Reeves’ muntjac populations continue to grow and spread across Great Britain and are invading continental Europe

The appropriate response for controlling an invasive non-native species depends on the extent to which its invasion has progressed, which can be revealed by information on its distribution and abundance. Reeves’ muntjac is a native deer to China and Taiwan, but has been introduced and become well-established in Great Britain. Moreover, in recent years, reports and verified records in the wild from other European countries have become more frequent. We reviewed the status of Reeves’ muntjac in Britain and evaluated its national range expansion from 2002 to 2016. While the British population appears to have tripled in size since 1995, the rate at which it has expanded its range seems to have peaked at approximately 12% per year between 2002 and 2005 and has since declined. We also consolidated observations on its international distribution, including a conservative evaluation of its presence in zoological collections. We predict that this species could expand its range to include every European country, although the availability of suitable landcover and climate is likely to vary substantially between countries. To prevent the significant impacts to conservation interests that have been observed in Great Britain from extending across Europe, national administrations should consider eradicating Reeves’ muntjac while that is still feasible

Magnetic resonance imaging-guided phase 1 trial of putaminal AADC gene therapy for Parkinson's disease.

ObjectiveTo understand the safety, putaminal coverage, and enzyme expression of adeno-associated viral vector serotype-2 encoding the complementary DNA for the enzyme, aromatic L-amino acid decarboxylase (VY-AADC01), delivered using novel intraoperative monitoring to optimize delivery.MethodsFifteen subjects (three cohorts of 5) with moderately advanced Parkinson's disease and medically refractory motor fluctuations received VY-AADC01 bilaterally coadministered with gadoteridol to the putamen using intraoperative magnetic resonance imaging (MRI) guidance to visualize the anatomic spread of the infusate and calculate coverage. Cohort 1 received 8.3 × 1011 vg/ml and ≤450 μl per putamen (total dose, ≤7.5 × 1011 vg); cohort 2 received the same concentration (8.3 × 1011 vg/ml) and ≤900 μl per putamen (total dose, ≤1.5 × 1012 vg); and cohort 3 received 2.6 × 1012 vg/ml and ≤900 μl per putamen (total dose, ≤4.7 × 1012 vg). (18)F-fluoro-L-dihydroxyphenylalanine positron emission tomography (PET) at baseline and 6 months postprocedure assessed enzyme activity; standard assessments measured clinical outcomes.ResultsMRI-guided administration of ascending VY-AADC01 doses resulted in putaminal coverage of 21% (cohort 1), 34% (cohort 2), and 42% (cohort 3). Cohorts 1, 2, and 3 showed corresponding increases in enzyme activity assessed by PET of 13%, 56%, and 79%, and reductions in antiparkinsonian medication of -15%, -33%, and -42%, respectively, at 6 months. At 12 months, there were dose-related improvements in clinical outcomes, including increases in patient-reported ON-time without troublesome dyskinesia (1.6, 3.3, and 1.5 hours, respectively) and quality of life.InterpretationNovel intraoperative monitoring of administration facilitated targeted delivery of VY-AADC01 in this phase 1 study, which was well tolerated. Increases in enzyme expression and clinical improvements were dose dependent. ClinicalTrials.gov Identifier: NCT01973543 Ann Neurol 2019;85:704-714

Differential Regulation of Formyl Peptide and Platelet-Activating Factor Receptors: Role of Phospholipase Cβ3 Phosphorylation by Protein Kinase A

Formylated peptides (e.g. n-formyl-Met-Leu-Phe (fMLP)) and platelet- activating factor (PAF) mediate chemotactic and cytotoxic responses in leukocytes through receptors coupled to G proteins that activate phospholipase C (PLC). In RBL-2H3 cells, fMLP utilizes a pertussis toxin (ptx)-sensitive G protein to activate PLC, whereas PAF utilizes a ptx- insensitive G protein. Here we demonstrate that fMLP, but not PAF, enhanced intracellular cAMP levels via a ptx-sensitive mechanism. Protein kinase A (PKA) inhibition by H-89 enhanced inositol phosphate formation stimulated by fMLP but not PAF. Furthermore, a membrane-permeable cAMP analog 8-(4- chlorophenylthio)-cAMP (cpt-cAMP) inhibited phosphoinositide hydrolysis and secretion stimulated by fMLP but not PAF. Both cpt-cAMP and fMLP stimulated PLCβ3 phosphorylation in intact RBL cells. The purified catalytic subunit of PKA phosphorylated PLCβ3 immunoprecipitated from RBL cell lysate. Pretreatment of intact cells with cpt-cAMP and fMLP, but not PAF, resulted in an inhibition of subsequent PLCβ3 phosphorylation by PKA in vitro. These data demonstrate that fMLP receptor, which couples to a ptx-sensitive G protein, activates both PLC and cAMP production. The resulting PKA activation phosphorylates PLCβ3 and appears to block the ability of G(βγ) to activate PLC. Thus, both fMLP and PAF generate stimulatory signals for PLCβ3, but only fMLP produces a PKA-dependent inhibitory signal. This suggests a novel mechanism for the bidirectional regulation of receptors which activate PLC by ptx-sensitive G proteins

Hyperpolarised 1H-13C benchtop NMR spectroscopy

Benchtop NMR spectrometers with sub-ppm spectral resolution have opened up new opportunities for performing NMR outside of the standard laboratory environment. However, the relatively weak magnetic fields of these devices (1 - 2 T) results in low sensitivity and significant peak overlap in 1H NMR spectra. Here we use hyperpolarised 13C{1H} NMR to overcome these challenges. Specifically, we demonstrate the use of the signal amplification by reversible exchange (SABRE) parahydrogen-based hyperpolarisation technique to enhance the sensitivity of natural abundance 1D and 2D 13C{1H} benchtop NMR spectra. We compare two detection methods for SABRE-enhanced 13C NMR and observe an optimal 13C{1H} signal-to-noise ratio (SNR) for a refocused INEPT approach, where hyperpolarisation is transferred from 1H to 13C. In addition, we exemplify SABRE-enhanced 2D 13C benchtop NMR through the acquisition of a 2D HETCOR spectrum of 260 mM of 4-methylpyridine at natural isotopic abundance in a total experiment time of 69 mins. In theory, signal averaging for over 300 days would be required to achieve a comparable SNR for a thermally polarised benchtop NMR spectrum acquired of a sample of the same concentration at natural abundanc

The science threshold learning outcomes: a ‘student-friendly’ version

BACKGROUND The Science Threshold Learning Outcomes (TLOs) are a nationally agreed set of learning outcomes for graduates of bachelor level degrees in science that are increasingly being used in curriculum review, design and bench-marking at Australian universities. The Science TLOs were published in the Science Standards Statement (Jones, Yates & Kelder 2011) together with notes on their interpretation and application: this is necessarily a formal document, aimed primarily at teaching academics and those with relevant quality assurance responsibilities. Talking with students during the development of the Science TLOs indicated that students were unlikely to engage with the TLOs as thus expressed. Therefore, if the Science TLOs are to be an effective means of informing students about the learning achieved through studying science at university, a modified version was required. AIM This project aimed to develop a ‘student-friendly’ version of the Science TLOs directed at potential and current students, their parents, future employers, teachers and career advisors. APPROACH The development was carried out in collaboration with The Bookend Trust (http://www.bookendtrust.com/), a not-for-profit organisation dedicated to inspiring students to undertake positive careers in environmental science. In particular, Bookend links media and journalism students with professional scientists or science students, thus fostering effective communication about contemporary science. STAGE 1 As a scoping exercise, a Bookend scholarship student investigated students’ attitudes to the formally expressed Science TLOs. She presented four college (Year 11/12) science classes with a short survey that explored their conceptions of studying science at university and potential career paths in science. She also sought their opinions on a DL card- sized flier of the Science TLOs, and asked how the same information could be presented in a way that students would find relevant and attractive. The survey showed that a ‘student-friendly’ flier would need pictures, catchy words, bright colours, and common-use language. The students were enthusiastic about adding a QR scan code linking to a website, saying that would increase the likelihood of their picking up such a flier. The survey results informed Stage 2 of this project, particularly the design approach. STAGE 2 To embed the Science TLOs into a concrete context, Bookend summer scholarship students interviewed employers using standard questions designed to elicit responses illustrating how the Science TLOs are directly relevant to working in science. The interviews were professionally recorded on video, and the footage was edited to create short clips that were loaded onto a website. THE FINAL PRODUCT We have produced a two-sided coloured flier that provides a ‘student-friendly’ version of the Science TLOs (re-phrased as questions) and a QR code linking to a website where the employer interviews can be viewed. The ‘Student-Friendly TLOs flier’ is now freely available as a downloadable pdf from the Office for Learning and Teaching (OLT) Resource Library (http://www.olt.gov.au/resource-library) and other relevant sites. We thank the OLT for funding this project

Engaging students through authentic research experiences

Student involvement is vital to engagement, making learning experiences more meaningful, and can be enriched by student-faculty interactions and diversity of learning environments (Smith et al. 2005). Experiential learning, in particular ‘hands on’ opportunities, can enhance undergraduate experiences and engender increased enthusiasm for the subject, as well as confidence on the part of students that they are being adequately prepared for science-related careers or postgraduate study (Gawel and Greengrove 2005). At the same time, quantifying the positive influence of student engagement with learning through authentic research experiences can be difficult (Griffiths 2004). Despite curricula emphasizing student-led enquiry, some students still struggle to find relevance and excitement in their undergraduate courses. Working from the Garnett and Holmes’ (1995) model of how both students and academics can benefit from research, we have designed an incremental suite of learning activities across the three years of the zoology undergraduate curriculum that extends and enhances the student experience. The aims of the program are to extend and challenge our undergraduate students by exposing them to current ‘hot topics’ in zoological research; enhance students’ appreciation of methodology, philosophy and outcomes of scientific research; enthuse students about the exciting research being carried out in zoology in Tasmania and encourage them to think of themselves as the researchers of the future. Here we describe several components of this program (summarised in Figure 1) which have been implemented and evaluated via student feedback

Multiple dispersal vectors drive range expansion in an invasive marine species

The establishment and subsequent spread of invasive species is widely recognised as one of the most threatening processes contributing to global biodiversity loss. This is especially true for marine and estuarine ecosystems, which have experienced significant increases in the number of invasive species with the increase in global maritime trade. Understanding the rate and mechanisms of range expansion is therefore of significant interest to ecologists and conservation managers alike. Using a combination of population genetic surveys, eDNA plankton sampling and hydrodynamic modelling we examined the patterns of introduction of the predatory Northern Pacific seastar (Asterias amurensis) and pathways of secondary spread within southeast Australia. Genetic surveys across the invasive range reveal some genetic divergence between the two main invasive regions and no evidence of ongoing gene flow; a pattern that is consistent with the establishment of the second invasive region via a human-mediated translocation event. In contrast hydrodynamic modelling combined with eDNA plankton sampling demonstrated that the establishment of range expansion populations within a region is consistent with natural larval dispersal and recruitment. Our results suggest that both anthropogenic and natural dispersal vectors have played an important role in the range expansion of this species in Australia. The multiple modes of spread combined with high levels of fecundity and a long larval duration in A. amurensis suggests it is likely to continue its range expansion and significantly impact Australian marine ecosystems

Protocol for a mixed-methods study to develop and feasibility test a digital system for the capture of Patient-Reported Outcomes (PROs) in patients receiving Chimeric Antigen Receptor T-cell (CAR-T) therapies (The PRO-CAR-T Study)

Introduction: Chimeric antigen receptor (CAR) T-cell therapies are novel, potentially curative therapies for haematological malignancies. CAR T-cell therapies are associated with severe toxicities, meaning patients require monitoring during acute and postacute treatment phases. Electronic patient-reported outcomes (ePROs), self-reports of health status provided via online questionnaires, can complement clinician observation with potential to improve patient outcomes. This study will develop and evaluate feasibility of a new ePRO system for CAR-T patients in routine care. Methods and analysis: Multiphase, mixed-methods study involving multiple stakeholder groups (patients, family members, carers, clinicians, academics/researchers and policy-makers). The intervention development phase comprises a Delphi study to select PRO measures for the digital system, a codesign workshop and consensus meetings to establish thresholds for notifications to the clinical team if a patient reports severe symptoms or side effects. Usability testing will evaluate how users interact with the digital system and, lastly, we will evaluate ePRO system feasibility with 30 CAR-T patients (adults aged 18+ years) when used in addition to usual care. Feasibility study participants will use the ePRO system to submit self-reports of symptoms, treatment tolerability and quality of life at specific time points. The CAR-T clinical team will respond to system notifications triggered by patients’ submitted responses with actions in line with standard clinical practice. Feasibility measures will be collected at prespecified time points following CAR T-cell infusion. A qualitative substudy involving patients and clinical team members will explore acceptability of the ePRO system. Ethics and dissemination: Favourable ethical opinion was granted by the Health and Social Care Research Ethics Committee B(HSC REC B) (ref: 23/NI/0104) on 28 September 2023. Findings will be submitted for publication in high-quality, peer-reviewed journals. Summaries of results, codeveloped with the Blood and Transplant Research Unit Patient and Public Involvement and Engagement group, will be disseminated to all interested groups. Trial registration number: ISCTRN11232653

Protocol for the development of a core outcome set and reporting guidelines for locoregional treatment in neoadjuvant systemic breast cancer treatment trials: the PRECEDENT project

Introduction: Neoadjuvant systemic anticancer therapy (neoSACT) is increasingly used in the treatment of early breast cancer. Response to therapy is prognostic and allows locoregional and adjuvant systemic treatments to be tailored to minimise morbidity and optimise oncological outcomes and quality of life. Accurate information about locoregional treatments following neoSACT is vital to allow the translation of downstaging benefits into practice and facilitate meaningful interpretation of oncological outcomes, particularly locoregional recurrence. Reporting of locoregional treatments in neoSACT studies, however, is currently poor. The development of a core outcome set (COS) and reporting guidelines is one strategy by which this may be improved. Methods and analysis: A COS for reporting locoregional treatment (surgery and radiotherapy) in neoSACT trials will be developed in accordance with Core Outcome Measures in Effectiveness Trials (COMET) and Core Outcome Set-Standards for Development guidelines. Reporting guidance will be developed concurrently. The project will have three phases: (1) generation of a long list of relevant outcome domains and reporting items from a systematic review of published neoSACT studies and interviews with key stakeholders. Identified items and domains will be categorised and formatted into Delphi consensus questionnaire items. (2) At least two rounds of an international online Delphi survey in which at least 250 key stakeholders (surgeons/oncologists/radiologists/pathologists/trialists/methodologists) will score the importance of reporting each outcome. (3) A consensus meeting with key stakeholders to discuss and agree the final COS and reporting guidance. Ethics and dissemination: Ethical approval for the consensus process will be obtained from the Queen’s University Belfast Faculty Ethics Committee. The COS/reporting guidelines will be presented at international meetings and published in peer-reviewed journals. Dissemination materials will be produced in collaboration with our steering group and patient advocates so the results can be shared widely. Registration: The study has been prospectively registered on the COMET website (https://www.comet-initiative.org/Studies/Details/2854)