Radio Planetary Nebulae in the Large Magellanic Cloud

We present 21 new radio-continuum detections at catalogued planetary nebula (PN) positions in the Large Magellanic Cloud (LMC) using all presently available data from the Australia Telescope Online Archive at 3, 6, 13 and 20 cm. Additionally, 11 previously detected LMC radio PNe are re-examined with $7$ detections confirmed and reported here. An additional three PNe from our previous surveys are also studied. The last of the 11 previous detections is now classified as a compact \HII\ region which makes for a total sample of 31 radio PNe in the LMC. The radio-surface brightness to diameter ($\Sigma$-D) relation is parametrised as $\Sigma \propto {D^{ - \beta }}$. With the available 6~cm $\Sigma$-$D$ data we construct $\Sigma$-$D$ samples from 28 LMC PNe and 9 Small Magellanic Cloud (SMC) radio detected PNe. The results of our sampled PNe in the Magellanic Clouds (MCs) are comparable to previous measurements of the Galactic PNe. We obtain $\beta=2.9\pm0.4$ for the MC PNe compared to $\beta = 3.1\pm0.4$ for the Galaxy. For a better insight into sample completeness and evolutionary features we reconstruct the $\Sigma$-$D$ data probability density function (PDF). The PDF analysis implies that PNe are not likely to follow linear evolutionary paths. To estimate the significance of sensitivity selection effects we perform a Monte Carlo sensitivity simulation on the $\Sigma$-$D$ data. The results suggest that selection effects are significant for values larger than $\beta \sim 2.6$ and that a measured slope of $\beta=2.9$ should correspond to a sensitivity-free value of $\sim 3.4$.Comment: 19 pages, 9 figures, 6 table

IKT 16: the first X-ray confirmed composite SNR in the SMC

Aims: IKT 16 is an X-ray and radio-faint supernova remnant (SNR) in the Small Magellanic Cloud (SMC). A detailed X-ray study of this SNR with XMM-Newton confirmed the presence of a hard X-ray source near its centre, indicating the detection of the first composite SNR in the SMC. With a dedicated Chandra observation we aim to resolve the point source and confirm its nature. We also acquire new ATCA observations of the source at 2.1 GHz with improved flux density estimates and resolution. Methods: We perform detailed spatial and spectral analysis of the source. With the highest resolution X-ray and radio image of the centre of the SNR available today, we resolve the source and confirm its pulsar wind nebula (PWN) nature. Further, we constrain the geometrical parameters of the PWN and perform spectral analysis for the point source and the PWN separately. We also test for the radial variations of the PWN spectrum and its possible east west asymmetry. Results: The X-ray source at the centre of IKT 16 can be resolved into a symmetrical elongated feature centering a point source, the putative pulsar. Spatial modeling indicates an extent of 5.2 arcsec of the feature with its axis inclined at 82 degree east from north, aligned with a larger radio feature consisting of two lobes almost symmetrical about the X-ray source. The picture is consistent with a PWN which has not yet collided with the reverse shock. The point source is about three times brighter than the PWN and has a hard spectrum of spectral index 1.1 compared to a value 2.2 for the PWN. This points to the presence of a pulsar dominated by non-thermal emission. The expected E_{dot} is ~ 10^37 erg s^-1 and spin period < 100 ms. However, the presence of a compact nebula unresolved by Chandra at the distance of the SMC cannot completely be ruled out.Comment: 9 pages, 6 figures, 2 tables, Accepted for publication in Astronomy & Astrophysic

LMC X-1: A New Spectral Analysis of the O-star in the binary and surrounding nebula

We provide new observations of the LMC X-1 O star and its extended nebula structure using spectroscopic data from VLT/UVES as well as H$\alpha$ imaging from the Wide Field Imager on the Max Planck Gesellschaft / European Southern Observatory 2.2m telescope and ATCA imaging of the 2.1 GHz radio continuum. This nebula is one of the few known to be energized by an X-ray binary. We use a new spectrum extraction technique that is superior to other methods to obtain both radial velocities and fluxes. This provides an updated spatial velocity of $\simeq 21.0~\pm~4.8$ km s$^{-1}$ for the O star. The slit encompasses both the photo-ionized and shock-ionized regions of the nebula. The imaging shows a clear arc-like structure reminiscent of a wind bow shock in between the ionization cone and shock-ionized nebula. The observed structure can be fit well by the parabolic shape of a wind bow shock. If an interpretation of a wind bow shock system is valid, we investigate the N159-O1 star cluster as a potential parent of the system, suggesting a progenitor mass of $\sim 60$ M$_{\odot}$ for the black hole. We further note that the radio emission could be non-thermal emission from the wind bow shock, or synchrotron emission associated with the jet inflated nebula. For both wind and jet-powered origins, this would represent one of the first radio detections of such a structure.Comment: 7 Figures, 4 Table

Radio Planetary Nebulae in the Small Magellanic Cloud

We present ten new radio continuum (RC) detections at catalogued planetary nebula (PN) positions in the Small Magellanic Cloud (SMC): SMPS6, LIN 41, LIN 142, SMP S13, SMP S14, SMP S16, J18, SMP S18, SMP S19 and SMP S22. Additionally, six SMC radio PNe previously detected, LIN 45, SMP S11, SMPS17, LIN321, LIN339 and SMPS24 are also investigated (re-observed) here making up a population of 16 radio detections of catalogued PNe in the SMC. These 16 radio detections represent ~15 % of the total catalogued PN population in the SMC. We show that six of these objects have characteristics that suggest that they are PN mimics: LIN 41, LIN 45, SMP S11, LIN 142, LIN 321 and LIN 339. We also present our results for the surface brightness - PN radius relation ({\Sigma}-D) of the SMC radio PN population. These are consistent with previous SMC and LMC PN measurements of the ({\Sigma}-D) relation.Comment: Accepted for publication in Astrophysics and Space Scienc

A clinical and economic evaluation of Control of Hyperglycaemia in Paediatric intensive care (CHiP): a randomised controlled trial.

BACKGROUND: Early research in adults admitted to intensive care suggested that tight control of blood glucose during acute illness can be associated with reductions in mortality, length of hospital stay and complications such as infection and renal failure. Prior to our study, it was unclear whether or not children could also benefit from tight control of blood glucose during critical illness. OBJECTIVES: This study aimed to determine if controlling blood glucose using insulin in paediatric intensive care units (PICUs) reduces mortality and morbidity and is cost-effective, whether or not admission follows cardiac surgery. DESIGN: Randomised open two-arm parallel group superiority design with central randomisation with minimisation. Analysis was on an intention-to-treat basis. Following random allocation, care givers and outcome assessors were no longer blind to allocation. SETTING: The setting was 13 English PICUs. PARTICIPANTS: Patients who met the following criteria were eligible for inclusion: ≥ 36 weeks corrected gestational age; ≤ 16 years; in the PICU following injury, following major surgery or with critical illness; anticipated treatment > 12 hours; arterial line; mechanical ventilation; and vasoactive drugs. Exclusion criteria were as follows: diabetes mellitus; inborn error of metabolism; treatment withdrawal considered; in the PICU > 5 consecutive days; and already in CHiP (Control of Hyperglycaemia in Paediatric intensive care). INTERVENTION: The intervention was tight glycaemic control (TGC): insulin by intravenous infusion titrated to maintain blood glucose between 4.0 and 7.0 mmol/l. CONVENTIONAL MANAGEMENT (CM): This consisted of insulin by intravenous infusion only if blood glucose exceeded 12.0 mmol/l on two samples at least 30 minutes apart; insulin was stopped when blood glucose fell below 10.0 mmol/l. MAIN OUTCOME MEASURES: The primary outcome was the number of days alive and free from mechanical ventilation within 30 days of trial entry (VFD-30). The secondary outcomes comprised clinical and economic outcomes at 30 days and 12 months and lifetime cost-effectiveness, which included costs per quality-adjusted life-year. RESULTS: CHiP recruited from May 2008 to September 2011. In total, 19,924 children were screened and 1369 eligible patients were randomised (TGC, 694; CM, 675), 60% of whom were in the cardiac surgery stratum. The randomised groups were comparable at trial entry. More children in the TGC than in the CM arm received insulin (66% vs. 16%). The mean VFD-30 was 23 [mean difference 0.36; 95% confidence interval (CI) -0.42 to 1.14]. The effect did not differ among prespecified subgroups. Hypoglycaemia occurred significantly more often in the TGC than in the CM arm (moderate, 12.5% vs. 3.1%; severe, 7.3% vs. 1.5%). Mean 30-day costs were similar between arms, but mean 12-month costs were lower in the TGC than in CM arm (incremental costs -£3620, 95% CI -£7743 to £502). For the non-cardiac surgery stratum, mean costs were lower in the TGC than in the CM arm (incremental cost -£9865, 95% CI -£18,558 to -£1172), but, in the cardiac surgery stratum, the costs were similar between the arms (incremental cost £133, 95% CI -£3568 to £3833). Lifetime incremental net benefits were positive overall (£3346, 95% CI -£11,203 to £17,894), but close to zero for the cardiac surgery stratum (-£919, 95% CI -£16,661 to £14,823). For the non-cardiac surgery stratum, the incremental net benefits were high (£11,322, 95% CI -£15,791 to £38,615). The probability that TGC is cost-effective is relatively high for the non-cardiac surgery stratum, but, for the cardiac surgery subgroup, the probability that TGC is cost-effective is around 0.5. Sensitivity analyses showed that the results were robust to a range of alternative assumptions. CONCLUSIONS: CHiP found no differences in the clinical or cost-effectiveness of TGC compared with CM overall, or for prespecified subgroups. A higher proportion of the TGC arm had hypoglycaemia. This study did not provide any evidence to suggest that PICUs should stop providing CM for children admitted to PICUs following cardiac surgery. For the subgroup not admitted for cardiac surgery, TGC reduced average costs at 12 months and is likely to be cost-effective. Further research is required to refine the TGC protocol to minimise the risk of hypoglycaemic episodes and assess the long-term health benefits of TGC. TRIAL REGISTRATION: Current Controlled Trials ISRCTN61735247. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 18, No. 26. See the NIHR Journals Library website for further project information

Control of hyperglycaemia in paediatric intensive care (CHiP): study protocol.

BACKGROUND: There is increasing evidence that tight blood glucose (BG) control improves outcomes in critically ill adults. Children show similar hyperglycaemic responses to surgery or critical illness. However it is not known whether tight control will benefit children given maturational differences and different disease spectrum. METHODS/DESIGN: The study is an randomised open trial with two parallel groups to assess whether, for children undergoing intensive care in the UK aged <or= 16 years who are ventilated, have an arterial line in-situ and are receiving vasoactive support following injury, major surgery or in association with critical illness in whom it is anticipated such treatment will be required to continue for at least 12 hours, tight control will increase the numbers of days alive and free of mechanical ventilation at 30 days, and lead to improvement in a range of complications associated with intensive care treatment and be cost effective. Children in the tight control group will receive insulin by intravenous infusion titrated to maintain BG between 4 and 7.0 mmol/l. Children in the control group will be treated according to a standard current approach to BG management. Children will be followed up to determine vital status and healthcare resources usage between discharge and 12 months post-randomisation. Information regarding overall health status, global neurological outcome, attention and behavioural status will be sought from a subgroup with traumatic brain injury (TBI). A difference of 2 days in the number of ventilator-free days within the first 30 days post-randomisation is considered clinically important. Conservatively assuming a standard deviation of a week across both trial arms, a type I error of 1% (2-sided test), and allowing for non-compliance, a total sample size of 1000 patients would have 90% power to detect this difference. To detect effect differences between cardiac and non-cardiac patients, a target sample size of 1500 is required. An economic evaluation will assess whether the costs of achieving tight BG control are justified by subsequent reductions in hospitalisation costs. DISCUSSION: The relevance of tight glycaemic control in this population needs to be assessed formally before being accepted into standard practice

The Chief Scientist Office cardiovascular and pulmonary imaging in SARS Coronavirus disease-19 (CISCO-19) study

Background: COVID-19 is typically a primary respiratory illness with multisystem involvement. The prevalence and clinical significance of cardiovascular and multisystem involvement in COVID-19 remain unclear. Methods: This is a prospective, observational, multicentre, longitudinal, cohort study with minimal selection criteria and a near-consecutive approach to screening. Patients who have received hospital care for COVID-19 will be enrolled within 28 days of discharge. Myocardial injury will be diagnosed according to the peak troponin I in relation to the upper reference limit (URL, 99th centile) (Abbott Architect troponin I assay; sex-specific URL, male: &gt;34 ng/L; female: &gt;16 ng/L). Multisystem, multimodality imaging will be undertaken during the convalescent phase at 28 days post-discharge (Visit 2). Imaging of the heart, lung, and kidneys will include multiparametric, stress perfusion, cardiovascular magnetic resonance imaging, and computed tomography coronary angiography. Health and well-being will be assessed in the longer term. The primary outcome is the proportion of patients with a diagnosis of myocardial inflammation. Conclusion: CISCO-19 will provide detailed insights into cardiovascular and multisystem involvement of COVID-19. Our study will inform the rationale and design of novel therapeutic and management strategies for affected patients

Justify your alpha

Benjamin et al. proposed changing the conventional “statistical significance” threshold (i.e.,the alpha level) from p ≤ .05 to p ≤ .005 for all novel claims with relatively low prior odds. They provided two arguments for why lowering the significance threshold would “immediately improve the reproducibility of scientific research.” First, a p-value near .05provides weak evidence for the alternative hypothesis. Second, under certain assumptions, an alpha of .05 leads to high false positive report probabilities (FPRP2 ; the probability that a significant finding is a false positive

Significant benefits of AIP testing and clinical screening in familial isolated and young-onset pituitary tumors

Context Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs). Objective To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients. Design 12-year prospective, observational study. Participants & Setting We studied probands and family members of FIPA kindreds and sporadic patients with disease onset ≤18 years or macroadenomas with onset ≤30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases. Interventions & Outcome AIP testing and clinical screening for pituitary disease. Comparison of characteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients (n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310). Results Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases, AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy, suprasellar extension, and more patients required multimodal therapy, including radiotherapy. AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650). Conclusions Prospectively diagnosed AIPmut patients show better outcomes than clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course