A recurrent nova super-remnant in the Andromeda galaxy.

The accretion of hydrogen onto a white dwarf star ignites a classical nova eruption1,2-a thermonuclear runaway in the accumulated envelope of gas, leading to luminosities up to a million times that of the Sun and a high-velocity mass ejection that produces a remnant shell (mainly consisting of insterstellar medium). Close to the upper mass limit of a white dwarf3 (1.4 solar masses), rapid accretion of hydrogen (about 10-7 solar masses per year) from a stellar companion leads to frequent eruptions on timescales of years4,5 to decades6. Such binary systems are known as recurrent novae. The ejecta of recurrent novae, initially moving at velocities of up to 10,000 kilometres per second7, must 'sweep up' the surrounding interstellar medium, creating cavities in space around the nova binary. No remnant larger than one parsec across from any single classical or recurrent nova eruption is known8-10, but thousands of successive recurrent nova eruptions should be capable of generating shells hundreds of parsecs across. Here we report that the most frequently recurring nova, M31N 2008-12a in the Andromeda galaxy (Messier 31 or NGC 224), which erupts annually11, is indeed surrounded by such a super-remnant with a projected size of at least 134 by 90 parsecs. Larger than almost all known remnants of even supernova explosions12, the existence of this shell demonstrates that the nova M31N 2008-12a has erupted with high frequency for millions of years.

What explains regional variation in privately provided out-of-area residential placement costs for people with intellectual disability in Ireland?

BACKGROUND: Expenditure on residential placements for people with intellectual disability (ID) in Ireland is considerable and expected to increase. Despite this, there is limited evidence on the factors driving variation in privately provided 'out-of-area' residential placement costs, including across Community Health Organisations (CHOs)/regions. This is important to help inform the delivery of services at best value. METHODS: We analyse unit cost data from 2019 for a sample of 278 high-cost publicly funded privately provided out-of-area residential placements for people with ID in Ireland. We undertake univariate analysis of the relationship between costs and a wide range of variables using t-tests and one-way analysis of variance. We employ multivariable regression analysis to examine how raw differentials in unit costs across regions can be accounted for by individual-level characteristics. RESULTS: We estimate average unit costs of €264 170 per annum in our sample. The univariate analysis shows considerable variation in costs across a range of personal, disability, psychiatry/psychological, forensic issues, behaviour and supports and plans related variables. We also find wide variation in average unit costs across CHOs/regions (F = 4.58, P < 0.001), ranging from €213 380 to €331 880. The multivariable analysis shows that regional differences remain even after accounting for a wide range of individual characteristics that influence costs. CONCLUSIONS: Our analysis shows that while the majority of differences in costs across regions can be explained, there is potential for cost savings in the provision of high-cost publicly funded out-of-area residential placements in Ireland. Overall this can help to develop and implement a more sustainable disability residential funding model in a context of rising demand for services. It also has potential implications for the approach to procurement of services.

Neurological factors and Cesarean section in Australian women with epilepsy.

OBJECTIVES: To analyze the records of the pregnancies of 2283 Australian women with epilepsy in the Australian Register of Antiepileptic Drugs in Pregnancy database to identify neurological factors relevant to the Cesarean sections carried out in these pregnancies. RESULTS: The Cesarean section rate in Australian women overall increased by an average of 0.59% annually over 20 years, from 26.0% to its calculated 2020 value of 37.3%. For the operations in women with epilepsy, the corresponding figures were 0.71% annually, and 34.4% and 48.7%. The average annual rate of increase for pre-labor operations was 0.89% to a 2020 value of 39.1%, the annual rate for operations during labor showing no statistically significant change. Multivariate regression analysis identified a number of characteristics of women with epilepsy that were statistically significantly associated with an increased likelihood of Cesarean section, but of these only seizures continuing to occur in the third trimester and having chronic illness, in particular migraine, were neurological ones. In 70 migraine-affected women, the Cesarean section rate was 51.4%, compared with 39% in the remaining pregnancies (P < 0.05). CONCLUSIONS: Having seizures in the final trimester of pregnancy and having chronic neurological illness, especially migraine, favored Cesarean section being carried out in Australian women with epilepsy, but did not adequately account for the increasing rates of occurrence of the operation over the past 20 years.

Determining concentric and eccentric force-velocity profiles during squatting.

PURPOSE: The force-velocity relationship of muscular contraction has been extensively studied. However, previous research has focussed either on isolated muscle or single-joint movements, whereas human movement consists of multi-joint movements (e.g. squatting). Therefore, the purpose of this study was to investigate the force-velocity relationship of isovelocity squatting. METHODS: Fifteen male participants (24 ± 2 years, 79.8 ± 9.1 kg, 177.5 ± 6 cm) performed isovelocity squats on a novel motorised isovelocity device (Kineo Training System) at three concentric (0.25, 0.5, and 0.75 m s-1) and three eccentric velocities (- 0.25, - 0.5, and - 0.75 m s-1). Peak vertical ground reaction forces, that occurred during the isovelocity phase, were collected using dual force plates (2000 Hz) (Kistler, Switzerland). RESULTS: The group mean squat force-velocity profile conformed to the typical in vivo profile, with peak vertical ground reaction forces during eccentric squatting being 9.5 ± 19% greater than isometric (P = 0.037), and occurring between - 0.5 and - 0.75 m s-1. However, large inter-participant variability was identified (0.84-1.62 × isometric force), with some participants being unable to produce eccentric forces greater than isometric. Sub-group analyses could not identify differences between individuals who could/could not produce eccentric forces above isometric, although those who could not tended to be taller. CONCLUSIONS: These finding suggest that variability exists between participants in the ability to generate maximum eccentric forces during squatting, and the magnitude of eccentric increase above isometric cannot be predicted solely based on a concentric assessment. Therefore, an assessment of eccentric capabilities may be required prior to prescribing eccentric-specific resistance training.

Empirically Estimated Electron Lifetimes in the Earth's Radiation Belts: Van Allen Probe Observations.

We use measurements from NASA's Van Allen Probes to calculate the decay time constants for electrons over a wide range of energies (30 keV to 4 MeV) and L values ( L = 1.3-6.0) in the Earth's radiation belts. Using an automated routine to identify flux decay events, we construct a large database of lifetimes for near-equatorially mirroring electrons over a 5-year interval. We provide the first accurate estimates of the long decay timescales in the inner zone ( ∼ 100 days), which are highly resolved in energy and free from proton contamination. In the slot region and outer zone, we compare our lifetime calculations with prior empirical estimates and find good quantitative agreement (lifetimes ∼ 1-20 days). The comparisons suggest that some prior estimates may overestimate electron lifetimes between L ≈ 2.5-4.5 due to instrumental effects and/or background contamination. Previously reported two-stage decays are explicitly demonstrated to be a consequence of using integral fluxes.

Empirically Estimated Electron Lifetimes in the Earth's Radiation Belts: Comparison With Theory.

We compute quasilinear diffusion rates due to pitch angle scattering by various mechanisms in the Earth's electron radiation belts. The calculated theoretical lifetimes are compared with observed decay rates, and we find excellent qualitative agreement between the two. The overall structure of the observed lifetime profiles as a function of energy and L is largely due to plasmaspheric hiss and Coulomb scattering. The results also reveal a local minimum in lifetimes in the inner zone at lower energy ( ∼ 50 keV), attributed to enhanced scattering via ground-based very low frequency transmitters, and a reduction in lifetimes at higher L and energy ( > 1 MeV), attributed to enhanced electromagnetic ion cyclotron wave scattering. In addition, we find significant quantitative disagreement at L < 3 . 5 , where the theoretical lifetimes are typically a factor of ∼ 10 larger than the observed, pointing to an additional loss process that is missing from current models. We discuss potential factors that could contribute to this disagreement.

Binary orbits as the driver of γ-ray emission and mass ejection in classical novae.

Classical novae are the most common astrophysical thermonuclear explosions, occurring on the surfaces of white dwarf stars accreting gas from companions in binary star systems. Novae typically expel about 10(-4) solar masses of material at velocities exceeding 1,000 kilometres per second. However, the mechanism of mass ejection in novae is poorly understood, and could be dominated by the impulsive flash of thermonuclear energy, prolonged optically thick winds or binary interaction with the nova envelope. Classical novae are now routinely detected at gigaelectronvolt γ-ray wavelengths, suggesting that relativistic particles are accelerated by strong shocks in the ejecta. Here we report high-resolution radio imaging of the γ-ray-emitting nova V959 Mon. We find that its ejecta were shaped by the motion of the binary system: some gas was expelled rapidly along the poles as a wind from the white dwarf, while denser material drifted out along the equatorial plane, propelled by orbital motion. At the interface between the equatorial and polar regions, we observe synchrotron emission indicative of shocks and relativistic particle acceleration, thereby pinpointing the location of γ-ray production. Binary shaping of the nova ejecta and associated internal shocks are expected to be widespread among novae, explaining why many novae are γ-ray emitters.

Embodiment and Estrangement: Results from a First-in-Human "Intelligent BCI" Trial.

While new generations of implantable brain computer interface (BCI) devices are being developed, evidence in the literature about their impact on the patient experience is lagging. In this article, we address this knowledge gap by analysing data from the first-in-human clinical trial to study patients with implanted BCI advisory devices. We explored perceptions of self-change across six patients who volunteered to be implanted with artificially intelligent BCI devices. We used qualitative methodological tools grounded in phenomenology to conduct in-depth, semi-structured interviews. Results show that, on the one hand, BCIs can positively increase a sense of the self and control; on the other hand, they can induce radical distress, feelings of loss of control, and a rupture of patient identity. We conclude by offering suggestions for the proactive creation of preparedness protocols specific to intelligent-predictive and advisory-BCI technologies essential to prevent potential iatrogenic harms.

Exploring the Interface of Oncology and Palliative Care in Ireland

Aims To explore the integration and delivery of oncology led referrals to palliative care (PC) by examining physician attitudes and referral practices. Methods An online survey was circulated to oncologists and PC physicians in Ireland. Results The study (N = 100) comprised sixty-nine oncologists (69%) and thirty-one PC physicians (31%). Ninety-two(92%) believe patients with advanced cancer should receive concurrent treatment, however only 53% of oncologists(N = 37) routinely refer. Regarding end-of-life (EOL) care: 81% of oncologists (N = 55) are directly involved in its administration, despite 84% (N = 53) agreeing patients benefit when PC specialists coordinate EOL care. Conclusion The gulf between positive attitudes and limited implementation suggests the need for interdisciplinary changes to facilitate integration of PC in clinical practice in Ireland.

Space Radiation and Plasma Effects on Satellites and Aviation: Quantities and Metrics for Tracking Performance of Space Weather Environment Models.

The Community Coordinated Modeling Center has been leading community-wide space science and space weather model validation projects for many years. These efforts have been broadened and extended via the newly launched International Forum for Space Weather Modeling Capabilities Assessment (https://ccmc.gsfc.nasa.gov/assessment/). Its objective is to track space weather models' progress and performance over time, a capability that is critically needed in space weather operations and different user communities in general. The Space Radiation and Plasma Effects Working Team of the aforementioned International Forum works on one of the many focused evaluation topics and deals with five different subtopics (https://ccmc.gsfc.nasa.gov/assessment/topics/radiation-all.php) and varieties of particle populations: Surface Charging from tens of eV to 50-keV electrons and internal charging due to energetic electrons from hundreds keV to several MeVs. Single-event effects from solar energetic particles and galactic cosmic rays (several MeV to TeV), total dose due to accumulation of doses from electrons (>100 keV) and protons (>1 MeV) in a broad energy range, and radiation effects from solar energetic particles and galactic cosmic rays at aviation altitudes. A unique aspect of the Space Radiation and Plasma Effects focus area is that it bridges the space environments, engineering, and user communities. The intent of the paper is to provide an overview of the current status and to suggest a guide for how to best validate space environment models for operational/engineering use, which includes selection of essential space environment and effect quantities and appropriate metrics.

Majorana-Based Fermionic Quantum Computation.

Because Majorana zero modes store quantum information nonlocally, they are protected from noise, and have been proposed as a building block for a quantum computer. We show how to use the same protection from noise to implement universal fermionic quantum computation. Our architecture requires only two Majorana modes to encode a fermionic quantum degree of freedom, compared to alternative implementations which require a minimum of four Majorana modes for a spin quantum degree of freedom. The fermionic degrees of freedom support both unitary coupled cluster variational quantum eigensolver and quantum phase estimation algorithms, proposed for quantum chemistry simulations. Because we avoid the Jordan-Wigner transformation, our scheme has a lower overhead for implementing both of these algorithms, allowing for simulation of the Trotterized Hubbard Hamiltonian in O(1) time per unitary step. We finally demonstrate magic state distillation in our fermionic architecture, giving a universal set of topologically protected fermionic quantum gates.

Antiepileptic drug polytherapy in pregnant women with epilepsy.

OBJECTIVE: To study seizure control and rates of foetal malformation in pregnancies of women with epilepsy treated with antiepileptic drug polytherapy. METHODS: The use of conventional statistical methods to analyse the Australian Pregnancy Register records of 1810 pregnancies in women with epilepsy, 508 treated with antiepileptic drug polytherapy. RESULTS: Polytherapy-treated pregnancies were less often seizure free than monotherapy-treated ones, for both focal (36.0% vs 51.9%: P < .05) and primary generalized epilepsies (41.1% vs 69.3%; P < .05). Drug combinations with dissimilar and similar mechanisms of action achieved similar rates of seizure freedom during pregnancy (36.3% vs 38.3%). The increased rate of malformed foetuses in polytherapy pregnancies depended on valproate or topiramate being in the drug combinations. The combinations of lamotrigine and levetiracetam offered the chance of seizure control and foetal safety. CONCLUSIONS: In pregnancy, the use of antiepileptic drug combinations is not necessarily disadvantageous to mother and foetus if valproate and topiramate are avoided.

Anti-epileptic drug exposure and risk of foetal death in utero.

OBJECTIVE: To clarify whether anti-epileptic drug exposure during pregnancy is associated with an increased risk of intrauterine foetal death. METHODS: Analysis of data from 2064 pregnancies with known outcomes included in the Australian Register of Antiepileptic Drugs in Pregnancy, 170 of the pregnancies being unexposed to the drugs in at least the first half of pregnancy. RESULTS: The relative risk (6.46; 95% C.I. 0.90, 46.22) of intrauterine death appeared higher, though not statistically significantly higher, in drug-exposed pregnancies compared with unexposed ones (3.44% vs 0.59%). There was no statistically significantly increased hazard associated with AED polytherapy as compared with monotherapy. Logistic regression analysis showed a statistically significantly increased and dose-related hazard of intrauterine death in relation to carbamazepine exposure. CONCLUSIONS: Intrauterine exposure to anti-epileptic drugs, particularly carbamazepine, may be associated with an increased risk of foetal death during pregnancy.

Predicting epileptic seizure control during pregnancy.

OBJECTIVE: The objective of the study was to assess whether the type of seizure disorder present in the prospective mother with epilepsy, her use of antiepileptic drugs (AEDs) in early pregnancy, and her seizure control before pregnancy help predict her prospects for seizure freedom throughout pregnancy. METHODS: This paper is based on data accumulated in the Australian Pregnancy Register (APR) between 1998 and late 2016. Information was analyzed concerning epileptic seizure occurrence and AED therapy taken before and during pregnancy, using simple statistical and confidence interval (C.I.) methods, mainly relative risk (R.R.) calculations. RESULTS: After excluding pregnancies lost to follow-up, and those that ended prematurely because of spontaneous abortion or stillbirth, 1939 pregnancies were available for study. Seizures had occurred during pregnancy in 829 (42.8%), and convulsive seizures in 385 (19.9%). Seizures of any type occurred in 78.4% of pregnancies where seizures had occurred in the previous year (active epilepsy) and in 22.3% of those associated with inactive epilepsy. Seizures of any type had occurred in 54.9% of pregnancies initially unexposed to AEDs and in 45.5% of those treated with AEDs throughout. The corresponding figures for convulsive seizures during pregnancy were 31.7% and 22.3%. There was statistically significant evidence that, in women with epilepsy (WWE), having a seizure disorder that was active in the prepregnancy year and one untreated in early pregnancy was associated with decreased prospects of seizure freedom during pregnancy. Decreased chances of seizure-free pregnancies in women with focal epilepsies and those treated with multiple AEDs were probably explained by greater frequencies of active seizure disorders in these patient categories. CONCLUSIONS: Women with epilepsy who experience seizures in the year prior to pregnancy appear 3 or 4 times more likely to continue to have seizures during pregnancy than women whose seizures are fully controlled prior to pregnancy. Not taking AEDs in early pregnancy also increases the hazard for seizure occurrence in pregnancy.

Bone loss with antiepileptic drug therapy: a twin and sibling study.

Changes in areal bone mineral density (aBMD) and other predictors of bone loss were evaluated in 48 same-sex twin/age-matched sibling pairs discordant for antiepileptic drug (AED) use. AED users had reduced BMD at the hip regions. Prolonged AED users had greater aBMD loss, predicting a higher risk of bone fragility. INTRODUCTION: To investigate the longitudinal associations of bone mineral measures with antiepileptic drug (AED) use, including enzyme-inducing (EIAED) and non-enzyme-inducing (NEIAED) types, and other predictors of bone loss in a study of 48 same-sex twin/age-matched sibling pairs (40 female, 8 male) discordant for AED use. METHODS: Using dual-energy X-ray absorptiometry (DXA), areal bone mineral density (aBMD) and content (BMC) at the hip regions, forearm, lumbar spine, and whole body were measured twice, at least 2 years apart. The mean within-pair difference (MWPD), MWPD%, and mean annual rate of aBMD change were adjusted for age, weight, and height. Predictors of bone loss were evaluated. RESULTS: AED users, compared to non-users, at baseline and follow-up, respectively, had reduced aBMD at the total hip (MWPD% 3.8, 4.4%), femoral neck (4.7, 4.5%), and trochanter regions (4.1, 4.6%) (p < 0.05). For the whole cohort, the annual rate of change in all aBMD/BMC (p > 0.05) regions did not differ within pairs. Nevertheless, EIAED users had greater aBMD loss than non-users (n = 20 pairs) at the total hip (1.7 vs. 0.3%, p = 0.013) and whole body regions (0.7% loss vs. 0.1% BMD gain, p = 0.019), which was not found in NEIAED-discordant pairs (n = 16). AED use >20 years predicted higher aBMD loss at the forearm (p = 0.028), whole body (p = 0.010), and whole body BMC (p = 0.031). CONCLUSIONS: AED users had reduced aBMD at the hip regions. Prolonged users and EIAED users had greater aBMD loss, predicting a higher risk of bone fragility. Further prospective studies of AED effects on bone microarchitecture are needed.

Superconductivity Provides Access to the Chiral Magnetic Effect of an Unpaired Weyl Cone.

The massless fermions of a Weyl semimetal come in two species of opposite chirality, in two cones of the band structure. As a consequence, the current j induced in one Weyl cone by a magnetic field B [the chiral magnetic effect (CME)] is canceled in equilibrium by an opposite current in the other cone. Here, we show that superconductivity offers a way to avoid this cancellation, by means of a flux bias that gaps out a Weyl cone jointly with its particle-hole conjugate. The remaining gapless Weyl cone and its particle-hole conjugate represent a single fermionic species, with renormalized charge e^{*} and a single chirality ± set by the sign of the flux bias. As a consequence, the CME is no longer canceled in equilibrium but appears as a supercurrent response ∂j/∂B=±(e^{*}e/h^{2})µ along the magnetic field at chemical potential µ.

Antiepileptic drugs, foetal malformations and spontaneous abortions.

BACKGROUND: Some recent studies have found an association between foetal malformations in earlier antiepileptic drug (AED)-exposed pregnancies and an increased hazard of such malformations in subsequent pregnancies. We investigated this matter further, and also considered the possible role of spontaneous abortions in previous pregnancies, in this situation. METHODS: Analysis of foetal malformation data for current and previous pregnancies in women taking AEDs and women with untreated epilepsy in the Australian Register of Antiepileptic Drugs in Pregnancy (APR) from 1999 to late 2014. RESULTS: Antiepileptic drug-treated women with either a malformed foetus or a spontaneous abortion in their previous pregnancy had a statistically significant twofold to threefold increased risk of foetal malformation in their next pregnancy, compared with similarly treated women with normal offspring in their previous pregnancy. This was not seen in the same circumstances in women with untreated epilepsy. On AED treatment, the women were more likely to have spontaneous abortions than in their previous untreated pregnancies. Possibly some of the increased abortion rate resulted from drug-related malformations that were incompatible with continuing intrauterine survival. CONCLUSIONS: In assessing the hazard of an AED-treated woman having a malformed foetus, it is important to know both the AEDs being taken and, if there had been a previous pregnancy, whether a foetal malformation or a spontaneous abortion occurred in it.

Magnetic Breakdown and Klein Tunneling in a Type-II Weyl Semimetal.

The band structure of a type-II Weyl semimetal has pairs of electron and hole pockets that coexist over a range of energies and touch at a topologically protected conical point. We identify signatures of this Weyl point in the magnetic quantum oscillations of the density of states, observable in thermodynamic properties. Tunneling between the electron and hole pockets in a magnetic field is the momentum space counterpart of Klein tunneling at a p-n junction in real space. This magnetic breakdown happens at a characteristic field strength that vanishes when the Fermi level approaches the Weyl point. The topological distinction between connected and disconnected pairs of type-II Weyl cones can be distinguished by the qualitatively different dependence of the quantum oscillations on the direction of the magnetic field.

Separating Family-Level and Direct Exposure Effects of Smoking During Pregnancy on Offspring Externalizing Symptoms: Bridging the Behavior Genetic and Behavior Teratologic Divide.

Maternal smoking during pregnancy (MSDP) has been robustly associated with externalizing problems and their developmental precursors in offspring in studies using behavioral teratologic designs (Wakschlag et al., Am J Public Health 92(6):966-974, 2002; Espy et al., Dev Psychol 47(1):153-169, 2011). In contrast, the use of behavior genetic approaches has shown that the effects commonly attributed to MSDP can be explained by family-level variables (D'Onofrio et al., Dev Psychopathol 20(01):139-164, 2008). Reconciling these conflicting findings requires integration of these study designs. We utilize longitudinal data on a preschool proband and his/her sibling from the Midwest Infant Development Study-Preschool (MIDS-P) to test for teratologic and family level effects of MSDP. We find considerable variation in prenatal smoking patterns both within and across pregnancies within families, indicating that binary smoking measures are not sufficiently capturing exposure. Structural equation models indicate that both conduct disorder and oppositional defiant disorder symptoms showed unique effects of MSDP over and above family level effects. Blending high quality exposure measurement with a within-family design suggests that it is premature to foreclose the possibility of a teratologic effect of MSDP on externalizing problems. Implications and recommendations for future studies are discussed.

Endothelial nitric oxide synthase induces heat shock protein HSPA6 (HSP70B') in human arterial smooth muscle cells.

Endothelial nitric oxide synthase (eNOS) is the major source of nitric oxide (NO) production in blood vessels. One of the pleitropic functions of eNOS derived NO is to inhibit vascular smooth muscle cell proliferation in the blood vessel wall, and whose dysfunction is a primary cause of atherosclerosis and restenosis. In this study there was an interest in examining the gene profile of eNOS adenoviral (Ad-eNOS) transduced human coronary artery smooth muscle cells (HCASMC) to further understand the eNOS inhibitory effect on smooth muscle cell proliferation. To this aim a whole genome wide analysis of eNOS transduced HCASMCs was performed. A total of 19 genes were up regulated, and 31 genes down regulated in Ad-eNOS transduced HCASMCs compared to cells treated with an empty adenovirus. Noticeably, a cluster of HSP70 gene family members was amongst the genes up regulated. Quantitative PCR confirmed that transcripts for HSPA1A (HSP70A), HSPA1B (HSP70B) and HSPA6 (HSP70B') were elevated 2, 1.7 and 14-fold respectively in Ad-eNOS treated cells. The novel gene HSPA6 was further explored as a potential mediator of eNOS signaling in HCASMC. Immunoblotting showed that HSPA6 protein was induced by Ade-NOS. To functionally examine the effect of HSPA6 on SMCs, an adenovirus harboring the HSPA6 gene under the control of a constitutive promoter was generated. Transduction of HCASMCs with Ad-HSPA6 inhibited SMC proliferation at 3 and 6 days post serum growth stimulation, and paralleled the Ad-eNOS inhibition of SMC growth. The identification in this study that HSPA6 overexpression inhibits SMC proliferation coupled with the recent finding that inhibition of HSP90 has a similar effect, progresses the field of targeting HSPs for vascular repair.