Accelerating COVID-19 Treatment Interventions and Vaccines (ACTIV) was initiated by the US government to rapidly develop and test vaccines and therapeutics against COVID-19 in 2020. The ACTIV Therapeutics-Clinical Working Group selected ACTIV trial teams and clinical networks to expeditiously develop and launch master protocols based on therapeutic targets and patient populations. The suite of clinical trials was designed to collectively inform therapeutic care for COVID-19 outpatient, inpatient, and intensive care populations globally. In this report, we highlight challenges, strategies, and solutions around clinical protocol development and regulatory approval to document our experience and propose plans for future similar healthcare emergencies.

The authors report on ancient DNA data from two human skeletons buried within the chancel of the 1608–1616 church at the North American colonial settlement of Jamestown, Virginia. Available archaeological, osteological and documentary evidence suggest that these individuals are Sir Ferdinando Wenman and Captain William West, kinsmen of the colony's first Governor, Thomas West, Third Baron De La Warr. Genomic analyses of the skeletons identify unexpected maternal relatedness as both carried the mitochondrial haplogroup H10e. In this unusual case, aDNA prompted further historical research that led to the discovery of illegitimacy in the West family, an aspect of identity omitted, likely intentionally, from genealogical records.

We present and evaluate the prospects for detecting coherent radio counterparts to gravitational wave (GW) events using Murchison Widefield Array (MWA) triggered observations. The MWA rapid-response system, combined with its buffering mode ($\sim$4 min negative latency), enables us to catch any radio signals produced from seconds prior to hours after a binary neutron star (BNS) merger. The large field of view of the MWA ($\sim$$1\,000\,\textrm{deg}^2$ at 120 MHz) and its location under the high sensitivity sky region of the LIGO-Virgo-KAGRA (LVK) detector network, forecast a high chance of being on-target for a GW event. We consider three observing configurations for the MWA to follow up GW BNS merger events, including a single dipole per tile, the full array, and four sub-arrays. We then perform a population synthesis of BNS systems to predict the radio detectable fraction of GW events using these configurations. We find that the configuration with four sub-arrays is the best compromise between sky coverage and sensitivity as it is capable of placing meaningful constraints on the radio emission from 12.6% of GW BNS detections. Based on the timescales of four BNS merger coherent radio emission models, we propose an observing strategy that involves triggering the buffering mode to target coherent signals emitted prior to, during or shortly following the merger, which is then followed by continued recording for up to three hours to target later time post-merger emission. We expect MWA to trigger on $\sim$$5-22$ BNS merger events during the LVK O4 observing run, which could potentially result in two detections of predicted coherent emission.

We report a case of hypoplastic left heart syndrome and with subsequent aortopathy and then found to have hereditary haemorrhagic telangiectasia/juvenile polyposis syndrome due to a germline SMAD4 pathologic variant. The patient’s staged palliation was complicated by the development of neoaortic aneurysms, arteriovenous malformations, and gastrointestinal bleeding thought to be secondary to Fontan circulation, but workup revealed a SMAD4 variant consistent with hereditary haemorrhagic telangiectasia/juvenile polyposis syndrome. This case underscores the importance of genetic modifiers in CHD, especially those with Fontan physiology.

In Paper I, we presented an overview of the Southern-sky MWA Rapid Two-metre (SMART) survey, including the survey design and search pipeline. While the combination of MWA’s large field-of-view and the voltage capture system brings a survey speed of ${\sim} 450\, {\textrm{deg}}^{2}\,\textrm{h}^{-1}$, the progression of the survey relies on the availability of compact configuration of the Phase II array. Over the past few years, by taking advantage of multiple windows of opportunity when the compact configuration was available, we have advanced the survey to 75% of the planned sky coverage. To date, about 10% of the data collected thus far have been processed for a first-pass search, where 10 min of observation is processed for dispersion measures out to 250 ${\textrm{pc cm}}^{-3}$, to realise a shallow survey that is largely sensitive to long-period pulsars. The ongoing analysis has led to two new pulsar discoveries, as well as an independent discovery and a rediscovery of a previously incorrectly characterised pulsar, all from ${\sim} 3\% $ of the data for which candidate scrutiny is completed. In this sequel to Paper I, we describe the strategies for further detailed follow-up including improved sky localisation and convergence to timing solution, and illustrate them using example pulsar discoveries. The processing has also led to re-detection of 120 pulsars in the SMART observing band, bringing the total number of pulsars detected to date with the MWA to 180, and these are used to assess the search sensitivity of current processing pipelines. The planned second-pass (deep survey) processing is expected to yield a three-fold increase in sensitivity for long-period pulsars, and a substantial improvement to millisecond pulsars by adopting optimal de-dispersion plans. The SMART survey will complement the highly successful Parkes High Time Resolution Universe survey at 1.2–1.5 GHz, and inform future large survey efforts such as those planned with the low-frequency Square Kilometre Array (SKA-Low).

We present an overview of the Southern-sky MWA Rapid Two-metre (SMART) pulsar survey that exploits the Murchison Widefield Array’s large field of view and voltage-capture system to survey the sky south of 30$^{\circ}$ in declination for pulsars and fast transients in the 140–170 MHz band. The survey is enabled by the advent of the Phase II MWA’s compact configuration, which offers an enormous efficiency in beam-forming and processing costs, thereby making an all-sky survey of this magnitude tractable with the MWA. Even with the long dwell times employed for the survey (4800 s), data collection can be completed in $<$100 h of telescope time, while still retaining the ability to reach a limiting sensitivity of $\sim$2–3 mJy (at 150 MHz, near zenith), which is effectively 3–5 times deeper than the previous-generation low-frequency southern-sky pulsar survey, completed in the 1990s. Each observation is processed to generate $\sim$5000–8000 tied-array beams that tessellate the full $\sim 610\, {\textrm{deg}^{2}}$ field of view (at 155 MHz), which are then processed to search for pulsars. The voltage-capture recording of the survey also allows a multitude of post hoc processing options including the reprocessing of data for higher time resolution and even exploring image-based techniques for pulsar candidate identification. Due to the substantial computational cost in pulsar searches at low frequencies, the survey data processing is undertaken in multiple passes: in the first pass, a shallow survey is performed, where 10 min of each observation is processed, reaching about one-third of the full-search sensitivity. Here we present the system overview including details of ongoing processing and initial results. Further details including first pulsar discoveries and a census of low-frequency detections are presented in a companion paper. Future plans include deeper searches to reach the full sensitivity and acceleration searches to target binary and millisecond pulsars. Our simulation analysis forecasts $\sim$300 new pulsars upon the completion of full processing. The SMART survey will also generate a complete digital record of the low-frequency sky, which will serve as a valuable reference for future pulsar searches planned with the low-frequency Square Kilometre Array.

Early in the COVID-19 pandemic, the World Health Organization stressed the importance of daily clinical assessments of infected patients, yet current approaches frequently consider cross-sectional timepoints, cumulative summary measures, or time-to-event analyses. Statistical methods are available that make use of the rich information content of longitudinal assessments. We demonstrate the use of a multistate transition model to assess the dynamic nature of COVID-19-associated critical illness using daily evaluations of COVID-19 patients from 9 academic hospitals. We describe the accessibility and utility of methods that consider the clinical trajectory of critically ill COVID-19 patients.

Many short gamma-ray bursts (GRBs) originate from binary neutron star mergers, and there are several theories that predict the production of coherent, prompt radio signals either prior, during, or shortly following the merger, as well as persistent pulsar-like emission from the spin-down of a magnetar remnant. Here we present a low frequency (170–200 MHz) search for coherent radio emission associated with nine short GRBs detected by the Swift and/or Fermi satellites using the Murchison Widefield Array (MWA) rapid-response observing mode. The MWA began observing these events within 30–60 s of their high-energy detection, enabling us to capture any dispersion delayed signals emitted by short GRBs for a typical range of redshifts. We conducted transient searches at the GRB positions on timescales of 5 s, 30 s, and 2 min, resulting in the most constraining flux density limits on any associated transient of 0.42, 0.29, and 0.084 Jy, respectively. We also searched for dispersed signals at a temporal and spectral resolution of 0.5 s and 1.28 MHz, but none were detected. However, the fluence limit of 80–100 Jy ms derived for GRB 190627A is the most stringent to date for a short GRB. Assuming the formation of a stable magnetar for this GRB, we compared the fluence and persistent emission limits to short GRB coherent emission models, placing constraints on key parameters including the radio emission efficiency of the nearly merged neutron stars ($\epsilon_r\lesssim10^{-4}$), the fraction of magnetic energy in the GRB jet ($\epsilon_B\lesssim2\times10^{-4}$), and the radio emission efficiency of the magnetar remnant ($\epsilon_r\lesssim10^{-3}$). Comparing the limits derived for our full GRB sample (along with those in the literature) to the same emission models, we demonstrate that our fluence limits only place weak constraints on the prompt emission predicted from the interaction between the relativistic GRB jet and the interstellar medium for a subset of magnetar parameters. However, the 30-min flux density limits were sensitive enough to theoretically detect the persistent radio emission from magnetar remnants up to a redshift of $z\sim0.6$. Our non-detection of this emission could imply that some GRBs in the sample were not genuinely short or did not result from a binary neutron star merger, the GRBs were at high redshifts, these mergers formed atypical magnetars, the radiation beams of the magnetar remnants were pointing away from Earth, or the majority did not form magnetars but rather collapse directly into black holes.

Seed retention, and ultimately seed shatter, are extremely important for the efficacy of harvest weed seed control (HWSC) and are likely influenced by various agroecological and environmental factors. Field studies investigated seed-shattering phenology of 22 weed species across three soybean [Glycine max (L.) Merr.]-producing regions in the United States. We further evaluated the potential drivers of seed shatter in terms of weather conditions, growing degree days, and plant biomass. Based on the results, weather conditions had no consistent impact on weed seed shatter. However, there was a positive correlation between individual weed plant biomass and delayed weed seed–shattering rates during harvest. This work demonstrates that HWSC can potentially reduce weed seedbank inputs of plants that have escaped early-season management practices and retained seed through harvest. However, smaller individuals of plants within the same population that shatter seed before harvest pose a risk of escaping early-season management and HWSC.

We examined the accuracy of International Classification of Disease 10th iteration (ICD-10) diagnosis codes within Canadian administrative data in identifying cerebral venous thrombosis (CVT). Of 289 confirmed cases of CVT admitted to our comprehensive stroke center between 2008 and 2018, 239/289 were new diagnoses and 204/239 were acute events with only 75/204 representing symptomatic CVTs not provoked by trauma or structural processes. Using ICD-10 codes in any position, sensitivity was 39.1% and positive predictive value was 94.2% for patients with a current or history of CVT and 84.0% and 52.5% for acute and symptomatic CVTs not provoked by trauma or structural processes.

Substantial progress has been made in the standardization of nomenclature for paediatric and congenital cardiac care. In 1936, Maude Abbott published her Atlas of Congenital Cardiac Disease, which was the first formal attempt to classify congenital heart disease. The International Paediatric and Congenital Cardiac Code (IPCCC) is now utilized worldwide and has most recently become the paediatric and congenital cardiac component of the Eleventh Revision of the International Classification of Diseases (ICD-11). The most recent publication of the IPCCC was in 2017. This manuscript provides an updated 2021 version of the IPCCC.

The International Society for Nomenclature of Paediatric and Congenital Heart Disease (ISNPCHD), in collaboration with the World Health Organization (WHO), developed the paediatric and congenital cardiac nomenclature that is now within the eleventh version of the International Classification of Diseases (ICD-11). This unification of IPCCC and ICD-11 is the IPCCC ICD-11 Nomenclature and is the first time that the clinical nomenclature for paediatric and congenital cardiac care and the administrative nomenclature for paediatric and congenital cardiac care are harmonized. The resultant congenital cardiac component of ICD-11 was increased from 29 congenital cardiac codes in ICD-9 and 73 congenital cardiac codes in ICD-10 to 318 codes submitted by ISNPCHD through 2018 for incorporation into ICD-11. After these 318 terms were incorporated into ICD-11 in 2018, the WHO ICD-11 team added an additional 49 terms, some of which are acceptable legacy terms from ICD-10, while others provide greater granularity than the ISNPCHD thought was originally acceptable. Thus, the total number of paediatric and congenital cardiac terms in ICD-11 is 367. In this manuscript, we describe and review the terminology, hierarchy, and definitions of the IPCCC ICD-11 Nomenclature. This article, therefore, presents a global system of nomenclature for paediatric and congenital cardiac care that unifies clinical and administrative nomenclature.

The members of ISNPCHD realize that the nomenclature published in this manuscript will continue to evolve. The version of the IPCCC that was published in 2017 has evolved and changed, and it is now replaced by this 2021 version. In the future, ISNPCHD will again publish updated versions of IPCCC, as IPCCC continues to evolve.

Here we present stringent low-frequency (185 MHz) limits on coherent radio emission associated with a short-duration gamma-ray burst (SGRB). Our observations of the short gamma-ray burst (GRB) 180805A were taken with the upgraded Murchison Widefield Array (MWA) rapid-response system, which triggered within 20s of receiving the transient alert from the Swift Burst Alert Telescope, corresponding to 83.7 s post-burst. The SGRB was observed for a total of 30 min, resulting in a $3\sigma$ persistent flux density upper limit of 40.2 mJy beam–1. Transient searches were conducted at the Swift position of this GRB on 0.5 s, 5 s, 30 s and 2 min timescales, resulting in $3\sigma$ limits of 570–1 830, 270–630, 200–420, and 100–200 mJy beam–1, respectively. We also performed a dedispersion search for prompt signals at the position of the SGRB with a temporal and spectral resolution of 0.5 s and 1.28 MHz, respectively, resulting in a $6\sigma$ fluence upper-limit range from 570 Jy ms at DM $=3\,000$ pc cm–3 ($z\sim 2.5$) to 1 750 Jy ms at DM$=200$ pc cm–3 ($z\sim 0.1)$, corresponding to the known redshift range of SGRBs. We compare the fluence prompt emission limit and the persistent upper limit to SGRB coherent emission models assuming the merger resulted in a stable magnetar remnant. Our observations were not sensitive enough to detect prompt emission associated with the alignment of magnetic fields of a binary neutron star just prior to the merger, from the interaction between the relativistic jet and the interstellar medium (ISM) or persistent pulsar-like emission from the spin-down of the magnetar. However, in the case of a more powerful SGRB (a gamma-ray fluence an order of magnitude higher than GRB 180805A and/or a brighter X-ray counterpart), our MWA observations may be sensitive enough to detect coherent radio emission from the jet-ISM interaction and/or the magnetar remnant. Finally, we demonstrate that of all current low- frequency radio telescopes, only the MWA has the sensitivity and response times capable of probing prompt emission models associated with the initial SGRB merger event.

We present the first Southern-Hemisphere all-sky imager and radio-transient monitoring system implemented on two prototype stations of the low-frequency component of the Square Kilometre Array (SKA-Low). Since its deployment, the system has been used for real-time monitoring of the recorded commissioning data. Additionally, a transient searching algorithm has been executed on the resulting all-sky images. It uses a difference imaging technique to enable identification of a wide variety of transient classes, ranging from human-made radio-frequency interference to genuine astrophysical events. Observations at the frequency 159.375 MHz and higher in a single coarse channel ($\approx$0.926 MHz) were made with 2 s time resolution, and multiple nights were analysed generating thousands of images. Despite having modest sensitivity ($\sim$ few Jy beam–1), using a single coarse channel and 2-s imaging, the system was able to detect multiple bright transients from PSR B0950+08, proving that it can be used to detect bright transients of an astrophysical origin. The unusual, extreme activity of the pulsar PSR B0950+08 (maximum flux density $\sim$155 Jy beam–1) was initially detected in a ‘blind’ search in the 2020 April 10/11 data and later assigned to this specific pulsar. The limitations of our data, however, prevent us from making firm conclusions of the effect being due to a combination of refractive and diffractive scintillation or intrinsic emission mechanisms. The system can routinely collect data over many days without interruptions; the large amount of recorded data at 159.375 and 229.6875 MHz allowed us to determine a preliminary transient surface density upper limit of $1.32 \times 10^{-9} \text{deg}^{-2}$ for a timescale and limiting flux density of 2 s and 42 Jy, respectively. In the future, we plan to extend the observing bandwidth to tens of MHz and improve time resolution to tens of milliseconds in order to increase the sensitivity and enable detections of fast radio bursts below 300 MHz.

The first demonstration of laser action in ruby was made in 1960 by T. H. Maiman of Hughes Research Laboratories, USA. Many laboratories worldwide began the search for lasers using different materials, operating at different wavelengths. In the UK, academia, industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications. This historical review looks at the contribution the UK has made to the advancement of the technology, the development of systems and components and their exploitation over the last 60 years.