Potential use of oxygen as a metabolic biosensor in combination with T2*-weighted MRI to define the ischemic penumbra

We describe a novel magnetic resonance imaging technique for detecting metabolism indirectly through changes in oxyhemoglobin:deoxyhemoglobin ratios and T2* signal change during ‘oxygen challenge’ (OC, 5 mins 100% O2). During OC, T2* increase reflects O2 binding to deoxyhemoglobin, which is formed when metabolizing tissues take up oxygen. Here OC has been applied to identify tissue metabolism within the ischemic brain. Permanent middle cerebral artery occlusion was induced in rats. In series 1 scanning (n=5), diffusion-weighted imaging (DWI) was performed, followed by echo-planar T2* acquired during OC and perfusion-weighted imaging (PWI, arterial spin labeling). Oxygen challenge induced a T2* signal increase of 1.8%, 3.7%, and 0.24% in the contralateral cortex, ipsilateral cortex within the PWI/DWI mismatch zone, and ischemic core, respectively. T2* and apparent diffusion coefficient (ADC) map coregistration revealed that the T2* signal increase extended into the ADC lesion (3.4%). In series 2 (n=5), FLASH T2* and ADC maps coregistered with histology revealed a T2* signal increase of 4.9% in the histologically defined border zone (55% normal neuronal morphology, located within the ADC lesion boundary) compared with a 0.7% increase in the cortical ischemic core (92% neuronal ischemic cell change, core ADC lesion). Oxygen challenge has potential clinical utility and, by distinguishing metabolically active and inactive tissues within hypoperfused regions, could provide a more precise assessment of penumbra

The effect of specific learning difficulties on general practice written and clinical assessments

Background Substantial numbers of medical students and doctors have specific learning difficulties (SpLDs) and failure to accommodate their needs can disadvantage them academically. Evidence about how SpLDs affect performance during postgraduate general practice (GP) specialty training across the different licencing assessments is lacking. We aimed to investigate the performance of doctors with SpLDs across the range of licencing assessments. Methods We adopted the social model of disability as a conceptual framework arguing that problems of disability are societal and that barriers that restrict life choices for people with disabilities need to be addressed. We used a longitudinal design linking Multi-Specialty Assessment (MSRA) records from 2016 and 2017 with their Applied Knowledge Test (AKT), Clinical Skills Assessment (CSA), Recorded Consultation Assessment (RCA) and Workplace Based Assessment (WPBA) outcomes up to 2021. Multivariable logistic regression models accounting for prior attainment and demographics were used to determine the SpLD doctors' likelihood of passing licencing assessments. Results The sample included 2070 doctors, with 214 (10.34%) declaring a SpLD. Candidates declaring a SpLD were significantly less likely to pass the CSA (OR 0.43, 95% CI 0.26, 0.71, p = 0.001) but not the AKT (OR 0.96, 95% CI 0.44, 2.09, p = 0.913) or RCA (OR 0.81, 95% CI 0.35, 1.85, p = 0.615). Importantly, they were significantly more likely to have difficulties with WPBA (OR 0.28, 95% CI 0.20, 0.40, p < 0.001). When looking at licencing tests subdomains, doctors with SpLD performed significantly less well on the CSA Interpersonal Skills (B = −0.70, 95% CI −1.2, −0.19, p = 0.007) and the RCA Clinical Management Skills (B = −1.68, 95% CI −3.24, −0.13, p = 0.034). Conclusions Candidates with SpLDs encounter difficulties in multiple domains of the licencing tests and during their training. More adjustments tailored to their needs should be put in place for the applied clinical skills tests and during their training

How is performance at selection to general practice related to performance at the endpoint of GP training?

Background The selection process for entry to speciality training for general practice (GP) in the UK was changed in 2016. Doctors scoring above an agreed threshold in the computer-marked Multi-Specialty Recruitment Assessment (MSRA) were deemed appointable on that score alone and were offered a direct pathway (DP) to training, exempting them from further assessment at the final Selection Centre (SC). The SC was subsequently suspended in response to the COVID-19 pandemic and has yet to be reinstated. We aimed to evaluate the relationship between performance at selection and outcomes of GP training at licensing, to reassess the threshold score in MSRA used to bypass the SC, and to estimate the incremental predictive value of the SC after MSRA. Methods We used a longitudinal design linking selection, licensing and demographic data from doctors applying to enter GP specialty training in 2016. MSRA scores were divided into 12 score bands and SC scores into seven score bands to better identify MSRA or SC scores that corresponded to dffering GP performance on licensing assessments. Multivariable logistic regression models were used to establish the predictive validity of the MSRA scores and score bands for passing or failing the Membership of the Royal College of General Practitioners (MRCGP) licensing assessments including the Applied Knowledge Test (AKT), Clinical Skills Assessment (CSA) or Recorded Consultation Assessment (RCA), Workplace Based Assessment - Annual Review of Competence Progression (WPBA-ARCP), and performance overall. The model adjusted for sex, ethnicity, country of qualification, and declared disability. Receiver Operating Characteristic (ROC) curves of MSRA scores against performance outcomes were constructed to determine the optimal MSRA threshold scores for achieving licensing. Results We included 3338 doctors who entered specialty training for general practice in 2016 of different sex (female 63.81% vs male 36.19%), ethnicity (White British 53.95%, minority ethnic 43.04% or mixed 3.01%), country of qualification (UK 76.76%, non-UK 23.24%), and declared disability (disability declared 11.98%, no disability declared 88.02%). MSRA scores or score bands were highly predictive for all assessments of GP training outcome (AKT, CSA, RCA, and WPBA-ARCP). Lower SC score bands were predictive of lower pass rates on summative assessments and /or ARCP outcomes 2, 3, or 4. Adding SC scores did not change the predictive validity of the MSRA, and therefore the SC did not add further information to MSRA scores. An MSRA threshold of 500 (or, more precisely, 497) was optimal for correctly identifying pass/fail rates on the AKT, RCA, and CSA within the study period, and only standard outcomes on WPBA-ARCP. Thirty-five percent of candidates in the lowest two MSRA Bands (i.e., scores below 420) had at least one developmental outcome (2, 3) or outcome 4. Ethnicity did not reduce the chance of passing GP licensing tests once sex, place of primary medical qualification, declared disability and MSRA scores were taken into account. Conclusion MSRA scores predict licensing outcomes for AKT, CSA, RCA, and WPBA-ARCP within five years of starting training. The optimal MSRA threshold score for predicting an uncomplicated training pathway to licensing was around 500 in this large cohort. The SC added little to the predictive validity of the MSRA. Doctors scoring below this threshold may need additional support during training to maximise their chances of achieving licensing

Hydrodynamic fluctuations in the Kolmogorov flow: Linear regime

The Landau-Lifshitz fluctuating hydrodynamics is used to study the statistical properties of the linearized Kolmogorov flow. The relative simplicity of this flow allows a detailed analysis of the fluctuation spectrum from near equilibrium regime up to the vicinity of the first convective instability threshold. It is shown that in the long time limit the flow behaves as an incompressible fluid, regardless of the value of the Reynolds number. This is not the case for the short time behavior where the incompressibility assumption leads in general to a wrong form of the static correlation functions, except near the instability threshold. The theoretical predictions are confirmed by numerical simulations of the full nonlinear fluctuating hydrodynamic equations.Comment: 20 pages, 4 figure

The Presence of Weak Active Galactic Nuclei in High Redshift Star Forming Galaxies

We present [OIII 5007A] observations of the star forming galaxy HDF-BMZ1299 (z=1.598) using Keck Observatory's Adaptive Optics system with the near-infrared integral field spectrograph OSIRIS. Using previous Halpha and [NII] measurements of the same source, we are able for the first time to use spatially resolved observations to place a high-redshift galaxy's substructure on a traditional HII diagnostic diagram. We find that HDF-BMZ1299's spatially concentrated nebular ratios in the central ~1.5 kiloparsec (0."2) are best explained by the presence of an AGN: log([NII]/Halpha)=-0.22+/-0.05 and 2sigma limit of log([OIII]/Hbeta)>0.26. The dominant energy source of this galaxy is star formation, and integrating a single aperture across the galaxy yields nebular ratios that are composite spectra from both AGN and HII regions. The presence of an embedded AGN in HDF-BMZ1299 may suggest a potential contamination in a fraction of other high-redshift star forming galaxies, and we suggest that this may be a source of the "elevated" nebular ratios previously seen in seeing-limited metallicity studies. HDF-BMZ1299's estimated AGN luminosity is L_Halpha = 3.7e41 erg/s and L_[OIII] = 5.8e41 erg/s, making it one of the lowest luminosity AGN discovered at this early epoch.Comment: 15 pages, 4 figures, ApJ Accepted, new version to be published (updated text, figures, and table

Dynamical quantum noise in Bose-Einstein condensates

We introduce the study of dynamical quantum noise in Bose-Einstein condensates through numerical simulation of stochastic partial differential equations obtained using phase space representations. We derive evolution equations for a single trapped condensate in both the positive-$P$ and Wigner representations, and perform simulations to compare the predictions of the two methods. The positive-$P$ approach is found to be highly susceptible to the stability problems that have been observed in other strongly nonlinear, weakly damped systems. Using the Wigner representation, we examine the evolution of several quantities of interest using from a variety of choices of initial state for the condensate, and compare results to those for single-mode models.Comment: 8 figures, submitted to Phys. Rev.

MAGIC (Maternal Glucose in Pregnancy) - Understanding the glycemic profile of pregnancy, intensive CGM glucose profiling and its relationship to fetal growth. An observational study protocol

Background: Continuous glucose monitoring (CGM) provides the most objective method of assessing glucose in daily life. Although there have been small, short-term physiologic studies of glucose metabolism in ‘healthy’ pregnant women a comprehensive, longitudinal description of changes in glucose over the course of pregnancy and how glucose dysregulation earlier in pregnancy relates to traditional third trimester screening for gestational diabetes, fetal growth and pregnancy outcomes is lacking. This study aims to characterise longitudinal changes in glycemia across gestation using CGM, in order to understand the evolution of dysglycemia and its relationship to fetal growth. Method/design: A multi-centre, prospective, observational, cohort study of 500 healthy pregnant women, recruited in the first trimester of pregnancy. Masked CGM will be performed for a 14-day period on five occasions across pregnancy at ~ 10-12, 18-20, 26-28, 34-36 weeks gestation and postnatally. Routinely collected anthropometric and sociodemographic information will be recorded at each visit including: weight, height, blood pressure, current medication. Age, parity, ethnicity, smoking will be recorded. Blood samples will be taken at each visit for HbA1c and a sample stored. Details on fetal growth from ultrasound scans and the OGTT results will be recorded. Maternal and neonatal outcomes will be collected. CGM glucose profiling is the exposure of interest, and will be performed using standard summary statistics, functional data analysis and glucotyping. The primary maternal outcome is clinical diagnosis of GDM. The primary neonatal outcome is large for gestational age (LGA) (>90th centile defined by customised birthweight centile). The relationship of glucose to key secondary maternal and neonatal outcomes will be explored. Discussion: This study will ascertain the relationship of maternal dysglycemia to fetal growth and outcomes. It will explore whether CGM glucose profiling can detect GDM before the OGTT; or indeed whether CGM glucose profiling may be more useful than the OGTT at detecting LGA and other perinatal outcomes. Trial registration: ISRCTN 5706303 https://www.isrctn.com/ISRCTN15706303 Registration date: 13th March 2023

Archiving multi-epoch data and the discovery of variables in the near infrared

We present a description of the design and usage of a new synoptic pipeline and database model for time series photometry in the VISTA Data Flow System (VDFS). All UKIRT-WFCAM data and most of the VISTA main survey data will be processed and archived by the VDFS. Much of these data are multi-epoch, useful for finding moving and variable objects. Our new database design allows the users to easily find rare objects of these types amongst the huge volume of data being produced by modern survey telescopes. Its effectiveness is demonstrated through examples using Data Release 5 of the UKIDSS Deep Extragalactic Survey (DXS) and the WFCAM standard star data. The synoptic pipeline provides additional quality control and calibration to these data in the process of generating accurate light-curves. We find that 0.6+-0.1% of stars and 2.3+-0.6% of galaxies in the UKIDSS-DXS with K<15 mag are variable with amplitudes \Delta K>0.015 magComment: 30 pages, 31 figures, MNRAS, in press Minor changes from previous version due to refereeing and proof-readin

Dynamics of fluctuations in a fluid below the onset of Rayleigh-B\'enard convection

We present experimental data and their theoretical interpretation for the decay rates of temperature fluctuations in a thin layer of a fluid heated from below and confined between parallel horizontal plates. The measurements were made with the mean temperature of the layer corresponding to the critical isochore of sulfur hexafluoride above but near the critical point where fluctuations are exceptionally strong. They cover a wide range of temperature gradients below the onset of Rayleigh-B\'enard convection, and span wave numbers on both sides of the critical value for this onset. The decay rates were determined from experimental shadowgraph images of the fluctuations at several camera exposure times. We present a theoretical expression for an exposure-time-dependent structure factor which is needed for the data analysis. As the onset of convection is approached, the data reveal the critical slowing-down associated with the bifurcation. Theoretical predictions for the decay rates as a function of the wave number and temperature gradient are presented and compared with the experimental data. Quantitative agreement is obtained if allowance is made for some uncertainty in the small spacing between the plates, and when an empirical estimate is employed for the influence of symmetric deviations from the Oberbeck-Boussinesq approximation which are to be expected in a fluid with its density at the mean temperature located on the critical isochore.Comment: 13 pages, 10 figures, 52 reference

10 simple rules to create a serious game, illustrated with examples from structural biology

Serious scientific games are games whose purpose is not only fun. In the field of science, the serious goals include crucial activities for scientists: outreach, teaching and research. The number of serious games is increasing rapidly, in particular citizen science games, games that allow people to produce and/or analyze scientific data. Interestingly, it is possible to build a set of rules providing a guideline to create or improve serious games. We present arguments gathered from our own experience ( Phylo , DocMolecules , HiRE-RNA contest and Pangu) as well as examples from the growing literature on scientific serious games