Three-point phase correlations: A new measure of non-linear large-scale structure

We derive an analytical expression for a novel large-scale structure observable: the line correlation function. The line correlation function, which is constructed from the three-point correlation function of the phase of the density field, is a robust statistical measure allowing the extraction of information in the non-linear and non-Gaussian regime. We show that, in perturbation theory, the line correlation is sensitive to the coupling kernel F_2, which governs the non-linear gravitational evolution of the density field. We compare our analytical expression with results from numerical simulations and find a 1-sigma agreement for separations r<30 Mpc/h. Fitting formulae for the power spectrum and the non-linear coupling kernel at small scales allow us to extend our prediction into the strongly non-linear regime where we find a 1-sigma agreement with the simulations for r<2 Mpc/h. We discuss the advantages of the line correlation relative to standard statistical measures like the bispectrum. Unlike the latter, the line correlation is independent of the bias, in the regime where the bias is local and linear. Furthermore, the variance of the line correlation is independent of the Gaussian variance on the modulus of the density field. This suggests that the line correlation can probe more precisely the non-linear regime of gravity, with less contamination from the power spectrum variance.Comment: 11 pages, 5 figures. v2: replacement of the low resolution simulations, more precise quantification of the agreement with simulations, references added. Matches published version. Our code to calculate the line correlation is available at http://blue-shift.ch/phas

Lung ultrasound education: simulation and hands-on

COVID-19 can cause damage to the lung, which can result in progressive respiratory failure and potential death. Chest radiography and CT are the imaging tools used to diagnose and monitor patients with COVID-19. Lung ultrasound (LUS) during COVID-19 is being used in some areas to aid decision-making and improve patient care. However, its increased use could help improve existing practice for patients with suspected COVID-19, or other lung disease. A limitation of LUS is that it requires practitioners with sufficient competence to ensure timely, safe, and diagnostic clinical/imaging assessments. This commentary discusses the role and governance of LUS during and beyond the COVID-19 pandemic, and how increased education and training in this discipline can be undertaken given the restrictions in imaging highly infectious patients. The use of simulation, although numerical methods or dedicated scan trainers, and machine learning algorithms could further improve the accuracy of LUS, whilst helping to reduce its learning curve for greater uptake in clinical practice

Cosmology with phase statistics: parameter forecasts and detectability of BAO

We consider an alternative to conventional three-point statistics such as the bispectrum, which is purely based on the Fourier phases of the density field: the line correlation function. This statistic directly probes the non-linear clustering regime and contains information highly complementary to that contained in the power spectrum. In this work, we determine, for the first time, its potential to constrain cosmological parameters and detect baryon acoustic oscillations (hereafter BAOs). We show how to compute the line correlation function for a discrete sampled set of tracers that follow a local Lagrangian biasing scheme and demonstrate how it breaks the degeneracy between the amplitude of density fluctuations and the bias parameters of the model.We then derive analytic expressions for its covariance and show that it can be written as a sum of a Gaussian piece plus non-Gaussian corrections.We compare our predictions with a large ensemble of N-body simulations and confirm that BAOs do indeed modulate the signal of the line correlation function for scales 50–100 h−1Mpc and that the characteristic S-shape feature would be detectable in upcoming Stage IV surveys at the level of ∼4σ.We then focus on the cosmological information content and compute Fisher forecasts for an idealized Stage III galaxy redshift survey of volume V ∼ 10 h−3 Gpc3 and out to z = 1. We show that combining the line correlation function with the galaxy power spectrum and a Planck-like microwave background survey yields improvements up to a factor of 2 for parameters such as σ8, b1 and b2, compared with using only the two-point information alone

Neonatal respiratory distress syndrome: Chest X-ray or lung ultrasound? A systematic review

Background and aim: Neonatal respiratory distress syndrome (NRDS) is a leading cause of morbidity in preterm new-born babies (< 37 weeks gestation age [GA]). The current diagnostic reference standard includes clinical testing and chest radiography (CXR) with associated exposure to ionising radiation. The aim of this review was to compare the diagnostic accuracy of lung ultrasound (LUS) against the reference standard in symptomatic neonates of ≤ 42 weeks GA. Methods: A systematic search of literature published between 1990 and 2016 identified 803 potentially relevant studies. Six studies met the review inclusion criteria and were retrieved for analysis. Quality assessment was performed before data extraction and meta-analysis. Results: Four prospective cohort studies and two case control studies included 480 neonates. All studies were of moderate methodological quality although heterogeneity was evident across the studies. The pooled sensitivity and specificity of LUS were 97% (95% confidence interval [CI] 94%-99%) and 91% (CI: 86%-95%) respectively. False positive diagnoses were made in sixteen cases due to pneumonia (n=8), transient tachypnoea (n=3), pneumothorax (n=1) and meconium aspiration syndrome (n=1); the diagnoses of the remaining three false positive results were not specified. False negatives diagnoses occurred in nine cases, only two were specified as air-leak syndromes. Conclusions: LUS was highly sensitive for the detection of NRDS although there is potential to miss co-morbid air-leak syndromes (ALS). Further research into LUS diagnostic accuracy for neonatal ALS and economic modelling for service integration is required before LUS can replace CXR as the imaging component of the reference standard

Cation-controlled enantioselective and diastereoselective synthesis of indolines : an autoinductive phase-transfer initiated 5-endo-trig process

The European Research Council has provided financial support under the European Community’s Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement no. 259056. We are grateful to EPSRC and Pfizer for an award (to CPJ, EP/G041628/1), and the Tata foundation for a scholarship (to K.S.). We also acknowledge computational support from the NSF’s XSEDE program.A catalytic enantioselective approach to the synthesis of indolines bearing two asymmetric centers, one of which is all-carbon and quaternary, is described. This reaction proceeds with high levels of diastereoselectivity (>20:1) and high levels of enantioselectivity (up to 99.5:0.5 er) in the presence of CsOH·H2O and a quinine-derived ammonium salt. The reaction most likely proceeds via a delocalized 2-aza-pentadienyl anion that cyclizes either by a suprafacial electrocyclic mechanism, or through a kinetically controlled 5-endo-trig Mannich process. Density functional theory calculations are used to probe these two mechanistic pathways and lead to the conclusion that a nonpericyclic mechanism is most probable. The base-catalyzed interconversion of diastereoisomeric indolines in the presence of certain quaternary ammonium catalysts is observed; this may be rationalized as a cycloreversion–cyclization process. Mechanistic investigations have demonstrated that the reaction is initiated via a Mąkosza-like interfacial process, and kinetic analysis has shown that the reaction possesses a significant induction period consistent with autoinduction. A zwitterionic quinine-derived entity generated by deprotonation of an ammonium salt with the anionic reaction product is identified as a key catalytic species and the role that protonation plays in the enantioselective process outlined. We also propose that the reaction subsequently occurs entirely within the organic phase. Consequently, the reaction may be better described as a phase-transfer-initiated rather than a phase-transfer-catalyzed process; this observation may have implications for mechanistic pathways followed by other phase-transfer-mediated reactions.Publisher PDFPeer reviewe

A clinical and cost effectiveness trial of a parent group intervention to manage challenging restricted and repetitive behaviours in young children with autism spectrum disorder: study protocol for a randomized controlled trial

Background Restricted and repetitive behaviours vary greatly across the autism spectrum, and although not all are problematic some can cause distress and interfere with learning and social opportunities. We have, alongside parents, developed a parent group based intervention for families of young children with autism, which aims to offer support to parents and carers; helping them to recognise, understand and learn how to respond to their child’s challenging restricted repetitive behaviours. Methods The study is a clinical and cost-effectiveness, multi-site randomised controlled trial of the Managing Repetitive Behaviours (MRB) parent group intervention versus a psychoeducation parent group Learning About Autism (LAA) (n = 250; 125 intervention/125 psychoeducation; ~ 83/site) for parents of young children aged 3–9 years 11 months with a diagnosis of autism. All analyses will be done under intention-to-treat principle. The primary outcome at 24 weeks will use generalised estimating equation (GEE) to compare proportion of children with improved RRB between the MRB group and the LAA group. The GEE model will account for the clustering of children by parent groups using exchangeable working correlation. All secondary outcomes will be analysed in a similar way using appropriate distribution and link function. The economic evaluation will be conducted from the perspective of both NHS costs and family access to local community services. A ‘within trial’ cost-effectiveness analysis with results reported as the incremental cost per additional child achieving at least the target improvement in CGI-I scale at 24 weeks. Discussion This is an efficacy trial to investigate the clinical and cost-effectiveness of a parent group based intervention designed to help parents understand and manage their child’s challenging RRB. If found to be effective, this intervention has the potential to improve the well-being of children and their families, reduce parental stress, greatly enhance community participation and potential for learning, and improve longer-term outcomes. Trial registration Trial ID: ISRCTN15550611 Date registered: 07/08/2018. Sponsor and Monitor: Cumbria, Northumberland, Tyne and Wear NHS Foundation Trust R&D Manager Lyndsey Dixon, Address: St Nicholas Hospital, Jubliee Road, Gosforth, Newcastle upon Tyne NE3 3XT, [email protected], Tel: 0191 246 722

Study protocol for a randomised placebo-controlled trial of pramipexole in addition to mood stabilisers for patients with treatment resistant bipolar depression (the PAX-BD study)

Abstract Background Treatment Resistant Bipolar Depression (TRBD) is a major contributor to the burden of disease associated with Bipolar Disorder (BD). Treatment options for people experiencing bipolar depression are limited to three interventions listed by National Institute for Health and Care: lamotrigine, quetiapine and olanzapine, of which the latter two are often not well tolerated. The majority of depressed people with BD are therefore prescribed antidepressants despite limited efficacy. This demonstrates an unmet need for additional interventions. Pramipexole has been shown to improve mood symptoms in animal models of depression, in people with Parkinson’s Disease and two proof of principle trials of pramipexole for people with BD who are currently depressed. Methods The PAX-BD study, funded by the United Kingdom (UK) National Institute for Health Research, aims to extend previous findings by assessing the efficacy, safety and health economic impact of pramipexole in addition to mood stabilisers for patients with TRBD. A randomised, double-blind, placebo controlled design is conducted in a naturalistic UK National Health Service setting. An internal pilot study to examine feasibility and acceptability of the study design is included. Participants with TRBD are screened from National Health Service secondary care services in up to 40 mental health trusts in the UK, with the aim of recruiting approximately 414 participants into a pre-randomisation phase to achieve a target of 290 randomised participants. Primary safety and efficacy measures are at 12 weeks following randomisation, with follow up of participants to 52 weeks. The primary outcome is depressive symptoms as measured by Quick Inventory for Depressive Symptomatology – Self Report. Secondary outcomes include changes in anxiety, manic symptoms, tolerability, acceptability, quality of life and cost-effectiveness. Outcome measures are collected remotely using self-report tools implemented online, and observer-rated assessments conducted via telephone. ANCOVA will be used to examine the difference in rating scale scores between treatment arms, and dependent on compliance in completion of weekly self-report measures. A mixed effects linear regression model may also be used to account for repeated measures. Trial registration ISRCTN72151939. Registered on 28 August 2019, http://www.isrctn.com/ISRCTN72151939 Protocol Version: 04-FEB-2021, Version 9.0

The development of a pragmatic, clinically driven ultrasound curriculum in a UK medical school

Whether ultrasound (US) should be incorporated into a medical undergraduate curriculum remains a matter of debate within the medical education arena. There are clear potential benefits to its early introduction particularly with respect to the study of living anatomy and physiology in addition to the learning of clinical skills and procedures required for the graduate clinical practice. However, this needs to be balanced against what is perceived as an added value in addition to financial and time constraints which may potentially lead to the sacrifice of other aspects of the curriculum. Several medical schools have already reported their experiences of teaching US either as a standalone course or as a fully integrated vertical curriculum. This article describes and discusses the initial experience of a UK medical school that has taken the steps to develop its own pragmatic vertical US curriculum based on clinical endpoints with the intent of using US to enhance the learning experience of students and equipping them with the skills required for the safe practice as a junior doctor