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SS 433 is a microquasar, a stellar binary system that launches collimated relativistic jets. We observed SS 433 in gamma rays using the High Energy Stereoscopic System (H.E.S.S.) and found an energy-dependent shift in the apparent position of the gamma-ray emission from the parsec-scale jets. These observations trace the energetic electron population and indicate that inverse Compton scattering is the emission mechanism of the gamma rays. Our modeling of the energy-dependent gamma-ray morphology constrains the location of particle acceleration and requires an abrupt deceleration of the jet flow. We infer the presence of shocks on either side of the binary system, at distances of 25 to 30 parsecs, and that self-collimation of the precessing jets forms the shocks, which then efficiently accelerate electrons.
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BACKGROUND: We aimed to study whether improvement in renal function by serelaxin in patients who were hospitalized for acute heart failure (HF) might explain any potential effect on clinical outcomes. METHODS: We included 6318 patients from the RELAXin in AHF-2 (RELAX-AHF2) study. Improvement in renal function was defined as a decrease in serum creatinine of ≥ 0.3 mg/dL and ≥ 25%, or increase in estimated glomerular filtration rate of ≥ 25% between baseline and day 2. Worsening renal function (WRF) was defined as the reverse. We performed causal mediation analyses regarding 180-day all-cause mortality (ACM), cardiovascular death (CVD), and hospitalization for HF/renal failure. RESULTS: Improvement in renal function was more frequently observed with serelaxin when compared with placebo [OR 1.88 (95% CI 1.64-2.15, p < 0.0001)], but was not associated with subsequent clinical outcomes. WRF occurred less frequent with serelaxin [OR 0.70 (95% CI 0.60-0.83, p < 0.0001)] and was associated with increased risk of ACM, worsening HF and the composite of CVD and HF or renal failure hospitalization. Improvement in renal function did not mediate the treatment effect of serelaxin [CVD HR 1.01 (0.99-1.04), ACM HR 1.01 (0.99-1.03), HF/renal failure hospitalization HR 0.99 (0.97-1.00)]. CONCLUSIONS: Despite the significant improvement in renal function by serelaxin in patients with acute HF, the potential beneficial treatment effect was not mediated by improvement in renal function. These data suggest that improvement in renal function might not be a suitable surrogate marker for potential treatment efficacy in future studies with novel relaxin agents in acute HF. Central illustration. Conceptual model explaining mediation analysis; treatment efficacy of heart failure therapies mediated by renal function.
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Insuficiencia Cardíaca , Relaxina , Insuficiencia Renal , Humanos , Enfermedad Aguda , Riñón , Proteínas Recombinantes/farmacología , Relaxina/farmacología , Insuficiencia Renal/complicaciones , Resultado del Tratamiento , Vasodilatadores/farmacologíaRESUMEN
The central region of the Milky Way is one of the foremost locations to look for dark matter (DM) signatures. We report the first results on a search for DM particle annihilation signals using new observations from an unprecedented γ-ray survey of the Galactic Center (GC) region, i.e., the Inner Galaxy Survey, at very high energies (â³100 GeV) performed with the H.E.S.S. array of five ground-based Cherenkov telescopes. No significant γ-ray excess is found in the search region of the 2014-2020 dataset and a profile likelihood ratio analysis is carried out to set exclusion limits on the annihilation cross section ⟨σv⟩. Assuming Einasto and Navarro-Frenk-White (NFW) DM density profiles at the GC, these constraints are the strongest obtained so far in the TeV DM mass range. For the Einasto profile, the constraints reach ⟨σv⟩ values of 3.7×10^{-26} cm^{3} s^{-1} for 1.5 TeV DM mass in the W^{+}W^{-} annihilation channel, and 1.2×10^{-26} cm^{3} s^{-1} for 0.7 TeV DM mass in the τ^{+}τ^{-} annihilation channel. With the H.E.S.S. Inner Galaxy Survey, ground-based γ-ray observations thus probe ⟨σv⟩ values expected from thermal-relic annihilating TeV DM particles.
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Recurrent novae are repeating thermonuclear explosions in the outer layers of white dwarfs, due to the accretion of fresh material from a binary companion. The shock generated when ejected material slams into the companion star's wind can accelerate particles. We report very-high-energy (VHE; [Formula: see text]) gamma rays from the recurrent nova RS Ophiuchi, up to 1 month after its 2021 outburst, observed using the High Energy Stereoscopic System (H.E.S.S.). The temporal profile of VHE emission is similar to that of lower-energy giga-electron volt emission, indicating a common origin, with a 2-day delay in peak flux. These observations constrain models of time-dependent particle energization, favoring a hadronic emission scenario over the leptonic alternative. Shocks in dense winds provide favorable environments for efficient acceleration of cosmic rays to very high energies.
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Gamma-ray bursts (GRBs), which are bright flashes of gamma rays from extragalactic sources followed by fading afterglow emission, are associated with stellar core collapse events. We report the detection of very-high-energy (VHE) gamma rays from the afterglow of GRB 190829A, between 4 and 56 hours after the trigger, using the High Energy Stereoscopic System (H.E.S.S.). The low luminosity and redshift of GRB 190829A reduce both internal and external absorption, allowing determination of its intrinsic energy spectrum. Between energies of 0.18 and 3.3 tera-electron volts, this spectrum is described by a power law with photon index of 2.07 ± 0.09, similar to the x-ray spectrum. The x-ray and VHE gamma-ray light curves also show similar decay profiles. These similar characteristics in the x-ray and gamma-ray bands challenge GRB afterglow emission scenarios.
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Aurorae are detected from all the magnetized planets in our Solar System, including Earth. They are powered by magnetospheric current systems that lead to the precipitation of energetic electrons into the high-latitude regions of the upper atmosphere. In the case of the gas-giant planets, these aurorae include highly polarized radio emission at kilohertz and megahertz frequencies produced by the precipitating electrons, as well as continuum and line emission in the infrared, optical, ultraviolet and X-ray parts of the spectrum, associated with the collisional excitation and heating of the hydrogen-dominated atmosphere. Here we report simultaneous radio and optical spectroscopic observations of an object at the end of the stellar main sequence, located right at the boundary between stars and brown dwarfs, from which we have detected radio and optical auroral emissions both powered by magnetospheric currents. Whereas the magnetic activity of stars like our Sun is powered by processes that occur in their lower atmospheres, these aurorae are powered by processes originating much further out in the magnetosphere of the dwarf star that couple energy into the lower atmosphere. The dissipated power is at least four orders of magnitude larger than what is produced in the Jovian magnetosphere, revealing aurorae to be a potentially ubiquitous signature of large-scale magnetospheres that can scale to luminosities far greater than those observed in our Solar System. These magnetospheric current systems may also play a part in powering some of the weather phenomena reported on brown dwarfs.
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Hospitalization for acute heart failure (AHF) is one of the burdensome aspects of 21st century medicine, leading to significant debilitating symptoms, high morbidity and mortality and consuming significant portion of the health care budget. Management of AHF is thought-provoking given the heterogeneity of the patient population, absence of a universally accepted definition, incomplete understanding of the pathophysiology and the beneficial and adverse effects of currently used therapies and lack of robust evidence-based guidelines. The article will discuss the clinical approach to the patients admitted with AHF, reviewing types of intervention (both approved and investigational) and will delineate their role and timing in specific AHF presentations. One of the challenges of AHF management is to effectively treat the subsets of patients with slow improvement or those with refractory AHF or early recurrence (worsening HF) during their initial admission. Unfortunately, the majority of these patients are at increased risk for subsequent complications and adverse outcomes. Therefore, considerable efforts in AHF management should be directed towards this population. Regretfully, to date no specific targeted therapy was proven beneficial for these patients, being one of the leading reasons for the lack of improvement in AHF outcomes over the last 30 years.
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Fármacos Cardiovasculares/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Enfermedad Aguda , Medicina Basada en la Evidencia , HumanosRESUMEN
UNLABELLED: Previously reported comparisons between cardiac output (CO) results in patients with cardiac conditions measured by thoracic impedance cardiography (TIC) versus thermodilution (TD) reveal upper and lower limits of agreement with two standard deviations (2SD) of approximately +/-2.2 l min(-1), a 44% disparity between the two technologies. We show here that if the electrodes are placed on one wrist and on a contralateral ankle instead of on the chest, a configuration designated as regional impedance cardiography (RIC), the 2SD limit of agreement between RIC and TD is +/-1.0 l min(-1), approximately 20% disparity between the two methods. To compare the performances of the TIC and RIC algorithms, the raw data of peripheral impedance changes yielded by RIC in 43 cardiac patients were used here for software processing and calculating the CO with the TIC algorithm. The 2SD between the TIC and TD was +/-1.7 l min(-1), and after annexing the correcting factors of the RIC formula to the TIC formula, the disparity between TIC and TD further declined to +/-1.25 l min(-1). CONCLUSIONS: (1) in cardiac conditions, the RIC technology is twice as accurate as TIC; (2) the advantage of RIC is the use of peripheral rather than thoracic impedance signals, supported by correcting factors.
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Algoritmos , Gasto Cardíaco , Cardiografía de Impedancia/métodos , Diagnóstico por Computador/métodos , Programas Informáticos , Humanos , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
Studies were conducted to compare and evaluate antimicrobial susceptibility test results for enterococci obtained by six national committee disk diffusion procedures. Variations in the incidence of isolates in resistance categories and errors were associated with the use of ciprofloxacin, gentamicin, nitrofurantoin, rifampin, and teicoplanin in a number of committee procedures. Results indicate that laboratories performing disk diffusion antimicrobial susceptibility testing may have problems correctly identifying resistance in enterococci with agents used to combat infections and that it may be difficult to compare resistance data for surveillance purposes.
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Antibacterianos/farmacología , Enterococcus faecalis/efectos de los fármacos , Enterococcus faecium/efectos de los fármacos , Infecciones por Bacterias Grampositivas/microbiología , Pruebas de Sensibilidad Microbiana , Farmacorresistencia Bacteriana , Humanos , Pruebas de Sensibilidad Microbiana/métodos , Pruebas de Sensibilidad Microbiana/normasRESUMEN
We examined a novel hypothesis that links symptoms of MI-related posttraumatic stress disorder (PTSD) to nonadherence. According to this hypothesis, patients who are traumatized by their medical illness do not take their medications as prescribed. As a part of the avoidance dimension of PTSD, patients who are traumatized may avoid being reminded of the MI by not taking the medication. MI survivors were prospectively followed for 6 months to 1 year. Adherence was assessed by pill count of Captopril. Demographic variables, medical risk factors, PTSD, and other psychiatric symptom dimensions were evaluated during follow-up. One hundred two of 140 recruited patients completed follow-up. Nonadherence to Captopril was associated with poor medical outcome (r=.93, P=.006). Above-Threshold PTSD symptoms were associated with nonadherence to medications (P=.05). No other psychiatric symptom dimensions were independently associated with nonadherence. Nonadherence to medications predicts adverse outcome during the first year after an acute MI. Nonadherence is associated with PTSD symptoms, which may either be a marker for or a cause of nonadherence. Treatment of PTSD may prove to be a useful approach for improving adherence.
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Infarto del Miocardio/psicología , Infarto del Miocardio/terapia , Cooperación del Paciente/estadística & datos numéricos , Trastornos por Estrés Postraumático/diagnóstico , Sobrevivientes/estadística & datos numéricos , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/mortalidad , Estudios Prospectivos , Trastornos por Estrés Postraumático/psicología , Tasa de SupervivenciaRESUMEN
BACKGROUND: Endothelin-1, a potent vasoconstrictor, is elevated in congestive heart failure and is postulated to play a major role in the pathogenesis of the disease. Endothelin receptor antagonism may be a specific therapeutic approach. This study was designed to determine the effective dosage range, hemodynamic effects, and tolerability of tezosentan, an intravenous dual endothelin receptor antagonist, in patients with advanced heart failure. METHODS: This randomized, double-blind, placebo-controlled multicenter trial enrolled 38 patients with symptomatic stable heart failure (New York Heart Association class III, left ventricular ejection fraction <35%) undergoing right heart catheterization. Patients were equally randomized to a 4-hour intravenous infusion of placebo or tezosentan in ascending doses (5, 20, 50, and 100 mg over 1 hour each). Angiotensin-converting enzyme inhibitors and diuretics were withheld 24hours before the study. Hemodynamics were measured during and for 4 hours after the infusion. RESULTS: Compared with placebo, tezosentan treatment produced a significant increase in cardiac index (treatment difference 0.59 L/min/m(2), P =.0001) and decreases in pulmonary and systemic vascular resistances (P =.01) without changes in heart rate. Consistently greater decreases in pulmonary capillary wedge pressure, mean right atrial pressure, and pulmonary and arterial pressures with tezosentan did not reach statistical significance. Hemodynamic changes were dose dependent with maximal effects at 20 and 50 mg per hour. Tezosentan was well tolerated. Despite increased endothelin-1 concentrations, hemodynamic rebound was not observed. CONCLUSION: Tezosentan rapidly and dose dependently improved hemodynamics. The favorable effects on cardiac index and pulmonary and systemic vascular resistances without changes in heart rate may be beneficial in the treatment of acute heart failure.
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Antagonistas de los Receptores de Endotelina , Insuficiencia Cardíaca/tratamiento farmacológico , Hemodinámica/efectos de los fármacos , Piridinas/farmacología , Piridinas/uso terapéutico , Tetrazoles/farmacología , Tetrazoles/uso terapéutico , Vasodilatadores/farmacología , Vasodilatadores/uso terapéutico , Adulto , Anciano , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Endotelina-1/sangre , Endotelina-1/efectos de los fármacos , Epinefrina/sangre , Femenino , Pruebas de Función Cardíaca/efectos de los fármacos , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Norepinefrina/sangre , Estudios Prospectivos , Piridinas/administración & dosificación , Piridinas/sangre , Tetrazoles/administración & dosificación , Tetrazoles/sangre , Vasodilatadores/administración & dosificación , Vasodilatadores/sangreRESUMEN
OBJECTIVE: This study investigated the effect of tezosentan (an intravenous endothelin-1 receptor antagonist) on vascular resistance and cardiac function and determined the dose response in patients with stable congestive heart failure (CHF) due to left ventricular systolic dysfunction. METHODS: In a double-blind fashion, tezosentan or placebo were administered in ascending doses (5, 20, 50, 100 mg h(-1)) to 38 CHF (NYHA class III) patients with ejection fraction
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Antagonistas de los Receptores de Endotelina , Insuficiencia Cardíaca/tratamiento farmacológico , Hipotensión/prevención & control , Piridinas/administración & dosificación , Tetrazoles/administración & dosificación , Adulto , Anciano , Presión Sanguínea/efectos de los fármacos , Intervalos de Confianza , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Estudios de Seguimiento , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/diagnóstico , Pruebas de Función Cardíaca , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Probabilidad , Receptores de Endotelina/administración & dosificación , Valores de Referencia , Índice de Severidad de la Enfermedad , Volumen Sistólico/efectos de los fármacos , Resultado del Tratamiento , Resistencia Vascular/efectos de los fármacosRESUMEN
Pulmonary edema is one of the most serious and life-threatening situations in emergency medicine. Lately it has become apparent that in most cases pulmonary edema is not caused by fluid accumulation but rather fluid redistribution that is directed into the lungs because of heart failure. Based on a series of recently published studies, we propose that often the pathogenesis of pulmonary edema is related to a combination of marked increase in systemic vascular resistance superimposed on insufficient systolic and diastolic myocardial functional reserve. This resistance results in increased left ventricular diastolic pressure causing increased pulmonary venous pressure, which yields a fluid shift from the intravascular compartment into the pulmonary interstitium and alveoli, inducing the syndrome of pulmonary edema. Therefore, the emphasis in treating pulmonary edema has shifted from diuretics (ie, furosemide) to vasodilators (ie, high-dose nitrates) combined with noninvasive positive airway pressure ventilation and rarely inotropes. New classes of drugs that are currently being investigated for treating decompensated heart failure such as natriuretic peptides, calcium promoters, and endothelin antagonist are also being assessed for treating pulmonary edema. This review will explore this new hypothesis put forward to explain the pathogenesis of pulmonary edema and the evolving management strategies.
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Edema Pulmonar/etiología , Edema Pulmonar/terapia , HumanosRESUMEN
The practice accreditation program of The American College of Radiology is described. Practice accreditation constitutes a facile mechanism to accomplish external quality assurance and to assess compliance with recognized standards. The process of accreditation includes critical review of each radiation therapy facility, the technical staff, all quality assurance procedures, medical physics staff, nursing and physician personnel as well as a whole host of other items, the most important of which is meticulous examination of selected patient charts. In the appendix, standards developed by the American College of Radiation Oncology, are reported.
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Acreditación/normas , Oncología por Radiación/normas , Acreditación/economía , Acreditación/estadística & datos numéricos , Honorarios y Precios , Humanos , Administración de la Práctica Médica , Oncología por Radiación/organización & administración , Sociedades Médicas/economía , Estados UnidosRESUMEN
The yeast Candida albicans is an opportunistic fungal pathogen that is capable of inducing a range of superficial and systemic diseases in the immunocompromised host. Although it displays a variety of virulence factors, one--the ability to adhere to host tissue--is considered essential in the early stages of colonisation and tissue invasion. Adherence is achieved by a combination of specific (ligand-receptor interactions) and non-specific (electrostatic charge, van der Waals forces) mechanisms which allow the yeast to attach to a wide range of tissue types and inanimate surfaces. Conventional methods for treating disease cause by C. albicans rely upon the use of antifungal drugs designed to kill the yeast or arrest its growth. An alternative approach, aimed at disrupting the adherence of the yeast to host tissue in cases of superficial infection, may have potential for controlling disease, particularly in situations where the unattached fungal cell can be removed from the affected site, either by the flushing action of the oropharynx or by the production of mucus in the vagina.
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Candida albicans/patogenicidad , Antifúngicos/farmacología , Candidiasis/tratamiento farmacológico , Adhesión Celular/efectos de los fármacos , Adhesión Celular/fisiología , Humanos , VirulenciaRESUMEN
OBJECTIVE: To determine the feasibility, safety and efficacy of bilevel positive airway ventilation (BiPAP) in the treatment of severe pulmonary edema compared to high dose nitrate therapy. BACKGROUND: Although noninvasive ventilation is increasingly used in the treatment of pulmonary edema, its efficacy has not been compared prospectively with newer treatment modalities. METHODS: We enrolled 40 consecutive patients with severe pulmonary edema (oxygen saturation <90% on room air prior to treatment). All patients received oxygen at a rate of 10 liter/min, intravenous (IV) furosemide 80 mg and IV morphine 3 mg. Thereafter patients were randomly allocated to receive 1) repeated boluses of IV isosorbide-dinitrate (ISDN) 4 mg every 4 min (n = 20), and 2) BiPAP ventilation and standard dose nitrate therapy (n = 20). Treatment was administered until oxygen saturation increased above 96% or systolic blood pressure decreased to below 110 mm Hg or by more than 30%. Patients whose conditions deteriorated despite therapy were intubated and mechanically ventilated. All treatment was delivered by mobile intensive care units prior to hospital arrival. RESULTS: Patients treated by BiPAP had significantly more adverse events. Two BiPAP treated patients died versus zero in the high dose ISDN group. Sixteen BiPAP treated patients (80%) required intubation and mechanical ventilation compared to four (20%) in the high dose ISDN group (p = 0.0004). Myocardial infarction (MI) occurred in 11 (55%) and 2 (10%) patients, respectively (p = 0.006). The combined primary end point (death, mechanical ventilation or MI) was observed in 17 (85%) versus 5 (25%) patients, respectively (p = 0.0003). After 1 h of treatment, oxygen saturation increased to 96 +/- 4% in the high dose ISDN group as compared to 89 +/- 7% in the BiPAP group (p = 0.017). Due to the significant deterioration observed in patients enrolled in the BiPAP arm, the study was prematurely terminated by the safety committee. CONCLUSIONS: High dose ISDN is safer and better than BiPAP ventilation combined with conventional therapy in patients with severe pulmonary edema.
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Dinitrato de Isosorbide/administración & dosificación , Respiración con Presión Positiva/métodos , Edema Pulmonar/terapia , Vasodilatadores/administración & dosificación , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Inyecciones Intravenosas , Dinitrato de Isosorbide/efectos adversos , Dinitrato de Isosorbide/uso terapéutico , Masculino , Oxígeno/sangre , Respiración con Presión Positiva/efectos adversos , Edema Pulmonar/sangre , Edema Pulmonar/tratamiento farmacológico , Resultado del Tratamiento , Vasodilatadores/efectos adversos , Vasodilatadores/uso terapéuticoRESUMEN
The purpose of the study was to assess the results of percutaneous transluminal coronary angioplasty (PTCA), performed with a single intravenous bolus of 2,500 U of heparin, in a nonemergency PTCA cohort. Three hundred of 341 consecutive patients (87.9%) undergoing PTCA were prospectively enrolled in the study. They received heparin, 2,500-U intravenous bolus, before PTCA, with intention of no additional heparin administration. Patient and lesion characteristics as well as PTCA results were evaluated independently by 2 physicians. Patients were followed up by structured telephone questionnaires at 1 and 6 months after PTCA. Mean activated clotting time obtained 5 minutes after heparin administration was 185+/-19 seconds (range 157 to 238). There were 3 (1%) in-hospital major adverse cardiovascular events: 2 deaths (0.66%), 1 (0.33%) Q-wave myocardial infarction. Emergency coronary surgery and stroke were not reported. Six patients (2%) experienced abrupt coronary occlusion within 14 days after PTCA, warranting repeat target vessel revascularization. Angiographic and clinical success were achieved in 96% and 93.3%, respectively. No bleeding or vascular complications were recorded. Six-month follow-up (184 patients) revealed 3 cardiac deaths (1 arrhythmic, 2 after cardiac surgery), 1 Q-wave myocardial infarction, and 9.7% repeat target vessel revascularization. This study suggests that very low doses of heparin and reduced activated clotting time target values are safe in non-emergency PTCA, and can reduce bleeding complications, hospital stay, and costs. Larger, randomized, double-blind heparin dose optimization studies need to confirm this notion.