Vaccines have revolutionised the field of medicine, eradicating and controlling many diseases. Recent pandemic vaccine successes have highlighted the accelerated pace of vaccine development and deployment. Leveraging this momentum, attention has shifted to cancer vaccines and personalised cancer vaccines, aimed at targeting individual tumour-specific abnormalities. The UK, now regarded for its vaccine capabilities, is an ideal nation for pioneering cancer vaccine trials. This article convened experts to share insights and approaches to navigate the challenges of cancer vaccine development with personalised or precision cancer vaccines, as well as fixed vaccines. Emphasising partnership and proactive strategies, this article outlines the ambition to harness national and local system capabilities in the UK; to work in collaboration with potential pharmaceutic partners; and to seize the opportunity to deliver the pace for rapid advances in cancer vaccine technology.

Tetflupyrolimet is the first herbicide with a novel site of action labeled preemergence (PRE) and early postemergence for use in agronomic crops in the last three decades. Direct-seeded paddy rice field experiments were conducted near Stuttgart on a silt loam soil, AR, and Keiser on a clay soil, AR, to evaluate tetflupyrolimet-containing herbicide programs in comparison to commercial standards in conventional, imidazolinone-, and quizalofop-resistant rice systems. Additionally, a furrow-irrigated rice experiment was conducted near Colt, AR, on a silt loam soil, and Keiser to ensure clomazone and tetflupyrolimet mixtures compared to commercial standards. Twelve commonly planted rice cultivars were also evaluated in response to a single PRE or postemergence (POST) (2- to 3-leaf rice) application of tetflupyrolimet at 200 and 400 g ai ha-1 in a paddy rice system, near Colt. When averaged over soil texture and site-year, all herbicide programs, provided ≥98% barnyardgrass control at 56 d after (DA) the last application. Visible rice injury varied for each rice system. Still, injury rarely differed amongst herbicide programs, except at a single evaluation timing in the conventional (7 DA 3- to 4-leaf applications) and quizalofop-resistant (preflood) systems. All 12 rice cultivars displayed a high tolerance level to a single PRE or POST application of tetflupyrolimet at 200 and 400 g ai ha-1. No visible injury, stand loss, or negative impact on rice maturity or reduced grain yield was observed for any cultivar. Tetflupyrolimet will be an effective alternative SOA in a program approach for barnyardgrass while maintaining excellent rice crop safety.

Tetflupyrolimet is the first herbicide with a novel site of action to be commercialized for use in agronomic crops in three decades. Direct-seed rice field experiments were conducted at research facilities near Stuttgart (silt loam), AR, and Keiser (clay), AR, to evaluate tetflupyrolimet as a preemergence herbicide versus commercial standards. Greenhouse experiments determined the influence of soil moisture on pre- and postemergence (POST) barnyardgrass control with tetflupyrolimet and clomazone, and the impact of a delayed flood on efficacy when POST-applied. For the field experiments, clomazone, tetflupyrolimet, and quinclorac were applied individually PRE at 336 and 560, 134 and 224, and 336 and 560 g ai ha-1, respectively, on a silt loam and clay soil, along with clomazone plus tetflupyrolimet and clomazone plus quinclorac at the same rates. The soil moisture experiment included a single PRE and POST application of clomazone at 336 g ai ha-1, tetflupyrolimet at 134 g ai ha-1, and a mixture at the respective rates, on a silt loam soil at 50, 75, and 100% of field capacity. For the flood timing experiment, tetflupyrolimet was applied to 2- to 3-leaf barnyardgrass at 134 g ai ha-1, and a flood was established at 4 hr after treatment (HAT) and 5 and 10 d after treatment (DAT). Barnyardgrass control with a tetflupyrolimet and clomazone mixture was comparable to clomazone plus quinclorac when averaged over all evaluations on silt loam and clay texture soils (≥91%). Soil moisture interacted with herbicide treatments for PRE and POST barnyardgrass efficacy when averaged over DAT, with tetflupyrolimet plus clomazone generally providing the greatest and most consistent control across regimes. Flooding barnyardgrass at 4 HAT provided superior control to later flood timings. Tetflupyrolimet is an effective residual barnyardgrass herbicide, and the addition of clomazone will aid in providing consistent control across varying soil moisture conditions.

We present a re-discovery of G278.94+1.35a as possibly one of the largest known Galactic supernova remnants (SNRs) – that we name Diprotodon. While previously established as a Galactic SNR, Diprotodon is visible in our new Evolutionary Map of the Universe (EMU) and GaLactic and Extragalactic All-sky MWA (GLEAM) radio continuum images at an angular size of $3{{{{.\!^\circ}}}}33\times3{{{{.\!^\circ}}}}23$, much larger than previously measured. At the previously suggested distance of 2.7 kpc, this implies a diameter of 157$\times$152 pc. This size would qualify Diprotodon as the largest known SNR and pushes our estimates of SNR sizes to the upper limits. We investigate the environment in which the SNR is located and examine various scenarios that might explain such a large and relatively bright SNR appearance. We find that Diprotodon is most likely at a much closer distance of $\sim$1 kpc, implying its diameter is 58$\times$56 pc and it is in the radiative evolutionary phase. We also present a new Fermi-LAT data analysis that confirms the angular extent of the SNR in gamma rays. The origin of the high-energy emission remains somewhat puzzling, and the scenarios we explore reveal new puzzles, given this unexpected and unique observation of a seemingly evolved SNR having a hard GeV spectrum with no breaks. We explore both leptonic and hadronic scenarios, as well as the possibility that the high-energy emission arises from the leftover particle population of a historic pulsar wind nebula.

As herbicide resistance continues to render commonly used rice herbicides ineffective, alternative sites of action are paramount to maintaining yield and producer profitability. Combining a slow-release formulation and a fenclorim seed treatment might allow the safe use of S-metolachlor in rice. Experiments were initiated in 2022 and 2023 near Colt, AR, on a silt loam soil to evaluate crop safety using a capsule suspension (CS) formulation of S-metolachlor and a fenclorim seed treatment in rice. The first experiment assessed the tolerance of two cultivars (‘Diamond’ and ‘DG263L’) to three rates (0.42, 0.84, and 1.68 kg ai ha−1) of a CS S-metolachlor at a delayed preemergence (DPRE) application timing in conjunction with a fenclorim seed treatment. The second experiment evaluated a 1- to 2-leaf (EPOST) application of a CS S-metolachlor at 0.56 and 1.12 kg ai ha−1 to fenclorim-treated rice. Fenclorim reduced injury and partially protected rice yield when S-metolachlor was applied DPRE at 1.68 kg ai ha−1 in both years. However, in one year, under adverse conditions, rice yields were only 65% and 66% of the nontreated control for fenclorim-treated ‘Diamond’ and ‘DG263L’, respectively. An EPOST application of S-metolachlor at 1.12 kg ai ha−1 resulted in 44% to 51% visible injury 35 d after treatment. Relative rice yields were 88% and 89% of the nontreated weed-free treatment in 2022 and 2023, respectively. Fenclorim provided enhanced crop safety at both the 0.84 and 1.68 kg ai ha−1 rates of S-metolachlor. However, the potential for reduced yield can arise when unfavorable conditions occur soon after application. An EPOST application timing of CS S-metolachlor at 0.56 kg ai ha−1 may be a viable option in rice, but 1.12 kg ai ha−1 is too high on a silt loam soil, resulting in significant rice injury.

1. 1. Understanding whether a species still persists, or the timing of its extinction is challenging, however, such knowledge is fundamental for effective species management.

2. 2. For the vast majority of species our understanding of their existence is based solely on sighting data that can range from museum specimens and clear photographs, through vocalisations, to markings and oral accounts.

3. 3. Here we review the methods that have been developed to infer the extinction of species from a sighting record, providing an understanding of their assumptions and applications. We have also produced an RShiny package which can be used to implement some of the methods presented in the article.

4. 4. While there are a number of potential areas that could be further developed, the methods reviewed provide a useful tool for inferring species extinction.

Italian ryegrass control is one of the most significant limitations in wheat production in the United States today. Resistance to Herbicide Resistance Action Committee (HRAC)/Weed Science Society of America (WSSA) Groups 1, 2, and 9 in Arkansas have further complicated postemergence control, whereas residual herbicides still show effective weed control. One problem is the potential of HRAC/WSSA Group 15 herbicides to injure wheat when applied preemergence, indicating the need for a herbicide safener. A series of experiments were conducted in Fayetteville, AR, to evaluate crop tolerance and Italian ryegrass control using a capsule suspension (CS) formulation of S-metolachlor in conjunction with fenclorim-treated wheat. Experiments were conducted as a two-factor factorial with S-metolachlor applied at three rates (0.37, 0.74, and 1.12 kg ai ha–1) and a microencapsulated formulation of acetochlor at 1.05 kg ai ha–1, and three rates of a fenclorim seed treatment at 0, 0.5, and 2.0 g ai kg–1 of seed. Separate experiments utilized either a preemergence (PRE) or a delayed-preemergence (DPRE) application timing. In both experiments, S-metolachlor at 0.74 and 1.12 kg ai ha–1 provided 77% to 96% control of Italian ryegrass by preharvest, whereas acetochlor only provided 49% to 72% control. Visible wheat injury from PRE applications ranged from 7% to 49% for all treatments 21 d after treatment (DAT), with a reduction in injury when fenclorim-treated wheat was used for both the 0.74 and 1.12 kg ai ha–1 rate of S-metolachlor. In the DPRE experiments, wheat injury ranged from 5% to 16% 21 DAT with no noticeable safening from the presence of fenclorim at any herbicide rate. The results of these experiments indicate that a DPRE application using a CS formulation of S-metolachlor would be more favorable for producers to mitigate the potential for injury to wheat while providing Italian ryegrass control. Additionally, at the DPRE application timing, fenclorim is unnecessary for S-metolachlor to be safely applied at the rates evaluated.

Rice producers battle herbicide-resistant weeds worldwide while producing rice for ≥50% of the world’s population. Oxyfluorfen can provide rice producers with an alternative site of action for barnyardgrass control, as there are no documented cases of grass weeds being resistant to the herbicide in the mid-southern United States. Oxyfluorfen is anticipated to be labeled in the Roxy Rice Production System and may be sold as a clomazone/oxyfluorfen premixture; hence, experiments were conducted in 2021 and 2022 to evaluate preemergence-applied clomazone/oxyfluorfen ratios compared to clomazone alone on silt loam and clay soils. All ratios of the herbicides caused less than 7% injury to rice in two of four site-years on silt loam soils, whereas, in the two other site-years, the mixtures caused 10% to 40% rice injury at all observation timings. All combinations of the two herbicides provided at least 73% barnyardgrass control 5 wk after rice emergence (WAE) in three of the four site-years on silt loam soils. In at least two of four site-years at 1 and 3 WAE, barnyardgrass control was improved when oxyfluorfen was added to clomazone compared to clomazone alone. On clay soil, barnyardgrass control in both site-years was ≥77% at 5 WAE for all clomazone and oxyfluorfen ratios. Injury to rice ranged from 13% to 30% for all treatments containing clomazone and oxyfluorfen in one of two site-years on clay soil at all observation timings. At 7 WAE, contrasts indicated that the 1:3 ratio of clomazone to oxyfluorfen provided greater barnyardgrass control than the 1:1.5 and 1:2 ratios in one of two site-years. Based on these findings, oxyfluorfen would improve the consistency of barnyardgrass control over clomazone alone in some instances. However, there is an increased risk of injury to rice with the addition of oxyfluorfen.

Commercialization of florpyrauxifen-benzyl as Loyant® in 2018 as a synthetic auxin herbicide in rice was followed by soybean injury due to off-target movement of spray applications in the mid-southern United States. Concerns surrounding off-target movement led to the exploration of an alternative application method to help alleviate the issue. Field experiments were conducted in 2020 and 2021 to explore the likelihood of a reduction in soybean injury following applications of florpyrauxifen-benzyl coated on urea in narrow- and wide-row soybean systems and to determine the likelihood of volatilization from this novel application method. Florpyrauxifen-benzyl spray-applied at 0.18 g ai ha−1 caused greater than 60% injury, whereas coating the herbicide on urea at 5.63 g ai ha−1 never exceeded 30% injury in narrow-row soybean. Similarly, florpyrauxifen-benzyl spray-applied at 0.18 g ai ha−1 caused greater than 50% injury, whereas coating the herbicide on urea at 5.63 g ai ha−1 never exceeded 30% injury in wide-row soybean. As soybean injury increased, relative yield decreased in both narrow- and wide-row soybean. Spray-applied florpyrauxifen-benzyl decreased relative soybean groundcover, yield components, and soybean survival rate as the herbicide rate increased, whereas coating the herbicide on urea resulted in little to no decrease in both narrow- and wide-row soybean assessments. No negative impacts on relative yield and yield components of soybean from florpyrauxifen-benzyl coated on urea indicates that even though visible injury may persist, there is a low likelihood of any yield losses associated with the herbicide exposure using this application method. Additionally, coating the florpyrauxifen-benzyl on urea did not increase the likelihood of volatilization under any of the evaluated soil moisture conditions. Overall, applying florpyrauxifen-benzyl coated on urea is likely to be a safer application method and can reduce soybean injury compared to spray-applying the herbicide when favorable off-target movement conditions exist.

This article presents the results of the 2008 excavation in the ancient theatre of Sparta conducted by the British School at Athens and the Ephorate of Antiquities of Laconia. Focused on the west side of the cavea, work aimed to locate the southern edge of the Late Antique settlement between the theatre and the sanctuary of Athena Chalkioikos; to establish the northern limits of the Late Antique settlement over the former orchestra; and to establish a more precise ceramic characterisation and chronology for the Early–Middle Byzantine period in Sparta. The area between settlement clusters on the acropolis and over the former orchestra was essentially open, with just a Byzantine terrace wall and path recorded. In the north-west part of the former cavea, a tomb built in the late eighth or early ninth century AD was used at least until the late thirteenth century for the burial of c. 29 individuals. This article presents the first results of a bioarchaeological study of the human remains, and studies of Byzantine pottery from the tomb interior and from the backfill of the pit in which the tomb was built (the latter including a notable quantity of Early Byzantine domestic ware). The 2008 findings are set in the larger context of research on post-antique phases in the theatre (drawing on the British School at Athens Archive) and on the material culture and urban topography of Byzantine Sparta. Almost all excavated contexts contained residual material of all periods. The article concludes with short catalogues of material which pre-dates the construction of the theatre and of inscriptions of all periods.

In the transitioning era towards the COVID-19 endemic, there is still a sizable population that has never been vaccinated against COVID-19 in the Netherlands. This study employs Bayesian spatio-temporal modelling to assess the relative chances of COVID-19 vaccination uptake – first, second, and booster doses – both at the municipal and regional (public health services) levels. Incorporating ecological regression modelling to consider socio-demographic factors, our study unveils a diverse spatio-temporal distribution of vaccination uptake. Notably, the areas located in or around the Dutch main urban area (Randstad) and regions that are more religiously conservative exhibit a below-average likelihood of vaccination. Analysis at the municipal level within public health service regions indicates internal heterogeneity. Additionally, areas with a higher proportion of non-Western migrants consistently show lower chances of vaccination across vaccination dose scenarios. These findings highlight the need for tailored national and local vaccination strategies. Particularly, more regional efforts are essential to address vaccination disparities, especially in regions with elevated proportions of marginalized populations. This insight informs ongoing COVID-19 campaigns, emphasizing the importance of targeted interventions for optimizing health outcomes during the second booster phase, especially in regions with a relatively higher proportion of marginalized populations.

Complaints regarding the sensitivity of rice to florpyrauxifen-benzyl and off-target movement of the herbicide occurred following its commercial launch in 2018 in the midsouthern United States. These two concerns encouraged the exploration of an alternative application method for florpyrauxifen-benzyl in rice. A field study was conducted in 2020 and 2021 to determine if coating florpyrauxifen-benzyl on urea would reduce negative impacts of the herbicide to rice. Five commercial rice lines were evaluated: ‘Diamond’, ‘Titan’, ‘RT7321 FP’, ‘RT7521 FP’, and ‘XP753’. Florpyrauxifen-benzyl coated on urea at a 2× rate (60 g ai ha–1) reduced rice injury in one of five commercial rice lines in 2020 and four of five commercial rice lines in 2021, compared to spray applications at the same rate. In 2020, ‘RT7521 FP’ exhibited a 17-percentage point injury reduction when coating florpyrauxifen-benzyl on urea at a 2× rate vs. the same rate sprayed. In 2021, rice injury was reduced by 26, 10, and 27 percentage points in the commercial rice lines ‘Diamond’, ‘Titan’, and ‘XP753’, respectively, following coated urea vs. spray applications at 4 wk after treatment (WAT). ‘XP753’ exhibited reduced injury (15 percentage points) by coating florpyrauxifen-benzyl at a 1× rate (30 g ai ha–1) 4 WAT in 2021, and another, ‘Diamond’, had comparable groundcover to nontreated plots when florpyrauxifen-benzyl was coated on urea at a 1× rate rather than the reductions observed from the spray application at a 2× rate. Yield differences were a function of urea rate rather than application method, where in six out of ten instances greater rough rice grain yield occurred at the higher rate. Findings from this experiment indicate that coating florpyrauxifen-benzyl on urea can reduce the amount of injury observed, especially in areas of overlap where you would have a 2× rate.

Carl Snyder was one of the most prominent US monetary economists of the 1920s and 1930s. His pioneering work on constructing the empirical counterparts of the terms in the equation of exchange led him to formulate a 4% monetary growth rule. Snyder is especially apposite because he was on the staff of the New York Federal Reserve Bank. Why, despite his pioneering empirical work and his position as an insider, did Snyder fail to effectively challenge the dominant real bills views of the Federal Reserve (Fed)? A short answer is that he did not possess a convincing version of the quantity theory that attributed the Great Depression to a contraction in the money stock produced by the Fed, as opposed to the dominant real bills view attributing it to the collapse of speculative excess.

Background: Automated sepsis alerts have become a widely implemented screening tool aimed at early detection of clinically unstable patients. Prior research has shown mixed results depending on the type of screening tools used and the patient population studied. This study aimed to evaluate the predictive value of an alert system created for identifying patients with sepsis to determine utility in clinical practice prior to implementation. Additionally, clinical management of those with and without sepsis was compared to measure potential added benefit of this system in clinical decision making. Methods: A TheraDoc® software sepsis alert was generated for non-ICU patients meeting >2 SIRS criteria within a 24-hour time period (temperature >38°C or 90, respiratory rate >20 or partial pressure CO2 12,000 or 10% bands/immature cells) during March 2023. Alerts were excluded if they were duplicates (using identical criteria or a second alert within 24 hours), triggered by labs collected >48 hours prior, or death or discharge occurred before the time of alert. The primary outcome was positive predictive value (PPV) of sepsis identification, confirmed by ICD-10 codes and diagnostic studies (cultures, imaging). Secondary outcomes included clinical management (antibiotic utilization [AU] and choice, infectious disease [ID] consultations and culture collection). Antibiotics were categorized as broad-spectrum using National Healthcare Safety Network (NSHN) criteria. Secondary outcomes were compared between sepsis and SIRS without infection groups (SIRS) by chi-square analysis. Results: After applying exclusion criteria, 116 of 166 alerts were analyzed; 55 of 116 alerts had confirmed sepsis (PPV 47.4%). Patients with sepsis were more likely to have an ID consult (16% [9/55] vs 7% [4/61]) and cultures collected (70.9% [39/55] vs 39.3% [24/61]) compared to SIRS patients, however these differences were not statistically significant. AU was higher with confirmed infections compared to SIRS patients (94.5% [52/55] vs 32.8% [20/61], p < 0 .05) along with use of broad-spectrum antibiotics (73% [38/52] vs 40% [ 8/20] p < 0 .05). Conclusions: While automated alerts may enable early identification of sepsis, use of SIRS criteria alone has poor specificity, which was borne out by the low PPV in this study. Our study found that management of sepsis patients (as measured by AU and culture ordering) was better than expected and combined with the low PPV of this alert system resulted in our team rejecting widespread adoption of SIRS-based sepsis alerts.