A magnetar-powered X-ray transient as the aftermath of a binary neutron-star merger.

Mergers of neutron stars are known to be associated with short γ-ray bursts1-4. If the neutron-star equation of state is sufficiently stiff (that is, the pressure increases sharply as the density increases), at least some such mergers will leave behind a supramassive or even a stable neutron star that spins rapidly with a strong magnetic field5-8 (that is, a magnetar). Such a magnetar signature may have been observed in the form of the X-ray plateau that follows up to half of observed short γ-ray bursts9,10. However, it has been expected that some X-ray transients powered by binary neutron-star mergers may not be associated with a short γ-ray burst11,12. A fast X-ray transient (CDF-S XT1) was recently found to be associated with a faint host galaxy, the redshift of which is unknown13. Its X-ray and host-galaxy properties allow several possible explanations including a short γ-ray burst seen off-axis, a low-luminosity γ-ray burst at high redshift, or a tidal disruption event involving an intermediate-mass black hole and a white dwarf13. Here we report a second X-ray transient, CDF-S XT2, that is associated with a galaxy at redshift z = 0.738 (ref. 14). The measured light curve is fully consistent with the X-ray transient being powered by a millisecond magnetar. More intriguingly, CDF-S XT2 lies in the outskirts of its star-forming host galaxy with a moderate offset from the galaxy centre, as short γ-ray bursts often do15,16. The estimated event-rate density of similar X-ray transients, when corrected to the local value, is consistent with the event-rate density of binary neutron-star mergers that is robustly inferred from the detection of the gravitational-wave event GW170817.

The exceptional X-ray evolution of SN 1996cr in high resolution.

We present X-ray spectra spanning 18 yr of evolution for SN 1996cr, one of the five nearest SNe detected in the modern era. Chandra HETG exposures in 2000, 2004, and 2009 allow us to resolve spectrally the velocity profiles of Ne, Mg, Si, S, and Fe emission lines and monitor their evolution as tracers of the ejecta-circumstellar medium interaction. To explain the diversity of X-ray line profiles, we explore several possible geometrical models. Based on the highest signal-to-noise 2009 epoch, we find that a polar geometry with two distinct opening angle configurations and internal obscuration can successfully reproduce all of the observed line profiles. The best-fitting model consists of two plasma components: (1) a mildly absorbed (2 × 1021 cm-2), cooler (≈2 keV) with high Ne, Mg, Si, and S abundances associated with a wide polar interaction region (half-opening angle ≈58°); (2) a moderately absorbed (2 × 1022 cm-2), hotter (≳20 keV) plasma with high Fe abundances and strong internal obscuration associated with a narrow polar interaction region (half-opening angle ≈20°). We extend this model to seven further epochs with lower signal-to-noise ratio and/or lower spectral-resolution between 2000 and 2018, yielding several interesting trends in absorption, flux, geometry, and expansion velocity. We argue that the hotter and colder components are associated with reflected and forward shocks, respectively, at least at later epochs. We discuss the physical implications of our results and plausible explosion scenarios to understand the X-ray data of SN 1996cr.

A kilonova as the electromagnetic counterpart to a gravitational-wave source.

Gravitational waves were discovered with the detection of binary black-hole mergers and they should also be detectable from lower-mass neutron-star mergers. These are predicted to eject material rich in heavy radioactive isotopes that can power an electromagnetic signal. This signal is luminous at optical and infrared wavelengths and is called a kilonova. The gravitational-wave source GW170817 arose from a binary neutron-star merger in the nearby Universe with a relatively well confined sky position and distance estimate. Here we report observations and physical modelling of a rapidly fading electromagnetic transient in the galaxy NGC 4993, which is spatially coincident with GW170817 and with a weak, short γ-ray burst. The transient has physical parameters that broadly match the theoretical predictions of blue kilonovae from neutron-star mergers. The emitted electromagnetic radiation can be explained with an ejected mass of 0.04 ± 0.01 solar masses, with an opacity of less than 0.5 square centimetres per gram, at a velocity of 0.2 ± 0.1 times light speed. The power source is constrained to have a power-law slope of -1.2 ± 0.3, consistent with radioactive powering from r-process nuclides. (The r-process is a series of neutron capture reactions that synthesise many of the elements heavier than iron.) We identify line features in the spectra that are consistent with light r-process elements (atomic masses of 90-140). As it fades, the transient rapidly becomes red, and a higher-opacity, lanthanide-rich ejecta component may contribute to the emission. This indicates that neutron-star mergers produce gravitational waves and radioactively powered kilonovae, and are a nucleosynthetic source of the r-process elements.

X-ray and radio emission from the luminous supernova 2005kd.

SN 2005kd is among the most luminous supernovae (SNe) to be discovered at X-ray wavelengths. We have re-analysed all good angular resolution (better than 20 arcsec full width at half-maximum point spread function) archival X-ray data for SN 2005kd. The data reveal an X-ray light curve that decreases as t -1.62±0.06. Our modelling of the data suggests that the early evolution is dominated by emission from the forward shock in a high-density medium. Emission from the radiative reverse shock is absorbed by the cold dense shell formed behind the reverse shock. Our results suggest a progenitor with a mass-loss rate towards the end of its evolution of ≥4.3 × 10-4 M⊙ yr-1, for a wind velocity of 10 km s-1, at 4.0 × 1016 cm. This mass-loss rate is too high for most known stars, except perhaps hypergiant stars. A higher wind velocity would lead to a correspondingly higher mass-loss rate. A luminous blue variable star undergoing a giant eruption could potentially fulfill this requirement, but would need a high mass-loss rate lasting for several hundred years, and need to explain the plateau observed in the optical light curve. The latter could perhaps be due to the ejecta expanding in the dense circum-stellar material at relatively small radii. These observations are consistent with the fact that Type IIn SNe appear to expand into high-density and high mass-loss rate environments, and also suggest rapid variability in the wind mass-loss parameters within at least the last 5000 yr of stellar evolution prior to core-collapse.

Rapid growth of black holes in massive star-forming galaxies.

The tight relationship between the masses of black holes and galaxy spheroids in nearby galaxies implies a causal connection between the growth of these two components. Optically luminous quasars host the most prodigious accreting black holes in the Universe, and can account for greater than or approximately equal to 30 per cent of the total cosmological black-hole growth. As typical quasars are not, however, undergoing intense star formation and already host massive black holes (> 10(8)M(o), where M(o) is the solar mass), there must have been an earlier pre-quasar phase when these black holes grew (mass range approximately (10(6)-10(8))M(o)). The likely signature of this earlier stage is simultaneous black-hole growth and star formation in distant (redshift z > 1; >8 billion light years away) luminous galaxies. Here we report ultra-deep X-ray observations of distant star-forming galaxies that are bright at submillimetre wavelengths. We find that the black holes in these galaxies are growing almost continuously throughout periods of intense star formation. This activity appears to be more tightly associated with these galaxies than any other coeval galaxy populations. We show that the black-hole growth from these galaxies is consistent with that expected for the pre-quasar phase.

Effects of standard breakfast on pharmacokinetics of oral zidovudine in patients with AIDS.

The influence of a standard breakfast on the single-dose pharmacokinetics of zidovudine (AZT) after oral administration of 100 and 250 mg of AZT was studied in 27 subjects with advanced human immunodeficiency virus infection (Centers for Disease Control stage IV). Concentrations of AZT and the 5'-glucuronide metabolite (GAZT) in serum and urine were measured by a high-pressure liquid chromatographic method. Pharmacokinetic analysis was done by an open one-compartment model as well as noncompartmentally. The results were summarized as medians with 50% confidence ranges because of the high degree of interindividual variability. Peak levels in plasma were moderately reduced after administration of 100 mg AZT in the nonfasting group (1.79 mumol/liter in the fasting group [F], 1.12 mumol/liter in the group that received breakfast [B]) and were markedly reduced after administration of 250 mg AZT (6.51 mumol/liter [F], 1.79 mumol/liter [B]). The terminal half-life in plasma was prolonged almost twofold after breakfast with 100 and 250 mg of AZT (100 mg, 36.4 min [F] and 51.6 min [B]; 250 mg, 35.3 min [F] and 63.6 min [B]). Recoveries (AZT and GAZT) in urine varied with both dosages, reflecting more a problem of accounting for the metabolite GAZT in urine than a relevant difference (100 mg, 115% [F] and 76.5% [B]; 250 mg, 71% [F] and 99.4% [B]). Our data suggest that absorption of AZT in human immunodeficiency virus-infected subjects is extremely variable, with a high degree of interindividual differences. Furthermore, breakfast had a marked influence on the absorption of AZT, suggesting that the drug should be taken in a fasting state.

The 13C-urea breath test--detection of Helicobacter pylori infection in patients with partial gastrectomy.

The 13C-urea breath test (13C-UBT) for diagnosis of Helicobacter pylori (Hp) infection was evaluated in 41 patients after partial gastrectomy and was used for determination of the Hp-prevalence after two different procedures of reconstruction of the gastrointestinal tract, i.e. Billroth's II operation and Roux-en-Y anastomosis. Breath samples were taken at various time points within 30 minutes after a motility inhibiting liquid test meal with citric acid followed by 75 mg of 13C-urea. The 13CO2/12CO2-ratio (delta-value) was measured using isotope ratio mass spectrometry and the recovery of tracer in the exhaled breath was calculated (UBT-value). In all patients and in the corresponding control groups comparison of established reference methods (culture, CLO test, and Fuchsin staining) with the 4 point breath analysis for detection of Hp was investigated. In patients with partial gastrectomy, the sensitivity of the 13C-UBT to detect the presence of Hp and the negative predictive values were 100%, whereas the specificity and the positive predictive values were about 80%. In patients without gastric surgery quality control parameters were not significantly different. Hp-prevalence in postoperative patients was about 45%. All results were independent of their expression either as delta-value or as UBT-value and were not significantly different between the patients with Billroth's II operation and the patients with Roux-en-Y anastomosis. In conclusion, the 13C-UBT is a suitable method for diagnosis and therapeutic monitoring of Hp-status in patients after partial gastrectomy.

Evaluation of the 13CO2 kinetics in humans after oral application of sodium bicarbonate as a model for breath testing.

The kinetics of 13CO2 have been investigated following oral administration at five doses between 12.5 and 100 mg of 13C labelled sodium bicarbonate to 10 healthy subjects in a randomized study. Sodium bicarbonate in this study served as a model compound for carbon dioxide/bicarbonate generated in breath tests. Exhalation of 13CO2 into breath was monitored by stable isotope ratio mass spectrometry. The kinetics of 13CO2 were characterized by an apparent terminal elimination half-life of 1 h and a mean recovery of 0.630 of the dose administered. The kinetics were not dose-dependent. These results were in agreement with the findings reported previously after i.v. application of sodium bicarbonate.

The simplified 13C-urea breath test--one point analysis for detection of Helicobacter pylori infection.

A 13C-urea breath test for detection of Helicobacter pylori infection was validated in 306 patients. Breath samples (four, two or one) were taken at various time points within 30 minutes after a motility inhibiting liquid test meal with citric acid followed by 75 mg of 13C-urea. The 13CO2/12 CO2-ratio (delta-value) was measured using isotope ratio mass spectrometry and the recovery of tracer in the exhaled breath was calculated (UBT-value). In 172 patients a comparison of established reference methods (culture, CLO test, and Fuchsin staining) with the 4 point breath analysis for detection of Helicobacter pylori showed high values of quality parameters (greater than 80% for sensitivity, specificity, positive and negative predictive value), independent of expression of the results as delta-value or as UBT-value. In 134 patients a reduction of samples to one single breath sample taken 30 minutes after ingestion of the tracer showed no significant differences in the quality parameters when compared with the standard 4 point breath analysis. This indicates that the analysis of a single breath sample is suitable for detection of Helicobacter pylori status in man.

[Helicobacter pylori colonization in surgical patients]. / Untersuchungen zur Helicobacter-pylori-Besiedlung bei operierten Patienten.

The prevalence of Helicobacter pylori (HP) was examined in 387 patients undergoing endoscopy of the upper gastrointestinal tract. Of central interest was the question to which extent surgical intervention influences the colonisation of the gastric mucosa with HP. The bacillic status was appraised using double microbiological examinations, histological determination and the CLO-test. In 229 patients a 13C-urea-breath test was also carried out (sensitivity 98%). HP could be detected in 90% of all patients presenting with duodenal ulcers as well as in 70% of patients with gastric ulcers, whereas in those patients in whom a lesion of the upper gastrointestinal tract could be excluded through endoscopy. HP was found in only 27%. The prevalence of HP did not increase with age. In patients having undergone distal gastric resection due to gastric ulcers, HP was only rarely found (19%) in the mucosa in the vicinity of the anastomosis following removal of the apparently pathogenetically important antrum mucosa. There was no association between anastomosis ulcers and bacillic colonisation. Following selective proximal vagotomy in patients with duodenal ulcers, HP was found in 80% of all cases. In these patients there was also no association between recurrent ulceration and a HP-positive status. Our results describe the postoperative HP-status after different surgical procedures of ulcer therapy: whereas a distal gastric resection removes the antrum mucosa, which provides the necessary environmental milieu, the HP-colonisation rate after selective proximal vagotomy is similar to that in non-operated ulcer disease.

Helicobacter pylori infection in healthy people: a dynamic process?

Epidemiological studies using serological tests have shown that a large proportion of healthy people have antibodies against Helicobacter pylori (anti-Hp). It is uncertain whether the presence of anti-Hp indicates active infection or only past exposure to the micro-organism. In this study we determined anti-Hp with a specific enzyme linked immunosorbent assay in 100 healthy volunteers who were at the same time investigated for active H pylori infection by means of the 13C-urea breath test. Forty nine per cent had a high anti-Hp titre, but only 24% had active H pylori infection. Our study suggests that a considerable number of healthy people previously infected with H pylori have spontaneously eliminated this microorganism. We suggest that the inability of ulcer patients to eliminate H pylori may be important in the pathogenesis of peptic ulcer disease.

Decreased and variable systemic availability of zidovudine in patients with AIDS if administered with a meal.

The systemic availability of oral zidovudine has been studied in 13 patients with the acquired immunodeficiency syndrome (AIDS) dosed either fasting or with breakfast. The mean peak plasma concentration and AUC of zidovudine were significantly 2.8- and 1.4-times higher in fasting patients than in those treated during meal. In both conditions the mean half-life was about 1.5 h and the period of plasma zidovudine concentrations greater than 1 mumol.l-1 was 2 h (NS). It is concluded that if zidovudine is taken on an empty stomach, high peak plasma concentrations and decreased variation in pharmacological parameters may be expected. Whether or not this will influence toxicity and efficacy remains to be shown.

Effect of pentoxifylline on liver plasma flow in normal man.

In ten healthy, male subjects the acute effect of pentoxifylline (a methylxanthine derivative) on liver plasma flow was investigated by the extrarenal sorbitol clearance method and on cardiac output by impedance cardiography. On the placebo day liver plasma flow decreased within 4 h from 769 to 683 ml.min-1 (P less than 0.05) and on the pentoxifylline day (300 mg i.v.) it increased from 764 to 801 ml.min-1 (NS). At the end of the experiment the difference between the groups was also significant (P less than 0.05). There was no significant change in cardiac output, blood pressure or heart rate and individual changes in those values were not correlated with liver plasma flow. There was no correlation either between the plasma concentrations of pentoxifylline or its metabolites and the changes in liver plasma flow. It is concluded that, relative to the spontaneous decrease in liver plasma flow at rest on the placebo day, pentoxifylline increased splanchnic perfusion independent of any change in cardiac output.

[Galanin: a new biologically active gastrointestinal neuropeptide]. / Galanin: Ein neues biologisch aktives gastrointestinales Neuropeptid.

The 29 amino acid containing neuropeptide galanin is localized in the intrinsic nervous system of the entire gastrointestinal tract and the pancreas. It was found in man and several animal species. Molecular biology studies revealed different molecular forms of galanin in several mammalian species including man. The galanin precursor was also found. Galanin shows several potent pharmacological actions: it inhibits gastrointestinal motility in man. It also has an inhibitory effect on intestinal smooth muscle contractility of several animal species. These actions are mediated directly by opening of potassium channels and indirectly by inhibition of acetylcholine release. In addition galanin inhibits pancreatic hormone secretion (i.e. hypoinsulinemia, hyperglycemia) and partly the release of hormones localized in the gastrointestinal tract. On exocrine glands in man (salivary glands) galanin has hydrokinetic actions. The physiological role of galanin might be regulation of gastrointestinal motility, control of secretory function of intestine and a regulatory role in endocrine and exocrine gland secretion.

Galanin: hydrokinetic action on salivary glands in man.

Galanin was infused intravenously into eight healthy volunteers at a dose of 40 pmol kg-1 min-1 for 1 h to investigate the pharmacological effects of this peptide on the postprandial sialagogical response in man. Galanin significantly increased the salivary volume and the saliva output of sodium, chloride and bicarbonate compared to control saline infusion, but had no effect on the output of potassium and alpha-amylase. An increase in salivary pH was also observed. The increase in salivary volume may indicate a physiological role of galanin in the control of salivary secretion.

Inhibitory effect of galanin on postprandial gastrointestinal motility and gut hormone release in humans.

Galanin was infused intravenously in 8 healthy volunteers at a dose of 40 pmol/kg.min for 1 h to investigate the pharmacologic effects of this peptide on postprandial gastrointestinal motility and gut peptide release in humans. Galanin strongly inhibited gastrointestinal motility. Gastric emptying was significantly delayed, with the time taken to empty 50% of the gastric contents increasing from 59.0 +/- 4.8 min (control infusion) to 99.3 +/- 4.7 min (galanin infusion). Mouth-to-cecum transit time increased from 67.5 +/- 6.9 to 126.3 +/- 18.5 min. Galanin potently suppressed the initial postprandial rise in plasma concentrations of glucose, insulin, peptide tyrosine tyrosine, neurotensin, enteroglucagon, pancreatic glucagon, somatostatin, and pancreatic polypeptide, but did not change gastric inhibitory polypeptide, motilin, peptide histidine methionine, and gastrin concentrations compared with control. The results indicate that an infusion of galanin has potent effects on the gastrointestinal tract in humans. The changes in motor activity in particular suggest that the local galaninergic innervation could have an important physiologic role in the control of human gastrointestinal propulsive motor activity.

Long-acting somatostatin analog controls acid and gastrin secretion in benign, not in malignant, Zollinger-Ellison syndrome.

The long-acting somatostatin (SMS) analog, SMS 201-995 has beneficial effects on APUDomas. In two Zollinger-Ellison syndrome (ZES) patients we assessed basal acid output (BAO) and 24-h pH under SMS and compared them to controls. We also assessed total gastrin, gastrin 17, insulin, glucagon, C-peptide, and SMS by radioimmunoassay. In the benign gastrinoma, an acid-controlling action of SMS was shown, elevating the 24-h pH threshold over the pH range 1.5-5 of 55-10% compared with control. A parallel inhibition of the gastrins greater than 90% was apparent. We found no beneficial effect on gastric acid secretion and on tumor gastrin in the malignant gastrinoma despite a fourfold higher plasma SMS level. Non-tumor-related peptides were suppressed by approximately 50% and in contrast to gastrin they again reached pre-SMS levels before the next dose of the drug. We conclude that SMS is more effective in benign than in malignant gastrinomas, and may be exclusively so.

[Various effects of secretin and pentagastrin on peripheral venous blood gas analysis]. / Unterschiedliche Wirkungen von Sekretin und Pentagastrin auf die peripher-venöse Blutgasanalyse.

Until recently, vasomotor effects of gastrointestinal polypeptide hormones have been observed primarily in animal experimentation. 33 volunteers were observed to survey the influence of secretin (1 CU/bw./h) and pentagastrin (0.75 micrograms/bw/h) on peripheral blood gas concentrations and on the acid/base balance. Compared to a control group, secretin caused a significant increase in pO2 and in O2 saturation (p less than 0.05). In contrast to secretin, pentagastrin caused a significant decrease in the pO2 as well as in the O2 saturation (p less than 0.05) pCO2, pH and HCO3 were not significantly affected by either secretin or pentagastrin. These results can be interpreted as possible direct vasodilatative/constrictive as well as local metabolic effects of secretin and pentagastrin.

Localization and molecular forms of galanin in human adrenals: elevated levels in pheochromocytomas.

Galanin immunoreactivity was measured by RIA, using antibodies directed against both the non-C- and C-terminal positions of porcine galanin, in tissue extracts of normal adrenals and pheochromocytomas and also in the plasma of normal subjects and patients with pheochromocytomas. No C-terminal galanin-like immunoreactivity was detected in plasma or tissue, suggesting differences in the amino acid sequence of human compared with porcine galanin. A non-C-terminally directed antibody was, therefore, used to characterize human galanin immunoreactivity by gel permeation chromatography and reverse phase high pressure liquid chromatography and to localize it by immunocytochemistry. The galanin content of whole adrenal gland was 2.6 +/- 0.9 (+/- SEM) pmol/g (n = 5). In contrast, however, pheochromocytomas had much greater concentrations (21 +/- 2.3 pmol/g; n = 16). Gel chromatography and reverse phase high pressure liquid chromatography revealed 2 molecular forms of galanin immunoreactivity with identical elution positions in both normal adrenals and tumors. The concentration of galanin in plasma from both normal subjects and pheochromocytoma patients was below the detection limit of the assay (less than 10 pmol/liter). Using immunocytochemistry, galanin was localized to scattered cells or clusters of tumor cells in 5 of 11 pheochromocytomas and only a few chromaffin cells and cortical nerve fibers in normal adrenals.