We report the first plausible optical electromagnetic counterpart to a (candidate) binary black hole merger. Detected by the Zwicky Transient Facility, the electromagnetic flare is consistent with ...expectations for a kicked binary black hole merger in the accretion disk of an active galactic nucleus B. McKernan, K. E. S. Ford, I. Bartoset al., Astrophys. J. Lett.884, L50 (2019) and is unlikely <O(0.01%)) due to intrinsic variability of this source. The lack of color evolution implies that it is not a supernova and instead is strongly suggestive of a constant temperature shock. Other false-positive events, such as microlensing ora tidal disruption event, are ruled out or constrained to be <O(0.1%). If the flare is associated withS190521g, we find plausible values of total mass M(BBH) ∼ 100 Mꙩ, kick velocity v(k) ∼ 200 km/s at θ ∼ 60° in a disk with aspect ratio H/a ∼ 0.01(i.e., disk height H at radius a) and gas density ρ ∼ 10^(−10)g/cu.cm. The merger could have occurred at a disk migration trap (a ∼ 700 r(g); r(g) ≡ GM(SMBH)/sq.c, where M(SMBH) is the mass of the active galactic nucleus supermassive black hole). The combination of parameters implies a significant spin for at least one of the black holes in S190521g. The timing of our spectroscopy prevents useful constraints on broad-line asymmetry due to an off-center flare. We predict a repeat flare in this source due to a reencountering with the disk in ∼ 1.6 yr(M(SMBH)/10^(8) Mꙩ)(a/10^(3)r(g))^(3/2).
A great deal of interest in psychiatric research is currently centered upon the pathogenic role of inflammatory processes. Positron emission tomography (PET) using radiolabeled ligands selective for ...the 18 kDa translocator protein (TSPO) has become the most widely used technique to assess putative neuroimmune abnormalities in vivo. Originally used to detect discrete neurotoxic damages, TSPO has generally turned into a biomarker of 'neuroinflammation' or 'microglial activation'. Psychiatric research has mostly accepted these denotations of TSPO, even if they may be inadequate and misleading under many pathological conditions. A reliable and neurobiologically meaningful diagnosis of 'neuroinflammation' or 'microglial activation' is unlikely to be achieved by the sole use of TSPO PET imaging. It is also very likely that the pathological meanings of altered TSPO binding or expression are disease-specific, and therefore, not easily generalizable across different neuropathologies or inflammatory conditions. This difficulty is intricately linked to the varying (and still ill-defined) physiological functions and cellular expression patterns of TSPO in health and disease. While altered TSPO binding or expression may indeed mirror ongoing neuroinflammatory processes in some cases, it may reflect other pathophysiological processes such as abnormalities in cell metabolism, energy production and oxidative stress in others. Hence, the increasing popularity of TSPO PET imaging has paradoxically introduced substantial uncertainty regarding the nature and meaning of neuroinflammatory processes and microglial activation in psychiatry, and likely in other neuropathological conditions as well. The ambiguity of conceiving TSPO simply as a biomarker of 'neuroinflammation' or 'microglial activation' calls for alternative interpretations and complimentary approaches. Without the latter, the ongoing scientific efforts and excitement surrounding the role of the neuroimmune system in psychiatry may not turn into therapeutic hope for affected individuals.
The role of serotonin (5-HT) in sleep is controversial: early studies suggested a sleep-promoting role, but eventually the paradigm shifted toward a wake-promoting function for the serotonergic ...raphe. Here, we provide evidence from zebrafish and mice that the raphe are critical for the initiation and maintenance of sleep. In zebrafish, genetic ablation of 5-HT production by the raphe reduces sleep, sleep depth, and the homeostatic response to sleep deprivation. Pharmacological inhibition or ablation of the raphe reduces sleep, while optogenetic stimulation increases sleep. Similarly, in mice, ablation of the raphe increases wakefulness and impairs the homeostatic response to sleep deprivation, whereas tonic optogenetic stimulation at a rate similar to baseline activity induces sleep. Interestingly, burst optogenetic stimulation induces wakefulness in accordance with previously described burst activity of the raphe during arousing stimuli. These results indicate that the serotonergic system promotes sleep in both diurnal zebrafish and nocturnal rodents.
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•The serotonergic system (STS) promotes sleep in zebrafish and mice•STS disruption reduces both sleep and the homeostatic response to sleep deprivation•Tonic stimulation of the STS induces sleep, but burst stimulation induces wake•We propose that baseline tonic STS activity during wake generates sleep pressure
The wake-active serotonergic system (STS) has been considered part of the ascending arousal system that promotes wakefulness. Using zebrafish and mice, Oikonomou, Altermatt et al. demonstrate that the STS promotes sleep, potentially by generating homeostatic sleep pressure during wakefulness.
Immune sera from convalescent patients have been shown to be effective in the treatment of patients infected with Severe Acute Respiratory Syndrome Virus (SARS-CoV) making passive immune therapy with ...human monoclonal antibodies an attractive treatment strategy for SARS. Previously, using Xenomouse (Amgen British Columbia Inc), we produced a panel of neutralizing Human monoclonal antibodies (HmAbs) that could specifically bind to the ectodomain of the SARS-CoV spike (S) glycoprotein. Some of the HmAbs were S1 domain specific, while some were not. In this study, we describe non-S1 binding neutralizing HmAbs that can specifically bind to the conserved S2 domain of the S protein. However, unlike the S1 specific HmAbs, the S2 specific HmAbs can neutralize pseudotyped viruses expressing different S proteins containing receptor binding domain sequences of various clinical isolates. These data indicate that HmAbs which bind to conserved regions of the S protein are more suitable for conferring protection against a wide range of SARS-CoV variants and have implications for generating therapeutic antibodies or subunit vaccines against other enveloped viruses.
Positron emission tomography (PET) imaging with radiotracers that target translocator protein 18 kDa (TSPO) has become a popular approach to assess putative neuroinflammatory processes and associated ...microglia activation in psychotic illnesses. It remains unclear, however, whether TSPO imaging can accurately capture low-grade inflammatory processes such as those present in schizophrenia and related disorders. Therefore, we evaluated the validity of TSPO as a disease-relevant marker of inflammation using a translational approach, which combined neurodevelopmental and neurodegenerative mouse models with PET imaging in patients with recent-onset schizophrenia and matched controls. Using an infection-mediated neurodevelopmental mouse model, we show that schizophrenia-relevant behavioral abnormalities and increased inflammatory cytokine expression are associated with reduced prefrontal TSPO levels. On the other hand, TSPO was markedly upregulated in a mouse model of acute neurodegeneration and reactive gliosis, which was induced by intrahippocampal injection of kainic acid. In both models, the changes in TSPO levels were not restricted to microglia but emerged in various cell types, including microglia, astrocytes and vascular endothelial cells. Human PET imaging using the second-generation TSPO radiotracer
CDPA-713 revealed a strong trend towards reduced TSPO binding in the middle frontal gyrus of patients with recent-onset schizophrenia, who were previously shown to display increased levels of inflammatory cytokines in peripheral and central tissues. Together, our findings challenge the common assumption that central low-grade inflammation in schizophrenia is mirrored by increased TSPO expression or ligand binding. Our study further underscores the need to interpret altered TSPO binding in schizophrenia with caution, especially when measures of TSPO are not complemented with other markers of inflammation. Unless more selective microglial markers are available for PET imaging, quantification of cytokines and other inflammatory biomarkers, along with their molecular signaling pathways, may be more accurate in attempts to characterize inflammatory profiles in schizophrenia and other mental disorders that lack robust reactive gliosis.
Background
This study aimed to determine the effect of local anesthesia administered before laparoscopic surgery (preemptive anesthesia) on postoperative pain.
Methods
The authors searched Medline, ...EMBase, and the Cochrane Central Register of Controlled Trials, as well as reference lists of textbooks and relevant articles. They contacted experts in the field of anesthesia and laparoscopic surgery for randomized controlled trials comparing preemptive administration of local anesthesia at the incision site or intraperitoneally with postoperative anesthesia administration or placebo. Trials were systematically assessed for eligibility and validity, and data were extracted in duplicate. The data were pooled across studies using a random effects model.
Results
The 26 studies that met the inclusion criteria were included in the analysis. Preemptive incisional local anesthetic was superior to placebo in terms of visual analog pain scores (VAS) at 4 h (weighted mean difference WMD, −9.49 mm; 95% confidence interval CI, −15.50 to −3.48) and 24 h (WMD, −4.75 mm; 95%CI, −8.90 to 0.60). However, no difference was found between these measures and those for postoperative incision-site infiltration. Preemptive intraperitoneal local anesthetic was superior to placebo in terms of VAS at 4 h (WMD, 5.76 mm; 95%CI, −11.27 to −0.25), 8 h (WMD, −9.64 mm; 95%CI, −13.68 to −5.60), 12 h (WMD, −4.68 mm; 95%CI, −5.86 to −3.49), and 24 h (WMD, −5.57 mm; 95%CI, −8.35 to −2.79), and superior to postoperative anesthesia administration at 8 h (WMD, −7.42; 95%CI, −13.40 to −1.45), 12 h (WMD, −7.27 mm; 95%CI, −10.26 to −4.28), and 24 h (WMD, −7.95 mm; 95%CI, −12.33 to −3.56).
Conclusion
Preemptive administration of local anesthetic at the incision site reduces postoperative pain compared with placebo but achieves an analgesic effect similar to that of postincisional anesthetic infiltration. Preemptive local anesthetic administered intraperitoneally decreases postoperative pain compared with both placebo and postoperative infiltration. Surgeons should use local analgesia in laparoscopic surgery to decrease postoperative pain, but the timing of administration is significant only for intraperitoneal infiltration.
Newtonian gravitational noise from seismic fields will become a limiting noise source at low frequency for second-generation, gravitational-wave detectors. It is planned to use seismic sensors ...surrounding the detectors' test masses to coherently subtract Newtonian noise using Wiener filters derived from the correlations between the sensors and detector data. In this Letter, we use data from a seismometer array deployed at the corner station of the Laser Interferometer Gravitational Wave Observatory (LIGO) Hanford detector combined with a tiltmeter for a detailed characterization of the seismic field and to predict achievable Newtonian-noise subtraction levels. As was shown previously, cancellation of the tiltmeter signal using seismometer data serves as the best available proxy of Newtonian-noise cancellation. According to our results, a relatively small number of seismometers is likely sufficient to perform the noise cancellation due to an almost ideal two-point spatial correlation of seismic surface displacement at the corner station, or alternatively, a tiltmeter deployed under each of the two test masses of the corner station at Hanford will be able to efficiently cancel Newtonian noise. Furthermore, we show that the ground tilt to differential arm-length coupling observed during LIGO's second science run is consistent with gravitational coupling.
We describe a dynamic science portal called the GROWTH Marshal that allows time-domain astronomers to define science programs; program filters to save sources from different discovery streams; ...coordinate follow-up with various robotic or classical telescopes; analyze the panchromatic follow-up data; and generate summary tables for publication. The GROWTH marshal currently serves 137 scientists, 38 science programs, and 67 telescopes. Every night, in real time, several science programs apply various customized filters to the 105 nightly alerts from the Zwicky Transient Facility. Here, we describe the schematic and explain the functionality of the various components of this international collaborative platform.
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