High Redshift Standard Candles: Predicted Cosmological Constraints

We investigate whether future measurements of high redshift standard candles (HzSCs) will be a powerful probe of dark energy, when compared to other types of planned dark energy measurements. Active galactic nuclei and gamma ray bursts have both been proposed as potential HzSC candidates. Due to their high luminosity, they can be used to probe unexplored regions in the expansion history of the universe. Information from these regions can help constrain the properties of dark energy, and in particular, whether it varies over time. We consider both linear and piecewise parameterizations of the dark energy equation of state, $w(z)$, and assess the optimal redshift distribution a high-redshift standard-candle survey could take to constrain these models. The more general the form of the dark energy equation of state $w(z)$ being tested, the more useful high-redshift standard candles become. For a linear parameterization of $w(z)$, HzSCs give only small improvements over planned supernova and baryon acoustic oscillation measurements; a wide redshift range with many low redshift points is optimal to constrain this linear model. However to constrain a general, and thus potentially more informative, form of $w(z)$, having many HzSCs can significantly improve limits on the nature of dark energy.Comment: Accepted MNRAS, 27 Pages, 15 figures, matches published versio

Neutrophil-bead collision assay: Pharmacologically induced changes in membrane mechanics regulate the PSGL-1/P-selectin adhesion lifetime

Visualization of flowing neutrophils colliding with adherent 1-µm-diameter beads presenting P-selectin allowed the simultaneous measurement of collision efficiency (ε), membrane tethering fraction (f), membrane tether growth dynamics, and PSGL-1/P-selectin binding lifetime. For 1391 collisions analyzed over venous wall shear rates from 25 to 200 s-1 ε decreased from 0.17 to 0.004, whereas f increased from 0.15 to 0.70, and the average projected membrane tether length, ∠mtether, increased from 0.35 µm to ⋍2.0 µm over this shear range. At all shear rates tested, adhesive collisions lacking membrane tethers had average bond lifetimes less than those observed for collisions with tethers. For adhesive collisions that failed to form membrane tethers, the regressed Bell parameters (consistent with single bond Monte Carlo simulation) were zero-stress offrate, Koff(0) = 0.56 s-1and reactive compliance, r = 0.10 nm, similar to published atomic force microscopy (AFM) measurements. For all adhesion events (± tethers), the bond lifetime distributions were more similar to those obtained by rolling assay and best simulated by Monte Carlo with the above Bell parameters and an average of 1.48 bonds (n = 1 bond (67%), n = 2 (22%), and n = 3–5 (11%)). For collisions at 100 s-1, pretreatment of neutrophils with actin depolymerizing agents, latrunculin or cytochalasin D, had no effect on ε, but increased ∠mtether by 1.74- or 2.65-fold and prolonged the average tether lifetime by 1.41- or 1.65-fold, respectively. Jasplakinolide, an actin polymerizing agent known to cause blebbing, yielded results similar to the depolymerizing agents. Conversely, cholesterol-depletion with methyl-ß-cyclodextrin or formaldehyde fixation had no effect on ε, but reduced ∠mtether by 66% or 97% and reduced the average tether lifetime by 30% or 42%, respectively. The neutrophilbead collision assay combines advantages of atomic force microscopy (small contact zone), aggregometry (discrete interactions), micropipette manipulation (tether visualization), and rolling assays (physiologic flow loading). Membrane tether growth can be enhanced or reduced pharmacologically with consequent effects on PSGL-1/P-selectin lifetimes

Dilemmas and solutions- experiences of a national Family Medicine applied knowledge licensing test during a pandemic

ABSTRACT: Background: The unprecedented COVID-19 pandemic brought significant challenges to all of medicine, including primary care training and examinations. The MRCGP AKT is high-stakes licensing 200-item MCQ for UK trainee family physicians and is part of an assessment tripos that, up to the onset of the pandemic, included a Clinical Skills Assessment using Simulated Patients and workplace based assessment. The AKT is blueprinted onto a curriculum content specification and computer delivered three times a year at test centres across the UK. It tests the knowledge base underpinning independent general practice within the context of the UK National Health Service. We report on the challenges and dilemmas faced during the pandemic, decisions taken, and lessons learned. Rapid exam changes needed to be made, and communicated effectively to candidates, whilst maintaining standards and fairness to candidates. Summary of Work: Challenges included lockdown travel restrictions, reduced capacity, social distancing and shielding candidates being unable to leave home. The April 2020 AKT was cancelled and prioritisation measures implemented to ensure candidates at the end of their training could enter the (stressed) workforce. We engaged with a wide range of stakeholders, carefully looked at remote testing, made contingency plans prioritised for those unable to sit exams and changed exam regulations to ensure fairness to candidates. In this emergency, we delivered a previously published exam which some candidates were unaware they had sat previously, and assessed how these candidates performed. We compared cohort performance before and during the pandemic. Summary of Results: We summarise why we did not remote test, how we obtained key worker status, and adapted contingency plans. Analysis of candidates who had previously sat the same exam showed they performed less well. Despite wide-ranging changes in training and workplace experience, there was no significant difference in cohort performance overall pre-and peri-pandemic. Discussion and Conclusions: COVID-19 constraints changed trainees clinical exposure, restricted training and supervisor support. However, exam preparedness did not appear adversely affected when measured by overall pass rates. Unexpectedly, candidates who sat an identical exam did not benefit from previous exposure. Take-home Messages: Involving stakeholders in key decisions and regular communications are essential. Test security and standards were not compromised

Chemical abundances of damped Lyman alpha systems in the XQ-100 survey

The XQ-100 survey has provided high signal-noise spectra of 100 redshift 3-4.5 quasars with the X-Shooter spectrograph. The metal abundances for 13 elements in the 41 damped Lyman alpha systems (DLAs) identified in the XQ-100 sample are presented, and an investigation into abundances of a variety of DLA classes is conducted. The XQ-100 DLA sample contains five DLAs within 5000 km/s of their host quasar (proximate DLAs; PDLAs) as well as three sightlines which contain two DLAs within 10,000 km/s of each other along the same line-of-sight (multiple DLAs; MDLAs). Combined with previous observations in the literature, we demonstrate that PDLAs with logN(HI)<21.0 show lower [S/H] and [Fe/H] (relative to intervening systems with similar redshift and N(HI)), whilst higher [S/H] and [Si/H] are seen in PDLAs with logN(HI)>21.0. These abundance discrepancies are independent of their line-of-sight velocity separation from the host quasar, and the velocity width of the metal lines (v90). Contrary to previous studies, MDLAs show no difference in [alpha/Fe] relative to single DLAs matched in metallicity and redshift. In addition, we present follow-up UVES data of J0034+1639, a sightline containing three DLAs, including a metal-poor DLA with [Fe/H]=-2.82 (the third lowest [Fe/H] in DLAs identified to date) at z=4.25. Lastly we study the dust-corrected [Zn/Fe], emphasizing that near-IR coverage of X-Shooter provides unprecedented access to MgII, CaII and TiII lines (at redshifts 3-4) to provide additional evidence for subsolar [Zn/Fe] ratio in DLAs.Comment: Accepted to MNRAS. 19 pages plus Appendix material (102 pages total

Systems Biology of Coagulation Initiation: Kinetics of Thrombin Generation in Resting and Activated Human Blood

Blood function defines bleeding and clotting risks and dictates approaches for clinical intervention. Independent of adding exogenous tissue factor (TF), human blood treated in vitro with corn trypsin inhibitor (CTI, to block Factor XIIa) will generate thrombin after an initiation time (Ti) of 1 to 2 hours (depending on donor), while activation of platelets with the GPVI-activator convulxin reduces Ti to ∼20 minutes. Since current kinetic models fail to generate thrombin in the absence of added TF, we implemented a Platelet-Plasma ODE model accounting for: the Hockin-Mann protease reaction network, thrombin-dependent display of platelet phosphatidylserine, VIIa function on activated platelets, XIIa and XIa generation and function, competitive thrombin substrates (fluorogenic detector and fibrinogen), and thrombin consumption during fibrin polymerization. The kinetic model consisting of 76 ordinary differential equations (76 species, 57 reactions, 105 kinetic parameters) predicted the clotting of resting and convulxin-activated human blood as well as predicted Ti of human blood under 50 different initial conditions that titrated increasing levels of TF, Xa, Va, XIa, IXa, and VIIa. Experiments with combined anti-XI and anti-XII antibodies prevented thrombin production, demonstrating that a leak of XIIa past saturating amounts of CTI (and not “blood-borne TF” alone) was responsible for in vitro initiation without added TF. Clotting was not blocked by antibodies used individually against TF, VII/VIIa, P-selectin, GPIb, protein disulfide isomerase, cathepsin G, nor blocked by the ribosome inhibitor puromycin, the Clk1 kinase inhibitor Tg003, or inhibited VIIa (VIIai). This is the first model to predict the observed behavior of CTI-treated human blood, either resting or stimulated with platelet activators. CTI-treated human blood will clot in vitro due to the combined activity of XIIa and XIa, a process enhanced by platelet activators and which proceeds in the absence of any evidence for kinetically significant blood borne tissue factor

Cosmic Ray Spallation in Radio-Quiet Active Galactic Nuclei: A Case Study of NGC 4051

We investigate conditions for and consequences of spallation in radio-quiet Seyfert galaxies. The work is motivated by the recent discovery of significant line emission at 5.44 keV in Suzaku data from NGC 4051. The energy of the new line suggests an identification as Cr I Ka emission, however the line is much stronger than would be expected from material with cosmic abundances, leading to a suggestion of enhancement owing to nuclear spallation of Fe by low energy cosmic rays from the active nucleus. We find that the highest abundance enhancements are likely to take place in gas out of the plane of the accretion disk and that timescales for spallation could be as short as a few years. The suggestion of a strong nuclear flux of cosmic rays in a radio-quiet Seyfert galaxy is of particular interest in light of the recent suggestion from Pierre Auger Observatory data that ultra-high-energy cosmic rays may originate in such sources.Comment: 14 pages, 1 figure. Accepted for publication in The Astrophysical Journa

A qualitative study of the infant feeding beliefs and behaviours of mothers with low educational attainment

© 2016 Russell et al. Background: Infancy is an important period for the promotion of healthy eating, diet and weight. However little is known about how best to engage caregivers of infants in healthy eating programs. This is particularly true for caregivers, infants and children from socioeconomically disadvantaged backgrounds who experience greater rates of overweight and obesity yet are more challenging to reach in health programs. Behaviour change interventions targeting parent-infant feeding interactions are more likely to be effective if assumptions about what needs to change for the target behaviours to occur are identified. As such we explored the precursors of key obesity promoting infant feeding practices in mothers with low educational attainment. Methods: One-on-one semi-structured telephone interviews were developed around the Capability Opportunity Motivation Behaviour (COM-B) framework and applied to parental feeding practices associated with infant excess or healthy weight gain. The target behaviours and their competing alternatives were (a) initiating breastfeeding/formula feeding, (b) prolonging breastfeeding/replacing breast milk with formula, (c) best practice formula preparation/sub-optimal formula preparation, (d) delaying the introduction of solid foods until around six months of age/introducing solids earlier than four months of age, and (e) introducing healthy first foods/introducing unhealthy first foods, and (f) feeding to appetite/use of non-nutritive (i.e., feeding for reasons other than hunger) feeding. The participants' education level was used as the indicator of socioeconomic disadvantage. Two researchers independently undertook thematic analysis. Results: Participants were 29 mothers of infants aged 2-11 months. The COM-B elements of Social and Environmental Opportunity, Psychological Capability, and Reflective Motivation were the key elements identified as determinants of a mother's likelihood to adopt the healthy target behaviours although the relative importance of each of the COM-B factors varied with each of the target feeding behaviours. Conclusions: Interventions targeting healthy infant feeding practices should be tailored to the unique factors that may influence mothers' various feeding practices, taking into account motivational and social influences

Simulations of the OzDES AGN Reverberation Mapping Project

As part of the OzDES spectroscopic survey we are carrying out a large scale reverberation mapping study of $\sim$500 quasars over five years in the 30 deg$^2$ area of the Dark Energy Survey (DES) supernova fields. These quasars have redshifts ranging up to 4 and have apparent AB magnitudes between $16.8<r<22.5$ mag. The aim of the survey is to measure time lags between fluctuations in the quasar continuum and broad emission line fluxes of individual objects in order to measure black hole masses for a broad range of AGN and constrain the radius-luminosity ($R-L$) relationship. Here we investigate the expected efficiency of the OzDES reverberation mapping campaign and its possible extensions. We expect to recover lags for $\sim$35-45\% of the quasars. AGN with shorter lags and greater variability are more likely to yield a lag, and objects with lags $\lesssim$6 months or $\sim$1 year are expected be recovered the most accurately. The baseline OzDES reverberation mapping campaign is predicted to produce an unbiased measurement of the $R-L$ relationship parameters for H$\beta$, Mg II $\lambda$2798, and C IV $\lambda$1549. However, extending the baseline survey by either increasing the spectroscopic cadence, extending the survey season, or improving the emission line flux measurement accuracy will significantly improve the $R-L$ parameter constraints for all broad emission lines.Comment: Published online in MNRAS. 28 page

Associations between insulin and glucose concentrations and anthropometric measures of fat mass in Australian adolescents

Background One of the most serious, yet common co-morbidities of obesity is insulin resistance, which if untreated may progress to type 2 diabetes. This paper describes the insulin and glucose concentration distributions, the prevalence of elevated insulin, the associations between insulin and body mass index (BMI), waist circumference, waist-to-height ratio (WHtR) and fat mass index in a representative sample of Australian adolescents. Methods Cross-sectional population-based study of adolescent boys and girls (N = 496, mean age 15.3 years) attending schools in metropolitan Sydney, Australia. Fasting venous blood collected and analysed for insulin and glucose concentrations. Height, weight, waist circumference measured, BMI and waist-to-height ratio calculated. Pubertal status self-reported. Results Glucose concentrations were normally distributed and were not associated with adiposity. Insulin concentrations were distributed logarithmically, were higher among girls than boys overall and within the same ranges of BMI and waist circumference, but were lower among girls than boys within the same ranges of fat mass adjusted for height. The prevalence of elevated insulin concentration (defined as \u3e 100 pmol/L) was 15.9% and 17.1% among boys and girls, respectively. Correlations between insulin concentration and BMI, waist circumference, WHtR and fat mass adjusted for height were 0.53, 0.49, 0.51 and 0.55, among boys, respectively, and 0.35, 0.40, 0.42 and 0.34, among girls, respectively. Conclusions Elevated insulin is highly correlated with adiposity in adolescents. BMI and WHtR are simple measures that can be used to identify young people who should be screened for insulin resistance and other co-morbidities