A luminous fast radio burst that probes the Universe at redshift 1.

Fast radio bursts (FRBs) are millisecond-duration pulses of radio emission originating from extragalactic distances. Radio dispersion is imparted on each burst by intervening plasma, mostly located in the intergalactic medium. In this work, we observe the burst FRB 20220610A and localize it to a morphologically complex host galaxy system at redshift 1.016 ± 0.002. The burst redshift and dispersion measure are consistent with passage through a substantial column of plasma in the intergalactic medium and extend the relationship between those quantities measured at lower redshift. The burst shows evidence for passage through additional turbulent magnetized plasma, potentially associated with the host galaxy. We use the burst energy of 2 × 1042 erg to revise the empirical maximum energy of an FRB.

The dispersion-brightness relation for fast radio bursts from a wide-field survey.

Despite considerable efforts over the past decade, only 34 fast radio bursts-intense bursts of radio emission from beyond our Galaxy-have been reported1,2. Attempts to understand the population as a whole have been hindered by the highly heterogeneous nature of the searches, which have been conducted with telescopes of different sensitivities, at a range of radio frequencies, and in environments corrupted by different levels of radio-frequency interference from human activity. Searches have been further complicated by uncertain burst positions and brightnesses-a consequence of the transient nature of the sources and the poor angular resolution of the detecting instruments. The discovery of repeating bursts from one source3, and its subsequent localization4 to a dwarf galaxy at a distance of 3.7 billion light years, confirmed that the population of fast radio bursts is located at cosmological distances. However, the nature of the emission remains elusive. Here we report a well controlled, wide-field radio survey for these bursts. We found 20, none of which repeated during follow-up observations between 185-1,097 hours after the initial detections. The sample includes both the nearest and the most energetic bursts detected so far. The survey demonstrates that there is a relationship between burst dispersion and brightness and that the high-fluence bursts are the nearby analogues of the more distant events found in higher-sensitivity, narrower-field surveys5.

Orexin-A, an hypothalamic peptide with analgesic properties.

The hypothalamic peptide orexin-A and the orexin-1 receptor are localized in areas of the brain and spinal cord associated with nociceptive processing. In the present study, localization was confirmed in the spinal cord and demonstrated in the dorsal root ganglion for both orexin-A and the orexin-1 receptor. The link with nociception was extended when orexin-A was shown to be analgesic when given i.v. but not s.c. in mouse and rat models of nociception and hyperalgesia. The efficacy of orexin-A was similar to that of morphine in the 50 degrees C hotplate test and the carrageenan-induced thermal hyperalgesia test. However, involvement of the opiate system in these effects was ruled out as they were blocked by the orexin-1 receptor antagonist SB-334867 but not naloxone. Orexin-1 receptor antagonists had no effect in acute nociceptive tests but under particular inflammatory conditions were pro-hyperalgesic, suggesting a tonic inhibitory orexin drive in these circumstances. These data demonstrate that the orexinergic system has a potential role in the modulation of nociceptive transmission.

Inhibition of inflammation-induced thermal hypersensitivity by sumatriptan through activation of 5-HT(1B/1D) receptors.

Migraine is effectively treated by drugs acting via 5-HT(1B/1D) receptors; however, the antinociceptive effects of such agents have not been fully investigated, particularly in models in which sensitization may be present. The aim of these studies was to evaluate the effects of the 5-HT(1B/1D) receptor agonist sumatriptan in specific models of pain states: a mouse model of inflammation-induced thermal hyperalgesia and a rat model of nerve injury-induced thermal hyperalgesia. In female mice, following intraplantar injection of carrageenan 225 min earlier, sumatriptan (300 microg/kg intraperitoneally; i.p.) increased paw withdrawal latency (PWL) from 3.1 +/- 0.4 s in the saline group to 5.6 +/- 0.9 s, measured 240 min postcarrageenan (P < 0.05 ANOVA followed by post hoc Dunnett's test). A similar effect was seen in male mice. Sumatriptan was also effective in male mice when given i.p. and subcutaneously 15 min precarrageenan, with a maximum effect at 30 microg/kg (i.p. latency 7.4 +/- 1.3 s compared to saline group, 2.6 +/- 0.7 s; i.v. latency 5.9 +/- 0.8 s compared to saline group, 2.9 +/- 0.3 s; P < 0.05 ANOVA followed by post hoc Dunnett's test). The number of mice required to give a response that could be reliably attributed to sumatriptan (number needed to treat) was calculated using discriminant analysis and found to be 2.6. The ability of sumatriptan to attenuate the carrageenan-induced reduction in PWL was blocked by the mixed 5-HT(1B/1D) receptor antagonist GR-127935 (3 mg/kg i.p.) but not by the 5-HT(1B) receptor antagonist SB-224289 (10 mg/kg i.p.). Sumatriptan had no effect on thermal hyperalgesia induced by sciatic nerve ligation in the rat at any time point. These data demonstrate that sumatriptan attenuates the hypersensitivity to noxious thermal stimuli induced by intraplantar carrageenan.

Carrageenan-induced thermal hyperalgesia in the mouse: role of nerve growth factor and the mitogen-activated protein kinase pathway.

NGF is an important link between inflammation and hyperalgesia and interacts with many different mediators of inflammation, including the MAPK signaling pathway. In these studies, carrageenan-induced thermal hyperalgesia was evaluated in the mouse and the role of NGF and the MAPK pathway investigated. Carrageenan induced a time-dependent inflammation and thermal hyperalgesia, which was maximal 4 h post administration. Both indomethacin (0.3, 1.0 and 10 mg/kg s.c., 30 min pre-carrageenan) and morphine (0.4, 1.2, 4.0 mg/kg; s.c., 30 min pre-hyperalgesia measurement) significantly inhibited carrageenan-induced thermal hyperalgesia and indomethicin inhibited paw inflammation, demonstrating the model as suitable for the assessment of anti-hyperalgesic and anti-inflammatory agents. Anti-NGF (0.67 mg/kg sc, 60 min pre-carrageenan) produced a significant inhibition of thermal hyperalgesia, but not inflammation. NGF itself produced a time-dependent hyperalgesia, but not inflammation, following intraplantar injection. The specific MAPK pathway inhibitor, PD98059 (0.1, 0.3 and 1 mg/kg sc, 30 min pre-carrageenan) significantly inhibited carrageenan-induced hyperalgesia, but not inflammation. These data demonstrate a role for both NGF and the MAPK signaling pathway in the production of thermal hyperalgesia, but not inflammation, in the mouse.

Efficacy of a brief psychosocial treatment for panic disorder in an active duty sample: implications for military readiness.

OBJECTIVE: The efficacy of a brief cognitive-behavioral treatment for panic in military personnel was evaluated. METHOD: Active duty military patients (N = 37) presenting at outpatient psychiatry and psychology clinics were randomly assigned to immediate or delayed treatment conditions. All patients met Diagnostic and Statistical Manual of Mental Disorders criteria for a primary diagnosis of panic disorder with or without agoraphobia. RESULTS: At posttreatment, 80% of the immediate treatment group, compared to 0% of the delayed treatment group, met recovery criteria on all major clinical facets of panic disorder (i.e., panic attacks, panic-related worry, phobic avoidance). At follow-up, 75% of the treated group continued to meet recovery criteria, suggesting maintenance of treatment gains. A majority of those patients (58%) taking benzodiazepines at the start of treatment were successfully discontinued by posttreatment. CONCLUSIONS: Brief, skill-based treatments for panic disorder are effective for a majority of active duty personnel. These treatments may also improve military readiness by facilitating benzodiazepine discontinuation.

Basic science training in psychopharmacology. How much is enough?

Training psychologists to administer psychotropic medication will require acquisition of a unique knowledge base and set of skills that are generally not components of graduate education in psychology. Nevertheless, the current level of basic science training in graduate education in psychology is substantial and should, with minor modification, allow adequate preparation for students to enter into specialized training to prescribe. The direct provision of psychopharmacology requires psychologists to demonstrate competencies in addition to those required in the general provision of psychological services. Such competencies are perhaps best taught at the postdoctoral level. The authors argue that all curricula training professional psychologists should be able to train psychologists capable of practicing as independent, full-fledged health care providers.

Prescription privileges and psychology: A reply to adams and Bieliauskas.

The ability to prescribe psychoactive medications is a legitimate extension of the practice of psychology. Arguments raised against this proposition by Adams and Bieliauskas should not deter the profession from attaining prescriptive authority. Prescription privileges will expand the range of disorders and patient populations that psychologists can treat. Their acquisition will be of benefit to both the profession and the patient alike.

Does being in the military affect nurses' perceptions of work life?

This study was a causal comparative investigation of military and civilian nurses' perceptions of selected aspects of work life. The Work Environment Scale, the Maslach Burnout Inventory and the Michigan Job Satisfaction Scale were administered to civilian and military samples matched on selected demographic variables. MANOVA procedures failed to reveal significant differences on measures of burnout and morale. Although military nurses were significantly more satisfied with issues of pay and fringe benefits, civilian nurses reported significantly greater job satisfaction, peer cohesion, supervisory support, decision making, autonomy, task orientation and opportunity to be innovative. These findings and suggested changes are discussed with attention to differences between the military and civilian work setting.

Personnel management in dairy practice. The professional staff.

Group practices have advantages and disadvantages. Effective management of the professional staff makes the most of the benefits and minimizes the drawbacks. Management does not mean controlling people; rather, it allows both the individual doctors and the practice as a whole attain maximum development and satisfaction.

Sizing of a vesicle drug formulation by quasi-elastic light scattering and comparison with electron microscopy and ultracentrifugation.

Quasi-elastic light scattering has been used for the sizing of a vesicle formulation. Porcine insulin was encapsulated in a vesicle preparation containing cholesterol, dipalmitoylphosphotidylcholine, digalactosyl digycerides, and dipalmitoylphosphotidylglycerol in a 40:40:15:5 ratio. The measurement requires less than 15 min to obtain mean size and distribution information and can be operated in a quality control environment. Advantages and limitations of quasi-elastic light scattering are described and this method is compared to electron microscopy and ultracentrifugation.

Determination of total and encapsulated insulin in a vesicle formulation.

A method for the determination of the amount of insulin in a vesicle formulation was developed. Samples were treated with anion exchange resin to quantitatively remove the insulin outside the vesicle walls. Encapsulated insulin was released from vesicles by disruption with a surfactant and the amount released was determined by reversed-phase HPLC. Recovery of insulin from the vesicle matrix was 99, 97, and 98% for vesicle solutions spiked with 1.0, 0.5, and 0.2 U/mL of insulin, respectively. The sample preparation steps resulted in removal of greater than 99.5% of the unencapsulated insulin; 98% recovery of the vesicles from the resin; 97% recovery of the encapsulated insulin from the resin; and greater than 99% disruption of the vesicles by the surfactant. Precision of the measurements for the amounts of total and encapsulated insulin was 2.7 and 3.3% relative standard deviations, respectively, for insulin levels of 0.7 U/mL.

Systemic metabolic alterations associated with repeated injections of a modified polyriboinosinic-polyribocytidylic acid complex.

Polyriboinosinic acid-polyribocytidylic acid complexed with poly-1-lysine and injected intramuscularly into rats (0.3 or 3.0 mg/kg) produced fever, altered leukocyte count, slightly depressed plasma zinc, increased amino acid uptake into liver, and increased plasma acute-phase globulins two- to threefold. It is suggested that these systemic metabolic alterations are indicative of a mild inflammatory response to this drug. The metabolic alterations may have to be taken into consideration when polyriboinosinic acid-polyribocytidylic acid complexed with poly-1-lysine is used in therapy.

Effect of a nuclease-resistant derivative of polyriboinosinic-polyribocytidylic acid complex on yellow fever in rhesus monkeys (Macaca mulatta).

Rhesus monkeys (Macaca mulatta) treated with a newly developed nuclease-resistant complex of polyriboinosinic-polyribocytidylic acid, poly-L-lysine, and carboxymethylcellulose [poly (ICLC)] did not die after challenge with virulent Asibi strain yellow fever (YF) virus. The strain of virus is sensitive to the effects of interferon in vitro and is lethal for rhesus monkeys four to six days after subcutaneous administration of 1,000 plaque-forming units of the virus. The mortality rate was reduced in monkeys initially treated 8 hr before or after inoculation of virus but was unchanged in monkeys initially treated 24 hr after challenge. Treated monkeys developed neutralizing antibody to YF virus. The successful treatment of yellow fever in a primate model with use of poly (ICLC) suggests a meaningful role for the interferon system in the host defense against this viral infection.

Interferon induction in cynomolgus and rhesus monkey after repeated doses of a modified polyriboinosinic-polyribocytidylic acid complex.

Serum interferon activity was determined in 12 cynomolgus and 12 rhesus monkeys injected intravenously once daily for 10 days with from 0.1 to 6.0 mg of a stabilized polyriboinosinic acid . polyribocytidylic acid complex per kg, composed of polyriboinosinic acid . polyribocytidylic acid, poly-1-lysine, and carboxymethylcellulose [poly(ICLC)]. Interferon activity was detected 2 h after the first injection, with maximum activity occurring 8 h after the second injection. A period of hyporesponsiveness occurred after the third injection of poly(ICLC) in all monkeys and lasted until the sixth injection in the rhesus monkeys, when interferon activity again became more elevated. The delayed rebound was not as apparent in cynomolgus monkeys. Rhesus monkeys injected with 6 mg/kg did not exhibit serious side effects.

Changes in blood pH in rats after infection with Streptococcus pneumoniae.

Acid-base alterations in Streptococcus pneumoniae infection were studied in 80 male albino rats. Hematocrit and concentrations of plasma electrolytes, glucose, and total protein were also measured. At 3-h intervals throughout a 27-h study, four control and four infected rats were anesthetized with ether, and blood samples were taken. Arterial blood pH, Po2, and hematocrit increased in the infected group, whereas arterial Pco2, HCO3-, and venous Po2 decreased. Plasma K+ concentration increased slightly and glucose levels decreased in the infected rats as the sepsis progressed. No significant changes were observed in venous blood pH, HCO3-, and Pco2. Plasma Na+, Cl-, and total protein remained unchanged. The increase in arterial blood pH and decrease in arterial Pco2 and HCO3- indicated respiratory alkalosis, which was present in rats infected with S. pneumoniae.