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We describe 14 yr of public data from the Parkes Pulsar Timing Array (PPTA), an ongoing project that is producing precise measurements of pulse times of arrival from 26 millisecond pulsars using the 64-m Parkes radio telescope with a cadence of approximately 3 weeks in three observing bands. A comprehensive description of the pulsar observing systems employed at the telescope since 2004 is provided, including the calibration methodology and an analysis of the stability of system components. We attempt to provide full accounting of the reduction from the raw measured Stokes parameters to pulse times of arrival to aid third parties in reproducing our results. This conversion is encapsulated in a processing pipeline designed to track provenance. Our data products include pulse times of arrival for each of the pulsars along with an initial set of pulsar parameters and noise models. The calibrated pulse profiles and timing template profiles are also available. These data represent almost 21 000 h of recorded data spanning over 14 yr. After accounting for processes that induce time-correlated noise, 22 of the pulsars have weighted root-mean-square timing residuals of
in at least one radio band. The data should allow end users to quickly undertake their own gravitational wave analyses, for example, without having to understand the intricacies of pulsar polarisation calibration or attain a mastery of radio frequency interference mitigation as is required when analysing raw data files.
Studies revealed that prenatal stress (PS) may increase the vulnerability to depression in their offspring, and ERK-CREB signal system might play a role in its mechanism.
Objectives and aims
The present study investigated the effect of MK-801 on depressive-like behavior and its impacts on ERK2, CREB, Bcl-2 mRNA expression in PS female rat offspring.
The pregnant rats were randomly divided into three groups, the control group (Con) was left undisturbed, the PS-saline group (PS-saline) and the PS-MK-801 group (PS-MK-801) were subjected to restraint stress on days 14–20 of pregnancy three times daily for 45 min, and received an i.p. administration of saline or MK-801(sigma, 0.2 mg/kg) 30 min before the first stress respectively. Forced swimming test was undertaken to assess depressive-like behavior in one month female offspring. ERK2, CREB, Bcl-2 mRNA in the hippocampus, frontal cortex, and striatum were detected by RT-PCR.
PS-saline spent significantly more immobile time compared to Con and PS-MK-801 (P < 0.05). ERK2 and CREB mRNA expression in hippocampus and frontal cortex was significantly decreased in PS-saline compared to Con and PS-MK-801 (P < 0.05), while in striatum CREB mRNA expression in PS-saline was lower than Con (P < 0.05). Bcl-2 mRNA expression in hippocampus and striatum was significantly decreased in PS-saline (P < 0.05), and in frontal cortex, its expression was significantly lower in PS-saline and PS-MK-801 (P < 0.05).
PS may suppress ERK-CREB signal pathway in female offspring rats, which could be partly prevented by MK- 801. (Supported by National Natural Science Foundation of China, No: 30970952).
Epidemiological studies have convinced that prenatal stress (PS) might cause offspring depression.
Objectives and aims:
Our pervious research work certified that PS can increases the glutamate level of hippocampus of rat offspring, which inspired us to explore the pathogenesis of depression by focusing on glutamatergic system.
Pregnant rats were randomly assigned to control group (CON), mid prenatal stress group (MPS) and late prenatal stress group (LPS). The pregnant rats of MPS and LPS were exposed to restraint stress on days 7–13, 14–20 of pregnancy three times for 45 min respectively. Tail suspension test (TST) was performed to examine the depression like behavior and Western-blot were used to test phosphorylated GluR1(pGluR1) of AMPAR expression in the hippocampus, striatum and frontal cortex of one month rat offspring.
For both male and female offspring, the time of immobility of TST in LPS (156±11, 155±12) and MPS (173±15, 155±12) was significantly longer (P< 0.05) than CON(118±8,113±12), the latency in MPS (18±3, 24±3) was significantly shorter (P< 0.05) than CON (30±5, 58±11). The pGluR1 expression in hippocampus and frontal cortex in LPS (1.77±0.45, 1.00±0.09) and MPS (1.65±0.51, 1.05±0.18) were significantly lower (P< 0.05) than CON (3.72±0.86, 2.05±0.34) in male rat offspring.
It is suggested that the PS may induce depression like behavior in rat offspring, and glutamate receptors subunit pGluR1 might be involved in the etiology of depression.
(The research is supported by National Natural Science Foundation of China, No: 30970952, 18110059).
Children with CHD who undergo cardiopulmonary bypass are at an increased risk of acute kidney injury. This study evaluated the association of end-organ specific injury plasma biomarkers for brain: glial fibrillary acidic protein and heart: Galectin 3, soluble suppression of tumorgenicity 2, and N-terminal pro b-type natriuretic peptide with acute kidney injury in children undergoing cardiopulmonary bypass.
Materials and Methods:
We enrolled consecutive children undergoing cardiac surgery with cardiopulmonary bypass. Blood samples were collected pre-bypass in the operating room and in the immediate post-operative period. Acute kidney injury was defined as a rise of serum creatinine ≥50% from pre-operative baseline within 7 days after surgery.
Overall, 162 children (mean age 4.05 years, sd 5.28 years) were enrolled. Post-operative acute kidney injury developed in 55 (34%) children. Post-operative plasma glial fibrillary acidic protein levels were significantly higher in patients with acute kidney injury (median 0.154 (inter-quartile range 0.059–0.31) ng/ml) compared to those without acute kidney injury (median 0.056 (inter-quartile range 0.001–0.125) ng/ml) (p = 0.043). After adjustment for age, weight, and The Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery category, each natural log increase in post-operative glial fibrillary acidic protein was significantly associated with a higher risk for subsequent acute kidney injury (adjusted odds ratio glial fibrillary acidic protein 1.25; 95% confidence interval 1.01–1.59). Pre/post-operative levels of galectin 3, soluble suppression of tumorgenicity 2, and N-terminal pro b-type natriuretic peptide did not significantly differ between patients with and without acute kidney injury.
Higher plasma glial fibrillary acidic protein levels measured in the immediate post-operative period were independently associated with subsequent acute kidney injury in children after cardiopulmonary bypass. Elevated glial fibrillary acidic protein likely reflects intraoperative brain injury which may occur in the context of acute kidney injury-associated end-organ dysfunction.
Childhoods in urban or rural environments may differentially affect risk for neuropsychiatric disorders. Here, we leveraged on dramatic urbanization and rural-urban migration since the 1980s in China to explore the hypothesis that rural or urban childhoods may differentially influence memory processing and neural responses to neutral and aversive stimuli.
Explore the underlying mechanisms of childhood environment effect on brain function and neuropsychiatric risk.
We examined 420 adult subjects with similar current socioeconomic status and living in Beijing, China, but with differing rural (n = 227) or urban (n = 193) childhoods. In an episodic memory paradigm scanned in a 3 T GE MRI, subjects viewed blocks of neutral or aversive pictures in the encoding and retrieval sessions.
Episodic memory accuracy for neutral stimuli was less than for aversive stimuli (P < 0.001). However, subjects with rural childhoods apparently performed less accurately for memory of aversive but not neutral stimuli (P < 0.01). In subjects with rural childhoods, there was relatively increased engagement of bilateral striatum at encoding, increased engagement of bilateral hippocampus at retrieval of neutral and aversive stimuli, and increased engagement of amygdala at aversive retrieval (P < 0.05 FDR corrected, cluster size > 50).
Rural or urban childhoods appear associated with physiological and behavioural differences, particularly in the neural processing of aversive episodic memory at medial temporal and striatal brain regions. It remains to be explored the extent to which these effects relate to individual risk for neuropsychiatric or stress-related disorders.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Numerous studies reported on the frequency of, and factors associated with inappropriate or unnecessary emergency department (ED) visits using clinician judgment as the gold standard of appropriateness. This study evaluated the reliability of clinician judgment for assessing appropriateness of pediatric ED visit.
We conducted a retrospective cohort study comparing 3 clinicians’ determination of ED visit appropriateness with and without guidance from a three-question structured algorithm. We used a cohort of scheduled ED return visits deemed appropriate by the index treating clinician between May 1, 2012, and April 30, 2013. We measured the level of agreement among three clinician investigators with and without use of the structured algorithm.
A total of 207 scheduled ED return visits were reviewed by the primary clinician reviewer who agreed with the index treating clinician for 79/207 visits (38.2%). Among a random subset of 90 return visits reviewed by all three clinicians, agreement was 67% with a Fleiss’ Kappa of 0.30 (0.17–0.44). Using a three-question algorithm based on objective criteria, agreement with the index treating provider increased to 115/207 (55.6%).
Although an important contributor to pediatric ED overcrowding, unnecessary or inappropriate visits are difficult to identify. We demonstrated poor reliability of clinician judgment to determine appropriateness of ED return visits, likely due to variability in clinical decision-making and risk-tolerance, social and systems factors impacting access and use of health care. We recommend that future studies evaluating the appropriateness of ED use standardized, objective criteria rather than clinician judgment alone.
The resection of a subaortic membrane remains far from a curative operation. We sought to examine factors associated with reoperation and the degree of aortic valve regurgitation as a potential long-term source for reoperation.
All patients who underwent resection of an isolated subaortic membrane between 1995 and 2018 were included. Patients who underwent other procedures were excluded. Paired categorical data were compared using McNemar’s test. Univariate time-to-event analyses were performed using Kaplan–Meier methods with log-rank tests for categorical variables and univariate Cox models for continuous variables.
A total of 84 patients (median age 6.6, 31% females) underwent resection of isolated subaortic membrane. At a median follow-up of 9.3 years (interquartile range 0.6–22.5), 12 (14%) patients required one reoperation and 1 patient required two reoperations. Median time to first reoperation was 4.6 years. The degree of aortic valve regurgitation improved post-operatively from pre-operatively (p = 0.0007); however, the degree of aortic valve regurgitation worsened over the course of follow-up (p = 0.010) to equivalence with pre-operative aortic valve regurgitation (p = 0.18). Performance of a septal myectomy was associated with longer freedom from reoperation (p = 0.004).
In patients with isolated subaortic membranes, performance of a septal myectomy can minimise risk for reoperation. Patients should be serially monitored for degradation of the aortic valve, even if aortic regurgitation is not present post-operatively.
Abnormal Ca homeostasis has been associated with impaired glucose metabolism. However, the epidemiological evidence is controversial. We aimed to assess the association between circulating Ca levels and the risk of type 2 diabetes mellitus (T2DM) or abnormal glucose homeostasis through conducting a systematic review and meta-analysis. Eligible studies were identified by searching electronic database (PubMed, Embase and Google Scholar) and related references with de novo results from primary studies up to December 2018. A random-effects meta-analysis was performed to estimate the weighted relative risks (RR) and 95 % CI for the associations. The search yielded twenty eligible publications with eight cohort studies identified for the meta-analysis, which included a total of 89 165 participants. Comparing the highest with the lowest category of albumin-adjusted serum Ca, the pooled RR was 1·14 (95 % CI 1·05, 1·24) for T2DM (n 51 489). Similarly, serum total Ca was associated with incident T2DM (RR 1·25; 95 % CI 1·10, 1·42) (n 64 502). Additionally, the adjusted RR for 1 mg/dl increments in albumin-adjusted serum Ca or serum total Ca levels was 1·16 (95 % CI 1·07, 1·27) and 1·19 (95 % CI 1·11, 1·28), respectively. The observed associations remained with the inclusion of a cohort study with ionised Ca as the exposure. However, data pooled from neither case–control (n 4) nor cross-sectional (n 8) studies manifested a significant correlation between circulating Ca and glucose homeostasis. In conclusion, accumulated data from the cohort studies suggest that higher circulating Ca levels are associated with an augmented risk of T2DM.
Identification of member stars in open clusters is still an open question. Thanks to Gaia DR2 data base, which improves our statistics regarding true members in clusters to understand cluster properties much better way. In this paper, we identify the cluster members using proper motion and colour magnitude diagram for NGC 5617. In addition to this, we have determined more precise fundamental parameters as well.
In the 2015 review paper ‘Petawatt Class Lasers Worldwide’ a comprehensive overview of the current status of high-power facilities of
was presented. This was largely based on facility specifications, with some description of their uses, for instance in fundamental ultra-high-intensity interactions, secondary source generation, and inertial confinement fusion (ICF). With the 2018 Nobel Prize in Physics being awarded to Professors Donna Strickland and Gerard Mourou for the development of the technique of chirped pulse amplification (CPA), which made these lasers possible, we celebrate by providing a comprehensive update of the current status of ultra-high-power lasers and demonstrate how the technology has developed. We are now in the era of multi-petawatt facilities coming online, with 100 PW lasers being proposed and even under construction. In addition to this there is a pull towards development of industrial and multi-disciplinary applications, which demands much higher repetition rates, delivering high-average powers with higher efficiencies and the use of alternative wavelengths: mid-IR facilities. So apart from a comprehensive update of the current global status, we want to look at what technologies are to be deployed to get to these new regimes, and some of the critical issues facing their development.
A new generation of high power laser facilities will provide laser pulses with extremely high powers of 10 petawatt (PW) and even 100 PW, capable of reaching intensities of
in the laser focus. These ultra-high intensities are nevertheless lower than the Schwinger intensity
at which the theory of quantum electrodynamics (QED) predicts that a large part of the energy of the laser photons will be transformed to hard Gamma-ray photons and even to matter, via electron–positron pair production. To enable the investigation of this physics at the intensities achievable with the next generation of high power laser facilities, an approach involving the interaction of two colliding PW laser pulses is being adopted. Theoretical simulations predict strong QED effects with colliding laser pulses of
focused to intensities
A multichannel calorimeter system is designed and constructed which is capable of delivering single-shot and broad-band spectral measurement of terahertz (THz) radiation generated in intense laser–plasma interactions. The generation mechanism of backward THz radiation (BTR) is studied by using the multichannel calorimeter system in an intense picosecond laser–solid interaction experiment. The dependence of the BTR energy and spectrum on laser energy, target thickness and pre-plasma scale length is obtained. These results indicate that coherent transition radiation is responsible for the low-frequency component (
1 THz) of BTR. It is also observed that a large-scale pre-plasma primarily enhances the high-frequency component (
3 THz) of BTR.
Previous studies have demonstrated that type 1 diabetes mellitus (T1DM) could be triggered by an early childhood infection. Whether maternal infection during pregnancy is associated with T1DM in offspring is unknown. Therefore, we aimed to study the association using a systematic review and meta-analysis. Eighteen studies including 4304 cases and 25 846 participants were enrolled in this meta-analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were synthesised using random-effects models. Subgroup analyses and sensitivity analyses were conducted to assess the robustness of associations. Overall, the pooled analysis yielded a statistically significant association between maternal infection during pregnancy and childhood T1DM (OR 1.31, 95% CI 1.07–1.62). Furthermore, six studies that tested maternal enterovirus infection showed a pooled OR of 1.54 (95% CI 1.05–2.27). Heterogeneity from different studies was evident (I2 = 70.1%, P < 0.001) and was mainly attributable to the different study designs, ascertaining methods and sample size among different studies. This study provides evidence for an association between maternal infection during pregnancy and childhood T1DM.
Extensive insecticide use has led to the resistance of mosquitoes to these insecticides, posing a major barrier to mosquito control. Previous Solexa high-throughput sequencing of Culex pipiens pallens in the laboratory has revealed that the abundance of a novel microRNA (miRNA), miR-13664, was higher in a deltamethrin-sensitive (DS) strain than a deltamethrin-resistant (DR) strain. Real-time quantitative PCR revealed that the miR-13664 transcript level was lower in the DR strain than in the DS strain. MiR-13664 oversupply in the DR strain increased the susceptibility of these mosquitoes to deltamethrin, whereas inhibition of miR-13664 made the DS strain more resistant to deltamethrin. Results of bioinformatic analysis, quantitative reverse-transcriptase polymerase chain reaction, luciferase assay and miR mimic/inhibitor microinjection revealed CpCYP314A1 to be a target of miR-13664. In addition, downregulation of CpCYP314A1 expression in the DR strain reduced the resistance of mosquitoes to deltamethrin. Taken together, our results indicate that miR-13664 could regulate deltamethrin resistance by interacting with CpCYP314A1, providing new insights into mosquito resistance mechanisms.
Toca 511 (vocimagene amiretrorepvec) is an investigational, conditionally lytic, retroviral replicating vector (RRV). RRVs selectively infect cancer cells due to innate and adaptive immune response defects in cancers that allow virus replication, and the requirement for cell division for virus integration into the genome. Toca 511 spreads through tumors, stably delivering an optimized yeast cytosine deaminase gene that converts the prodrug Toca FC (investigational, extended-release 5-FC) into 5-FU within the tumor microenvironment. 5-FU kills infected dividing cancer cells and surrounding tumor, myeloid derived suppressor cells, and tumor associated macrophages, resulting in long-term tumor immunity in preclinical models. Data from a Phase 1 resection trial showed six durable CRs and extended mOS compared to historical controls. The FDA granted Breakthrough Therapy Designation for Toca 511 & Toca FC in the treatment of patients with rHGG. Toca 5 is an international, randomized, open-label Phase 3 trial (NCT02414165) of Toca 511 & Toca FC versus SOC in patients undergoing resection for first or second recurrence of rHGG. Patients will be stratified by IDH1 status, KPS, and geographic region. Primary endpoint is OS, and secondary endpoints are durable response rate, durable clinical benefit rate, duration of durable response, and 12-month survival rate. Key inclusion criteria are histologically proven GBM or AA, tumor size ≥1cm and ≤5cm, and KPS ≥70. Immune monitoring and molecular profiling will be performed. Approximately 380 patients will be randomized. An IDMC is commissioned to review the safety and efficacy data which includes 2 interim analyses. Enrollment is ongoing.