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.

Perinatal exposure to 5-methoxytryptamine, behavioural-stress reactivity and functional response of 5-HT1A receptors in the adolescent rat.

Serotonin is involved in a wide range of physiological and patho-physiological mechanisms. In particular, 5-HT1A receptors are proposed to mediate stress-adaptation. The aim of this research was to investigate in adolescent rats: first, the consequences of perinatal exposure to 5-metoxytryptamine (5MT), a 5-HT1/5-HT2 serotonergic agonist, on behavioural-stress reactivity in elevated plus maze, open field and forced swim tests; secondly, whether the behavioural effects induced by perinatal exposure to 5MT on open field and forced swim tests were affected by the selective 5-HT1A receptor agonist LY 228729, a compound able to elicit a characteristic set of motor behaviours on these experimental models, and by the co-administration of the selective and silent 5-HT1A antagonist WAY 100635. Results indicate that a single daily injection of 5MT to, pregnant dams from gestational days 12 to 21 (1mg/kg s.c.), and to the pups from postnatal days 2 to 18 (0.5mg kg s.c.), induce in the adolescent rat offspring: an increase in the percentage of entries and time spent on the open arms in the elevated plus maze; a reduction in locomotor activity and rearing frequency, and an increase in the time spent on the central areas in the open field test; a decrease in immobility and an increase in swimming in the forced swim test. Acute administration of LY 228729 (1.5mg/kg s.c.) strongly decreases rearing frequency and increases peripheral activity in the open field test, and decreases immobility and increases swimming in the forced swim test both in perinatally vehicle and 5MT-exposed offspring. Co-administration of WAY 100635 (0.25mg/kg s.c.) abolishes the effects exerted by LY 228729. These results suggest that, in the adolescent rat, perinatal exposure to 5MT enhances the stress-related adaptive behavioural responses, presumably through a predominant action on presynaptic 5-HT1A receptors and does not deteriorate the functional response of 5-HT1A receptors to selective agonist and antagonist compounds.

Reversal of prenatal diazepam-induced deficit in a spatial-object learning task by brief, periodic maternal separation in adult rats.

In the rat, prenatal exposure to diazepam (DZ) induces a permanent reduction in GABA/BZ receptor (R) function and behavioural abnormalities. Environmental modifications during early stages of life can influence brain development and induce neurobiological and behavioural changes throughout adulthood. Indeed, a subtle, periodic, postnatal manipulation increases GABA/BZ R activity and produces facilitatory effects on neuroendocrine and behavioural responses. We here investigated the impact of prenatal treatment with DZ on learning performance in adult 3- and 8-month-old male rats and the influence of a brief, periodic maternal separation on the effects exerted by prenatal DZ exposure. Learning performance was examined employing a non-aversive spatial, visual and/or tactile task, the "Can test". Behavioural reactivity, emotional state and fear/anxiety-driven behaviour were also examined using open field (OF), acoustic startle reflex (ASR) and elevated plus-maze (EPM) tests. A single daily injection of DZ (1.5mg/kg, s.c.), over gestational days (GD) 14-20, induced, in an age-independent manner, a severe deficit in learning performance, a decrease in locomotor and explorative activity and an increase in peak amplitude in the ASR. Furthermore, anxiety-driven behaviour in EPM was disrupted. Daily maternal separation for 15 min over postnatal days 2-21 exerted opposite effects in all the paradigms examined. Prenatally DZ-exposed maternal separated rats, in contrast to respective non-separated rats, showed an improvement in learning performance, a decrease in emotionality and a normalization of the exploratory behaviour in EPM. These results suggest that a greater maternal care, induced by separation, can serve as a source for the developing brain to enhance neuronal plasticity and to prevent the behavioural abnormalities induced by prenatal DZ exposure.

A multicenter trial on interobserver and intraobserver reproducibility of segmental scoring of thallium-201 planar myocardial imaging before and after reinjection. Italian Group of Nuclear Cardiology.

UNLABELLED: Inter- and intraobserver reproducibility (R) of segmental 201Tl scores after stress (ST), redistribution (RD) and reinjection (RI) planar imaging were evaluated. METHODS: Images were examined from 396 patients with suspected coronary artery disease, demonstrated by means of post-ST imaging of at least one perfusion defect. To eliminate external sources of variability, the same gamma camera, acquisition protocol and computer software were used in this multicenter study. Thallium-201 images of the anterior, left anterior oblique and left lateral projections were obtained immediately, 4 hr after exercise and 30 min after the injection of additional 201Tl either on the same day or on a different day. The left ventricle was divided into 15 segments and evaluated by three independent observers, blinded to clinical data, according to a five-point scale. RESULTS: The R score for ST, RD and RI images, expressed as an intraclass correlation coefficient, was 0.76, 0.74 and 0.72, respectively. After averaging multiple observer scores, R increased to 0.91, 0.90 and 0.89, respectively. Individual observer measurement of the R score was 0.48, 0.51 and 0.32 for ST-RD, ST-RI and RD-RI image pairs, respectively, and multiple observer scores showed R increases to 0.74, 0.76 and 0.58. CONCLUSION: This qualitative scale reliably assesses the severity of 201Tl perfusion defects, particularly when multiple-observer scores are averaged. Individual observer change scores should be taken with great caution, especially in studies involving the visual evaluation of RD-RI image changes.

Assessment of myocardial viability after thallium-201 reinjection or rest-redistribution imaging: a multicenter study. The Italian Group of Nuclear Cardiology.

UNLABELLED: To establish the real nature of 201Tl defects in the assessment of myocardial viability (e.g., fixed versus reversible), 201Tl reinjection was evaluated in a multicenter trial involving 402 consecutive patients with ischemic heart disease and exercise 201Tl defects. METHODS: Twelve hospitals, using the same type of gamma camera and computer software, adopted one of the two most widely used reinjection protocols. In 230 patients (Group A), reinjection was performed immediately after stress-redistribution planar imaging; in 172 patients (Group B), reinjection was performed on a separate day and followed by rest-redistribution imaging. The images were interpreted by three blinded observers in a core laboratory on a five-point qualitative scale; the reproducibility in visual scoring was excellent. RESULTS: Groups A and B had a similar prevalence of myocardial segments with abnormal uptake at stress (39%, 40%), as well as with reversible (16%, 17%), partially reversible (21%, 19%) and irreversible (63%, 64%) defects at redistribution. After reinjection, 201Tl uptake improved in 27% and 36% of both partially reversible and irreversible defects in Groups A and B. No differences were found when comparing early and delayed reinjection imaging in Group B. CONCLUSION: This study confirms the validity of 201Tl reinjection in a large, unselected population, but the discordance with stress/redistribution is less than has been previously reported for both 201Tl reinjection protocols, the prevalence of improved segments after reinjection was higher with the separate day approach.

Assessment of right ventricular function in patients with congestive heart failure by echocardiographic automated boundary detection.

In patients with chronic heart failure, echocardiographic automated boundary detection (ABD) can reliably assess right ventricular function. The measurements obtained by ABD were highly reproducible, strongly correlated with radionuclide right ventricular ejection fraction, and superior to those obtained by conventional manual echocardiographic methods.

Exercise thallium scintigraphy versus high-dose dipyridamole echocardiography testing for detection of asymptomatic restenosis in patients with positive exercise tests after coronary angioplasty.

The usefulness of high-dose (< or = 0.84 mg/kg over 10 minutes) dipyridamole echocardiography testing was compared with that of exercise thallium-201 scintigraphy in detecting restenosis (> 70% lumen reduction) in 50 asymptomatic patients with ST-segment depression during maximal exercise testing 3 months after successful coronary angioplasty. Dipyridamole echocardiography testing and exercise thallium scintigraphy showed a similar sensitivity (75 vs 83%; p = NS) and specificity (90 vs 84%; p = NS) for the detection of restenoses, which occurred in 12 patients. It is concluded that dipyridamole echocardiography testing is as accurate as exercise thallium testing for the noninvasive detection of severe restenosis in patients with exercise-induced asymptomatic ST-segment depression after successful angioplasty. Furthermore, the site, extent and severity of the thallium perfusion defects during exercise are correlated to those of the dyssynergy during dipyridamole echocardiography.

Influence of the suspension of continued treatment with flurazepam and amobarbital on two discrimination learning schedules.

The authors have studied the effect of the suspension of chronic treatment with flurazepam and amobarbital on the operant behavior of rats that for the first time were in the presence of two fixed-interval discrimination schedules. With the sound discrimination schedule, the responses emitted by the treated animals had charactistics similar to those of control animals. With the temporal discrimination schedule, though it is not possible to distinguish between learning rates, modifications in the intensity of the effect (increases in lever pressing) indicate that, considering the doses, the action of flurazepam is slight and that of amobarbital clear and statistically significant.

Antidepressant and anxiolytic effects of alprazolam versus the conventional antidepressant desipramine and the anxiolytic diazepam in the forced swim test in rats.

The antidepressant and anxiolytic effects of alprazolam were compared to those of desipramine, diazepam and buspirone in the forced swim test. Subchronic alprazolam induced a reduction in immobility similar to that of desipramine in 'non-pretested' and 'pretested' rats. In 'non-pretested' rats, the anti-immobility effect of desipramine was potentiated by diazepam and alprazolam, given before subchronic desipramine, while the anti-immobility effect of subchronic alprazolam was counteracted by diazepam. Diazepam, administered before the pretest session, counteracted, 24 h later, the anti-immobility effect of subchronic desipramine and alprazolam; alprazolam counteracted the anti-immobility effect of alprazolam but not of desipramine, buspirone at the highest doses tested potentiated the anti-immobility effect of subchronic desipramine but not of alprazolam. These data provide further support for the hypothesis that the GABA/benzodiazepine/Cl complex is directly implicated in the action of antidepressants and that systems other than the GABA system are involved in the antidepressant and anxiolytic effects of alprazolam.

Effects of desipramine and alprazolam on forced swimming behaviour of adult rats exposed to prenatal diazepam.

Pregnant rats were treated with a single daily s.c. injection of diazepam (2 mg/kg) over gestation days 14-20. This treatment led to a reduction in GABA receptor complex function since adult male offspring showed a strong decrease in electrographic hippocampal responses to alprazolam and a strongly increased response to picrotoxin after intra-locus coeruleus injection of the two compounds. No difference in immobility time in the forced swimming test and in spontaneous motor activity was observed between prenatally vehicle- and diazepam-exposed offspring. Conversely, prenatal exposure to diazepam potentiated the anti-immobility effect of subchronic desipramine (10 mg/kg i.p.) and made active a dose of desipramine (5 mg/kg i.p.) that was ineffective in prenatally vehicle-exposed rats. This effect was observed only in pretested rats. Prenatal exposure to diazepam blocked the anti-immobility effect of subchronic alprazolam (15 mg/kg i.p.) in both non-pretested and pretested rats. Spontaneous motor activity was strongly reduced in all groups. These findings suggest that a persistent reduction in GABA receptor complex function, induced by prenatal exposure to diazepam, does not alter the mobility of adult progeny in the forced swimming test, but it may have consequences when drugs acting on the GABA receptor complex are used.

Antidipsogenic action of naloxone under different water deprivation conditions.

Naloxone (1 mg/Kg s.c.), in the light phase of the daily light-dark cycles during the 30 and 60 min of the test, shows an antidipsogenic effect of the same intensity in chronically water-deprived rats which drink more (+ 176% and + 162%) than the acutely water-deprived animals. In chronically water-deprived rats, the time interval from the drug introduction (5, 30, 60 and 90 min) is not critical for the intensity of the antidipsogenic action of naloxone. When water intake is controlled by a 20% variable ratio schedule that does not allow the animals to satisfy, during the session, more than 50% of their thirst, the time interval from the introduction of naloxone is critical. When the rats can drink freely for 30 min in their home-cage after they satisfied their thirst partially by means of bar-pressing, naloxone, paradoxically shows a weaker and not significant antidipsogenic action. The results and the usefulness of the behavioural test are briefly discussed.

Effects of desipramine and alprazolam in the forced swim test in rats after long-lasting termination of chronic exposure to picrotoxin and pentylenetetrazol.

Rats were treated for 5 weeks with three subconvulsant doses of picrotoxin (PTX) and pentylenetetrazol (PTZ) per week to induce a persistent reduction of the GABAA receptor function which results in chemical kindling. Fifteen days after termination of this treatment schedule, the effect of desipramine (DMI) and alprazolam (ALP) on immobility time in the forced swim test (FST) was evaluated. Chronic PTX and PTZ did not alter the immobility time. Acute PTX and PTZ reduced the immobility of rats chronically treated with vehicle but not of those exposed chronically to PTX and PTZ. Chronic PTX did not influence the anti-immobility effect of DMI, but blocked that of ALP. Chronic PTZ markedly potentiated the anti-immobility effect of DMI but blocked that of ALP. Concomitant administration of chlordiazepoxide prevented the effects of chronic PTX and PTZ. These findings suggest that a long-lasting reduction in GABAA receptor function, unlike acute reduction, does not play an important role in the mobility of rats in the FST and in the anti-immobility effect of DMI while it blocks that of ALP.

NMDA-GABA interactions in an animal model of behaviour: a gating mechanism from motivation toward psychotic-like symptoms.

We studied the effects of desipramine, alprazolam, muscimol and dizocilpine (MK-801) (alone or associated with desipramine) in the forced swimming test in rats after long-lasting termination of chronic exposure to vehicle and pentylenetetrazol. Sensitisation with pentylenetetrazol was ineffective in changing immobility time in the forced swimming test compared to vehicle treatment; pentylenetetrazol enhanced the anti-immobility effect of desipramine, abolished the anti-immobility effect of alprazolam and did not affect the anti-immobility effect of muscimol. MK-801 at the dose that did not modify immobility time in vehicle-treated rats and in pentylenetetrazol-treated animals strongly potentiated the anti-immobility effect of desipramine in pentylenetetrazol-treated rats. MK-801 in association with desipramine induced a marked hyperlocomotion and hyperexcitability, with swaying movements and oral stereotypies in pentylenetetrazol-sensitised rats. Results are considered the experimental representation of a 'gating mechanism' toward psychotic-like symptoms.

Results of treatment with sodium sulbenicillin in thirty elderly patients with acute bronchopulmonary infection.

Thirty elderly patients with acute bronchopulmonary infections were treated with intravenous sodium sulbenicillin for up to 20 days at a dose of 4-6 g/day. Clinical results were excellent in 19 cases and good in 10 cases. In one case treatment had to be discontinued due to a dermal side-effect. It is concluded that sulbenicillin is a useful therapy for acute bronchopulmonary infections in the elderly.

Theophylline serum levels unmodified by postprandial administration of a sustained-release preparation (Teonova).

The authors studied serum theophylline levels after administration of new single-dose capsules: Teonova. Special attention was paid to possible fluctuations of serum theophylline after administration of the drug following a standardized meal. For this purpose a test was carried out on eight male patients with intrinsic asthma. The patients were given a dose able to produce a serum concentration of theophylline of between 10 mcg and 20 mcg at the tenth hour after the administration. This dose was found to be 400 mg (2 tablets of 200 mg) for one patient and 600 mg (2 tablets of 300 mg) for the remaining seven. The capsules of Teonova were administered to each patient for two subsequent days at 07h00. On the first day the patients had their capsules after fasting, and on the second day after a standardized meal. The test proved that Teonova assured a satisfactory serum theophylline level throughout the 24 hours in all patients; food in no way affected the absorption kinetics of the drug. Such features make Teonova suitable for long-term theophylline therapy.

Correction of hypoxia and hypercapnia in COPD patients: effects on cerebrovascular flow.

To assess the responsiveness of cerebral blood flow to arterial carbon dioxide tension (Pa,CO2), arterial oxygen tension (Pa,O2), and pH modifications, in chronic hypercapnia, we measured middle cerebral blood flow velocity (CBFV) by transcranial Doppler ultrasound in 13 chronically hypercapnic, long-term ventilated patients with chronic obstructive pulmonary disease (COPD), in the following conditions: 1) breathing room air; 2) with oxygen supplementation; 3) during mechanical noninvasive intermittent positive pressure ventilation (nIPPV) with O2 enrichment. Under baseline conditions (room air), the CBFV was within the normal range. During oxygen administration, a statistically significant increase was obtained in Pa,O2 (6.5 +/- 0.6 vs 11.2 +/- 1.9 kPa (49.1 +/- 4.3 vs 84.3 +/- 14.6 mmHg)), without relevant variations in: CBFV (54.2 +/- 9.1 cm.s-1), Pa,CO2 (8.6 +/- 1.0 kPa (64.7 +/- 7.7 mmHg)) and hydrogen ion concentration [H+] (42.9 +/- 2.9 nM), compared to baseline values (CBFV = 52.8 +/- 10.7 cm.s-1; Pa,CO2 = (8.4 +/- 0.9 kPa (63.1 +/- 7.1 mmHg; [H+] = 41.8 +/- 2.8 nM). After nIPPV, Pa,O2 did not increase any further (10.6 +/- 1.7 kPa (79.2 +/- 12.7 mmHg)), while CBFV (40.9 +/- 12.6 cm.s-1), Pa,CO2 (7.5 +/- 1.3 kPa (56.2 +/- 9.4 mmHg)) and [H+] (39.1 +/- 4.6 nM) showed a significant reduction compared to oxygen therapy (p < 0.01). We therefore conclude that in chronically hypercapnic long-term ventilated patients cerebral blood flow depends mainly on changes in Pa,CO2 and [H+], whilst oxygen does not seem to interfere with cerebral flow velocity. The reduction of Pa,CO2, due to mechanical ventilation, may determine cerebral blood vessel constriction, with possible impairment of cerebral functions.

[Transtracheal oxygen therapy with oxycath: introduction technic, complications, results in 12 treated patients]. / L'ossigenoterapia transtracheale con oxycath: tecnica di introduzione, complicazioni, risultati in 12 pazienti trattati.

Continuous oxygen therapy is essential in the treatment of advanced chronic obstructive pulmonary disease (COPD). A transtracheal oxygen administration system is more effective in the rehabilitation of these patients than are traditional systems, nasal canula or Venturi mask devices. In the present work the authors describe a simple technique for introducing the transtracheal catheter. The procedure is performed under local anesthesia and a Teflon catheter is inserted between the second and third tracheal rings. In a case study of 12 patients the complications encountered included purulent drainage of the skin tract and accidental displacement of the transtracheal catheter. No procedure related deaths were incurred. Subjectively, the patients experience a sensation of being able to breathe more easily, thus resulting in increased outdoor activity.

[Use of ultrasonography methods in the diagnosis of neurogenic paraosteoarthropathy in spinal cord injury]. / Utilizzo della metodica ecografica nella diagnosi prococe delle paraosteoartropatie neurogene nei pazienti mielolesi.

To assess the role of the ultrasonic imaging evaluation of articular lesions suspected to be the initial presentation of heterotopic ossifications (HO), 59 consecutive injured patients were studied. 32 out of 59 patients showed clinical signs of local inflammation in one of the articular sites of the upper or lower limbs, sonographic scans proved to be diagnostic of HO in 7 out of those 32 patients before their radiographic findings. Serial sonographic examinations were performed utilizing a 7.5 MegaHertz transducer probe for 2 months. The imaging abnormalities were correlated with biochemical levels of serum alkaline phosphatase, modifications of radiographic features and bone 99nTC scintigraphy. Scintigraphy revealed to have a high sensitivity but a low specificity for the diagnosis of HO. Also the serum levels of alkaline phosphatase were not a sensitive indicator of early HO in our group of patients. Moreover serial sonographic scans confidently excluded the HO in the 25 patients with no initial signs of the disease without any false negative results. Thus, early sonographic assessment of patients, with spinal cord injury in which local signs of inflammation suggest initial HO formation, revealed to be superior to the other utilized technique for the diagnosis of HO and may be considered a valuable alternative in particular to evaluate the evolutive pattern of this disease.

National policies for risk management in Italy.

The Ministry of Health in Italy considers risk management (RM) to be one of the specific objectives to be developed by its national policies, as suggested by the European Union recommendations and by several international organizations, such as the World Health Organization (WHO), the Council of Europe, and the Organization for Economic Cooperation and Development. The National Health Plan stated the need to guarantee and monitor safety of health care and biomedical technology, with the development of a standardized computerized method to collect and analyze data on adverse events and with specific actions for education and training of all stakeholders, which is to be conducted at different levels of the health system governance, national, regional, and local. Over a 4-year period, the National Observatory for the Monitoring of Sentinel Events has collected data on 385 sentinel events, with a mortality rate of 54.8%. Compared with earlier reports, we have observed a reduction from 41% to 17% of sentinel events classified in the "nonspecified sentinel event" and an increase from 20% to 40% of cases in which an action plan has been developed. A manual for root cause analysis has been released with the aim of offering health operators an instrument to analyze the occurrence of an adverse event. Ten recommendations and a manual for safety in the operating room, which includes a checklist for safe surgery adapted on the basis of WHO suggestions, have been published. To date, eight guidelines for safety have been released to improve stakeholders' accountability. The Ministry of Health has also elaborated a program of specific actions to be developed over the next 2 years in several areas of RM. These initiatives confirm the strategic role of policies for RM in our country, allowing for a dynamic and proactive process, ensuring continuity of action and promoting a deep understanding of patient safety issues.