The role of pre-school quality in promoting resilience in the cognitive development of young children

The study reported here investigates the role of pre-school education as a protective factor in the development of children who are at risk due to environmental and individual factors. This investigation builds upon earlier research by examining different kinds of 'quality' in early education and tests the hypothesis that pre-schools of high quality can moderate the impacts of risks upon cognitive development. Cognitive development was measured in 2857 English pre-schoolers at 36 and 58 months of age, together with 22 individual risks to children's development, and assessments were made of the quality of their pre-school provision. Multilevel Structural Equation Modelling revealed that: the global quality of pre-school can moderate the effects of familial risk (such as poverty); the relationships between staff and children can moderate the effects of child level risk (such as low birth weight); and the specific quality of curricular provision can moderate the effects of both. Policy makers need to take quality into account in their efforts to promote resilience in young 'at risk' children through early childhood services

Two-Screen Scattering in CRAFT FRBs

Temporal broadening is a commonly observed property of fast radio bursts (FRBs), associated with turbulent media which cause radiowave scattering. Similarly to dispersion, scattering is an important probe of the media along the line of sight to an FRB source, such as the circum-burst or circum-galactic mediums (CGM). Measurements of characteristic scattering times alone are insufficient to constrain the position of the dominant scattering media along the line of sight. However, where more than one scattering screen exists, Galactic scintillation can be leveraged to form strong constraints. We quantify the scattering and scintillation in 10 FRBs with 1) known host galaxies and redshifts and 2) captured voltage data enabling high time resolution analysis, obtained from the Commensal Real-time ASKAP (Australian Square Kilometre Array Pathfinder) Fast Transient survey science project (CRAFT). We find strong evidence for two screens in three cases. For FRBs 20190608B and 20210320C, we find evidence for scattering screens less than approximately 16.7 and 3000 kpc respectively, from their sources. For FRB 20201124A we find evidence for a scattering screen at $\approx$26 kpc. Each of these measures is consistent with the scattering occurring in the host ISM (inter-stellar medium) or CGM. If pulse broadening is assumed to be contributed by the host galaxy ISM or circum-burst environment, the definitive lack of observed scintillation in four FRBs in our sample suggests that existing models may be over-estimating scattering times associated with the Milky Way's ISM, similar to the anomalously low scattering observed for FRB 20201124A.Comment: 13 pages, 9 figures, 1 table. Submitted to MNRA

First Constraints on Compact Dark Matter from Fast Radio Burst Microstructure

Despite existing constraints, it remains possible that up to $35\%$ of all dark matter is comprised of compact objects, such as the black holes in the 10-100\,M$_\odot$ range whose existence has been confirmed by LIGO. The strong gravitational lensing of transients such as FRBs and GRBs has been suggested as a more sensitive probe for compact dark matter than intensity fluctuations observed in microlensing experiments. Recently ASKAP has reported burst substructure down to $15\mu$s timescales in FRBs in the redshift range $0.3-0.5$. We investigate here the implications of this for the detectability of compact dark matter by FRBs. We find that a sample size of $\sim130$ FRBs would be required to constrain compact dark matter to less than the existing 35$\%$ limit with 95$\%$ confidence, if it were distributed along $\gtrsim 1\,$Gpc-long FRB sightlines through the cosmic web. Conversely, existing constraints on the fraction of compact dark matter permit as many as 1 in $\approx 40$ of all $z \lesssim 0.4$ FRBs to exhibit micro-lensed burst structure. Approximately $170$ FRBs intercepting halos within $\sim 50\,$kpc would be required to exclude the fraction of compact dark matter in each intercepted halo to a similar level. Furthermore, we consider the cumulative effects of lensing of the FRB signal by a macroscopic dark matter distribution. We conclude that lensing from a uniform distribution of compact objects is likely not observable, but suggest that FRBs may set meaningful limits on power-law distributions of dark matter.Comment: 3 Figures, 1 tabl

Mitotic stress is an integral part of the oncogene-induced senescence program that promotes multinucleation and cell cycle arrest

Oncogene-induced senescence (OIS) is a tumor suppression mechanism that blocks cell proliferation in response to oncogenic signaling. OIS is frequently accompanied by multinucleation; however, the origin of this is unknown. Here, we show that multinucleate OIS cells originate mostly from failed mitosis. Prior to senescence, mutant H-RasV12 activation in primary human fibroblasts compromised mitosis, concordant with abnormal expression of mitotic genes functionally linked to the observed mitotic spindle and chromatin defects. Simultaneously, H-RasV12 activation enhanced survival of cells with damaged mitoses, culminating in extended mitotic arrest and aberrant exit from mitosis via mitotic slippage. ERK-dependent transcriptional upregulation of Mcl1 was, at least in part, responsible for enhanced survival and slippage of cells with mitotic defects. Importantly, mitotic slippage and oncogene signaling cooperatively induced senescence and key senescence effectors p21 and p16. In summary, activated Ras coordinately triggers mitotic disruption and enhanced cell survival to promote formation of multinucleate senescent cells

Raising standards in American schools: the case of No Child Left Behind

In January 2002, President George W Bush signed into law what is arguably the most important piece of US educational legislation for the past 35 years. For the first time, Public Law 107-110 links high stakes testing with strict accountability measures designed to ensure that, at least in schools that receive government funding, no child is left behind. The appropriately named No Child Left Behind Act (NCLB) links government funding to strict improvement policies for America’s public schools. Much of what is undertaken in NCLB is praiseworthy, the Act is essentially equitable for it ensures that schools pay due regard to the progress of those sections of the school population who have traditionally done less well in school, in particular, students from economically disadvantaged homes, as well as those from ethnic minority backgrounds and those who have limited proficiency to speak English. However, this seemingly salutatory aspect of the Act is also the one that has raised the most objections. This paper describes the key features of this important piece of legislation before outlining why it is that a seemingly equitable Act has produced so much consternation in US education circles. Through an exploration of school level data for the state of New Jersey, the paper considers the extent to which these concerns have been justified during the early days of No Child Left Behind

Systematic review of safety in paediatric drug trials published in 2007

Background: There is now greater involvement of children in drug trials to ensure that paediatric medicines are supported by sound scientific evidence. The safety of the participating children is of paramount importance. Previous research shows that these children can suffer moderate and severe adverse drug reactions (ADRs) in clinical trials, yet very few of the trials designated a data safety monitoring board (DSMB) to oversee the trial. Methods: Safety data from a systematic review of paediatric drug randomised controlled trials (RCTs) published in 2007 were analysed. All reported adverse events (AEs) were classified and assessed to determine whether an ADR had been experienced. ADRs were then categorised according to severity. Each trial report was examined as to whether an independent DSMB was in place. Results: Of the 582 paediatric drug RCTs analysed, 210 (36%) reported that a serious AE had occurred, and in 15% mortality was reported. ADRs were detected in more than half of the RCTs (305); 66 (11%) were severe, and 79 (14%) were moderate. Severe ADRs involved a wide range of organ systems and were frequently associated with cytotoxic drugs, antiparasitics, anticonvulsants and psychotropic drugs. Two RCTs reported significantly higher mortality rates in the treatment group. Only 69 (12%) of the RCTs stated there was a DSMB. DSMBs terminated five RCTs and changed the protocol in one. Conclusions: Children participating in drug RCTs experience a significant amount and a wide range of ADRs. DSMBs are needed to ensure the safety of paediatric participants in clinical drug trial

The unseen host galaxy and high dispersion measure of a precisely-localised Fast Radio Burst suggests a high-redshift origin

FRB 20210912A is a fast radio burst (FRB), detected and localised to sub-arcsecond precision by the Australian Square Kilometre Array Pathfinder. No host galaxy has been identified for this burst despite the high precision of its localisation and deep optical and infrared follow-up, to 5-$\sigma$ limits of $R=26.7$ mag and $K_\mathrm{s}=24.9$ mag with the Very Large Telescope. The combination of precise radio localisation and deep optical imaging has almost always resulted in the secure identification of a host galaxy, and this is the first case in which the line-of-sight is not obscured by the Galactic disk. The dispersion measure of this burst, $\mathrm{DM_{FRB}}=1233.696\pm0.006~\mathrm{pc}\ \mathrm{cm}^{-3}$, allows for a large source redshift of $z>1$ according to the Macquart relation. It could thus be that the host galaxy is consistent with the known population of FRB hosts, but is too distant to detect in our observations ($z>0.7$ for a host like that of the first repeating FRB source, FRB 20121102A); that it is more nearby with a significant excess in $\mathrm{DM_{host}}$, and thus dimmer than any known FRB host; or, least likely, that the FRB is truly hostless. We consider each possibility, making use of the population of known FRB hosts to frame each scenario. The fact of the missing host has ramifications for the FRB field: even with high-precision localisation and deep follow-up, some FRB hosts may be difficult to detect, with more distant hosts being the less likely to be found. This has implications for FRB cosmology, in which high-redshift detections are valuable.Comment: 14 pages, 6 figures. Revised based on referee's comments and accepted to MNRA

Probing the distant universe with a very luminous fast radio burst at redshift 1

Fast radio bursts are millisecond-duration pulses of radio emission that have been found to originate at extragalactic distances. The bursts show dispersion imparted by intervening plasma, with the bulk attributed to the intergalactic medium. Here we report the discovery of a burst, FRB20220610A, in a complex host galaxy system at a redshift of $z=1.016 \pm 0.002$. The relationship between its redshift and dispersion confirm that the bulk of the baryonic matter was ionized and in the intergalactic medium when the universe was almost half its present age. The burst shows evidence for passage through a significant additional column of turbulent and magnetized high-redshift plasma. It extends the maximum observed burst energy by a factor of four, confirming the presence of an energetic burst population at high redshift.Comment: 40 page