The bright radio source, GLEAM J091734$-$001243 (hereafter GLEAM J0917$-$0012), was previously selected as a candidate ultra-high redshift ($z \gt 5$) radio galaxy due to its compact radio size and faint magnitude ($K(\mathrm{AB})=22.7$). Its redshift was not conclusively determined from follow-up millimetre and near-infrared spectroscopy. Here we present new HST WFC3 G141 grism observations which reveal several emission lines including [NeIII]$\lambda$3867, [NeV]$\lambda$3426 and an extended ($\approx 4.8\,$kpc), [OII]$\lambda$3727 line which confirm a redshift of $3.004\pm0.001$. The extended component of the [OII]$\lambda$3727 line is co-spatial with one of two components seen at 2.276 GHz in high resolution ($60\times 20\,$mas) Long Baseline Array data, reminiscent of the alignments seen in local compact radio galaxies. The BEAGLE stellar mass ($\approx 2\times 10^{11}\,\textit{M}_\odot$) and radio luminosity ($L_{\mathrm{500MHz}}\approx 10^{28}\,$W Hz$^{-1}$) put GLEAM J0917$-$0012 within the distribution of the brightest high-redshift radio galaxies at similar redshifts. However, it is more compact than all of them. Modelling of the radio jet demonstrates that this is a young, $\approx 50\,$kyr old, but powerful, $\approx 10^{39}\,$W, compact steep spectrum radio source. The weak constraint on the active galactic nucleus bolometric luminosity from the [NeV]$\lambda$3426 line combined with the modelled jet power tentatively implies a large black hole mass, $\ge 10^9\,\textit{M}_\odot$, and a low, advection-dominated accretion rate, i.e. an Eddington ratio $\le 0.03$. The [NeV]$\lambda$3426/[NeIII]$\lambda$3867 vs [OII]$\lambda$3727/[NeIII]$\lambda$3867 line ratios are most easily explained by radiative shock models with precursor photoionisation. Hence, we infer that the line emission is directly caused by the shocks from the jet and that this radio source is one of the youngest and most powerful known at cosmic noon. We speculate that the star-formation in GLEAM J0917$-$0012 could be on its way to becoming quenched by the jet.

This paper argues that tone-driven epenthesis is possible in tonal languages. In Wamey, an epenthetic [ə] is inserted to host a high tone in two contexts: first, to host a tone which would otherwise be left floating due to a restriction on rising tones (/cv̀cⒽ/ maps to [cv̀cə́] due to a ban *[cv̌c]); and second, to host a tone which is introduced by word-level morphology but is restricted from associating across a stem boundary. These patterns cannot be attributed to syllable phonotactics, which freely allow all consonants in the coda position. We assemble the evidence for tone-driven epenthesis, focusing on the distribution of final [ə] in lexical stem structure and [ə]-alternating suffixes. A simple OT analysis derives [ə]-epenthesis, utilising common constraints (e.g. *Rise, OCP(H), etc.) together with constraints against associating tone across prosodic boundaries. In total, Wamey epenthesis exemplifies the cultivation of segmental environments for the purpose of realising pitch targets.

Asymptomatic coronavirus disease 2019 (COVID-19) has been reported as a significant driver of COVID-19 outbreaks. Our hospital ward outbreak analysis suggests that comprehensive symptoms and signs assessment, in combination with adequate follow-up, allows a more precise determination of COVID-19 symptoms. Asymptomatic infection was quite uncommon among adults in this setting.

OBJECTIVES/GOALS: #NAME? METHODS/STUDY POPULATION: Cell culture & protein identification: human T cells were purified from healthy blood, then activated & cultured for 5d. CAR-T cells were collected from infusion bags of cancer patients undergoing CAR-T. Silver staining of naive & activated healthy T-cell lysates was compared; B-II spectrin was upregulated and confirmed by Western blot. Migration assays: naive & activated T-cells were imaged during migration on ICAM-1 and ICAM-1 + CXCL12 coated plates. T-cells were transfected with BII-spectrin cDNA & the chemokine dependence of migration was compared with controls. In-vivo studies: in a melanoma mouse model, BII-spectrin transfected or control T-cells were injected; tumors were followed with serial imaging. Human patient records were examined to correlate endogenous BII-spectrin levels and CAR-T response. RESULTS/ANTICIPATED RESULTS: Activated T-cells downregulate the cytoskeletal protein B-II spectrin compared to naive cells, leading to chemokine-independent migration in in vitro assays and off-target trafficking when CAR-T cells are given in vivo. Restoration of B-II spectrin levels via transfection restores chemokine-dependence of activated T-cells. In a mouse melanoma model, control mice injected with standard activated T-cells showed fewer cells in the tumor site and more cells in the off-target organs (spleen, lungs) when compared to mice injected with B-II spectrin transfected cells. Furthermore, among 3 human patients undergoing CAR-T therapy, those with higher endogenous B-II spectrin levels experienced fewer side-effects, measured by the neurotoxicity and cytokine release syndrome grades. DISCUSSION/SIGNIFICANCE: A major hurdle to widespread CAR-T therapy for cancer is significant, often fatal side-effects. Our work shows that the protein B-II spectrin is downregulated during CAR-T production, and that restoring B-II spectrin levels decreases side-effects while increasing tumor clearance--hopefully translating to better CAR-T regimens for the future.

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.

In view of the increasing complexity of both cardiovascular implantable electronic devices (CIEDs) and patients in the current era, practice guidelines, by necessity, have become increasingly specific. This document is an expert consensus statement that has been developed to update and further delineate indications and management of CIEDs in pediatric patients, defined as ≤21 years of age, and is intended to focus primarily on the indications for CIEDs in the setting of specific disease categories. The document also highlights variations between previously published adult and pediatric CIED recommendations and provides rationale for underlying important differences. The document addresses some of the deterrents to CIED access in low- and middle-income countries and strategies to circumvent them. The document sections were divided up and drafted by the writing committee members according to their expertise. The recommendations represent the consensus opinion of the entire writing committee, graded by class of recommendation and level of evidence. Several questions addressed in this document either do not lend themselves to clinical trials or are rare disease entities, and in these instances recommendations are based on consensus expert opinion. Furthermore, specific recommendations, even when supported by substantial data, do not replace the need for clinical judgment and patient-specific decision-making. The recommendations were opened for public comment to Pediatric and Congenital Electrophysiology Society (PACES) members and underwent external review by the scientific and clinical document committee of the Heart Rhythm Society (HRS), the science advisory and coordinating committee of the American Heart Association (AHA), the American College of Cardiology (ACC), and the Association for European Paediatric and Congenital Cardiology (AEPC). The document received endorsement by all the collaborators and the Asia Pacific Heart Rhythm Society (APHRS), the Indian Heart Rhythm Society (IHRS), and the Latin American Heart Rhythm Society (LAHRS). This document is expected to provide support for clinicians and patients to allow for appropriate CIED use, appropriate CIED management, and appropriate CIED follow-up in pediatric patients.

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.

The ‘16Up’ study conducted at the QIMR Berghofer Medical Research Institute from January 2014 to December 2018 aimed to examine the physical and mental health of young Australian twins aged 16−18 years (N = 876; 371 twin pairs and 18 triplet sets). Measurements included online questionnaires covering physical and mental health as well as information and communication technology (ICT) use, actigraphy, sleep diaries and hair samples to determine cortisol concentrations. Study participants generally rated themselves as being in good physical (79%) and mental (73%) health and reported lower rates of psychological distress and exposure to alcohol, tobacco products or other substances than previously reported for this age group in the Australian population. Daily or near-daily online activity was almost universal among study participants, with no differences noted between males and females in terms of frequency or duration of internet access. Patterns of ICT use in this sample indicated that the respondents were more likely to use online information sources for researching physical health issues than for mental health or substance use issues, and that they generally reported partial levels of satisfaction with the mental health information they found online. This suggests that internet-based mental health resources can be readily accessed by adolescent Australians, and their computer literacy augurs well for future access to online health resources. In combination with other data collected as part of the ongoing Brisbane Longitudinal Twin Study, the 16Up project provides a valuable resource for the longitudinal investigation of genetic and environmental contributions to phenotypic variation in a variety of human traits.

Potential effectiveness of harvest weed seed control (HWSC) systems depends upon seed shatter of the target weed species at crop maturity, enabling its collection and processing at crop harvest. However, seed retention likely is influenced by agroecological and environmental factors. In 2016 and 2017, we assessed seed-shatter phenology in 13 economically important broadleaf weed species in soybean [Glycine max (L.) Merr.] from crop physiological maturity to 4 wk after physiological maturity at multiple sites spread across 14 states in the southern, northern, and mid-Atlantic United States. Greater proportions of seeds were retained by weeds in southern latitudes and shatter rate increased at northern latitudes. Amaranthus spp. seed shatter was low (0% to 2%), whereas shatter varied widely in common ragweed (Ambrosia artemisiifolia L.) (2% to 90%) over the weeks following soybean physiological maturity. Overall, the broadleaf species studied shattered less than 10% of their seeds by soybean harvest. Our results suggest that some of the broadleaf species with greater seed retention rates in the weeks following soybean physiological maturity may be good candidates for HWSC.

Seed shatter is an important weediness trait on which the efficacy of harvest weed seed control (HWSC) depends. The level of seed shatter in a species is likely influenced by agroecological and environmental factors. In 2016 and 2017, we assessed seed shatter of eight economically important grass weed species in soybean [Glycine max (L.) Merr.] from crop physiological maturity to 4 wk after maturity at multiple sites spread across 11 states in the southern, northern, and mid-Atlantic United States. From soybean maturity to 4 wk after maturity, cumulative percent seed shatter was lowest in the southern U.S. regions and increased moving north through the states. At soybean maturity, the percent of seed shatter ranged from 1% to 70%. That range had shifted to 5% to 100% (mean: 42%) by 25 d after soybean maturity. There were considerable differences in seed-shatter onset and rate of progression between sites and years in some species that could impact their susceptibility to HWSC. Our results suggest that many summer annual grass species are likely not ideal candidates for HWSC, although HWSC could substantially reduce their seed output during certain years.

Previous genetic association studies have failed to identify loci robustly associated with sepsis, and there have been no published genetic association studies or polygenic risk score analyses of patients with septic shock, despite evidence suggesting genetic factors may be involved. We systematically collected genotype and clinical outcome data in the context of a randomized controlled trial from patients with septic shock to enrich the presence of disease-associated genetic variants. We performed genomewide association studies of susceptibility and mortality in septic shock using 493 patients with septic shock and 2442 population controls, and polygenic risk score analysis to assess genetic overlap between septic shock risk/mortality with clinically relevant traits. One variant, rs9489328, located in AL589740.1 noncoding RNA, was significantly associated with septic shock (p = 1.05 × 10–10); however, it is likely a false-positive. We were unable to replicate variants previously reported to be associated (p < 1.00 × 10–6 in previous scans) with susceptibility to and mortality from sepsis. Polygenic risk scores for hematocrit and granulocyte count were negatively associated with 28-day mortality (p = 3.04 × 10–3; p = 2.29 × 10–3), and scores for C-reactive protein levels were positively associated with susceptibility to septic shock (p = 1.44 × 10–3). Results suggest that common variants of large effect do not influence septic shock susceptibility, mortality and resolution; however, genetic predispositions to clinically relevant traits are significantly associated with increased susceptibility and mortality in septic individuals.

A detailed assessment of the inter-scale energy budget of the turbulent flow in a von Kármán mixing tank has been performed based on two extensive experimental data sets. Measurements were performed at a Taylor microscale Reynolds number of $Re_{\unicode[STIX]{x1D706}}=199$ in the central region of the tank, using scanning particle image velocimetry (PIV) to fully resolve the velocity gradient tensor (VGT), and stereoscopic PIV for an expanded field of view. Following a basic flow characterisation, the Kármán–Howarth–Monin–Hill equation was used to investigate the inter-scale energy transfer. Access to the full VGT enabled the contribution of the different terms of the energy budget to be evaluated without any assumptions or approximations. The scale-space distribution of the dominant terms was also reported to assess the isotropy of the energy transfer. The results show a highly anisotropic distribution of energy transfer in scale space. Energy transfer was shown in a spherically averaged sense to be dominated at the small scales by the nonlinear inter-scale transfer term. However, in contrast to flows considered in previous studies, the local energy transfer is found to depend heavily on the linear contribution associated with the mean flow. Analysis of the scale-to-scale transfer of energy also allowed direct assessment of the classical picture of the energy cascade. It was found that while the inter-scale energy cascade driven by the turbulent fluctuations always proceeds in the forward direction, the total energy cascade driven by both the turbulent fluctuations and the mean flow exhibits significant inverse cascade regions, where energy is transferred from smaller to larger scales.

A national need is to prepare for and respond to accidental or intentional disasters categorized as chemical, biological, radiological, nuclear, or explosive (CBRNE). These incidents require specific subject-matter expertise, yet have commonalities. We identify 7 core elements comprising CBRNE science that require integration for effective preparedness planning and public health and medical response and recovery. These core elements are (1) basic and clinical sciences, (2) modeling and systems management, (3) planning, (4) response and incident management, (5) recovery and resilience, (6) lessons learned, and (7) continuous improvement. A key feature is the ability of relevant subject matter experts to integrate information into response operations. We propose the CBRNE medical operations science support expert as a professional who (1) understands that CBRNE incidents require an integrated systems approach, (2) understands the key functions and contributions of CBRNE science practitioners, (3) helps direct strategic and tactical CBRNE planning and responses through first-hand experience, and (4) provides advice to senior decision-makers managing response activities. Recognition of both CBRNE science as a distinct competency and the establishment of the CBRNE medical operations science support expert informs the public of the enormous progress made, broadcasts opportunities for new talent, and enhances the sophistication and analytic expertise of senior managers planning for and responding to CBRNE incidents.