Time-varying flow separation on an accelerating prolate spheroid has been studied at various angles of incidence. Instantaneous pressure and scanning stereoscopic particle image velocimetry were used to shed light on the evolution of cross-flow structures for the Reynolds number ($Re$) range of $1.0\times 10^6\leq Re \leq 1.5\times 10^6$. The movement of separation lines is examined for various model accelerations to investigate on the interplay between acceleration and flow separation. The results demonstrate that for axial accelerations, the streamwise pressure distribution in the rear part of the prolate spheroid switches from an adverse to a favourable pressure gradient. At the same time, the circumferential adverse pressure gradient present during steady motion vanishes during said accelerations. In contrast, both streamwise and circumferential adverse pressure gradients strengthen when the model is axially decelerated. These dynamic pressure distributions influence the location of the separation line, which in turn moves closer to the model meridian during accelerations while moving outwards during decelerations. The streamwise vorticity distribution and the streamwise circulation both show how the separation-line position impacts the vortex formation. A high-vorticity region near the model surface is established during acceleration. In contrast, a decelerating model leads to transport of high-vorticity fluid into the outer area of the cross-flow separation. We further assess the memory effects following the near-impulsive velocity changes. The cross-flow retains the memory of moving separation lines shortly after the acceleration. However, the separation recovers quickly to a steady state.

Zinc (Zn) is an essential mineral and its deficiency manifests in non-specific clinical signs that require long time to develop. The response of swine intestine to Zn restriction was evaluated to identify early changes that can be indicative of Zn deficiency. Twenty-seven pigs (body weight = 77⋅5 ± 2⋅5 kg) were assigned to one of three diets: diet without added Zn (Zn-restricted diet, ZnR), and ZnR-supplemented with either 50 (Zn50) or 100 mg of Zn/kg of diet (Zn100) of Zn supplied by ZnCl2. After 32 d consuming the diets, serum Zn concentration in ZnR pigs was below the range of 0⋅59–1⋅37 μg/ml considered sufficient, thereby confirming subclinical Zn deficiency. Pigs showed no obvious health or growth changes. RNA-seq analysis followed by qPCR showed decreased expression of metallothionein-1 (MT1) (P < 0⋅05) and increased expression of Zn transporter ZIP4 (P < 0⋅05) in jejunum and ileum of ZnR pigs compared with Zn-supplemented pigs. Ingenuity pathway analysis revealed that Zn50 and Zn100 induced changes in genes related to nucleotide excision repair and integrin signalling pathways. The top gene network in the ZnR group compared with Zn100 was related to lipid and drug metabolism; and compared with Zn50, was related to cellular proliferation, assembly and organisation. Dietary Zn concentrations resulted in differences in genes related to immune pathways. Our analysis showed that small intestine presents changes associated with Zn deficiency after 32 d of Zn restriction, suggesting that the intestine could be a sentinel organ for Zn deficiency.

Background: A phase 3 trial, ADVANCE (NCT03777059), demonstrated that atogepant, an oral, CGRP receptor antagonist dosed once daily, results in clinically meaningful reductions in mean monthly migraine days. This open-label extension for ADVANCE trial completers evaluated long-term safety and tolerability of atogepant over 40-weeks. Methods: Participants in this trial (NCT03939312), rolled over from the ADVANCE trial, were treated with atogepant 60mg once daily for 40-weeks, with a 4-week safety follow-up. Only safety data were collected. Results: 685 participants took at least one dose of study drug, 74.6% completed the 40-week treatment period; mean age of 41.8 years, 88.2% female, 84.4% white, and mean BMI of 30.58 kg/m2. Mean (SD) treatment duration was 233.6 (89.32) days. 62.5% of participants experienced a treatment-emergent adverse event (TEAE), with 8.8% considered treatment-related by the investigator; serious adverse events (SAEs) occurred in 3.4% of participants, none were treatment-related. The most frequent AEs leading to discontinuation was nausea (0.4%, n=3); the most frequent TEAEs observed included upper respiratory tract infection (5.5%, n=38) and urinary tract infection (5.3%, n=36). No deaths or hepatic safety issues were observed. Conclusions: Safety results are consistent with known safety profile of atogepant and support long-term safety and tolerability of once daily dosing of atogepant 60mg.

In this paper, to address the cooperative localisation of a heterogeneous UAV swarm in the GNSS-denied environment, an adaptive simulated annealing-particle swarm optimisation (SA-PSO) cooperative localisation algorithm is proposed. Firstly, the forming principle of the communication and measurement framework is investigated in light of a heterogeneous UAV swarm composition. Secondly, a reasonably cooperative localisation function is established based on the proposed forming principle, which can minimise the relative localisation error with limited available information. Then, an adaptive weight principle is incorporated into the particle swarm optimisation (PSO) for better performance. Furthermore, in order to overcome the drawbacks of PSO algorithm easily falling into the local extreme point, an adaptive SA-PSO algorithm is improved to promote the convergence speed of cooperative localisation. Finally, comparative simulations are performed among the adaptive SA-PSO, adaptive PSO, and PSO algorithms to demonstrate the feasibility and superiority of the proposed adaptive SA-PSO algorithm. Simulation results show that the proposed algorithm has better performance in convergence speed, and the cooperative localisation precision can be guaranteed.

This study aimed to identify gender-specific co-developmental trajectories of internalizing and externalizing problems from middle childhood to early adolescence, along with key environmental and individual predictors among Chinese youth. A total of 1653 Chinese elementary school students (Mage = 9.40; SD = 0.51; 54.57% boys) participated in assessments at six time points, using 6-month assessment intervals. Parallel process latent class growth modeling identified four trajectories for boys: Congruent-low (65.74%), moderate-decreasing internalizing and moderate-stable externalizing problems (18.40%), high increasing-internalizing and low-stable externalizing problems (8.20%), and high decreasing-internalizing and low-stable externalizing problems (7.65%). Three trajectories were identified for girls: Congruent-low (81.09%), moderate co-occurring (7.19%), and high increasing-internalizing and low-stable externalizing problems (11.72%). Multivariate logistic regression analyses revealed that peer victimization served as an environmental risk predictor for the adverse co-developmental trajectories of internalizing and externalizing problems for boys and girls. High sensation-seeking and low self-control served as individual risk variables predicting the trajectories of high increasing-internalizing and low-stable externalizing problems, and low self-control also predicted the trajectories of high decreasing-internalizing and low-stable externalizing problems for boys. The findings highlight the importance of gender differences in understanding the progression of internalizing and externalizing problems and inform effective strategies for prevention and intervention.

Drug-induced liver injury (DILI) is a common adverse drug reaction leading to the interruption of tuberculosis (TB) therapy. We aimed to identify whether the hepatitis B virus (HBV) infection would increase the risk of DILI during first-line TB treatment. A meta-analysis of cohort studies searched in PubMed, Web of Science and China National Knowledge Infrastructure was conducted. Effect sizes were reported as risk ratios (RRs) and 95% confidence intervals (CIs) and calculated by R software. Sixteen studies with 3960 TB patients were eligible for analysis. The risk of DILI appeared to be higher in TB patients co-infected with HBV (RR 2.66; 95% CI 2.13–3.32) than those without HBV infection. Moreover, patients with positive hepatitis B e antigen (HBeAg) were more likely to develop DILI (RR 3.42; 95% CI 1.95–5.98) compared to those with negative HBeAg (RR 2.30; 95% CI 1.66–3.18). Co-infection with HBV was not associated with a higher rate of anti-TB DILI in latent TB patients (RR 4.48; 95% CI 0.80–24.99). The effect of HBV infection on aggravating anti-TB DILI was independent of study participants, whether they were newly diagnosed with TB or not. Besides, TB and HBV co-infection patients had a longer duration of recovery from DILI compared to non-co-infected patients (SMD 2.26; 95% CI 1.87–2.66). To conclude, the results demonstrate that HBV infection would increase the risk of DILI during TB therapy, especially in patients with positive HBeAg, and close liver function monitoring is needed for TB and HBV co-infection patients.

Introduction: There is ongoing concern about the burden placed on healthcare systems by lab tests. Although these concerns are widespread, it is difficult to quantify the extent of the problem. One approach involves use of a metric known as the Mean Abnormal Response Rate (MARR), which is the proportion of tests ordered that return an abnormal result; a higher MARR value indicates higher yield. The primary objective of this study was to calculate MARRs for tests ordered between April 2014 and March 2019 at the four adult emergency departments (EDs) covering a metropolitan population of 1.3 million. Secondary objectives included identifying tests with highest and lowest MARRs; comparison of MARRs for nurse- and physician-initiated orders; correlation of the number of tests per order requisition to MARR; and correlation of physician experience to MARR. Methods: In total, 40 laboratory tests met inclusion criteria for this study. Administrative data on these tests as ordered at the four EDs were obtained and analyzed. Multi-component test results, such as from CBC, were consolidated such that an abnormal result for any component was coded as an abnormal result for the entire test. Repeat tests ordered within a single patient visit were excluded. Physician experience was quantified for 209 ED physicians as number of years since licensure. Analyses were descriptive where appropriate for whole-population data. Risk of bias was attenuated by the focus on administrative data. Results: The population dataset comprised 33,757,004 test results on 415,665 unique patients. Of these results, 30.3% were the outcomes of nurse-initiated orders. The 5-year MARRs for the four hospitals were 38.3%, 40.0%, 40.7% and 40.9%. The highest per-test MARRs were for BNP (80.5%) and CBC (62.6%), while the lowest were for glucose (7.9%) and sodium (11.6%). MARRs were higher for nurse-initiated orders than for physician-initiated orders (44.7% vs. 38.1%), likely due to the greater order frequency of high-yield CBC in nurse-initiated orders (38.6% vs. 18.1%). The number of tests per order requisition was inversely associated with MARR (r = -0.90, p < 0.001). Finally, the number of years since licensure was modestly but significantly associated with MARR (r = 0.28, p < 0.001). Conclusion: This is the first and largest study to apply the MARR in an ED setting. As a metric, MARR effectively identifies differences in test ordering practices on per-test and per-hospital bases, which could be useful for data-informed practice optimization.

Tuberculosis (TB) is generally considered a disease that principally afflicts the low-income segments of a population. In the Nanshan District of Shenzhen, China, with the economic transformation and a new Headquarters Economy (HE) emerging, there are now more cases in office workers than in manufacturing workers. To illustrate this trend, we describe a small TB outbreak in an office building located in the centre of the rapidly growing HE district. Two active pulmonary tuberculosis cases were found in workers who shared an office, and whole genome sequencing showed that the genetic distance between the strains of the two cases was just one single nucleotide polymorphism, consistent with intra-office transmission. Investigation of 30 other workers in the same or adjacent offices with interviews, interferon-gamma release assays (IGRAs) and chest X-rays, identified one new TB case and latent tuberculosis infection (LTBI) in 40.0% (12/30) of the contacts. The offices were under-ventilated. None of the IGRA positive, asymptomatic contacts agreed to receive treatment for LTBI, presumably due to TB stigma, and over the next 2 years 69.0% (20/29) of the contacts were lost to follow-up. Treatment for LTBI and stigma of TB remain challenges here. Office workers in the HE of rapidly economic developing areas should be targeted with increased vigilance by TB control programmes.

We use the results of a supernova light-curve population synthesis to predict the range of possible supernova light curves arising from a population of single-star progenitors that lead to type IIP supernovae. We calculate multiple models varying the initial mass, explosion energy, nickel mass and nickel mixing and then compare these to type IIP supernovae with detailed light curve data and pre-explosion imaging progenitor constraints. Where a good fit is obtained to observations, we are able to achieve initial progenitor and nickel mass estimates from the supernova lightcurve that are comparable in precision to those obtained from progenitor imaging. For 2 of the 11 IIP supernovae considered our fits are poor, indicating that more progenitor models should be included in our synthesis or that our assumptions, regarding factors such as stellar mass loss rates or the rapid final stages of stellar evolution, may need to be revisited in certain cases. Using the results of our analysis we are able to show that most of the type IIP supernovae have an explosion energy of the order of log(Eexp/ergs) = 50.52 ± 0.10 and that both the amount of nickel in the supernovae and the amount of mixing may have a dependence on initial progenitor mass.

Laser interaction with an ultra-thin pre-structured target is investigated with the help of both two-dimensional and three-dimensional particle-in-cell simulations. With the existence of a periodic structure on the target surface, the laser seems to penetrate through the target at its fundamental frequency even if the plasma density of the target is much higher than the laser’s relativistically critical density. The particle-in-cell simulations show that the transmitted laser energy behind the pre-structured target is increased by about two orders of magnitude compared to that behind the flat target. Theoretical analyses show that the transmitted energy behind the pre-structured target is actually re-emitted by electron ‘islands’ formed by the surface plasma waves on the target surfaces. In other words, the radiation with the fundamental frequency is actually ‘surface emission’ on the target rear surface. Besides the intensity of the component with the fundamental frequency, the intensity of the high-order harmonics behind the pre-structured target is also much enhanced compared to that behind the flat target. The enhancement of the high-order harmonics is also related to the surface plasma waves generated on the target surfaces.

Type 2 diabetes (T2D) is a chronic disease that disproportionately affects Indigenous Australians. We have previously reported the localization of a novel T2D locus by linkage analysis to chromosome 2q24 in a large admixed Indigenous Australian pedigree (Busfield et al. (2002). American Journal of Human Genetics, 70, 349–357). Here we describe fine mapping of this region in this pedigree, with the identification of SNPs showing strong association with T2D: rs3845724 (diabetes p = 7 × 10−4), rs4668106 (diabetes p = 9 × 10−4) and rs529002 (plasma glucose p = 3 × 10−4). These associations were successfully replicated in an independent collection of Indigenous Australian T2D cases and controls. These SNPs all lie within the gene encoding ceramide synthase 6 (CERS6) and thus may regulate ceramide synthesis.

We present results of a supernova lightcurve population synthesis, predicting the range of possible supernova lightcurves arising from a population of progenitor stars that include interacting binary systems. We show that the known diversity of supernova lightcurves can be interpreted as arising from binary interactions. Given detailed models of the progenitor stars, we are able to the determine what parameters within these stars determine the shape of their supernova lightcurve. The primary factors are the mass of supernova ejecta and the mass of hydrogen in the final progenitor. We find that there is a continuum of lightcurve behaviour from type IIP, IIL, to IIb supernovae related to the range of hydrogen and ejecta masses. Most type IIb supernovae arise from a relatively narrow range of initial masses from 10 to 15 M⊙. We also find a few distinct lightcurves that are the result of stellar mergers.