Passage and survival of Acaciella angustissima (Mill.) Britton & Rose and Aeschynomene paniculata Willd. ex Vogel seed through the sheep gut

Acaciella angustissima (syn. Acacia angustissima) (white ball acacia) and Aeschynomene paniculata Willd. ex Vogel (pannicle joint vetch), were rejected for release after their identification as potential weeds in pasture evaluation trials. These plants are now targeted for control and, where possible, eradication from old experimental sites across Queensland. It is suspected that domestic livestock, feral and native animals contribute to the movement of these seeds through the ingestion and defecation of viable seeds across the landscape. This aspect was explored by feeding the intact seeds of these two species to sheep in metabolism cages. Sheep faeces were collected each day for 5 days after which time the faeces were sieved and the surviving intact seeds were then collected, counted and germination tests undertaken. The results show that seeds of both species pass through sheep with most seeds being passed after 48 h with a percentage of these seeds being viable. Of the number of seeds fed, 4.25% were recovered for A. angustissima and 1.4% for A. paniculata. Seed recovered from the faeces had 0% and 13% germination for A. angustissima and A. paniculata respectively, but with additional post-digestion hot water scarification germination increased to 75% and 33% for A. angustissima and A. paniculata respectively. This paper discusses these results and the implications for the possible spread of these species across the northern Australian landscape

FIRE (facilitating implementation of research evidence) : a study protocol

Research evidence underpins best practice, but is not always used in healthcare. The Promoting Action on Research Implementation in Health Services (PARIHS) framework suggests that the nature of evidence, the context in which it is used, and whether those trying to use evidence are helped (or facilitated) affect the use of evidence. Urinary incontinence has a major effect on quality of life of older people, has a high prevalence, and is a key priority within European health and social care policy. Improving continence care has the potential to improve the quality of life for older people and reduce the costs associated with providing incontinence aids

TRE-FX:Delivering a federated network of trusted research environments to enable safe data analytics

Trusted Research Environments (TREs) are secure locations in which data are placed for researchers to analyse. TREs host administrative data, hospital data or any other data that needs to remain securely isolated, but it is hard for a researcher to perform an analysis across multiple TREs, requesting and gathering the outputs from each one. This is a common problem in the UK's devolved healthcare system of geographical and governance boundaries. There are different ways of implementing TREs and the analysis tools that use them. A solution must be straightforward for existing, independent systems to adopt, must cope with the variety of system implementations, and must work within the "Five Safes" framework that enables data services to provide safe research access to data. TRE-FX assembled leading infrastructure researchers, analysis tool makers, TRE providers and public engagement specialists to streamline the exchange of data requests and results. The "Five Safes RO-Crate" standard packages up (Crates) the Objects needed for Research requests and results with the information needed for the tools and TRE providers to ensure that the crates are reviewed and processed according to Five Safes principles. TRE-FX showed how this works using software components and an end-to-end demonstrator implemented by a TRE in Wales. Two other TREs, in Scotland and England, are preparing to follow suit. Two analysis tool providers (Bitfount and DataSHIELD) modified their systems to use the RO-Crates. The next step is practical implementation as part of the HDR UK programme. Two large European projects will develop the approach further. TRE-FX shows that it is possible to streamline how analysis tools access multiple TREs while enabling the TREs to ensure that the access is safe. The approach scales as more TREs are added and can be adopted by established systems. Researchers will then be able to perform an analysis across multiple TREs much more easily, widening the scope of their research and making more effective use of the UK's data. If we had had this for COVID-19 data analysis, it would have super-charged researchers to be able to quickly answer pressing questions across the UK. This work was funded by UK Research & Innovation [Grant Number MC_PC_23007] as part of Phase 1 of the DARE UK (Data and Analytics Research Environments UK) programme, delivered in partnership with Health Data Research UK (HDR UK) and Administrative Data Research UK (ADR UK)

Facilitating implementation of research evidence (FIRE): A randomised controlled trial and process evaluation of two models of facilitation informed by the promoting action on research implementation in health services (PARIHS) framework

Background: The PARIHS framework proposes that successful implementation of research evidence results from the complex interplay between the evidence to be implemented, the context of implementation and the facilitation processes employed. Facilitation is defined as a role (the facilitator) and a process (facilitation strategies/methods). Empirical evidence comparing different facilitation approaches is limited; this paper reports a trial of two different types of facilitation represented in the PARIHS framework. Methods: A pragmatic cluster randomised controlled trial with embedded process evaluation was undertaken in 24 long-term nursing care settings in four European countries. In each country, sites were randomly allocated to standard dissemination of urinary incontinence guideline recommendations and one of two types of external-internal facilitation, labelled Type A and B. Type A facilitation was a less resource intensive approach, underpinned by improvement methodology; Type B was a more intensive, emancipatory model of facilitation, informed by critical social science. The primary outcome was percentage documented compliance with guideline recommendations. Process evaluation was framed by realist methodology and involved quantitative and qualitative data collection from multiple sources. Findings: Quantitative data were obtained from reviews of 2313 records. Qualitative data included over 332 hours of observations of care; 39 hours observation of facilitation activity; 471 staff interviews; 174 resident interviews; 120 next of kin/carer interviews; and 125 stakeholder interviews. There were no significant differences in the primary outcome between study arms and all study arms improved over time. Process data revealed three core mechanisms that influenced the trajectory of the facilitation intervention: alignment of the facilitation approach to the needs and expectations of the internal facilitator and colleagues; engagement of internal facilitators and staff in attitude and action; and learning over time. Data from external facilitators demonstrated that the facilitation interventions did not work as planned, issues were cumulative and maintenance of fidelity was problematic. Implications for D&I Research: Evaluating an intervention - in this case facilitation - that is fluid and dynamic within the methodology of a randomised controlled trial is complex and challenging. For future studies, we suggest a theoretical approach to fidelity, with a focus on mechanisms, as opposed to dose and intensity of the intervention

Multidrug resistant pulmonary tuberculosis treatment regimens and patient outcomes: an individual patient data meta-analysis of 9,153 patients.

Treatment of multidrug resistant tuberculosis (MDR-TB) is lengthy, toxic, expensive, and has generally poor outcomes. We undertook an individual patient data meta-analysis to assess the impact on outcomes of the type, number, and duration of drugs used to treat MDR-TB

Application of a new approach methodology (NAM)-based strategy for genotoxicity assessment of data-poor compounds

The conventional battery for genotoxicity testing is not well suited to assessing the large number of chemicals needing evaluation. Traditional in vitro tests lack throughput, provide little mechanistic information, and have poor specificity in predicting in vivo genotoxicity. New Approach Methodologies (NAMs) aim to accelerate the pace of hazard assessment and reduce reliance on in vivo tests that are time-consuming and resource-intensive. As such, high-throughput transcriptomic and flow cytometry-based assays have been developed for modernized in vitro genotoxicity assessment. This includes: the TGx-DDI transcriptomic biomarker (i.e., 64-gene expression signature to identify DNA damage-inducing (DDI) substances), the MicroFlow® assay (i.e., a flow cytometry-based micronucleus (MN) test), and the MultiFlow® assay (i.e., a multiplexed flow cytometry-based reporter assay that yields mode of action (MoA) information). The objective of this study was to investigate the utility of the TGx-DDI transcriptomic biomarker, multiplexed with the MicroFlow® and MultiFlow® assays, as an integrated NAM-based testing strategy for screening data-poor compounds prioritized by Health Canada’s New Substances Assessment and Control Bureau. Human lymphoblastoid TK6 cells were exposed to 3 control and 10 data-poor substances, using a 6-point concentration range. Gene expression profiling was conducted using the targeted TempO-Seq™ assay, and the TGx-DDI classifier was applied to the dataset. Classifications were compared with those based on the MicroFlow® and MultiFlow® assays. Benchmark Concentration (BMC) modeling was used for potency ranking. The results of the integrated hazard calls indicate that five of the data-poor compounds were genotoxic in vitro, causing DNA damage via a clastogenic MoA, and one via a pan-genotoxic MoA. Two compounds were likely irrelevant positives in the MN test; two are considered possibly genotoxic causing DNA damage via an ambiguous MoA. BMC modeling revealed nearly identical potency rankings for each assay. This ranking was maintained when all endpoint BMCs were converted into a single score using the Toxicological Prioritization (ToxPi) approach. Overall, this study contributes to the establishment of a modernized approach for effective genotoxicity assessment and chemical prioritization for further regulatory scrutiny. We conclude that the integration of TGx-DDI, MicroFlow®, and MultiFlow® endpoints is an effective NAM-based strategy for genotoxicity assessment of data-poor compounds

GWAS in the SIGNAL/PHARE clinical cohort restricts the association between the FGFR2 locus and estrogen receptor status to HER2-negative breast cancer patients

International audienceGenetic polymorphisms are associated with breast cancer risk. Clinical and epidemiological observations suggest that clinical characteristics of breast cancer, such as estrogen receptor or HER2 status, are also influenced by hereditary factors. To identify genetic variants associated with pathological characteristics of breast cancer patients, a Genome Wide Association Study was performed in a cohort of 9365 women from the French nationwide SIGNAL/PHARE studies (NCT00381901/RECF1098). Strong association between the FGFR2 locus and ER status of breast cancer patients was observed (ER-positive n=6211, ER-negative n=2516; rs3135718 OR=1.34 p=5.46x10-12). This association was limited to patients with HER2-negative tumors (ER-positive n=4267, ER-negative n=1185; rs3135724 OR=1.85 p=1.16x10-11). The FGFR2 locus is known to be associated with breast cancer risk. This study provides sound evidence for an association between variants in the FGFR2 locus and ER status among breast cancer patients, particularly among patients with HER2-negative disease. This refinement of the association between FGFR2 variants and ER-status to HER2-negative disease provides novel insight to potential biological and clinical influence of genetic polymorphisms on breast tumors

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Characterization, deployment, and in-flight performance of the BLAST-TNG cryogenic receiver

The Next Generation Balloon-borne Large Aperture Submillimeter Telescope (BLAST-TNG) is a submillimeter polarimeter designed to map interstellar dust and galactic foregrounds at 250, 350, and 500 microns during a 24-day Antarctic flight. The BLAST-TNG detector arrays are comprised of 918, 469, and 272 MKID pixels, respectively. The pixels are formed from two orthogonally oriented, crossed, linear-polarization sensitive MKID antennae. The arrays are cooled to sub 300mK temperatures and stabilized via a closed cycle $^3$He sorption fridge in combination with a $^4$He vacuum pot. The detectors are read out through a combination of the second-generation Reconfigurable Open Architecture Computing Hardware (ROACH2) and custom RF electronics designed for BLAST-TNG. The firmware and software designed to readout and characterize these detectors was built from scratch by the BLAST team around these detectors, and has been adapted for use by other MKID instruments such as TolTEC and OLIMPO. We present an overview of these systems as well as in-depth methodology of the ground-based characterization and the measured in-flight performance.Comment: Presented at SPIE Millimeter, Submillimeter, and Far-Infrared Detectors and Instrumentation for Astronomy X, December 13-18, 202

The Balloon-Borne Large Aperture Submillimeter Telescope Observatory

The BLAST Observatory is a proposed superpressure balloon-borne polarimeter designed for a future ultra-long duration balloon campaign from Wanaka, New Zealand. To maximize scientific output while staying within the stringent superpressure weight envelope, BLAST will feature new 1.8m off-axis optical system contained within a lightweight monocoque structure gondola. The payload will incorporate a 300L $^4$He cryogenic receiver which will cool 8,274 microwave kinetic inductance detectors (MKIDs) to 100mK through the use of an adiabatic demagnetization refrigerator (ADR) in combination with a $^3$He sorption refrigerator all backed by a liquid helium pumped pot operating at 2K. The detector readout utilizes a new Xilinx RFSOC-based system which will run the next-generation of the BLAST-TNG KIDPy software. With this instrument we aim to answer outstanding questions about dust dynamics as well as provide community access to the polarized submillimeter sky made possible by high-altitude observing unrestricted by atmospheric transmission. The BLAST Observatory is designed for a minimum 31-day flight of which 70$\%$ will be dedicated to observations for BLAST scientific goals and the remaining 30$\%$ will be open to proposals from the wider astronomical community through a shared-risk proposals program.Comment: Presented at SPIE Ground-based and Airborne Telescopes VIII, December 13-18, 202