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Long-duration γ-ray bursts (GRBs) originate from ultra-relativistic jets launched from the collapsing cores of dying massive stars. They are characterized by an initial phase of bright and highly variable radiation in the kiloelectronvolt-to-megaelectronvolt band, which is probably produced within the jet and lasts from milliseconds to minutes, known as the prompt emission1,2. Subsequently, the interaction of the jet with the surrounding medium generates shock waves that are responsible for the afterglow emission, which lasts from days to months and occurs over a broad energy range from the radio to the gigaelectronvolt bands1–6. The afterglow emission is generally well explained as synchrotron radiation emitted by electrons accelerated by the external shock7–9. Recently, intense long-lasting emission between 0.2 and 1 teraelectronvolts was observed from GRB 190114C10,11. Here we report multi-frequency observations of GRB 190114C, and study the evolution in time of the GRB emission across 17 orders of magnitude in energy, from 5 × 10−6 to 1012 electronvolts. We find that the broadband spectral energy distribution is double-peaked, with the teraelectronvolt emission constituting a distinct spectral component with power comparable to the synchrotron component. This component is associated with the afterglow and is satisfactorily explained by inverse Compton up-scattering of synchrotron photons by high-energy electrons. We find that the conditions required to account for the observed teraelectronvolt component are typical for GRBs, supporting the possibility that inverse Compton emission is commonly produced in GRBs. A multi-frequency observing campaign of the γ-ray burst GRB 190114C reveals a broadband double-peaked spectral energy distribution, and the teraelectronvolt emission could be attributed to inverse Compton scattering. [ABSTRACT FROM AUTHOR]

Long-duration γ-ray bursts (GRBs) are the most luminous sources of electromagnetic radiation known in the Universe. They arise from outflows of plasma with velocities near the speed of light that are ejected by newly formed neutron stars or black holes (of stellar mass) at cosmological distances1,2. Prompt flashes of megaelectronvolt-energy γ-rays are followed by a longer-lasting afterglow emission in a wide range of energies (from radio waves to gigaelectronvolt γ-rays), which originates from synchrotron radiation generated by energetic electrons in the accompanying shock waves3,4. Although emission of γ-rays at even higher (teraelectronvolt) energies by other radiation mechanisms has been theoretically predicted5–8, it has not been previously detected7,8. Here we report observations of teraelectronvolt emission from the γ-ray burst GRB 190114C. γ-rays were observed in the energy range 0.2–1 teraelectronvolt from about one minute after the burst (at more than 50 standard deviations in the first 20 minutes), revealing a distinct emission component of the afterglow with power comparable to that of the synchrotron component. The observed similarity in the radiated power and temporal behaviour of the teraelectronvolt and X-ray bands points to processes such as inverse Compton upscattering as the mechanism of the teraelectronvolt emission9–11. By contrast, processes such as synchrotron emission by ultrahigh-energy protons10,12,13 are not favoured because of their low radiative efficiency. These results are anticipated to be a step towards a deeper understanding of the physics of GRBs and relativistic shock waves. Observations of teraelectronvolt-energy γ-rays starting about one minute after the γ-ray burst GRB 190114C reveal a distinct component of the afterglow emission with power comparable to the synchrotron emission. [ABSTRACT FROM AUTHOR]

At least 50% of surgically resected non-functioning pituitary adenomas (NFPA) recur. Either early or late adjuvant radiotherapy is highly efficacious in controlling recurrent NFPA but associates potentially burdensome complications like hypopituitarism, vascular complications or secondary neoplasm. Reoperation is indicated in bulky tumor rests compressing the optic pathway. To date, no standardized medical therapy is available for recurrent NFPA although cabergoline and temozolomide show promising results. Guidelines on the management of recurrent NFPAs are now available. The new 2017 WHO pituitary tumor classification, based on immunohistochemistry and transcription factor assessment, identifies a group of aggressive NFPA variants that may benefit from earlier adjuvant therapy. Nevertheless, NFPA patients exhibit a reduced overall life expectancy largely due to hypopituitarism and treatment-related morbidity. The management of recurrent NFPA benefits from a multidisciplinary teamwork of surgeons, endocrinologists, radiation oncologists, ophthalmologists, pathologists and neuro-radiologists in order to provide individualized therapy and anticipate deterioration. [ABSTRACT FROM AUTHOR]

Background: Helicobacter pylori eradication therapy with a proton pump inhibitor (PPI), clarithromycin, and amoxicillin fails in >20 % of cases. A rescue therapy with PPI-amoxicillin-levofloxacin still fails in >20 % of patients. Aim: To evaluate the efficacy and tolerability of a bismuth-containing quadruple regimen in patients with two consecutive eradication failures. Methods: Prospective multicenter study of patients in whom 1st treatment with PPI-clarithromycin-amoxicillin and 2nd with PPI-amoxicillin-levofloxacin had failed. A 3rd eradication regimen with a 7- to 14-day PPI (standard dose b.i.d.), bismuth subcitrate (120 mg q.i.d. or 240 mg b.i.d.), tetracycline (from 250 mg t.i.d. to 500 mg q.i.d.) and metronidazole (from 250 mg t.i.d. to 500 mg q.i.d.). Eradication was confirmed by C-urea-breath-test 4-8 weeks after therapy. Compliance was determined through questioning and recovery of empty medication envelopes. Adverse effects were evaluated by means of a questionnaire. Results: Two hundred patients (mean age 50 years, 55 % females, 20 % peptic ulcer/80 % uninvestigated-functional dyspepsia) were initially included, and two were lost to follow-up. In all, 97 % of patients complied with the protocol. Per-protocol and intention-to-treat eradication rates were 67 % (95 % CI 60-74 %) and 65 % (58-72 %). Adverse effects were reported in 22 % of patients, the most common being nausea (12 %), abdominal pain (11 %), metallic taste (8.5 %), and diarrhea (8 %), none of them severe. Conclusion: A bismuth-containing quadruple regimen is an acceptable third-line strategy and a safe alternative after two previous H. pylori eradication failures with standard clarithromycin- and levofloxacin-containing triple therapies. [ABSTRACT FROM AUTHOR]

Sea cucumbers are conspicuous organisms inhabiting almost all marine habitats across the globe. Despite their importance as effective consumers of detritus, little is known about their behavior. We studied organic matter (OM) consumption and nocturnal movement patterns of Holothuria sanctori through indoors assays and in situ experiments at shallow bottoms off Gran Canaria Island (Canary Islands, Spain). H. sanctori has a selective feeding toward high OM concentration sediments. Consumption of OM increased with OM availability, particularly during formation of the gonads. OM consumption did not differ in situ between two adjacent habitats arranged in mosaics: macroalgal beds and urchin-grazed 'barrens.' Larger distances and fastest displacements were covered by H. sanctori during the end than the middle and start of the nighttime. Overall, we did not detect a clear 'homing' behavior by H. sanctori, yet some individuals showed a fidelity for refuges when shelter availability was lacking. [ABSTRACT FROM AUTHOR]

We show how the ultrafast laser inscription of nanodimple arrays enables near-field local enhancement in high refractive-index crystals. We first demonstrate both experimentally and numerically how, when two nanodimples are separated by intermediate distances (700-1000 nm), near-field interference can take place resulting in a near-field enhancement between nanodimples. Based on this effect, near-field enhancements close to 60% are then demonstrated at the center of nanodimple arrays, and strong optical contrasts in excess of 100% are produced. The integration of these arrays into crystal substrates provides a versatile tool for new optical trapping and evanescent-field nanosensing devices. [ABSTRACT FROM AUTHOR]

A set of fragments of metallic artefacts from the medieval period excavated from Ciudad Real in Spain has been studied. The objects are gilded copper buckles with a champlevé enamelling decoration. The composition of predominantly blue-coloured enamels has been analysed using three non-destructive techniques, SEM-EDAX (scanning electron microscopy coupled with energy-dispersive X-ray analysis), X-ray fluorescence (XRF) and PIXE (particle-induced X-ray emission). Analyses show that Co is responsible for the blue colour. The results of the two techniques are compared, as well as the main components which constitute the enamel. Analyses suggest that Cu is responsible for red colour. [ABSTRACT FROM AUTHOR]

Numerous metallic objects with very aesthetic and technological qualities have been recovered by archaeological excavations. Adequate processes of restoration and conservation treatments require the accurate determination of the elemental composition and distribution within the objects, as well as the identification of the nature and distribution of the corrosion products. Ideally the identification method should cause no alteration in the sample. In this work, different archaeological pieces with a gilded look have been characterized using simultaneously PIXE and RBS at the CMAM external microprobe in order to study the gilding metalworking done in the Iberian Peninsula during the Middle Ages. The gold layer thickness and its elemental concentrations of Ag, Au and Hg were determined by both techniques and compared with the scanning electron microscopy images obtained for some fragments of pieces. [ABSTRACT FROM AUTHOR]

Objectives: Establish new approaches for early diagnosis of dementia, based on imaging amyloid and tau pathology, cell losses and neuronal function, in subjects with mild cognitive impairment (MCI),. The overall aim is to develop effective tools for monitoring disease progression in the living patient to facilitate discovery of early therapeutic interventions to modify the course of the disease. Design: Use 2-(1-{6-[(2-1F-18]fluoroethyl) (methyl)amino]-2-naphthyl}ethylidene)malononitrile ([F-18]FDDNP) in combination with positron emission tomography (PET) to produce dynamic images for quantification of regional cortical brain deposition in MCI patients and compare them with controls subjects and patients with Alzheimer's disease (AD). Comparison with other molecular imaging probes for neuronal losses and function were also made. Setting: Patients are positioned supine in the tomograph bed with his/her head in the detector ring field. Upon injection of the molecular imaging probe (e.g., [F-18]FDDNP) images are obtained at very short time intervals for up to two hours. This results in dynamic sequences of brain distribution of the probe. Participant: Patients with clinical diagnosis of AD, MCI and control subjects. Measurements: Subjects in the categories established above were scanned with [F-18]FDDNP-PET and quantification performed using Logan parametric graphical analysis to measure relative quantitative amyloid loads throughout the brain within patient groups. These results were compared in the same patients with cell losses in hippocampus using 4-[F-18]fluoro-N-{2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl} -N-(2-pyridinyl)benzamide,([F-18]MPPF) and regional cerebral glucose metabolic rates using 2-deoxy-2-[F-18]fluoro-2-deoxy-D-glucose (2-1F-18]FDG). Results: [F-18]FDDNP reliably follows neuropathological progression (amyloid plaques [SP]; neurofibrillary tangles [NIT]) in the living brain of AD patients and those with MCI. The distribution of [F-18]FDDNP brain cortical accumulation correlates well with behavioral measures (e.g.. MMSE scores) and follows known patterns of pathological distribution observed at autopsy. We have also established conversion of controls to MCI and MCI to AD with precision and sensitivity in patients and control subjects in follow-up studies. Moreover, we have established that hemispheric cortical surface mapping of [F-18]FDDNP binding is a powerful tool for assessment and visualization of the rate of brain pathology deposition. A strong correlation of [F-18]FDDNP binding, cell losses in hippocampus and decreased glucose utilization ([F-18]FDG PET) in several neocortical regions was found in the same AD and MCI subjects. Conclusions: The combined evaluation of [F-18]FDDNP PET (targeting NIT and_SP) with neuronal losses in the hippocampus and with [F-18]FDG PET (targeting neuronal function) offers the opportunity for reliable. noninvasive detection of MCI patients at risk for AD. The approach offers a glimpse to the molecular and cellular mechanisms associated with dementia and provides a means for their assessment in the living patient. Monitoring disease progression in MCI patients demonstrates the usefulness of this imaging approach for early diagnosis and provides a means for evaluation of neuroprotective agents and drugs aimed at prevention and modification of disease progression. [ABSTRACT FROM AUTHOR]

This paper mainly aims to study the linear element influence on the estimation of vascular plant species diversity in five Mediterranean landscapes modeled as land cover patch mosaics. These landscapes have several core habitats and a different set of linear elements -habitat edges or ecotones, roads or railways, rivers, streams and hedgerows on farm land- whose plant composition were examined. Secondly, it aims to check plant diversity estimation in Mediterranean landscapes using parametric and non-parametric procedures, with two indices: Species richness and Shannon index. Land cover types and landscape linear elements were identified from aerial photographs. Their spatial information was processed using GIS techniques. Field plots were selected using a stratified sampling design according to relieve and tree density of each habitat type. A 50×20 m2 multi-scale sampling plot was designed for the core habitats and across the main landscape linear elements. Richness and diversity of plant species were estimated by comparing the observed field data to ICE (Incidence-based Coverage Estimator) and ACE (Abundance-based Coverage Estimator) non-parametric estimators. The species density, percentage of unique species, and alpha diversity per plot were significantly higher ( p < 0.05) in linear elements than in core habitats. ICE estimate of number of species was 32% higher than of ACE estimate, which did not differ significantly from the observed values. Accumulated species richness in core habitats together with linear elements, were significantly higher than those recorded only in the core habitats in all the landscapes. Conversely, Shannon diversity index did not show significant differences. [ABSTRACT FROM AUTHOR]

Approaches linking biodiversity assessment with landscape structure are necessary in the framework of sustainable rural development. The present paper describes a methodology to estimate plant diversity involving landscape structure as a proportional weight associated with different plant communities found in the landscape mosaic. The area occupied by a plant community, its patch number or its spatial distribution of patches are variables that could be expressed in gamma plant diversity of a territory. The methodology applies (1) remote sensing information, to identify land cover and land use types; (2) aspect, to discriminate composition of plant communities in each land cover type; (3) multi-scale field techniques, to asses plant diversity; (4) affinity analysis of plant community composition, to validate the stratified random sampling design and (5) the additive model that partitions gamma diversity into its alpha and beta components. The method was applied to three Spanish rural areas and was able to record 150–260 species per ha. Species richness, Shannon information index and Simpson concentration index were used to measure diversity in each area. The estimation using Shannon diversity index and the product of patch number and patch interspersion as weighting of plant community diversity was found to be the most appropriate method of measuring plant diversity at the landscape level. [ABSTRACT FROM AUTHOR]

Current gene therapy protocols often suffer from an inability to monitor the site, level and persistence of gene expression following somatic DNA delivery. Herpes simplex virus 1 thymidine kinase (HSV1-tk) is currently under intensive investigation as a reporter gene for in vivo imaging of reporter gene expression. The presence of the HSV1-tk reporter gene is repetitively and non-invasively monitored by systemic injection of positron-emitting, radionuclide-labeled thymidine analogues or acycloguanosine HSV1-TK substrates and subsequent detection, by positron emission tomography, of trapped, phosphorylated product. To improve the efficacy of the HSV1-tk PET reporter gene system, both alternative substrates and mutations in the HSV1-tk gene have been described. We used a replication defective adenovirus to deliver the HSV1-sr39tk mutant enzyme and the wild-type HSV1-tk enzyme to mice. HSV1-sr39TK demonstrates greater sensitivity than wild-type HSV1-TK enzyme in vivo, using 9-[(4-[[sup 18]F]fluoro-3-hydroxymethylbutyl)guanine as probe, following adenovirus-mediated hepatic expression in mice. Using this adenoviral delivery system, the location, magnitude and duration of HSV1-sr39tk PET reporter gene expression could be non-invasively, quantitatively and repetitively monitored for over 3 months by microPET. [ABSTRACT FROM AUTHOR]

Objective: Classic cardiovascular risk factors, such as smoking, arterial hypertension and hypercholesterolaemia, cannot explain a substantial part of the geographic differences in cardiovascular mortality. Anthropometric and nutritional factors in early stages of life may contribute to adult cardiovascular disease. Therefore, this work examines certain anthropometric variables and diet among children aged 6-7 y, living in four Spanish cities with widely differing ischaemic heart disease (IHD) mortality.Design and Setting: Cross-sectional anthropometric and dietary survey in four cities in Spain.Subjects: A total of 1112 children (50.1% males, 49.9% females) attending public and private schools in Cadiz and Murcia, cities with a relatively high IHD mortality, and Madrid and Orense, cities with a relatively low IHD mortality. A standardized method was used to measure anthropometric variables, and a food-frequency questionnaire completed by subjects' mothers, to measure diet.Outcome Measures: Body mass index (BMI), overweight (BMI>17.6 kg/m(2)), obesity (BMI>20.1 kg/m(2)) and intake of food and nutrients.Results: Children in the four cities showed a high prevalence of overweight (range across cities, 28.9-34.5%) and obesity (8.5-15.7%). They also had a moderately hypercaloric diet (range, 2078-2218 kcal/day), marked by an excessive intake of lipids (45.0-47.3% kcal), particularly saturated fats (16.6-16.9% kcal), proteins (17.0-17.3% kcal), sugars (20.0-21.9% kcal) and cholesterol (161.6-182.9 mg/1000 kcal/day), and a low intake of complex carbohydrates (17.5-18.1% kcal) and fibre (19.6-19.9 g/day). Compared with children in the two low-IHD-mortality cities, those in the two high-IHD-mortality cities had a greater BMI (mean difference, 0.61 kg/m(2); P=0.0001) and ponderal index (0.58 kg/m(3); P=0.0001) and a higher intake of energy (104 kcal/day; P=0.007), cholesterol (16.00 mg/1000 kcal/day; P=0.0001) and sodium (321 mg/day; P=0.0001). Inter-city differences in anthropometric variables remained after adjustment for birthweight.Conclusions: Intake of fats, especially saturated fats, and cholesterol should be reduced among Spanish children. It could contribute to a needed reduction of the high prevalence of overweight and obesity in children. If the differences in anthropometric variables and diet between children from the cities with high and low coronary mortality are maintained in future or continue into adulthood, this could contribute to consolidate or even increase the IHD mortality gradient across cities. The finding that differences in anthropometric variables are independent of birthweight suggests that the childhood, rather than intrauterine environment, is involved in the development of such differences.Sponsorship: This study was partly funded by grants from the International Olive Oil Board (Consejo Oleícola Internacional), Comunidad Autónoma de Madrid, Fundación Pedro Barrié de la Maza, and Fundación Eugenio Rodríguez Pascual. [ABSTRACT FROM AUTHOR]

Methods to repeatedly, non-invasively, and quantitatively image gene expression in living animals are rapidly emerging and should fundamentally change studies of gene expression in vivo. We previously developed assays utilizing positron emission tomography (PET) to image reporter gene expression. In this paper we: (1) describe a new bi-directional, tetracycline-inducible system that can be used to pharmacologically induce target gene expression and to quantitatively image induced expression by using a PET reporter gene; (2) demonstrate the potential of this system in transient and stable cell transfection assays; and (3) demonstrate the ability to repetitively and quantitatively image tetracycline and tetracycline analog induction of gene expression in living animals. We utilize the dopamine type-2 receptor (D[sub 2]R) and the mutant herpes-simplex virus type 1 thymidine kinase (HSV1-sr39tk) reporter genes to validate this system. We utilize microPET technology to show that quantitative tomographic imaging of gene induction is possible. We find a high correlation (r² = 0.98) between 'target' and reporter gene expression. This work establishes a new technique for imaging time-dependent variation of gene expression both from vectors with inducible promoters and in transgenic animals in which pharmacologic induction of gene expression must be monitored. These techniques may be applied both in gene therapy and for the study of gene expression in transgenic animals. [ABSTRACT FROM AUTHOR]

The dopamine D2 receptor (D2R) has been used in adenoviral delivery systems and in tumor ceil xenografts as an in vivo reporter gene. D2R reporter gene expression has been non-invasively, repetitively and quantitatively imaged by positron emission tomography (PET), following systemic injection of a positron-labeled ligand (3-(2'-[[sup 18]F]-fluoroethyl)spiperone; FESP) and subsequent D2R-dependent sequestration. However, dopamine binding to the D2R can modulate cyclic AMP levels. For optimal utilization of D2R as a reporter gene, it is important to uncouple ligand-binding from Gi-protein-mediated inhibition of cAMP production. Mutation of Asp80 or Ser194 produces D2Rs that still bind [³H]spiperone in transfected cells. The D2R80A mutation completely eliminates the ability of the D2R to suppress forskolin-stimulated cAMP accumulation in response to dopamine, in cells transfected with a D2R80A expression plasmid and in cells infected with replication-defective adenovirus expressing D2R8OA. The D2R194A mutation substantially reduces, but does not completely eliminate, dopamine modulation of cAMP levels. Cultured cells infected with adenoviruses expressing D2R and D2R80A demonstrated equivalent [³H]spiperone binding activity. Moreover, hepatic FESP sequestration is equivalent, following intravenous injection of adenoviruses expressing D2R and D2R80A. The D2R80A mutant, which can no longer modulate cAMP levels following ligand binding, has full capability as a PET reporter gene. [ABSTRACT FROM AUTHOR]

Biodistribution, magnitude and duration of a therapeutic transgene's expression may be assessed by linking it to the expression of a positron emission tomography (PET) reporter gene (PRG) and then imaging the PRG's expression by a PET reporter probe (PRP) in living animals. We validate the simple approach of co-administering two distinct but otherwise identical adenoviruses, one expressing a therapeutic transgene and the other expressing the PRG, to track the therapeutic gene's expression. Two PET reporter genes, a mutant herpes simplex virus type 1 thymidine kinase (HSV1-sr39tk) and dopamine-2 receptor (D[sub 2]R), each regulated by the same cytomegalovirus (CMV) promoter, have been inserted into separate adenoviral vectors (Ad). We demonstrate that cells co-infected with equivalent titers of Ad-CMV-HSV1sr39tk and Ad-CMV-D[sub 2]R express both reporter genes with good correlation (r² = 0.93). Similarly, a high correlation (r² = 0.97) was observed between the expression of both PRGs in the rivers of mice co-infected via tail-vein injection with equivalent titers of these two adenoviruses. Finally, microPET imaging of HSV1-sr39tk and D2R expression with 9-(4-[[sup 18]F]fluoro-3hydroxymethylbutyl) guanine ([[sup 18]F]FHBG) and 3-(2[[sup 18]F]fiuoroethyl)spiperone ([[sup 18]F]FESP), utilizing several adenovirus-mediated delivery routes, illustrates the feasibility of evaluating relative levels of transgene expression in riving animals, using this approach. [ABSTRACT FROM AUTHOR]

Arctostaphylos uva-ursi uses vegetative resprouting to recover rapidly after disturbances. This study aims to widen knowledge of its regeneration response, so it was subjected to experimental cutting and burning. Fifteen pairs of small circular plots (50 cm diameter) were situated at random in an area where this species is abundant and forms homogeneous carpets with close to 100% cover. One plot of each pair was burned and the other one was cut. Initial biomass was estimated as dry weight from the cut plots. A 50 cm diameter circular sampling quadrat, divided into two concentric circles, was used in order to determine cover recovery and the way in which this occurred (predominantly by colonization from outside or uniformly over the whole surface). Initial recovery was very fast after both disturbances, exceeding 30% cover from the fourth month. Recovery of aboveground biomass was also similar on comparing both types of disturbance, but statistically significant differences with respect to initial values were detected. [ABSTRACT FROM AUTHOR]

Reporter genes (eg β-galactosidase, chloramphenicol-acetyltransferase, green fluorescent protein, luciferase) play critical roles in investigating mechanisms of gene expression in transgenic animals and in developing gene delivery systems for gene therapy. However, measuring expression of these reporter genes requires biopsy or death. We now report a procedure to image reporter gene expression repetitively and non-invasively in living animals with positron emission tomography (PET), using the dopamine type 2 receptor (D2R) as a reporter gene and 3-(2′-[18F]fluoroethyl)spiperone (FESP) as a reporter probe. We use a viral delivery system to demonstrate the ability of this PET reporter gene/PET reporter probe system to image reporter gene expression following somatic gene transfer. In mice injected intravenously with replication-deficient adenovirus carrying a D2R reporter gene, PET in vivo measures of hepatic [18F] retention are proportional to in vitro measures of hepatic FESP retention, D2R ligand binding and D2R mRNA. We use tumor-forming cells carrying a stably transfected D2R gene to demonstrate imaging of this PET reporter gene/PET reporter probe system in ‘tissues’. Tumors expressing the transfected D2R reporter gene retain substantially more FESP than control tumors. The D2R/FESP reporter gene/reporter probe system should be a valuable technique to monitor, in vivo, expression from both gene therapy vectors and transgenes. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor about fluoxetine.