Among nursing home outbreaks of coronavirus disease 2019 (COVID-19) with ≥3 breakthrough infections when the predominant severe acute respiratory coronavirus virus 2 (SARS-CoV-2) variant circulating was the SARS-CoV-2 δ (delta) variant, fully vaccinated residents were 28% less likely to be infected than were unvaccinated residents. Once infected, they had approximately half the risk for all-cause hospitalization and all-cause death compared with unvaccinated infected residents.

This study explores the use of Free Choice Profiling (FCP) methodology for the qualitative behaviour assessment of emotional expression in the domestic dog (Canis familiaris). Qualitative behaviour assessment is based upon the integration of many pieces of information that in conventional quantitative approaches are recorded separately or not at all. Observers are asked to focus on an animal's interaction with its surrounding environment, and to describe the animal's expressive demeanor, or ‘body language’. A specific characteristic of FCP methodology is that it allows observers the freedom to devise their own descriptive terms, and then to use these personal terms to quantitatively score observed subjects. Application of FCP to qualitative behaviour assessment in animals was originally tested for pigs, and more recently for dairy cows, horses, and ponies. The goal of this study was to apply FCP to the domestic dog, and to investigate the inter-observer reliability of assessments of emotional expression in 10 individual Beagles by a group of 18 untrained observers. The data was analysed using Generalised Procrustes Analysis (GPA), a multivariate statistical technique associated with FCP. The observers achieved highly-significant agreement in their assessments of the dogs’ expressions, thereby establishing the applicability of this methodology for the first time in the domestic dog.

Stereotypic behaviours (SBs) are linked with behavioural inflexibility and resemble symptoms of autism, suggesting that stereotypic animals could have autistic-like social impairments. SBs are also common in caged mice. We therefore hypothesised relationships between stereotypic and social behaviours, predicting that highly stereotypic mice would give/receive more agonism and be less effective in social learning tasks. Experiment One used C57BL/6 and DBA/2 mice in non-enriched or enriched housing (15 cages each); Experiment Two, more cages (six non-enriched, 44 enriched) plus a third strain (BALB/c). Across both experiments, enrichment reduced SB and agonism (aggression, plus ‘displacements’ where one mouse supplants another at a resource). These effects appeared related: housing effects on agonism became negligible when SB was statistically controlled for, and, at least in enriched cages, SB covaried with receiving aggression. In Experiment Three, 20 DBAs varying in SB from Experiment Two acted as demonstrators in a ‘social transmission of food preferences’ task. They were fed a novel flavour (shatavari powder), then each mingled with a familiar but flavour-naïve C57 observer. Observers were subsequently offered two novel flavours: shatavari or marjoram. Those spontaneously choosing more shatavari (n = 10) tended to have had less stereotypic demonstrators than the other ten observer mice. Overall, highly stereotypic mice thus received more agonism — an effect with obvious welfare implications that can be reduced with enrichment — and seemed potentially less effective at inducing flavour preferences in conspecifics. Such effects are consistent with social impairment, suggesting that reducing SB may perhaps enhance interactions between conspecifics.

While unobscured and radio-quiet active galactic nuclei are regularly being found at redshifts $z > 6$ , their obscured and radio-loud counterparts remain elusive. We build upon our successful pilot study, presenting a new sample of low-frequency-selected candidate high-redshift radio galaxies (HzRGs) over a sky area 20 times larger. We have refined our selection technique, in which we select sources with curved radio spectra between 72–231 MHz from the GaLactic and Extragalactic All-sky Murchison Widefield Array (GLEAM) survey. In combination with the requirements that our GLEAM-selected HzRG candidates have compact radio morphologies and be undetected in near-infrared $K_{\rm s}$ -band imaging from the Visible and Infrared Survey Telescope for Astronomy Kilo-degree Infrared Galaxy (VIKING) survey, we find 51 new candidate HzRGs over a sky area of approximately $1200\ \mathrm{deg}^2$ . Our sample also includes two sources from the pilot study: the second-most distant radio galaxy currently known, at $z=5.55$ , with another source potentially at $z \sim 8$ . We present our refined selection technique and analyse the properties of the sample. We model the broadband radio spectra between 74 MHz and 9 GHz by supplementing the GLEAM data with both publicly available data and new observations from the Australia Telescope Compact Array at 5.5 and 9 GHz. In addition, deep $K_{\rm s}$ -band imaging from the High-Acuity Widefield K-band Imager (HAWK-I) on the Very Large Telescope and from the Southern Herschel Astrophysical Terahertz Large Area Survey Regions $K_{\rm s}$ -band Survey (SHARKS) is presented for five sources. We discuss the prospects of finding very distant radio galaxies in our sample, potentially within the epoch of reionisation at $z \gtrsim 6.5$ .

We describe a new low-frequency wideband radio survey of the southern sky. Observations covering 72–231 MHz and Declinations south of $+30^\circ$ have been performed with the Murchison Widefield Array “extended” Phase II configuration over 2018–2020 and will be processed to form data products including continuum and polarisation images and mosaics, multi-frequency catalogues, transient search data, and ionospheric measurements. From a pilot field described in this work, we publish an initial data release covering 1,447 $\mathrm{deg}^2$ over $4\,\mathrm{h}\leq \mathrm{RA}\leq 13\,\mathrm{h}$ , $-32.7^\circ \leq \mathrm{Dec} \leq -20.7^\circ$ . We process twenty frequency bands sampling 72–231 MHz, with a resolution of 2′–45′′, and produce a wideband source-finding image across 170–231 MHz with a root mean square noise of $1.27\pm0.15\,\mathrm{mJy\,beam}^{-1}$ . Source-finding yields 78,967 components, of which 71,320 are fitted spectrally. The catalogue has a completeness of 98% at ${{\sim}}50\,\mathrm{mJy}$ , and a reliability of 98.2% at $5\sigma$ rising to 99.7% at $7\sigma$ . A catalogue is available from Vizier; images are made available via the PASA datastore, AAO Data Central, and SkyView. This is the first in a series of data releases from the GLEAM-X survey.

This work investigates the application of origami as the underlying principle to realize a novel 3D printed hand orthosis design. Due to the special property of some origami to become rigid when forming a closed surface, the orthosis can be printed flat to alleviate the most of the post-processing, and at the same time provide rigid support for the immobilized limb in the folded state. The contributions are the origami-based hand orthosis design and corresponding computational design method, as well as lessons learned regarding the application of origami for the hand orthosis design.

OBJECTIVES/GOALS: Immunomodulatory drugs (IMiDs) are critical to multiple myeloma (MM) disease control. IMiDs act by inducing Cereblon-dependent degradation of IKZF1 and IKZF3, which leads to IRF4 and MYC downregulation (collectively termed the “Ikaros axis”). We therefore hypothesized that IMiD treatment fails to downregulate the Ikaros axis in IMiD resistant MM. METHODS/STUDY POPULATION: To measure IMiD-induced Ikaros axis downregulation, we designed an intracellular flow cytometry assay that measured relative protein levels of IKZF1, IKZF3, IRF4 and MYC in MM cells following ex vivo treatment with the IMiD Pomalidomide (Pom). We established this assay using Pom-sensitive parental and dose-escalated Pom-resistant MM cell lines before assessing Ikaros axis downregulation in CD38+CD138+ MM cells in patient samples (bone marrow aspirates). To assess the Ikaros axis in the context of MM intratumoral heterogeneity, we used a 35-marker mass cytometry panel to simultaneously characterize MM subpopulations in patient samples. Lastly, we determined ex vivo drug sensitivity in patient samples via flow cytometry. RESULTS/ANTICIPATED RESULTS: Our hypothesis was supported in MM cell lines, as resistant lines showed no IMiD-induced decrease in any Ikaros axis proteins. However, when assessed in patient samples, Pom treatment caused a significant decrease in IKZF1, IKZF3 and IRF4 regardless of IMiD sensitivity. Mass cytometry in patient samples revealed that individual Ikaros axis proteins were differentially expressed between subpopulations. When correlating this with ex vivo Pom sensitivity of MM subpopulations, we observed that low IKZF1 and IKZF3 corresponded to Pom resistance. Interestingly, most of these resistant populations still expressed MYC. We therefore assessed whether IMiD resistant MM was MYC dependent by treating with MYCi975. In 88% (7/8) of patient samples tested, IMiD resistant MM cells were sensitive to MYC inhibition. DISCUSSION/SIGNIFICANCE: While our findings did not support our initial hypothesis, our data suggest a mechanism where MYC expression becomes Ikaros axis independent to drive IMiD resistance, and resistant MM is still dependent on MYC. This suggests targeting MYC directly or indirectly via a mechanism to be determined may be an effective strategy to eradicate IMiD resistant MM.

Metabolites produced by microbial fermentation in the human intestine, especially short-chain fatty acids (SCFAs), are known to play important roles in colonic and systemic health. Our aim here was to advance our understanding of how and why their concentrations and proportions vary between individuals. We have analysed faecal concentrations of microbial fermentation acids from 10 human volunteer studies, involving 163 subjects, conducted at the Rowett Institute, Aberdeen, UK over a 7-year period. In baseline samples, the % butyrate was significantly higher, whilst % iso-butyrate and % iso-valerate were significantly lower, with increasing total SCFA concentration. The decreasing proportions of iso-butyrate and iso-valerate, derived from amino acid fermentation, suggest that fibre intake was mainly responsible for increased SCFA concentrations. We propose that the increase in % butyrate among faecal SCFA is largely driven by a decrease in colonic pH resulting from higher SCFA concentrations. Consistent with this, both total SCFA and % butyrate increased significantly with decreasing pH across five studies for which faecal pH measurements were available. Colonic pH influences butyrate production through altering the stoichiometry of butyrate formation by butyrate-producing species, resulting in increased acetate uptake and butyrate formation, and facilitating increased relative abundance of butyrate-producing species (notably Roseburia and Eubacterium rectale).

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.

We discuss present and developing techniques for studying radiocarbon in marine organic carbon (C). Bulk DOC (dissolved organic C) Δ14C measurements reveal information about the cycling time and sources of DOC in the ocean, yet they are time consuming and need to be streamlined. To further elucidate the cycling of DOC, various fractions have been separated from bulk DOC, through solid phase extraction of DOC, and ultrafiltration of high and low molecular weight DOC. Research using 14C of DOC and particulate organic C separated into organic fractions revealed that the acid insoluble fraction is similar in 14C signature to that of the lipid fraction. Plans for utilizing this methodology are described. Studies using compound specific radiocarbon analyses to study the origin of biomarkers in the marine environment are reviewed and plans for the future are outlined. Development of ramped pyrolysis oxidation methods are discussed and scientific questions addressed. A modified elemental analysis (EA) combustion reactor is described that allows high particulate organic C sample throughput by direct coupling with the MIniCArbonDAtingSystem.

Background: Objective markers of disease progression are needed for patients with multiple sclerosis (MS). Increased randomness in neural networks is hypothesized to be an important cause of morbidity that can be objectified using graph theory. Methods: We use voxel-based structural similarity determined from T1-weighted MRI scans of 23 patients with MS receiving autologous stem cell transplant (ASCT) to compute cortical covariance network parameters. We examine associations between measures of cortical integration or segregation and biochemical/clinical measures of cortical health or function using Spearman correlation coefficients. P<0.05 was considered significant. Results: Path length increase was associated with markers of greater inflammation (ρ=0.56,P<.046) at baseline and reduced Naa/Cr ratio (P<.041) at 12 months. Reduced lambda was associated with markers of greater grey matter atrophy (ρ=0.55,P<.019) after 12 months and lower cognition (ρ=0.56,P<.008) at 12 months. Reduced clustering was associated with higher neurofilament (ρ=-0.68,P<.010) at baseline, greater white matter atrophy (ρ=0.62,P<.006) after 12 months, lower 2-second PASAT performance (ρ=0.56,P<.011) at baseline, and reduced Naa/Cr ratio (P<.001) at 12 months. Conclusions: Reduced cortical integration and segregation (random network features) co-occur with unfavourable markers of cortical health and function in patients with MS receiving ASCT. Network features show promise as important longitudinal markers of patient status and progression.

This study aimed to explore effects of adjunctive minocycline treatment on inflammatory and neurogenesis markers in major depressive disorder (MDD). Serum samples were collected from a randomised, placebo-controlled 12-week clinical trial of minocycline (200 mg/day, added to treatment as usual) for adults (n = 71) experiencing MDD to determine changes in interleukin-6 (IL-6), lipopolysaccharide binding protein (LBP) and brain derived neurotrophic factor (BDNF). General Estimate Equation modelling explored moderation effects of baseline markers and exploratory analyses investigated associations between markers and clinical outcomes. There was no difference between adjunctive minocycline or placebo groups at baseline or week 12 in the levels of IL-6 (week 12; placebo 2.06 ± 1.35 pg/ml; minocycline 1.77 ± 0.79 pg/ml; p = 0.317), LBP (week 12; placebo 3.74 ± 0.95 µg/ml; minocycline 3.93 ± 1.33 µg/ml; p = 0.525) or BDNF (week 12; placebo 24.28 ± 6.69 ng/ml; minocycline 26.56 ± 5.45 ng/ml; p = 0.161). Higher IL-6 levels at baseline were a predictor of greater clinical improvement. Exploratory analyses suggested that the change in IL-6 levels were significantly associated with anxiety symptoms (HAMA; p = 0.021) and quality of life (Q-LES-Q-SF; p = 0.023) scale scores. No other clinical outcomes were shown to have this mediation effect, nor did the other markers (LBP or BDNF) moderate clinical outcomes. There were no overall changes in IL-6, LBP or BDNF following adjunctive minocycline treatment. Exploratory analyses suggest a potential role of IL-6 on mediating anxiety symptoms with MDD. Future trials may consider enrichment of recruitment by identifying several markers or a panel of factors to better represent an inflammatory phenotype in MDD with larger sample size.

We present a broadband radio study of the transient jets ejected from the black hole candidate X-ray binary MAXI J1535–571, which underwent a prolonged outburst beginning on 2017 September 2. We monitored MAXI J1535–571 with the Murchison Widefield Array (MWA) at frequencies from 119 to 186 MHz over six epochs from 2017 September 20 to 2017 October 14. The source was quasi-simultaneously observed over the frequency range 0.84–19 GHz by UTMOST (the Upgraded Molonglo Observatory Synthesis Telescope) the Australian Square Kilometre Array Pathfinder (ASKAP), the Australia Telescope Compact Array (ATCA), and the Australian Long Baseline Array (LBA). Using the LBA observations from 2017 September 23, we measured the source size to be $34\pm1$ mas. During the brightest radio flare on 2017 September 21, the source was detected down to 119 MHz by the MWA, and the radio spectrum indicates a turnover between 250 and 500 MHz, which is most likely due to synchrotron self-absorption (SSA). By fitting the radio spectrum with a SSA model and using the LBA size measurement, we determined various physical parameters of the jet knot (identified in ATCA data), including the jet opening angle ( $\phi_{\rm op} = 4.5\pm1.2^{\circ}$ ) and the magnetic field strength ( $B_{\rm s} = 104^{+80}_{-78}$ mG). Our fitted magnetic field strength agrees reasonably well with that inferred from the standard equipartition approach, suggesting the jet knot to be close to equipartition. Our study highlights the capabilities of the Australian suite of radio telescopes to jointly probe radio jets in black hole X-ray binaries via simultaneous observations over a broad frequency range, and with differing angular resolutions. This suite allows us to determine the physical properties of X-ray binary jets. Finally, our study emphasises the potential contributions that can be made by the low-frequency part of the Square Kilometre Array (SKA-Low) in the study of black hole X-ray binaries.

The GaLactic and Extragalactic All-sky Murchison Widefield Array (GLEAM) is a radio continuum survey at 76–227 MHz of the entire southern sky (Declination $<\!{+}30^{\circ}$ ) with an angular resolution of ${\approx}2$ arcmin. In this paper, we combine GLEAM data with optical spectroscopy from the 6dF Galaxy Survey to construct a sample of 1 590 local (median $z \approx 0.064$ ) radio sources with $S_{200\,\mathrm{MHz}} > 55$ mJy across an area of ${\approx}16\,700\,\mathrm{deg}^{2}$ . From the optical spectra, we identify the dominant physical process responsible for the radio emission from each galaxy: 73% are fuelled by an active galactic nucleus (AGN) and 27% by star formation. We present the local radio luminosity function for AGN and star-forming (SF) galaxies at 200 MHz and characterise the typical radio spectra of these two populations between 76 MHz and ${\sim}1$ GHz. For the AGN, the median spectral index between 200 MHz and ${\sim}1$ GHz, $\alpha_{\mathrm{high}}$ , is $-0.600 \pm 0.010$ (where $S \propto \nu^{\alpha}$ ) and the median spectral index within the GLEAM band, $\alpha_{\mathrm{low}}$ , is $-0.704 \pm 0.011$ . For the SF galaxies, the median value of $\alpha_{\mathrm{high}}$ is $-0.650 \pm 0.010$ and the median value of $\alpha_{\mathrm{low}}$ is $-0.596 \pm 0.015$ . Among the AGN population, flat-spectrum sources are more common at lower radio luminosity, suggesting the existence of a significant population of weak radio AGN that remain core-dominated even at low frequencies. However, around 4% of local radio AGN have ultra-steep radio spectra at low frequencies ( $\alpha_{\mathrm{low}} < -1.2$ ). These ultra-steep-spectrum sources span a wide range in radio luminosity, and further work is needed to clarify their nature.