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 Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) Cross-Trial Statistics Group gathered lessons learned from statisticians responsible for the design and analysis of the 11 ACTIV therapeutic master protocols to inform contemporary trial design as well as preparation for a future pandemic. The ACTIV master protocols were designed to rapidly assess what treatments might save lives, keep people out of the hospital, and help them feel better faster. Study teams initially worked without knowledge of the natural history of disease and thus without key information for design decisions. Moreover, the science of platform trial design was in its infancy. Here, we discuss the statistical design choices made and the adaptations forced by the changing pandemic context. Lessons around critical aspects of trial design are summarized, and recommendations are made for the organization of master protocols in the future.

Bubble growth, departure and sliding in low-pressure flow boiling has received considerable attention in the past. However, most applications of boiling heat transfer rely on high-pressure flow boiling, for which very little is known, as experimental data are scarce and very difficult to obtain. In this work, we conduct an experiment using high-resolution optical techniques. By combining backlit shadowgraphy and phase-detection imaging, we track bubble shape and physical footprint with high spatial ($6\,\mathrm {\mu }{\rm m}$) and temporal ($33\,\mathrm {\mu }{\rm s}$) resolutions, as well as bubble size and position as bubbles nucleate and slide on top of the heated surface. We show that at pressures above 1 MPa bubbles retain a spherical shape throughout the growth and sliding process. We analytically derive non-dimensional numbers to correlate bubble velocity and liquid velocity throughout the turbulent boundary layer and predict the sliding of bubbles on the surface, solely from physical properties and the bubble growth rate. We also show that these non-dimensional solutions can be leveraged to formulate elementary criteria that predict the effect of pressure and flow rate on bubble departure diameter and growth time.

We recently reported on the radio-frequency attenuation length of cold polar ice at Summit Station, Greenland, based on bi-static radar measurements of radio-frequency bedrock echo strengths taken during the summer of 2021. Those data also allow studies of (a) the relative contributions of coherent (such as discrete internal conducting layers with sub-centimeter transverse scale) vs incoherent (e.g. bulk volumetric) scattering, (b) the magnitude of internal layer reflection coefficients, (c) limits on signal propagation velocity asymmetries (‘birefringence’) and (d) limits on signal dispersion in-ice over a bandwidth of ~100 MHz. We find that (1) attenuation lengths approach 1 km in our band, (2) after averaging 10 000 echo triggers, reflected signals observable over the thermal floor (to depths of ~1500 m) are consistent with being entirely coherent, (3) internal layer reflectivities are ≈–60$\to$–70 dB, (4) birefringent effects for vertically propagating signals are smaller by an order of magnitude relative to South Pole and (5) within our experimental limits, glacial ice is non-dispersive over the frequency band relevant for neutrino detection experiments.

Two specimens of Metaconularia manni (Roy, 1935) from the lower Middle Silurian Scotch Grove Formation (eastern Iowa) exhibit well-defined, relict soft parts replicated in silica. One of these specimens bears phosphatic periderm, whereas the other specimen is a mold. Present within the erect, undistorted apical region of the specimen preserving periderm, on opposite sides of the peridermal cavity, are two small, elongate masses of silica located near the midlines of two of the four faces. Present in the central portion of the other specimen, at a somewhat greater distance from the apex, are five pairs of hollow, elongate, keeled pouch-like bodies (hereafter pouches), the long axes of which converge on the center of the fossil. Each pair of pouches is associated with a short, narrow, gently curved or broadly U-shaped tube, also composed of silica. Additionally, two of the pouch/tube combinations are associated with a pair of rectilinear furrows that correspond to the paired internal carinae that straddled the conulariid's facial midlines. We interpret the paired pouches and short tubes in the moldic specimen as relic conulariid soft parts homologous, respectively, to the interradial gonads and retractor muscles of extant, stauromedusan and polypoid scyphozoan cnidarians. Unlike most conulariids, which exhibit four faces, this individual had five faces, an aberrant morphology known in one other conulariid. The two small masses in the other specimen are more difficult to interpret, but they, too, could be relic gonads or longitudinal muscles. These interpretations suggest that, as in certain extant scyphozoans, at least one conulariid lost the free-living, sexual medusoid life phase.

A great deal of the research into the determinants of labour market outcomes has focussed on the role of human capital and the structure of the labour market. Relatively little attention has been paid to the role of social capital. This paper investigates the extent to which an individual’s social capital relates to their labour market outcomes. The relationships between social capital and labour force status and social capital and job search method are explored using data collected from a national random sample of Australians. Both a network and typology approach to measuring social capital are used.

North-western Arabia is marked by thousands of prehistoric stone structures. Of these, the monumental, rectilinear type known as mustatils has received only limited attention. Recent fieldwork in AlUla and Khaybar Counties, Saudi Arabia, demonstrates that these monuments are architecturally more complex than previously supposed, featuring chambers, entranceways and orthostats. These structures can now be interpreted as ritual installations dating back to the late sixth millennium BC, with recent excavations revealing the earliest evidence for a cattle cult in the Arabian Peninsula. As such, mustatils are amongst the earliest stone monuments in Arabia and globally one of the oldest monumental building traditions yet identified.

Women in academic publishing and academic psychiatry face many challenges of gender inequality, including significant pay differentials, poor visibility in senior positions and a male-dominated hierarchical system. We discuss this problem and outline how the BJPsych plans to tackle these issues it in its own publishing.

A synapse is a junction between two biological neurons, and the strength, or weight of the synapse, determines the communication strength between the neurons. Building a neuromorphic (i.e. neuron isomorphic) computing architecture, inspired by a biological network or brain, requires many engineered synapses. Furthermore, recent investigation in neuromorphic photonics, i.e. neuromorphic architectures on photonics platforms, have garnered much interest to enable high-bandwidth, low-latency, low-energy applications of neural networks in machine learning and neuromorphic computing. We propose a graphene-based synapse model as a core element to enable large-scale photonic neural networks based on on-chip multiwavelength techniques. This device consists of an electro-absorption modulator embedded in a microring resonator. We also introduce an encoding protocol that allows for the representation of synaptic weights on our photonic device with 15.7 bits of resolution using current control hardware. Recent work has suggested that graphene-based modulators could operate in excess of 100 GHz. Combined with our work, such a graphene-based synapse could enable applications for ultrafast and online learning.

Spotted fever group rickettsiae (SFG) are a neglected group of bacteria, belonging to the genus Rickettsia, that represent a large number of new and emerging infectious diseases with a worldwide distribution. The diseases are zoonotic and are transmitted by arthropod vectors, mainly ticks, fleas and mites, to hosts such as wild animals. Domesticated animals and humans are accidental hosts. In Asia, local people in endemic areas as well as travellers to these regions are at high risk of infection. In this review we compare SFG molecular and serological diagnostic methods and discuss their limitations. While there is a large range of molecular diagnostics and serological assays, both approaches have limitations and a positive result is dependent on the timing of sample collection. There is an increasing need for less expensive and easy-to-use diagnostic tests. However, despite many tests being available, their lack of suitability for use in resource-limited regions is of concern, as many require technical expertise, expensive equipment and reagents. In addition, many existing diagnostic tests still require rigorous validation in the regions and populations where these tests may be used, in particular to establish coherent and worthwhile cut-offs. It is likely that the best strategy is to use a real-time quantitative polymerase chain reaction (qPCR) and immunofluorescence assay in tandem. If the specimen is collected early enough in the infection there will be no antibodies but there will be a greater chance of a PCR positive result. Conversely, when there are detectable antibodies it is less likely that there will be a positive PCR result. It is therefore extremely important that a complete medical history is provided especially the number of days of fever prior to sample collection. More effort is required to develop and validate SFG diagnostics and those of other rickettsial infections.