Very-high-frequency oscillations in the main peak of a magnetar giant flare.

Magnetars are strongly magnetized, isolated neutron stars1-3 with magnetic fields up to around 1015 gauss, luminosities of approximately 1031-1036 ergs per second and rotation periods of about 0.3-12.0 s. Very energetic giant flares from galactic magnetars (peak luminosities of 1044-1047 ergs per second, lasting approximately 0.1 s) have been detected in hard X-rays and soft γ-rays4, and only one has been detected from outside our galaxy5. During such giant flares, quasi-periodic oscillations (QPOs) with low (less than 150 hertz) and high (greater than 500 hertz) frequencies have been observed6-9, but their statistical significance has been questioned10. High-frequency QPOs have been seen only during the tail phase of the flare9. Here we report the observation of two broad QPOs at approximately 2,132 hertz and 4,250 hertz in the main peak of a giant γ-ray flare11 in the direction of the NGC 253 galaxy12-17, disappearing after 3.5 milliseconds. The flare was detected on 15 April 2020 by the Atmosphere-Space Interactions Monitor instrument18,19 aboard the International Space Station, which was the only instrument that recorded the main burst phase (0.8-3.2 milliseconds) in the full energy range (50 × 103 to 40 × 106 electronvolts) without suffering from saturation effects such as deadtime and pile-up. Along with sudden spectral variations, these extremely high-frequency oscillations in the burst peak are a crucial component that will aid our understanding of magnetar giant flares.

Nonlinear Dynamics of Spinning Bosonic Stars: Formation and Stability.

We perform numerical evolutions of the fully nonlinear Einstein (complex, massive) Klein-Gordon and Einstein (complex) Proca systems, to assess the formation and stability of spinning bosonic stars. In the scalar (vector) case these are known as boson (Proca) stars. Firstly, we consider the formation scenario. Starting with constraint-obeying initial data, describing a dilute, axisymmetric cloud of spinning scalar or Proca field, gravitational collapse toward a spinning star occurs, via gravitational cooling. In the scalar case the formation is transient, even for a nonperturbed initial cloud; a nonaxisymmetric instability always develops ejecting all the angular momentum from the scalar star. In the Proca case, by contrast, no instability is observed and the evolutions are compatible with the formation of a spinning Proca star. Secondly, we address the stability of an existing star, a stationary solution of the field equations. In the scalar case, a nonaxisymmetric perturbation develops, collapsing the star to a spinning black hole. No such instability is found in the Proca case, where the star survives large amplitude perturbations; moreover, some excited Proca stars decay to, and remain as, fundamental states. Our analysis suggests bosonic stars have different stability properties in the scalar (vector) case, which we tentatively relate to its toroidal (spheroidal) morphology. A parallelism with instabilities of spinning fluid stars is briefly discussed.

[Hyperintense punctiform images in the white matter: a diagnostic approach]. / Imágenes puntiformes hiperintensas en la sustancia blanca: una aproximación diagnóstica.

The presence of hyperintense punctiform images in the white matter in T2 weighted magnetic resonance (MR) sequences is a very common finding and is occasionally a diagnostic challenge for the radiologist. The present article attempts, using an anatomical approach to the brain circulation, as well as from histopathology correlation studies, to simplify the task of interpreting these images from the description of the three main patterns of hyperintense punctiform images in the white matter: vascular pattern, which corresponds to microvascular lesions; perivascular pattern, which represents inflammatory disease of which the paradigm is multiple sclerosis; and a non-specific pattern, which has to be a microvascular disease. From the various semiological elements in the MR images, a predominant pattern can be determined in each case and, in this way, helps in the differential diagnosis.

Dragon 1 Protocol Manuscript: Training, Accreditation, Implementation and Safety Evaluation of Portal and Hepatic Vein Embolization (PVE/HVE) to Accelerate Future Liver Remnant (FLR) Hypertrophy.

STUDY PURPOSE: The DRAGON 1 trial aims to assess training, implementation, safety and feasibility of combined portal- and hepatic-vein embolization (PVE/HVE) to accelerate future liver remnant (FLR) hypertrophy in patients with borderline resectable colorectal cancer liver metastases. METHODS: The DRAGON 1 trial is a worldwide multicenter prospective single arm trial. The primary endpoint is a composite of the safety of PVE/HVE, 90-day mortality, and one year accrual monitoring of each participating center. Secondary endpoints include: feasibility of resection, the used PVE and HVE techniques, FLR-hypertrophy, liver function (subset of centers), overall survival, and disease-free survival. All complications after the PVE/HVE procedure are documented. Liver volumes will be measured at week 1 and if applicable at week 3 and 6 after PVE/HVE and follow-up visits will be held at 1, 3, 6, and 12 months after the resection. RESULTS: Not applicable. CONCLUSION: DRAGON 1 is a prospective trial to assess the safety and feasibility of PVE/HVE. Participating study centers will be trained, and procedures standardized using Work Instructions (WI) to prepare for the DRAGON 2 randomized controlled trial. Outcomes should reveal the accrual potential of centers, safety profile of combined PVE/HVE and the effect of FLR-hypertrophy induction by PVE/HVE in patients with CRLM and a small FLR. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04272931 (February 17, 2020). Toestingonline.nl: NL71535.068.19 (September 20, 2019).

Enhanced in vivo absorption of CB-1 antagonist in rats via solid solutions prepared by hot-melt extrusion.

The aim of the present work was to investigate in vitro dissolution properties of three binary solid solutions prepared by a hot-melt extrusion (HME) process with vinyl pirrolidone--vinyl acetate copolymer (Kollidon VA 64), ethyl acrylate, methyl methacrylate polymer (Eudragit E) polyetilenglicol 8000 (PEG 8000) with a cannabinoid type 1 (CB-1) antagonist. Hansen solubility parameters were calculated from the chemical structures of the drug and the individual polymers in order to predict miscibility. Solid state characterizations of drug substance, physical blends and HME formulations were performed with differential scanning calorimetry. The dissolution testing conducted under sink conditions revealed that the dissolution rate of HME formulations improved around 1.8-fold vs drug substance. Supersaturation dissolution study demonstrated that HME formulations composed by Eudragit E and Kollidon VA64 increased drug solubility between 30- and 35-fold, respectively comparing to the drug substance. Physical and chemical stability of formulations were studied at 40°C/75%HR with open dish during 15 days. The formulation composed by the drug and Eudragit E at 10:90 was evaluated for in vivo drug absorption in male Wistar-Hannover rats and it was found to increase CB-1 absorption threefold greater than pure drug oral suspension.

[Muscle catabolism in patients with chronic obstructive pulmonary disease]. / Catabolismo muscular en pacientes con enfermedad pulmonar obstructiva crónica.

BACKGROUND AND OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is accompanied by muscle involvement. Pseudouridine, a catabolite of RNA, has been used in other conditions to assess muscle catabolism. We have examined the excretion of pseudouridine in patients with different stages of COPDs evolution. SUBJECTS AND METHODS: We have defined four population groups: control group (without disease), chronic bronchitis group, emerging COPD group, and advanced COPD group. Pseudouridine was determined by high performance liquid chromatography, RESULTS: Pseudouridine extraction (pseudouridine/creatinine ratio) was (mean+19.9 (6.6) µmol/mmol in control group and was found to be very increased in all the patients with pulmonary condition: chronic bronchitis, 44.1 (60.75) µmol/mmol, 81.6 (56.8) µmol/mmol in emerging COPD group and 140.1 (68) µmol/mmol in advanced COPD for all the comparisons with normal subjects and among patients with lung disease). Age and gender did not affect pseudouridine excretion. CONCLUSIONS: The urinary excretion of pseudouridine is increased in chronic bronchitis and COPD and is related to disease stage. Its excretion is independent of age and gender.

Statistical control of processes applied to geometric uncertainties for CTV expansion margins determination in prostate cancer patients treated with VMAT: a prospective study in 57 patients.

PURPOSE: To study the control graphs applicability for the geometric uncertainties of VMAT treatments in prostate cancer patients, and their use to verify the hypothesis of the data obtained randomness, to apply the margins of Van Herk expression. MATERIAL AND METHODS: During the first 5 days of treatment, and then once a week, a Kv CBCT was performed, compared with the simulation CT and adjusted the displacements, to determine the inter-fraction errors. Immediately after radiation therapy, another CBCT was performed (for intra-fraction errors). With these data, the X, R position control charts have been made. The patients, not maintained the deviations within the charts control limits, were called "anomalies". Then, we compared the deviations and margins calculated with the van Herk expression for all patients and for those without anomalies. RESULTS: The margins determined show appreciable differences if there were calculated for the total set of patients or for the set of them without anomalies in the control charts. For the overall set of patients, the lateral, longitudinal, and vertical margins were 0.45 cm, 0.52 cm, 0.56 cm, while for the set of patients without anomalies were 0.29 cm, 0.35 cm, and 0.38 cm. CONCLUSIONS: The use of control charts allows tracking geometric deviations both inter and intra-fraction, variability real-time control and to detect situations in which it can change for non-random reasons, and require immediate investigation. Maintaining geometric deviations in the control state decreases the margins needed to administer a high dose to CTV in a high percentage of cancer prostate patients.

A review of the anatomy of the middle cerebral artery for the era of thrombectomy: A radiologic tool based on CT angiography and perfusion CT.

The middle cerebral artery (MCA) is one of the principal intracranial vessels. It is also the one that is most often involved in ischemic cerebrovascular disease, which accounts for a significant volume of brain imaging tests. With recent updates in the management of ischemic stroke (including intravascular treatment in increasingly distal vessels and in an increasingly widening spectrum of patients), it is becoming more important to know the details of the cerebral vascular anatomy to reach accurate diagnoses quickly and thereby improve patients' prognoses. For these reasons, we present this anatomic review of the MCA, reviewing its segments and anatomic limits, its branching patterns, and its anatomic variants. We also provide a radiologic tool based on correlations between CT angiography and perfusion CT to facilitate the identification of the points of occlusion within the branches of the MCA, taking into account its different variants.

A review of the anatomy of the middle cerebral artery for the era of thrombectomy: a radiologic tool based on CT angiography and perfusion CT. / Repaso anatómico de la arteria cerebral media en la era de la trombectomía: una herramienta radiológica basada en la angio-TC y la TC perfusión.

The middle cerebral artery (MCA) is one of the principal intracranial vessels. It is also the one that is most often involved in ischemic cerebrovascular disease, which accounts for a significant volume of brain imaging tests. With recent updates in the management of ischemic stroke (including intravascular treatment in increasingly distal vessels and in an increasingly widening spectrum of patients), it is becoming more important to know the details of the cerebral vascular anatomy to reach accurate diagnoses quickly and thereby improve patients' prognoses. For these reasons, we present this anatomic review of the MCA, reviewing its segments and anatomic limits, its branching patterns, and its anatomic variants. We also provide a radiologic tool based on correlations between CT angiography and perfusion CT to facilitate the identification of the points of occlusion within the branches of the MCA, taking into account its different variants.

The 10-year follow-up data of the Euro-Lupus Nephritis Trial comparing low-dose and high-dose intravenous cyclophosphamide.

OBJECTIVE: To update the follow-up of the Euro-Lupus Nephritis Trial (ELNT), a randomised prospective trial comparing low-dose (LD) and high-dose (HD) intravenous (IV) cyclophosphamide (CY) followed by azathioprine (AZA) as treatment for proliferative lupus nephritis. PATIENTS AND METHODS: Data for survival and kidney function were prospectively collected during a 10-year period for the 90 patients randomised in the ELNT, except in 6 lost to follow-up. RESULTS: Death, sustained doubling of serum creatinine and end-stage renal disease rates did not differ between the LD and HD group (5/44 (11%) vs 2/46 (4%), 6/44 (14%) vs 5/46 (11%) and 2/44 (5%) vs 4/46 (9%), respectively) nor did mean serum creatinine, 24 h proteinuria and damage score at last follow-up. Most patients in both groups were still treated with glucocorticoids, other immunosuppressant agents and blood pressure lowering drugs. After 10 years of follow-up, the positive predictive value for a good outcome of an early drop in proteinuria in response to initial immunosuppressive therapy was confirmed. CONCLUSION: The data confirm that a LD IVCY regimen followed by AZA-the "Euro-Lupus regimen"-achieves good clinical results in the very long term.

[2 + 2] Photocycloaddition of 2(5H)-furanone to unsaturated compounds. insights from first principles calculations and transient-absorption measurements.

The [2 + 2] photocycloaddition reaction of 2(5H)-furanone to ethylene and acetylene has been investigated by means of DFT and CASSCF methods. In both cases, the reaction involves the formation of a triplet 1,4-biradical intermediate that evolves to the cyclobutane product after spin inversion. For acetylene, the lowest energy path in the triplet surface occurs through the (3)(pi-pi*) state of the 2(5H)-furanone. However, in the reaction with ethylene the lowest energy path in the triplet surface involves the (3)(pi-pi*) state of the alkene. Although reaction through the triplet state of olefins is usually disregarded due to the short lifetime of these species, we have experimentally measured that sensitization of ethylene triplet state can occur at typical synthetic conditions and, thus, lead to photochemical addition to the lactone.

Recovery of proteins from wastewater of tannery beamhouse operations: influence on the main pollution parameters.

The recovery of proteins from effluents of beamhouse operations in a hair-pulping process of hides is proposed. Precipitation with sulphuric acid at the isoelectric pH was chosen for protein recovery. The precipitates were characterized in order to study their potential uses. Apart from the protein nitrogen, the precipitate also contained a considerable content of fats resulting from the co-precipitation of natural fat of the hide in the wastewaters. The precipitation of the protein fraction resulted in a reduction of 80-85% of COD, whereas the protein content decreased 68-78%. This diminution of the contamination load led to a notable reduction of the tax on wastewater. The content of protein material in the precipitate varied from 15 to 44%. As expected, the protein in the precipitate did not result from the collagen decomposition of the hide but from soluble proteins such as albumin and globulin and remains of keratin. The precipitates obtained met the maximum limits of heavy metals according to legislation on organic fertilizers. The potential uses of the protein fraction recovered from tannery wastewaters are currently being investigated.

Characterizing the transient electrocardiographic signature of ischemic stress using Laplacian Eigenmaps for dimensionality reduction.

OBJECTIVE: Despite a long history of ECG-based monitoring of acute ischemia quantified by several widely used clinical markers, the diagnostic performance of these metrics is not yet satisfactory, motivating a data-driven approach to leverage underutilized information in the electrograms. This study introduces a novel metric for acute ischemia, created using a machine learning technique known as Laplacian eigenmaps (LE), and compares the diagnostic and temporal performance of the LE metric against traditional metrics. METHODS: The LE technique uses dimensionality reduction of simultaneously recorded time signals to map them into an abstract space in a manner that highlights the underlying signal behavior. To evaluate the performance of an electrogram-based LE metric compared to current standard approaches, we induced episodes of transient, acute ischemia in large animals and captured the electrocardiographic response using up to 600 electrodes within the intramural and epicardial domains. RESULTS: The LE metric generally detected ischemia earlier than all other approaches and with greater accuracy. Unlike other metrics derived from specific features of parts of the signals, the LE approach uses the entire signal and provides a data-driven strategy to identify features that reflect ischemia. CONCLUSION: The superior performance of the LE metric suggests there are underutilized features of electrograms that can be leveraged to detect the presence of acute myocardial ischemia earlier and more robustly than current methods. SIGNIFICANCE: The earlier detection capabilities of the LE metric on the epicardial surface provide compelling motivation to apply the same approach to ECGs recorded from the body surface.

EULAR points to consider for conducting clinical trials in systemic lupus erythematosus.

OBJECTIVE: Systemic lupus erythematosus (SLE) is a complex multi-organ disease, characterised by relapses and remissions. DESIGN: ng a high-quality randomised controlled trial poses many challenges. We have developed evidenced-based recommendations for points to consider in conducting clinical trials in patients with SLE. METHODS: The EULAR Task Force on SLE comprised 19 specialists and a clinical epidemiologist. Initially, the evidence for clinical trial end-points in SLE was evaluated and this has been reported separately. A consensus approach was developed by the SLE Task Force in formulating recommendations for points to consider when conducting clinical trials in SLE. RESULTS: The literature review revealed that most outcome measures used in phase 2/3 trials in SLE have not actually been validated in clinical trials, although other forms of validation have been undertaken. The final recommendations for points to consider for conducting clinical trials in SLE address the following areas: study design, eligibility criteria, outcome measures including adverse events, concomitant therapies for SLE and its complications. CONCLUSIONS: Recommendations for points to consider when conducting clinical trials in SLE were developed using an evidence-based approach followed by expert consensus. The recommendations should be disseminated, implemented and then reviewed in detail and revised using an evidence-based approach in about 5 years, by which time there will be further evidence to consider from current clinical trials.

EULAR points to consider for conducting clinical trials in systemic lupus erythematosus: literature based evidence for the selection of endpoints.

OBJECTIVE: To assess available evidence on the use of end-points (outcome measures) in clinical trials in systemic lupus erythematosus (SLE), as a part of the development of evidence-based recommendations for points to consider in clinical trials in SLE. METHODS: The European League Against Rheumatism (EULAR) Task Force on SLE comprised 19 specialists, a clinical epidemiologist and a research fellow. Key questions addressing the evidence for clinical trial end-points in SLE were compiled using the Delphi technique. A systematic search of the PubMed and Cochrane Library databases was performed using McMaster/Hedges clinical query strategies and an array of relevant terms. Evidence was categorised based on sample size and type of design, and the categories of available evidence were identified for each recommendation. The strength of recommendation was assessed based on the category of available evidence and agreement on the statements was measured across the 19 specialists. RESULTS: Eight questions were generated regarding end-points for clinical trials. The evidence to support each proposition was evaluated. The literature review revealed that most outcome measures used in phase 2/3 trials in SLE have not been formally validated in clinical trials, although some indirect validation has been undertaken. CONCLUSION: This systematic literature review forms the evidence base considered in the development of the EULAR recommendations for end-points in clinical trials in SLE.

Leaf biochemical adjustments in two Mediterranean resprouter species facing enhanced UV levels and reduced water availability before and after aerial biomass removal.

Effects of supplemented UV radiation and diminished water supply on the leaf concentrations of phenols and antioxidants of two Mediterranean resprouter species, Arbutus unedo and Quercus suber, were assessed before and after entire aerial biomass removal. Potted seedlings of both species were grown outdoors for 8 months with enhanced UV-A + UV-B, enhanced UV-A or ambient UV, in combination with two watering conditions (field capacity or watering reduction). After this period, all aerial biomass was removed and new shoots (resprouts) developed for a further 8 months under the two treatments. In general, the investment in leaf phenols was substantially greater in A. unedo than in Q. suber, while Q. suber allocated more resources to non-phenolic antioxidants (ascorbate and glutathione). In response to enhanced UV-B radiation, Q. suber leaves rose their UV-screening capacity mainly via accumulation of kaempferols, accompanied by an increased concentration of rutins, being these effects exacerbated under low-watering conditions. Conversely, A. unedo leaves responded to UV-B radiation reinforcing the antioxidant machinery by increasing the overall amount of flavonols (especially quercetins) in seedlings, and of ascorbate and glutathione, along with catalase activity, in resprouts. Nevertheless, UV effects on the amount/activity of non-phenolic antioxidants of A. unedo resprouts were modulated by water supply. Indeed, the highest concentration of glutathione was found under the combination of enhanced UV-B radiation and reduced watering, suggesting an enlargement of the antioxidant response in A. unedo resprouts. Different biochemical responses to enhanced UV and drier conditions in seedlings and resprouts of these two species might modulate their competitive interactions in the near future.

EULAR recommendations for the management of systemic lupus erythematosus. Report of a Task Force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics.

OBJECTIVE: Systemic lupus erythematosus (SLE) is a complex disease with variable presentations, course and prognosis. We sought to develop evidence-based recommendations addressing the major issues in the management of SLE. METHODS: The EULAR Task Force on SLE comprised 19 specialists and a clinical epidemiologist. Key questions for the management of SLE were compiled using the Delphi technique. A systematic search of PubMed and Cochrane Library Reports was performed using McMaster/Hedges clinical queries' strategies for questions related to the diagnosis, prognosis, monitoring and treatment of SLE. For neuropsychiatric, pregnancy and antiphospholipid syndrome questions, the search was conducted using an array of relevant terms. Evidence was categorised based on sample size and type of design, and the categories of available evidence were identified for each recommendation. The strength of recommendation was assessed based on the category of available evidence, and agreement on the statements was measured across the 19 specialists. RESULTS: Twelve questions were generated regarding the prognosis, diagnosis, monitoring and treatment of SLE, including neuropsychiatric SLE, pregnancy, the antiphospholipid syndrome and lupus nephritis. The evidence to support each proposition was evaluated and scored. After discussion and votes, the final recommendations were presented using brief statements. The average agreement among experts was 8.8 out of 10. CONCLUSION: Recommendations for the management of SLE were developed using an evidence-based approach followed by expert consensus with high level of agreement among the experts.

[Study of maternal nutrition and genetic on the foetal adiposity programming (The PREOBE study)]. / Estudio de la influencia de la nutrición y genética maternas sobre la programación del desarrollo del tejido adiposo fetal (Estudio PREOBE).

BACKGROUND: Maternal genetics and feeding before and during pregnancy, different maternal metabolic pathologies, as well as nutrient intakes of newborns in their first months of life may be involved in the obesity aetiology and its long-term consequences. The possible role of these and others factors, the mechanisms and the effects on the metabolism, and the development of this disease need further research. OBJECTIVE: To acquire more knowledge about foetal adipose tissue development and the influence of genetic, dietetic and environmental factors on the risk to suffer from obesity. METHODOLOGY: Four study groups have been established with 30 pregnant women in each one: 1) control group; 2) mothers with glucose intolerance/gestational diabetes; 3) women with low weight gain during pregnancy, and 4) women with overweight/obesity at the beginning of the pregnancy. The magnitudes to be studied are: 1) dietary intake; 2) life-style habits; 3) physical activity; 4) anthropometry and body composition; 5) haematological study; 6) biochemical study (lipid and metabolic biomarkers); 7) immune function profile related to nutritional status; 8) psychological profile; 9) genetic biomarkers, and 10) microbiological markers; all of them in relation to the development of the foetal adipose tissue in the first stages of life and the risk of suffering from obesity in the future. CONCLUSION: This project, coordinated by the Department of Paediatrics of the School of Medicine in the University of Granada, and with the collaboration of well-known and expert research groups, tries to contribute to the knowledge about the obesity aetiology in infancy and its subsequent development in later periods of life.

Zero-valent iron supported on nitrogen-doped carbon xerogel as catalysts for the oxidation of phenol by fenton-like system.

Nitrogen-free and nitrogen-doped carbon xerogel materials, from urea and melamine precursors, were prepared at different pH and evaluated as adsorbents/catalysts in the removal of phenol. Then, zero-valent iron (ZVI) was supported on these carbon xerogel materials and its activity was again evaluated for phenol removal by adsorption and catalytic wet peroxide oxidation (CWPO). The prepared samples were characterized by N2 adsorption at -196°C, pH at the point of zero charge (pHPZC) and elemental analysis. The textural properties of the N-free and N-doped carbon xerogels are strongly influenced by pH of the preparation solution and precursor used. The presence of ZVI on all carbon xerogel supports improved the phenol removal efficiency. ZVI supported on urea- and melamine-doped carbon xerogels show a good performance, reaching above 87% phenol conversion after 60 min of CWPO. On the contrary, pure adsorption and CWPO using the same materials without the presence of ZVI gives low phenol removal efficiency. A correlation was found between the activity of ZVI catalysts in CWPO and the N-content of the supports.