos Animales de Enfermedad , Humanos , Estudios Longitudinales , Masculino , Ratones , Estrés Psicológico/etiología , Estrés Psicológico/psicología , Factores de TiempoRESUMEN
BACKGROUND AND PURPOSE: Transient global amnesia (TGA) is a sudden onset of anterograde and retrograde amnesia. We aimed to assess differences in terms of cortical thickness and structural brain connectome between patients with TGA (at acute and delayed postrecovery stages) and matched controls. MATERIALS AND METHODS: We report on 18 consecutive patients with TGA who underwent 3T MR imaging, including DTI and MPRAGE sequences, at the acute (mean delay postonset: 44 hours) and delayed post-recovery (mean delay: 35 days) stages. Structural connectome was assessed in patients with TGA and in 18 age- and sex-matched controls by using probabilistic fiber- tracking and segmentation of 164 cortical/subcortical structures ("nodes"). Connectivity graphs were computed and global network metrics were calculated. Network-based statistical analysis (NBS) was applied to compare patients with TGA at each stage with controls. We also compared cortical thickness between patients with TGA and healthy controls. RESULTS: Global network metrics were not altered in patients with TGA. NBS-analysis showed structural connectome alterations in patients with TGA compared with controls, in core regions involving the limbic network, with 113 nodes and 114 connections (33 left intrahemispheric, 31 right intrahemispheric, and 50 interhemispheric connections) showing significantly decreased structural connectivity (P < .05 NBS corrected, t-values ranging from 3.03 to 8.73). Lower cortical thickness compared with controls was associated with these structural alterations in patients with TGA, involving the orbitofrontal, cingulate, and inferior temporal cortices. All the abnormalities were visible at both acute and delayed postrecovery stages. CONCLUSIONS: Our preliminary study suggests there are structural abnormalities of the limbic network in patients with TGA compared with controls, including decreased structural connectivity and cortical thickness.
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Amnesia Global Transitoria/diagnóstico por imagen , Amnesia Global Transitoria/fisiopatología , Conectoma/métodos , Adulto , Anciano , Anciano de 80 o más Años , Amnesia Global Transitoria/patología , Femenino , Humanos , Interpretación de Imagen Asistida por Computador/métodos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana EdadRESUMEN
Finding reliable discrete approximations of complex systems is a key prerequisite when applying many of the most popular modeling tools. Common discretization approaches (e.g., the very popular K-means clustering) are crucially limited in terms of quality, parallelizability, and cost. We introduce a low-cost improved quality scalable probabilistic approximation (SPA) algorithm, allowing for simultaneous data-driven optimal discretization, feature selection, and prediction. We prove its optimality, parallel efficiency, and a linear scalability of iteration cost. Cross-validated applications of SPA to a range of large realistic data classification and prediction problems reveal marked cost and performance improvements. For example, SPA allows the data-driven next-day predictions of resimulated surface temperatures for Europe with the mean prediction error of 0.75°C on a common PC (being around 40% better in terms of errors and five to six orders of magnitude cheaper than with common computational instruments used by the weather services).
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The charge density wave in the high-temperature superconductor YBa2Cu3O7-x (YBCO) has two different ordering tendencies differentiated by their c-axis correlations. These correspond to ferro- (F-CDW) and antiferro- (AF-CDW) couplings between CDWs in neighbouring CuO2 bilayers. This discovery has prompted several fundamental questions: how does superconductivity adjust to two competing orders and are either of these orders responsible for the electronic reconstruction? Here we use x-ray diffraction to study YBa2Cu3O6.67 as a function of magnetic field and temperature. We show that regions with F-CDW correlations suppress superconductivity more strongly than those with AF-CDW correlations. This implies that an inhomogeneous superconducting state exists, in which some regions show a fragile form of superconductivity. By comparison of F-CDW and AF-CDW correlation lengths, it is concluded that F-CDW ordering is sufficiently long-range to modify the electronic structure. Our study thus suggests that F-CDW correlations impact both the superconducting and normal state properties of YBCO.
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Meningiomas represent about 20% of intracranial tumors. Involvement of the medial sphenoid wing includes anterior clinoid, cavernous sinus and superior orbital fissure meningiomas. Due to the proximity of these tumors to the optic nerve, typically progressive unilateral vision loss, over several months to years, is the classic clinical presentation. We report three cases of acute monocular vision loss, two transient and one permanent, ipsilateral to a sphenoid meningioma. Ophthalmological involvement with sphenoid meningiomas is most often chronic, due to interruption of axoplasmic flow and demyelination of the optic nerve by local compression. However, vascular involvement with ischemia of the optic nerve or transient low blood flow secondary to compression of the carotid branches vascularizing these structures is another possible mechanism. In our series, two patients had amaurosis fugax, and one patient had sudden, persistent visual loss in relation to acute anterior ischemic optic neuropathy on the side of the meningioma. The mean age of patients with acute visual manifestations was 62 years. These ischemic and non-compressive visual symptoms, ipsilateral to sphenoid meningiomas, are difficult to interpret. Whether these temporary visual disturbances of vascular origin should be considered an early sign of future severe or permanent visual impairment when no optic nerve compression is observed is not certain. The place of these acute visual disturbances in the therapeutic decision, particularly surgical, remains to be defined. Larger multicentric prospective studies are needed to better understand the role of local circulatory factors attributable to meningioma in the occurrence of these acute visual signs.
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Neoplasias Meníngeas/complicaciones , Meningioma/complicaciones , Neoplasias Craneales/complicaciones , Hueso Esfenoides/patología , Trastornos de la Visión/etiología , Enfermedad Aguda , Anciano , Ceguera/diagnóstico , Ceguera/etiología , Femenino , Humanos , Masculino , Neoplasias Meníngeas/diagnóstico , Meningioma/diagnóstico , Persona de Mediana Edad , Neoplasias Craneales/diagnóstico , Trastornos de la Visión/diagnósticoRESUMEN
PURPOSE: Pseudo-continuous arterial spin labeling (pCASL) is a non-invasive magnetic resonance (MR) perfusion technique. Our study aimed at estimating the diagnostic performance of the pCASL sequence in assessing the perfusion of skull base lesions both qualitatively and quantitatively and at providing cut-off values for differentiation of specific skull base lesions. METHODS: In this study 99 patients with histopathologically confirmed skull base lesions were retrospectively enrolled. Based on a pathological analysis, the lesions were classified as hypervascular and non-hypervascular. Patients were divided into two subgroups according to the anatomical origin of each lesion. The MRI study included pCASL and 3D T1-weighted fat-saturated post-contrast sequences. Of the patients seven were excluded due to technical difficulties or patient movement. The lesions were classified by two raters, blinded to the diagnosis as either hyperperfused or non-hyperperfused, based on the pCASL sequence. The normalized tumor blood flow (nTBF) of each lesion was determined. Qualitative and quantitative characteristics of hypervascular and non-hypervascular lesions were compared. RESULTS: Visual assessment enabled correct classification of 98% of the lesions to be performed. Quantitatively, we found significant differences between the nTBF values for hypervascular and non-hypervascular lesions (p < 0.001) and provided cut-off values, allowing meningioma and schwannoma to be distinguished from meningioma and adenoma. Significant differences were also found within the hypervascular group, namely, paraganglioma was more hyperperfused than meningioma (p = 0.003) or metastases (p = 0.009). CONCLUSION: The present study demonstrates the high diagnostic performance of pCASL in characterizing skull base lesions by either visual assessment or nTBF quantification. Adding the pCASL sequence to the conventional protocol of skull base assessment can be recommended.
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Imagen por Resonancia Magnética/métodos , Neoplasias de la Base del Cráneo/diagnóstico por imagen , Adenoma/irrigación sanguínea , Adenoma/diagnóstico por imagen , Adulto , Anciano , Medios de Contraste , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Neoplasias Meníngeas/diagnóstico por imagen , Meningioma/irrigación sanguínea , Meningioma/diagnóstico por imagen , Persona de Mediana Edad , Neurilemoma/irrigación sanguínea , Neurilemoma/diagnóstico por imagen , Neuroma Acústico/irrigación sanguínea , Neuroma Acústico/diagnóstico por imagen , Neoplasias Orbitales/irrigación sanguínea , Neoplasias Orbitales/diagnóstico por imagen , Neoplasias Hipofisarias/irrigación sanguínea , Neoplasias Hipofisarias/diagnóstico por imagen , Estudios Retrospectivos , Neoplasias de la Base del Cráneo/irrigación sanguínea , Neoplasias de la Base del Cráneo/clasificación , Marcadores de Spin , Hueso Temporal/diagnóstico por imagenRESUMEN
The efficient production of cold antihydrogen atoms in particle traps at CERN's Antiproton Decelerator has opened up the possibility of performing direct measurements of the Earth's gravitational acceleration on purely antimatter bodies. The goal of the AEgIS collaboration is to measure the value of g for antimatter using a pulsed source of cold antihydrogen and a Moiré deflectometer/Talbot-Lau interferometer. The same antihydrogen beam is also very well suited to measuring precisely the ground-state hyperfine splitting of the anti-atom. The antihydrogen formation mechanism chosen by AEgIS is resonant charge exchange between cold antiprotons and Rydberg positronium. A series of technical developments regarding positrons and positronium (Ps formation in a dedicated room-temperature target, spectroscopy of the n=1-3 and n=3-15 transitions in Ps, Ps formation in a target at 10 K inside the 1 T magnetic field of the experiment) as well as antiprotons (high-efficiency trapping of [Formula: see text], radial compression to sub-millimetre radii of mixed [Formula: see text] plasmas in 1 T field, high-efficiency transfer of [Formula: see text] to the antihydrogen production trap using an in-flight launch and recapture procedure) were successfully implemented. Two further critical steps that are germane mainly to charge exchange formation of antihydrogen-cooling of antiprotons and formation of a beam of antihydrogen-are being addressed in parallel. The coming of ELENA will allow, in the very near future, the number of trappable antiprotons to be increased by more than a factor of 50. For the antihydrogen production scheme chosen by AEgIS, this will be reflected in a corresponding increase of produced antihydrogen atoms, leading to a significant reduction of measurement times and providing a path towards high-precision measurements.This article is part of the Theo Murphy meeting issue 'Antiproton physics in the ELENA era'.
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BACKGROUND AND PURPOSE: The use of 3D FLAIR improves the detection of brain lesions in MS patients, but requires long acquisition times. Compressed sensing reduces acquisition time by using the sparsity of MR images to randomly undersample the k-space. Our aim was to compare the image quality and diagnostic performance of 3D-FLAIR with and without compressed sensing for the detection of multiple sclerosis lesions at 3T. MATERIALS AND METHODS: Twenty-three patients with relapsing-remitting MS underwent both conventional 3D-FLAIR and compressed sensing 3D-FLAIR on a 3T scanner (reduction in scan time 1 minute 25 seconds, 27%; compressed sensing factor of 1.3). Two blinded readers independently evaluated both conventional and compressed sensing FLAIR for image quality (SNR and contrast-to-noise ratio) and the number of MS lesions visible in the periventricular, intra-juxtacortical, infratentorial, and optic nerve regions. The volume of white matter lesions was measured with automatic postprocessing segmentation software for each FLAIR sequence. RESULTS: Image quality and the number of MS lesions detected by the readers were similar between the 2 FLAIR acquisitions (P = .74 and P = .094, respectively). Almost perfect agreement was found between both FLAIR acquisitions for total MS lesion count (Lin concordance correlation coefficient = 0.99). Agreement between conventional and compressed sensing FLAIR was almost perfect for periventricular and infratentorial lesions and substantial for intrajuxtacortical and optic nerve lesions. Postprocessing with the segmentation software did not reveal a significant difference between conventional and compressed sensing FLAIR in total MS lesion volume (P = .63) or the number of MS lesions (P = .15). CONCLUSIONS: With a compressed sensing factor of 1.3, 3D-FLAIR is 27% faster and preserves diagnostic performance for the detection of MS plaques at 3T.
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Encéfalo/diagnóstico por imagen , Interpretación de Imagen Asistida por Computador/métodos , Imagen por Resonancia Magnética/métodos , Esclerosis Múltiple Recurrente-Remitente/diagnóstico por imagen , Adulto , Encéfalo/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Recurrente-Remitente/patología , Nervio Óptico/diagnóstico por imagen , Nervio Óptico/patología , Programas InformáticosRESUMEN
Since the emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, there have been a number of clusters of human-to-human transmission. These cases of human-to-human transmission involve close contact and have occurred primarily in healthcare settings, and they are suspected to result from repeated zoonotic introductions. In this study, we sequenced whole MERS-CoV genomes directly from respiratory samples collected from 23 confirmed MERS cases in the United Arab Emirates (UAE). These samples included cases from three nosocomial and three household clusters. The sequences were analysed for changes and relatedness with regard to the collected epidemiological data and other available MERS-CoV genomic data. Sequence analysis supports the epidemiological data within the clusters, and further, suggests that these clusters emerged independently. To understand how and when these clusters emerged, respiratory samples were taken from dromedary camels, a known host of MERS-CoV, in the same geographic regions as the human clusters. Middle East respiratory syndrome coronavirus genomes from six virus-positive animals were sequenced, and these genomes were nearly identical to those found in human patients from corresponding regions. These data demonstrate a genetic link for each of these clusters to a camel and support the hypothesis that human MERS-CoV diversity results from multiple zoonotic introductions.
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Infecciones por Coronavirus/virología , Coronavirus del Síndrome Respiratorio de Oriente Medio/genética , Zoonosis/transmisión , Animales , Camelus/virología , Infecciones por Coronavirus/epidemiología , Genoma Viral , Humanos , Filogenia , Emiratos Árabes Unidos/epidemiologíaRESUMEN
The interactions that lead to the emergence of superconductivity in iron-based materials remain a subject of debate. It has been suggested that electron-electron correlations enhance electron-phonon coupling in iron selenide (FeSe) and related pnictides, but direct experimental verification has been lacking. Here we show that the electron-phonon coupling strength in FeSe can be quantified by combining two time-domain experiments into a "coherent lock-in" measurement in the terahertz regime. X-ray diffraction tracks the light-induced femtosecond coherent lattice motion at a single phonon frequency, and photoemission monitors the subsequent coherent changes in the electronic band structure. Comparison with theory reveals a strong enhancement of the coupling strength in FeSe owing to correlation effects. Given that the electron-phonon coupling affects superconductivity exponentially, this enhancement highlights the importance of the cooperative interplay between electron-electron and electron-phonon interactions.
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The existence of charge-density-wave (CDW) correlations in cuprate superconductors has now been established. However, the nature of the CDW ground state has remained uncertain because disorder and the presence of superconductivity typically limit the CDW correlation lengths to only a dozen unit cells or less. Here we explore the field-induced 3D CDW correlations in extremely pure detwinned crystals of YBa2Cu3O2 (YBCO) ortho-II and ortho-VIII at magnetic fields in excess of the resistive upper critical field ([Formula: see text]) where superconductivity is heavily suppressed. We observe that the 3D CDW is unidirectional and possesses a long in-plane correlation length as well as significant correlations between neighboring CuO2 planes. It is significant that we observe only a single sharply defined transition at a critical field proportional to [Formula: see text], given that the field range used in this investigation overlaps with other high-field experiments including quantum oscillation measurements. The correlation volume is at least two to three orders of magnitude larger than that of the zero-field CDW. This is by far the largest CDW correlation volume observed in any cuprate crystal and so is presumably representative of the high-field ground state of an "ideal" disorder-free cuprate.
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Charge density wave (CDW) correlations have been shown to universally exist in cuprate superconductors. However, their nature at high fields inferred from nuclear magnetic resonance is distinct from that measured with x-ray scattering at zero and low fields. We combined a pulsed magnet with an x-ray free-electron laser to characterize the CDW in YBa2Cu3O6.67 via x-ray scattering in fields of up to 28 tesla. While the zero-field CDW order, which develops at temperatures below ~150 kelvin, is essentially two dimensional, at lower temperature and beyond 15 tesla, another three-dimensionally ordered CDW emerges. The field-induced CDW appears around the zero-field superconducting transition temperature; in contrast, the incommensurate in-plane ordering vector is field-independent. This implies that the two forms of CDW and high-temperature superconductivity are intimately linked.
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BACKGROUND: Lung transplant recipients (LTR) are at increased risk for squamous cell carcinoma of the skin (SCC), but risk factors (RF) are incompletely understood. OBJECTIVE: To assess associations between exposure to certain medications and viral infections, and subsequent SCC development. METHODS: Retrospective study examining incidence and potential RF for SCC in LTR transplanted from 1992 to 2010 followed up at one centre. Cumulative incidence and Cox proportional hazards regression models were used to evaluate RF in the first year post-transplant for SCC formation during the follow-up. RESULTS: In 205 analysed LTR, 46 patients were diagnosed with SCC during a median follow-up of 4.9 years. The cumulative incidences of first SCC were 16.7% and 34.1%, for 5 and 10 years post-transplantation respectively. Multivariable analysis identified CMV replication (HR 7.69, 95% CI 2.93-20.2, P < 0.001) and moxifloxacin exposure (HR 2.35, 95% CI 1.15-4.81, P = 0.020) during the first year post-transplantation as independent RF for SCC development during follow-up. CONCLUSION: In our cohort, moxifloxacin use and CMV replication during the first year post-transplantation were associated with increased risk for SCC. These two factors could be indicators of over-immunosuppression. Their role in SCC development requires investigations in larger cohorts and prospective studies.
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Antibacterianos/uso terapéutico , Carcinoma de Células Escamosas/epidemiología , Infecciones por Citomegalovirus/epidemiología , Fluoroquinolonas/uso terapéutico , Trasplante de Pulmón , Neoplasias Cutáneas/epidemiología , Adulto , Carcinoma de Células Escamosas/etiología , Citomegalovirus/fisiología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Moxifloxacino , Estudios Retrospectivos , Factores de Riesgo , Neoplasias Cutáneas/etiología , Replicación ViralRESUMEN
INTRODUCTION: Defects in placental angiogenesis and spiral artery remodeling have been proposed to play essential roles in the development of preeclampsia. However, the specific molecular mechanism(s) responsible for aberrant placental angiogenesis in preeclampsia are incompletely understood. The vascular endothelial growth factor receptors (VEGFR1, R2, R3) and STAT3 have critical functions in normal blood vessel development, but their potential roles in preeclampsia are currently unclear. In this study, we utilized a novel whole mount immunofluorescence (WMIF) method to compare expression of VEGFR1, R2, R3 and activated, phosphorylated STAT3 (pSTAT3) in placentas of preeclamptic (PE) versus normotensive (NT) pregnancies. METHODS: Placental biopsies collected from NT and PE pregnant women were fixed and stained with fluorochrome-conjugated antibodies to identify specific cell populations as follows: CD31 for blood vessel endothelial cells, cytokeratin-7 for trophoblast cells, and CD45 for immune cells. Expression of the VEGFRs and pSTAT3 were subsequently characterized by WMIF in conjunction with confocal microscopy. RESULTS: A total of 18 PE and 18 NT placentas were evaluated. No significant differences in the cell type-specific expression patterns or expression levels of VEGFR1, VEGFR2 or VEGFR3 were detected between NT and PE placentas. In contrast, statistically significant increases in pSTAT3 staining were detected in endothelial cells of PE placentas versus NT controls. DISCUSSION: Our study demonstrates that increased pSTAT3 expression in placental endothelial cells is associated with PE. We speculate that elevated pSTAT3 expression in the blood vessels of PE placentas may be due to aberrant angiogenesis, increased pro-inflammatory cytokine expression, and/or placental stress.
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Placenta/metabolismo , Preeclampsia/metabolismo , Receptores de Factores de Crecimiento Endotelial Vascular/metabolismo , Factor de Transcripción STAT3/metabolismo , Estudios de Casos y Controles , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , EmbarazoRESUMEN
Ultrafast light pulses can modify electronic properties of quantum materials by perturbing the underlying, intertwined degrees of freedom. In particular, iron-based superconductors exhibit a strong coupling among electronic nematic fluctuations, spins and the lattice, serving as a playground for ultrafast manipulation. Here we use time-resolved X-ray scattering to measure the lattice dynamics of photoexcited BaFe2As2. On optical excitation, no signature of an ultrafast change of the crystal symmetry is observed, but the lattice oscillates rapidly in time due to the coherent excitation of an A1g mode that modulates the Fe-As-Fe bond angle. We directly quantify the coherent lattice dynamics and show that even a small photoinduced lattice distortion can induce notable changes in the electronic and magnetic properties. Our analysis implies that transient structural modification can be an effective tool for manipulating the electronic properties of multi-orbital systems, where electronic instabilities are sensitive to the orbital character of bands.
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The therapeutic management of brain metastases depends upon their diagnosis and characteristics. It is therefore imperative that imaging provides accurate diagnosis, identification, size and localization information of intracranial lesions in patients with presumed cerebral metastatic disease. MRI exhibits superior sensitivity to CT for small lesions identification and to evaluate their precise anatomical location. The CT-scan will be made only in case of MRI's contraindication or if MRI cannot be obtained in an acceptable delay for the management of the patient. In clinical practice, the radiologic metastasis evaluation is based on visual image analyses. Thus, a particular attention is paid to the imaging protocol with the aim to optimize the diagnosis of small lesions and to evaluate their evolution. The MRI protocol must include: 1) non-contrast T1, 2) diffusion, 3) T2* or susceptibility-weighted imaging, 4) dynamic susceptibility contrast perfusion, 5) FLAIR with contrast injection, 6) T1 with contrast injection preferentially using the 3D spin echo images. The role of the nuclear medicine imaging is still limited in the diagnosis of brain metastasis. The Tc-sestamibi brain imaging or PET with amino acid tracers can differentiate local brain metastasis recurrence from radionecrosis but still to be evaluated.
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Neoplasias Encefálicas/secundario , Diagnóstico por Imagen/métodos , Neuroimagen/métodos , Neoplasias Encefálicas/diagnóstico , Radioisótopos de Carbono , Carcinoma/epidemiología , Carcinoma/secundario , Protocolos Clínicos , Medios de Contraste/efectos adversos , Gadolinio/efectos adversos , Humanos , Enfermedades Renales/inducido químicamente , Imagen por Resonancia Magnética , Melanoma/epidemiología , Melanoma/secundario , Metionina , Tomografía de Emisión de Positrones , Radiofármacos , Tecnecio Tc 99m Sestamibi , Tomografía Computarizada por Rayos XRESUMEN
In solid organ transplant recipients, immune reconstitution inflammatory syndrome (IRIS) is a rare complication of cryptococcosis, which may require steroids in its most severe forms. Here, we report the case of a renal transplant recipient who developed severe cryptococcal meningitis-associated IRIS 1 week after immunosuppression reduction. High-dose steroids failed to improve the disease. Finally, a recombinant human monoclonal tumor necrosis factor-α (TNF-α) antagonist, adalimumab, was prescribed, and the patient rapidly experienced dramatic neurological improvement. No IRIS relapse occurred within 14 months following adalimumab discontinuation.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Criptococosis/complicaciones , Síndrome Inflamatorio de Reconstitución Inmune/tratamiento farmacológico , Síndrome Inflamatorio de Reconstitución Inmune/etiología , Trasplante de Riñón , Índice de Severidad de la Enfermedad , Receptores de Trasplantes , Adalimumab , Adulto , Antiinflamatorios/uso terapéutico , Encéfalo/patología , Femenino , Humanos , Inmunosupresores , Imagen por Resonancia Magnética , Meningitis Criptocócica/tratamiento farmacológico , Meningitis Criptocócica/etiología , Meningitis Criptocócica/patología , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
BACKGROUND: To improve the therapeutic index of whole-brain radiation therapy (WBRT) in the treatment of brain metastases (BM) from breast cancer, we investigated the efficacy and safety of WBRT combined with temozolomide (TMZ) in this population. PATIENTS AND METHODS: This phase II multicenter prospective randomized study included patients with newly diagnosed intraparenchymal BMs from breast cancer, unsuitable for surgery or radiosurgery. All patients received conformal WBRT (3 Gy × 10-30 Gy), with or without concomitant TMZ administered at a dosage of 75 mg/m(2)/day during the irradiation period. The primary end point was objective response rate (ORR) 6 weeks after the end of treatment, defined as a partial or complete response on systematic brain MRI (modified WHO criteria). Secondary end points were progression-free survival (PFS) and overall survival (OS), neurologic symptoms, and tolerability. RESULTS: Between February 2008 and November 2010, 100 patients were enrolled in the study (50 in the WBRT + TMZ arm, 50 in the WBRT arm). Median age was 55 years (29-79). Median follow-up was 9.4 months [1.0-68.1]. ORRs at 6 weeks were 36% in the WBRT arm and 30% in the WBRT + TMZ arm (NS). In the WBRT arm, median PFS was 7.4 months and median OS was 11.1 months. In the WBRT + TMZ arm, median PFS was 6.9 months and median OS was 9.4 months. Treatment was well tolerated in this arm: the most common ≥grade 2 acute toxicity was reversible lymphopenia. CONCLUSION: WBRT combined with TMZ did not significantly improve local control and survival in patients with BMs from breast cancer. CLINICALTRIALS.GOV: NCT00875355.