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We present frb-voe, a publicly available software package that enables radio observatories to broadcast fast radio burst (FRB) alerts to subscribers through low-latency virtual observatory events (VOEvents). We describe a use-case of frb-voe by the Canadian Hydrogen Intensity Mapping Experiment Fast Radio Burst (CHIME/FRB) Collaboration, which has broadcast thousands of FRB alerts to subscribers worldwide. Using this service, observers have daily opportunities to conduct rapid multi-wavelength follow-up observations of new FRB sources. Alerts are distributed as machine-readable reports and as emails containing FRB metadata, and are available to the public within approximately 13 seconds of detection. A sortable database and a downloadable JSON file containing FRB metadata from all broadcast alerts can be found on the CHIME/FRB public webpage. The frb-voe service also provides users with the ability to retrieve FRB names from the Transient Name Server (TNS) through the frb-voe client user interface (CLI). The frb-voe service can act as a foundation on which any observatory that detects FRBs can build its own VOEvent broadcasting service to contribute to the coordinated multi-wavelength follow-up of astrophysical transients.

The Canadian Hydrogen Intensity Mapping Experiment Fast Radio Burst (CHIME/FRB) project has discovered the most repeating fast radio burst (FRB) sources of any telescope. However, most of the physical conclusions derived from this sample are based on data with a time resolution of \\(\\sim\\)1 ms. In this work, we present for the first time a morphological analysis of the raw voltage data for 118 bursts from 32 of CHIME/FRB's repeating sources. We do not find any significant correlations amongst fluence, dispersion measure (DM), burst rate, and burst duration. Performing the first large-scale morphological comparison at timescales down to microseconds between our repeating sources and 125 non-repeating FRBs, we find that repeaters are narrower in frequency and broader in duration than non-repeaters, supporting previous findings. However, we find that the duration-normalized sub-burst widths of the two populations are consistent, possibly suggesting a shared physical emission mechanism. Additionally, we find that the spectral fluences of the two are consistent. When combined with the larger bandwidths and previously found larger DMs of non-repeaters, this suggests that non-repeaters may have higher intrinsic specific energies than repeating FRBs. We do not find any consistent increase or decrease in the DM (\\(\\lessapprox 1\\) pc cm\\(^{-3}\\) yr\\(^{-1}\\)) and scattering timescales (\\(\\lessapprox 2\\) ms yr\\(^{-1}\\)) of our sources over \\(\\sim2-4\\) year periods.

Zebrafish larvae have several biological features that make them useful for cellular investigations of the mechanisms underlying learning and memory. Of particular interest in this regard is a rapid escape, or startle, reflex possessed by zebrafish larvae; this reflex, the C-start, is mediated by a relatively simple neuronal circuit and exhibits habituation, a non-associative form of learning. Here we demonstrate a rapid form of habituation of the C-start to touch that resembles the previously reported rapid habituation induced by auditory or vibrational stimuli. We also show that touch-induced habituation exhibits input specificity. This work sets the stage for in vivo optical investigations of the cellular sites of plasticity that mediate habituation of the C-start in the larval zebrafish.

Background Tumour hypoxia resulting from inadequate perfusion is common in many solid tumours, including prostate cancer, and constitutes a major limiting factor in radiation therapy that contributes to treatment resistance. Emerging research in preclinical animal models indicates that exercise has the potential to enhance the efficacy of cancer treatment by modulating tumour perfusion and reducing hypoxia; however, evidence from randomised controlled trials is currently lacking. The ‘Exercise medicine as adjunct therapy during RADIation for CAncer of the prostaTE’ (ERADICATE) study is designed to investigate the impact of exercise on treatment response, tumour physiology, and adverse effects of treatment in prostate cancer patients undergoing external beam radiation therapy (EBRT). Methods The ERADICATE study is a two-arm, parallel group, phase II randomised controlled trial. Fifty patients diagnosed with prostate cancer will be randomised (1:1) to either an exercise intervention group (EBRT + exercise) or a usual care control group (EBRT only) for the duration of treatment (i.e., 2 to 8 weeks of EBRT). The exercise intervention will be clinic-based and supervised by exercise physiologists. Exercise sessions will include moderate- to vigorous-intensity aerobic and resistance exercise conducted two to three times per week for 60 min per session. Treatment response (primary outcome) will be assessed by change in tumour apparent diffusion coefficient derived from magnetic resonance imaging. Secondary outcomes will include acute and chronic changes in tumour perfusion and hypoxia, treatment-related toxicity, body composition, physical function, and quality of life. Survival outcomes will be assessed as exploratory endpoints. Study measurements will be conducted at baseline (i.e., prior to commencing EBRT), immediately after completion of EBRT, and during follow-up at 3 months as well as 2 years and 5 years post treatment. The study was approved by the Human Research Ethics Committee at Edith Cowan University. Discussion The ERADICATE study will investigate exercise as a novel therapeutic approach for sensitising prostate cancer to EBRT by targeting a known mechanism of treatment resistance. Improving treatment efficacy of EBRT with exercise may result in better patient outcomes clinically, while also addressing adverse effects of treatment and quality of life in prostate cancer patients. Trial registration The study was registered on the Australian New Zealand Clinical Trials Registry (ACTRN12624000786594) on 26/06/2024.

The transcriptional scaffolds C-terminal Binding Proteins (CtBP) 1 and 2 are overexpressed and act as oncogenic dependencies in multiple cancers but importantly encode a chemically targetable dehydrogenase domain. CtBP promotes survival of high grade serous ovarian carcinoma (HGSOC) cells by repressing expression of Death Receptors (DR) 4 and 5, which activate caspase 8-dependent apoptosis. We have previously developed a series of substrate competitive CtBP dehydrogenase inhibitors active in multiple cell and preclinical solid tumor models. In the current study, we validated CtBP1 and 2 overexpression in a longitudinal series of primary and metastatic/recurrent HGSOC cases. Our lead CtBP dehydrogenase inhibitor, JW-98, induced apoptosis and exhibited variable single agent IC 50 values in HGSOC cell lines. Importantly, depletion of nicotinamide adenine dinucleotide (NAD) species using the NAD synthesis inhibitor GMX1778 strikingly sensitized HGSOC cells to JW-98 treatment. Mechanistically, the JW-98/GMX1778 combination effectively abrogated CtBP dimerization that requires stoichiometric levels of intracellular NAD and is required for CtBP’s oncogenic transcriptional activities. Highlighting translational potential in late-stage HGSOC, combined JW-98/GMX1778 treatment of platinum-resistant OVCAR3 HGSOC mouse xenografts abrogated tumor growth without observable toxicity. Combined inhibition of CtBP and NAD synthesis represents a novel therapeutic strategy that could improve outcomes in chemoresistant HGSOC.

Staphylococcus aureus causes a spectrum of human infection. Diagnostic delays and uncertainty lead to treatment delays and inappropriate antibiotic use. A growing literature suggests the host's inflammatory response to the pathogen represents a potential tool to improve upon current diagnostics. The hypothesis of this study is that the host responds differently to S. aureus than to E. coli infection in a quantifiable way, providing a new diagnostic avenue. This study uses Bayesian sparse factor modeling and penalized binary regression to define peripheral blood gene-expression classifiers of murine and human S. aureus infection. The murine-derived classifier distinguished S. aureus infection from healthy controls and Escherichia coli-infected mice across a range of conditions (mouse and bacterial strain, time post infection) and was validated in outbred mice (AUC>0.97). A S. aureus classifier derived from a cohort of 94 human subjects distinguished S. aureus blood stream infection (BSI) from healthy subjects (AUC 0.99) and E. coli BSI (AUC 0.84). Murine and human responses to S. aureus infection share common biological pathways, allowing the murine model to classify S. aureus BSI in humans (AUC 0.84). Both murine and human S. aureus classifiers were validated in an independent human cohort (AUC 0.95 and 0.92, respectively). The approach described here lends insight into the conserved and disparate pathways utilized by mice and humans in response to these infections. Furthermore, this study advances our understanding of S. aureus infection; the host response to it; and identifies new diagnostic and therapeutic avenues.

Plant functional traits can predict community assembly and ecosystem functioning and are thus widely used in global models of vegetation dynamics and land–climate feedbacks. Still, we lack a global understanding of how land and climate affect plant traits. A previous global analysis of six traits observed two main axes of variation: (1) size variation at the organ and plant level and (2) leaf economics balancing leaf persistence against plant growth potential. The orthogonality of these two axes suggests they are differently influenced by environmental drivers. We find that these axes persist in a global dataset of 17 traits across more than 20,000 species. We find a dominant joint effect of climate and soil on trait variation. Additional independent climate effects are also observed across most traits, whereas independent soil effects are almost exclusively observed for economics traits. Variation in size traits correlates well with a latitudinal gradient related to water or energy limitation. In contrast, variation in economics traits is better explained by interactions of climate with soil fertility. These findings have the potential to improve our understanding of biodiversity patterns and our predictions of climate change impacts on biogeochemical cycles. The authors investigate the broad-scale climatological and soil properties that co-vary with major axes of plant functional traits. They find that variation in plant size is attributed to latitudinal gradients in water or energy limitation, while variation in leaf economics traits is attributed to both climate and soil fertility including their interaction.

AbstractObjectiveTo determine whether coronary computed tomography angiography (CTA) should be performed in patients with any clinical probability of coronary artery disease (CAD), and whether the diagnostic performance differs between subgroups of patients.DesignProspectively designed meta-analysis of individual patient data from prospective diagnostic accuracy studies.Data sourcesMedline, Embase, and Web of Science for published studies. Unpublished studies were identified via direct contact with participating investigators.Eligibility criteria for selecting studiesProspective diagnostic accuracy studies that compared coronary CTA with coronary angiography as the reference standard, using at least a 50% diameter reduction as a cutoff value for obstructive CAD. All patients needed to have a clinical indication for coronary angiography due to suspected CAD, and both tests had to be performed in all patients. Results had to be provided using 2×2 or 3×2 cross tabulations for the comparison of CTA with coronary angiography. Primary outcomes were the positive and negative predictive values of CTA as a function of clinical pretest probability of obstructive CAD, analysed by a generalised linear mixed model; calculations were performed including and excluding non-diagnostic CTA results. The no-treat/treat threshold model was used to determine the range of appropriate pretest probabilities for CTA. The threshold model was based on obtained post-test probabilities of less than 15% in case of negative CTA and above 50% in case of positive CTA. Sex, angina pectoris type, age, and number of computed tomography detector rows were used as clinical variables to analyse the diagnostic performance in relevant subgroups.ResultsIndividual patient data from 5332 patients from 65 prospective diagnostic accuracy studies were retrieved. For a pretest probability range of 7-67%, the treat threshold of more than 50% and the no-treat threshold of less than 15% post-test probability were obtained using CTA. At a pretest probability of 7%, the positive predictive value of CTA was 50.9% (95% confidence interval 43.3% to 57.7%) and the negative predictive value of CTA was 97.8% (96.4% to 98.7%); corresponding values at a pretest probability of 67% were 82.7% (78.3% to 86.2%) and 85.0% (80.2% to 88.9%), respectively. The overall sensitivity of CTA was 95.2% (92.6% to 96.9%) and the specificity was 79.2% (74.9% to 82.9%). CTA using more than 64 detector rows was associated with a higher empirical sensitivity than CTA using up to 64 rows (93.4% v 86.5%, P=0.002) and specificity (84.4% v 72.6%, P<0.001). The area under the receiver-operating-characteristic curve for CTA was 0.897 (0.889 to 0.906), and the diagnostic performance of CTA was slightly lower in women than in with men (area under the curve 0.874 (0.858 to 0.890) v 0.907 (0.897 to 0.916), P<0.001). The diagnostic performance of CTA was slightly lower in patients older than 75 (0.864 (0.834 to 0.894), P=0.018 v all other age groups) and was not significantly influenced by angina pectoris type (typical angina 0.895 (0.873 to 0.917), atypical angina 0.898 (0.884 to 0.913), non-anginal chest pain 0.884 (0.870 to 0.899), other chest discomfort 0.915 (0.897 to 0.934)).ConclusionsIn a no-treat/treat threshold model, the diagnosis of obstructive CAD using coronary CTA in patients with stable chest pain was most accurate when the clinical pretest probability was between 7% and 67%. Performance of CTA was not influenced by the angina pectoris type and was slightly higher in men and lower in older patients.Systematic review registrationPROSPERO CRD42012002780.

Zebrafish larvae have several biological features that make them useful for cellular investigations of the mechanisms underlying learning and memory. Of particular interest in this regard is a rapid escape, or startle, reflex possessed by zebrafish larvae; this reflex, the C-start, is mediated by a relatively simple neuronal circuit and exhibits habituation, a non-associative form of learning. Here we demonstrate a rapid form of habituation of the C-start to touch that resembles the previously reported rapid habituation induced by auditory or vibrational stimuli. We also show that touch-induced habituation exhibits input specificity. This work sets the stage for in vivo optical investigations of the cellular sites of plasticity that mediate habituation of the C-start in the larval zebrafish.

Lung disease (LD) is an increasingly recognized complication of systemic juvenile idiopathic arthritis (sJIA). As there are no currently available guidelines for pulmonary screening in sJIA, we sought to develop such an algorithm at our institution. A multidisciplinary workgroup was convened, including members representing rheumatology, pulmonary, stem cell transplantation, and patient families. The workgroup leaders drafted an initial algorithm based on published literature and experience at our center. A modified Delphi approach was used to achieve agreement through three rounds of anonymous, asynchronous voting and a consensus meeting. Statements approved by the workgroup were rated as appropriate with moderate or high levels of consensus. These statements were organized into the final approved screening algorithm for LD in sJIA. The workgroup ultimately rated 20 statements as appropriate with a moderate or high level of consensus. The approved algorithm recommends pulmonary screening for newly diagnosed patients with sJIA with clinical features that the workgroup agreed may confer increased risk for LD. These \"red flag features\" include baseline characteristics (young age of sJIA onset, human leukocyte antigen type, trisomy 21), high disease activity (macrophage activation syndrome [MAS], sJIA-related ICU admission, elevated MAS biomarkers), respiratory symptoms or abnormal pulmonary examination findings, and features of drug hypersensitivity-like reactions (eosinophilia, atypical rash, anaphylaxis). The workgroup achieved consensus on the recommended pulmonary work-up and monitoring guidelines. We developed a pulmonary screening algorithm for sJIA-LD through a multidisciplinary consensus-building process, which will be revised as our understanding of sJIA-LD continues to evolve.