Background: Sex differences in treatment response to intravenous thrombolysis (IVT) are poorly characterized. We compared sex-disaggregated outcomes in patients receiving IVT for acute ischemic stroke in the Alteplase compared to Tenecteplase (AcT) trial, a Canadian multicentre, randomised trial. Methods: In this post-hoc analysis, the primary outcome was excellent functional outcome (modified Rankin Score [mRS] 0-1) at 90 days. Secondary and safety outcomes included return to baseline function, successful reperfusion (eTICI≥2b), death and symptomatic intracerebral hemorrhage. Results: Of 1577 patients, there were 755 women and 822 men (median age 77 [68-86]; 70 [59-79]). There were no differences in rates of mRS 0-1 (aRR 0.95 [0.86-1.06]), return to baseline function (aRR 0.94 [0.84-1.06]), reperfusion (aRR 0.98 [0.80-1.19]) and death (aRR 0.91 [0.79-1.18]). There was no effect modification by treatment type on the association between sex and outcomes. The probability of excellent functional outcome decreased with increasing onset-to-needle time. This relation did not vary by sex (pinteraction 0.42). Conclusions: The AcT trial demonstrated comparable functional, safety and angiographic outcomes by sex. This effect did not differ between alteplase and tenecteplase. The pragmatic enrolment and broad national participation in AcT provide reassurance that there do not appear to be sex differences in outcomes amongst Canadians receiving IVT.

Very little is known about the fate of the large numbers of injured and orphaned wild animals taken to wildlife rehabilitation centres in the UK each year. We reviewed the reasons for admission and outcomes for 2,653 woodpigeons (Columba palumbus), 68% of which were juveniles, brought to an RSPCA wildlife rehabilitation centre in Cheshire, UK over a five-year period (2005-2009). Reasons for admission varied with the most common reason for adults and juveniles being ‘injury (cause uncertain)’ and ‘orphan’, respectively. Twenty-one percent of adults and 16% of juveniles had been attacked by cats. Sixty-five percent of adults and 37% of juveniles were euthanased on admission or within the first 48 h to prevent further suffering. Only 14% of adults and 31% of juveniles were released back into the wild. The remainder were either euthanased or died despite treatment more than 48 h after admission. Body condition on admission was not a good predictor of the likelihood of release, but age, weight on admission and severity of symptoms were significant factors. A reduction in the median number of days in care for those birds euthanased more than 48 h after being admitted was recorded for 2007 to 2009, possibly due to the introduction of radiography for all birds on admission. Leg-band recovery data for 15 birds revealed post-release survival ranging from 21-2,545 days (median = 231 days) compared to 1-2,898 days (median = 295) for non-rehabilitated birds.

This article evaluates Agriculture Risk Coverage (ARC) and Revenue Protection (RP) used in conjunction as an optimal risk management strategy for representative producers in the Corn Belt and Mississippi Delta. Using a simulation procedure to produce representative farm revenues, we find it is optimal under expected utility for producers to enroll in RP, despite having RP through ARC. Results are robust across alternative sampling methods and regions. These findings imply that ARC is better suited as a complementary program, and that it is optimal for a producer to enroll in higher coverage levels than we currently observe.

Genetic studies of complex traits often show disparities in estimated heritability depending on the method used, whether by genomic associations or twin and family studies. We present a simulation of individual genomes with dynamic environmental conditions to consider how linear and nonlinear effects, gene-by-environment interactions, and gene-by-environment correlations may work together to govern the long-term development of complex traits and affect estimates of heritability from common methods. Our simulation studies demonstrate that the genetic effects estimated by genome wide association studies in unrelated individuals are inadequate to characterize gene-by-environment interaction, while including related individuals in genome-wide complex trait analysis (GCTA) allows gene-by-environment interactions to be recovered in the heritability. These theoretical findings provide an explanation for the “missing heritability” problem and bridge the conceptual gap between the most common findings of GCTA and twin studies. Future studies may use the simulation model to test hypotheses about phenotypic complexity either in an exploratory way or by replicating well-established observations of specific phenotypes.

For many, declining biodiversity represents an emotionally and psychologically distant ‘cost’ – similar to how a number of people perceive climate change. Using an expectancy-value theory framework, we showed participants photographs that visibly illustrated the threat of biodiversity loss. Specifically, we tested a combination of preregistered and exploratory hypotheses through an online experiment (n = 843) to understand whether viewing photographs of plants and animals (with and without captions) bolstered people’s valuing of biodiversity and willingness to donate to a nature-focused charity relative to a control group. Participants who viewed photographs (without captions) valued biodiversity more and donated more to the nature-focused charity; those who viewed photographs with captions showed similar though more muted (non-statistically significant) effects. Follow-up mediation analyses on the photographs-only participants suggested that the photographs may have catalysed negative emotions that increased valuing of biodiversity and, in turn, increased donations. This study provides preregistered evidence that thoughtfully selected photographs boost people’s valuing of biodiversity and exploratory evidence that the pathway through which that might occur is more likely via negative emotions than through reduced psychological distance. Educators, conservationists, journalists and others may find these results informative as they develop strategies for addressing the acute problem of biodiversity loss.

Rapid whole genome sequencing (rapid WGS) is a powerful diagnostic tool that is becoming increasingly practical for widespread clinical use. However, protocols for its use are challenging to implement. A significant obstacle to clinical adoption is that laboratory certification requires an initial research development phase, which is constrained by regulations from returning results. Regulations preventing return of results have ethical implications in cases which might impact patient outcomes. Here, we describe our experience with the development of a rapid WGS research protocol, that balanced the requirements for laboratory-validated test development with the ethical needs of clinically relevant return of results.

The purpose of this study was to determine if the mixed evidence of almond consumption on HbA1c stems from testing people with different body fat distributions (BFD) associated with different risks of glucose intolerance. A 6-month randomised controlled trial in 134 adults was conducted. Participants were randomly assigned to the almond (A) or control (C) group based on their BFD. Those in the almond group consumed 1·5 oz of almonds with their breakfast and as their afternoon snack daily. Those in the control group continued their habitual breakfast and afternoon snack routines. Body weight and composition were measured and blood samples were collected for determination of HbA1c, glycaemia and lipaemia at 0 and 6 months. Appetite ratings, energy intake and diet quality were collected at 0, 2, 4 and 6 months. Participants consuming almonds ingested 816 (sem 364) kJ/d more than participants in the control group (P = 0·03), but this did not result in any differences in body weight (A: –0·3 (sem 0·4), C: –0·4 (sem 0·4); P > 0·3). Participants in the almond, high android subcutaneous adipose tissue (SAT) group had a greater reduction in android fat mass percentage (A: –1·0 (sem 0·6), C: 1·1 (sem 0·6); P = 0·04), preserved android lean mass percentage (A: 0·9 (sem 0·6), C: –1 (sem 0·6); P = 0·04) and tended to decrease android visceral adipose tissue mass (A: –13 (sem 53) g, C: 127 (sem 53) g; P = 0·08) compared with those in the control, high SAT group. There were no differences in HbA1c between groups (A: 5·4 (sem 0·04), C: 5·5 (sem 0·04); P > 0·05). Thus, BFD may not explain the mixed evidence on almond consumption and HbA1c. Long-term almond consumption has limited ability to improve cardiometabolic health in those who are overweight and obese but otherwise healthy.

COVID-19 is the latest episode of shortages of critical medical supplies. Historically and to the present day, medical supplies have been sourced from single regions in the world, thus rendering the supply chain vulnerable to a myriad of harmful circumstances. We argue that shortages in medications related and unrelated to COVID have illustrated the need for the United States to diversify its medical supply sources before future pandemics, political crises, or natural disasters occur.

Previous research has shown that glufosinate and nicosulfuron at low rates can cause yield loss to grain sorghum. However, research has not been conducted to pinpoint the growth stage at which these herbicides are most injurious to grain sorghum. Therefore, field tests were conducted in 2016 and 2017 to determine the most sensitive growth stage for grain sorghum exposure to both glufosinate and nicosulfuron. Field test were designed with factor A being the herbicide applied (glufosinate or nicosulfuron). Factor B consisted of timing of herbicide application including V3, V8, flagleaf, heading, and soft dough stages. Factor C was glufosinate or nicosulfuron rate where a proportional rate of 656 g ai ha−1 of glufosinate and 35 g ai ha−1 of nicosulfuron was applied at 1/10×, 1/50×, and 1/250×. Visible injury, crop canopy heights (cm), and yield were reported as a percent of the nontreated. At the V3 growth stage visible injury of 32% from the 1/10× rate of glufosinate and 51% from the 1/10× rate of nicosulfuron was observed. This injury was reduced by 4 wk after application (WAA) and no yield loss occurred. Nicosulfuron was more injurious than glufosinate at a 1/10× and 1/50× rate when applied at the V8 and flagleaf growth stages resulting in death of the shoot, reduced heading, and yield. Yield losses from the 1/10× rate of nicosulfuron were observed from V8 through early heading and ranged from 41% to 96%. Yield losses from the 1/50× rate of nicosulfuron were 14% to 16% at the flagleaf and V8 growth stages respectively. The 1/10× rate of glufosinate caused 36% visible injury 2 WAA when applied at the flagleaf stage, which resulted in a 16% yield reduction. By 4 WAA visible injury from either herbicide at less than the 1/10× rate was not greater than 4%. Results indicate that injury can occur, but yield losses are more probable from low rates of nicosulfuron at V8 and flagleaf growth stages.

A non-GMO trait called Inzen™ was recently commercialized in grain sorghum to combat weedy grasses, allowing the use of nicosulfuron POST in the crop. Inzen™ grain sorghum carries a double mutation in the acetolactate synthase (ALS) gene Val560Ile and Trp574Leu, which potentially results in cross-resistance to a wide assortment of ALS-inhibiting herbicides. To evaluate the scope of cross-resistance to Weed Science Society of America Group 2 herbicides in addition to nicosulfuron, tests were conducted in 2016 and 2017 at the Lon Mann Cotton Research Station near Marianna, AR, the Arkansas Agricultural Research and Extension Center in Fayetteville, AR, and in 2016 at the Pine Tree Research Station near Colt, AR. The tests included ALS-inhibiting herbicides from all five families: sulfonylureas, imidazolinones, pyrimidinylthiobenzoics, triazolinones, and triazolopyrimidines. Treatments were made PRE or POST to grain sorghum at a 1× rate for crops in which each herbicide is labeled. Grain sorghum planted in the PRE trial were Inzen™ and a conventional cultivar. Visible estimates of injury and sorghum heights were recorded at 2 and 4 wk after herbicide application, and yield data were collected at crop maturity. In the PRE trial, no visible injury, sorghum height reduction, or yield loss were observed in plots containing the Inzen™ cultivar. Applications made POST to the Inzen™ grain sorghum caused visible injury, sorghum height reduction, and yield loss of 20%, 13%, and 35%, respectively, only in plots where bispyribac-Na was applied. There was no impact on the crop from other POST-applied ALS-inhibiting herbicides. These results demonstrate that the Inzen™ trait confers cross-resistance to most ALS-inhibiting herbicides and could offer promising new alternatives for weed control and protection from carryover of residual ALS-inhibiting herbicides in grain sorghum.

We derive a dispersion relation for the damping of acoustic waves in equi-molar deuterium–tritium (DT) gas due to radiation coupling and electron thermal conduction and discuss its significance for inertial confinement fusion (ICF) targets with high-Z shells surrounding a central DT fuel region. As the shell implodes around DT fuel in such a target, shocks and waves are transmitted through the DT gas. If the shell is perturbed due to drive non-uniformity or manufacturing imperfection, these shocks and waves may be perturbed as well, and can potentially re-perturb the shell. This can complicate calculation of shell stability and implosion asymmetry and in general make the target less robust against implosion non-uniformity. Damping of perturbations in DT gas can alleviate these complications. Also, damping of low-order modes, which is primarily due to radiation coupling, can drive the DT gas to an isobaric and isothermal ‘equilibrium’ configuration during ignition. We find that for the range of common ignition temperatures in targets with high-Z shells, $2.5\lesssim T_{ig}\lesssim 3.5$  keV, damping of low-order modes is significant for areal densities ($\unicode[STIX]{x1D70C}r$) in the broad range of $0.6\lesssim \unicode[STIX]{x1D70C}r\lesssim 1.8~\text{g}~\text{cm}^{-2}$. This suggests it is advantageous to design these targets to achieve areal densities at ignition within this range. Furthermore, we derive a simple constraint between areal density and temperature, $\unicode[STIX]{x1D70C}r=0.34T_{o}$ where $T_{o}$ is in keV, such that DT gas undergoing equilibrium ignition is optimally robust against non-uniformity.

Introduction: Although use of point of care ultrasound (PoCUS) protocols for patients with undifferentiated hypotension in the Emergency Department (ED) is widespread, our previously reported SHoC-ED study showed no clear survival or length of stay benefit for patients assessed with PoCUS. In this analysis, we examine if the use of PoCUS changed fluid administration and rates of other emergency interventions between patients with different shock types. The primary comparison was between cardiogenic and non-cardiogenic shock types. Methods: A post-hoc analysis was completed on the database from an RCT of 273 patients who presented to the ED with undifferentiated hypotension (SBP <100 or shock index > 1) and who had been randomized to receive standard care with or without PoCUS in 6 centres in Canada and South Africa. PoCUS-trained physicians performed scans after initial assessment. Shock categories and diagnoses recorded at 60 minutes after ED presentation, were used to allocate patients into subcategories of shock for analysis of treatment. We analyzed actual care delivered including initial IV fluid bolus volumes (mL), rates of inotrope use and major procedures. Standard statistical tests were employed. Sample size was powered at 0.80 (α:0.05) for a moderate difference. Results: Although there were expected differences in the mean fluid bolus volume between patients with non-cardiogenic and cardiogenic shock, there was no difference in fluid bolus volume between the control and PoCUS groups (non-cardiogenic control 1878 mL (95% CI 1550 – 2206 mL) vs. non-cardiogenic PoCUS 1687 mL (1458 – 1916 mL); and cardiogenic control 768 mL (194 – 1341 mL) vs. cardiogenic PoCUS 981 mL (341 – 1620 mL). Likewise there were no differences in rates of inotrope administration, or major procedures for any of the subcategories of shock between the control group and PoCUS group patients. The most common subcategory of shock was distributive. Conclusion: Despite differences in care delivered by subcategory of shock, we did not find any significant difference in actual care delivered between patients who were examined using PoCUS and those who were not. This may help to explain the previously reported lack of outcome difference between groups.

Introduction: Point of care ultrasound has been reported to improve diagnosis in non-traumatic hypotensive ED patients. We compared diagnostic performance of physicians with and without PoCUS in undifferentiated hypotensive patients as part of an international prospective randomized controlled study. The primary outcome was diagnostic performance of PoCUS for cardiogenic vs. non-cardiogenic shock. Methods: SHoC-ED recruited hypotensive patients (SBP < 100 mmHg or shock index > 1) in 6 centres in Canada and South Africa. We describe previously unreported secondary outcomes relating to diagnostic accuracy. Patients were randomized to standard clinical assessment (No PoCUS) or PoCUS groups. PoCUS-trained physicians performed scans after initial assessment. Demographics, clinical details and findings were collected prospectively. Initial and secondary diagnoses including shock category were recorded at 0 and 60 minutes. Final diagnosis was determined by independent blinded chart review. Standard statistical tests were employed. Sample size was powered at 0.80 (α:0.05) for a moderate difference. Results: 273 patients were enrolled with follow-up for primary outcome completed for 270. Baseline demographics and perceived category of shock were similar between groups. 11% of patients were determined to have cardiogenic shock. PoCUS had a sensitivity of 80.0% (95% CI 54.8 to 93.0%), specificity 95.5% (90.0 to 98.1%), LR+ve 17.9 (7.34 to 43.8), LR-ve 0.21 (0.08 to 0.58), Diagnostic OR 85.6 (18.2 to 403.6) and accuracy 93.7% (88.0 to 97.2%) for cardiogenic shock. Standard assessment without PoCUS had a sensitivity of 91.7% (64.6 to 98.5%), specificity 93.8% (87.8 to 97.0%), LR+ve 14.8 (7.1 to 30.9), LR- of 0.09 (0.01 to 0.58), Diagnostic OR 166.6 (18.7 to 1481) and accuracy of 93.6% (87.8 to 97.2%). There was no significant difference in sensitivity (-11.7% (-37.8 to 18.3%)) or specificity (1.73% (-4.67 to 8.29%)). Diagnostic performance was also similar between other shock subcategories. Conclusion: As reported in other studies, PoCUS based assessment performed well diagnostically in undifferentiated hypotensive patients, especially as a rule-in test. However performance was similar to standard (non-PoCUS) assessment, which was excellent in this study.

Laser-based compact MeV X-ray sources are useful for a variety of applications such as radiography and active interrogation of nuclear materials. MeV X rays are typically generated by impinging the intense laser onto ~mm-thick high-Z foil. Here, we have characterized such a MeV X-ray source from 120 TW (80 J, 650 fs) laser interaction with a 1 mm-thick tantalum foil. Our measurements show X-ray temperature of 2.5 MeV, flux of 3 × 1012 photons/sr/shot, beam divergence of ~0.1 sr, conversion efficiency of ~1%, that is, ~1 J of MeV X rays out of 80 J incident laser, and source size of 80 m. Our measurement also shows that MeV X-ray yield and temperature is largely insensitive to nanosecond laser contrasts up to 10−5. Also, preliminary measurements of similar MeV X-ray source using a double-foil scheme, where the laser-driven hot electrons from a thin foil undergoing relativistic transparency impinging onto a second high-Z converter foil separated by 50–400 m, show MeV X-ray yield more than an order of magnitude lower compared with the single-foil results.