Using fisher local ecological knowledge to improve management: the Murray crayfish in Australia

a b s t r a c t The use of data provided by fishers is a contentious topic in fishery management. We compare fisher local ecological knowledge, fisher catch data and scientific data for Murray crayfish (Euastacus armatus) size and sex ratios in the River Murray, Australia, to determine if these data are consistent and if fisher knowledge can be a reliable input into fisheries management. Data were obtained through field surveys of crayfish populations, face-to-face fisher interviews and catch cards completed by fishers. All data sources indicated that there were higher numbers of crayfish <90 mm OCL compared to ≥90 mm OCL and the sex ratio of larger crayfish (≥90 mm OCL) was skewed towards females. Fisher catch card and scientific survey data showed the size frequencies of male and female crayfish were significantly different. Study results suggest that fisher local ecological knowledge can be a reliable source of information to improve fisheries management

The politicisation of science in the Murray-Darling Basin, Australia:discussion of ‘Scientific integrity, public policy and water governance’

Many water scientists aim for their work to inform water policy and management, and in pursuit of this objective, they often work alongside government water agencies to ensure their research is relevant, timely and communicated effectively. A paper in this issue, examining 'Science integrity, public policy and water governance in the Murray-Darling Basin, Australia’, suggests that a large group of scientists, who work on water management in the Murray-Darling Basin (MDB) including the Basin Plan, have been subject to possible ‘administrative capture'. Specifically, it is suggested that they have advocated for policies favoured by government agencies with the objective of gaining personal benefit, such as increased research funding. We examine evidence for this claim and conclude that it is not justified. The efforts of scientists working alongside government water agencies appear to have been misinterpreted as possible administrative capture. Although unsubstantiated, this claim does indicate that the science used in basin water planning is increasingly caught up in the politics of water management. We suggest actions to improve science-policy engagement in basin planning, to promote constructive debate over contested views and avoid the over-politicisation of basin science

Identifying challenges to implementation of clinical practice guidelines for sentinel lymph node biopsy in patients with melanoma in Australia: protocol paper for a mixed methods study

Introduction Sentinel lymph node biopsy (SLNB) is a diagnostic procedure developed in the 1990s. It is currently used to stage patients with primary cutaneous melanoma, provide prognostic information and guide management. The Australian Clinical Practice Guidelines state that SLNB should be considered for patients with cutaneous melanoma >1 mm in thickness (or >0.8 mm with high-risk pathology features). Until recently, sentinel lymph node (SLN) status was used to identify patients who might benefit from a completion lymph node dissection, a procedure that is no longer routinely recommended. SLN status is now also being used to identify patients who might benefit from systemic adjuvant therapies such as anti-programmed cell death 1 (PD1) checkpoint inhibitor immunotherapy or BRAF-directed molecular targeted therapy, treatments that have significantly improved relapse-free survival for patients with resected stage III melanoma and improved overall survival of patients with unresectable stage III and stage IV melanoma. Australian and international data indicate that approximately half of eligible patients receive an SLNB. Methods and analysis This mixed-methods study seeks to understand the structural, contextual and cultural factors affecting implementation of the SLNB guidelines. Data collection will include: (1) cross-sectional questionnaires and semistructured interviews with general practitioners and dermatologists; (2) semistructured interviews with other healthcare professionals involved in the diagnosis and early definitive care of melanoma patients and key stakeholders including researchers, representatives of professional colleges, training organisations and consumer melanoma groups; and (3) documentary analysis of documents from government, health services and non-government organisations. Descriptive analyses and multivariable regression models will be used to examine factors related to SLNB practices and attitudes. Qualitative data will be analysed using thematic analysis. Ethics and dissemination Ethics approval has been granted by the University of Sydney. Results will be disseminated through publications and presentations to clinicians, patients, policymakers and researchers and will inform the development of strategies for implementing SLNB guidelines in Australia

‘Multi-Epitope-Targeted’ Immune-Specific Therapy for a Multiple Sclerosis-Like Disease via Engineered Multi-Epitope Protein Is Superior to Peptides

Antigen-induced peripheral tolerance is potentially one of the most efficient and specific therapeutic approaches for autoimmune diseases. Although highly effective in animal models, antigen-based strategies have not yet been translated into practicable human therapy, and several clinical trials using a single antigen or peptidic-epitope in multiple sclerosis (MS) yielded disappointing results. In these clinical trials, however, the apparent complexity and dynamics of the pathogenic autoimmunity associated with MS, which result from the multiplicity of potential target antigens and “epitope spread”, have not been sufficiently considered. Thus, targeting pathogenic T-cells reactive against a single antigen/epitope is unlikely to be sufficient; to be effective, immunospecific therapy to MS should logically neutralize concomitantly T-cells reactive against as many major target antigens/epitopes as possible. We investigated such “multi-epitope-targeting” approach in murine experimental autoimmune encephalomyelitis (EAE) associated with a single (“classical”) or multiple (“complex”) anti-myelin autoreactivities, using cocktail of different encephalitogenic peptides vis-a-vis artificial multi-epitope-protein (designated Y-MSPc) encompassing rationally selected MS-relevant epitopes of five major myelin antigens, as “multi-epitope-targeting” agents. Y-MSPc was superior to peptide(s) in concomitantly downregulating pathogenic T-cells reactive against multiple myelin antigens/epitopes, via inducing more effective, longer lasting peripheral regulatory mechanisms (cytokine shift, anergy, and Foxp3+ CTLA4+ regulatory T-cells). Y-MSPc was also consistently more effective than the disease-inducing single peptide or peptide cocktail, not only in suppressing the development of “classical” or “complex EAE” or ameliorating ongoing disease, but most importantly, in reversing chronic EAE. Overall, our data emphasize that a “multi-epitope-targeting” strategy is required for effective immune-specific therapy of organ-specific autoimmune diseases associated with complex and dynamic pathogenic autoimmunity, such as MS; our data further demonstrate that the “multi-epitope-targeting” approach to therapy is optimized through specifically designed multi-epitope-proteins, rather than myelin peptide cocktails, as “multi-epitope-targeting” agents. Such artificial multi-epitope proteins can be tailored to other organ-specific autoimmune diseases

Genome-wide identification and phenotypic characterization of seizure-associated copy number variations in 741,075 individuals

Copy number variants (CNV) are established risk factors for neurodevelopmental disorders with seizures or epilepsy. With the hypothesis that seizure disorders share genetic risk factors, we pooled CNV data from 10,590 individuals with seizure disorders, 16,109 individuals with clinically validated epilepsy, and 492,324 population controls and identified 25 genome-wide significant loci, 22 of which are novel for seizure disorders, such as deletions at 1p36.33, 1q44, 2p21-p16.3, 3q29, 8p23.3-p23.2, 9p24.3, 10q26.3, 15q11.2, 15q12-q13.1, 16p12.2, 17q21.31, duplications at 2q13, 9q34.3, 16p13.3, 17q12, 19p13.3, 20q13.33, and reciprocal CNVs at 16p11.2, and 22q11.21. Using genetic data from additional 248,751 individuals with 23 neuropsychiatric phenotypes, we explored the pleiotropy of these 25 loci. Finally, in a subset of individuals with epilepsy and detailed clinical data available, we performed phenome-wide association analyses between individual CNVs and clinical annotations categorized through the Human Phenotype Ontology (HPO). For six CNVs, we identified 19 significant associations with specific HPO terms and generated, for all CNVs, phenotype signatures across 17 clinical categories relevant for epileptologists. This is the most comprehensive investigation of CNVs in epilepsy and related seizure disorders, with potential implications for clinical practice

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Framing Two Environmental Flow Trials in the Murray-Darling Basin, South-Eastern Australia

We make sense of the world around us through mental knowledge structures called ‘frames’. Frames, and the metaphors that help to form and maintain them, can be studied through examining discourse. In this paper, we aim to understand the framing of two trials with environmental water by analysing interview-derived discourse. Two separate flow trials, involving changes to river operating rules and practices, were undertaken in the Edward/Kolety-Wakool river system in Australia’s Murray-Darling Basin in 2017 and 2018, as part of the adaptive delivery of water for the environment. Semi-structured interviews with 18 actors in the Edward/Kolety-Wakool river system were undertaken in 2019, in which they reflected on the trials and the use of environmental water in the area. Analysis of the interviews suggest four framings of environmental water, which we have labelled business, engineering, science and medical. Each frame privileges expert practice, potentially marginalising other ways of experiencing and knowing the river system. ‘Participants’ in the social learning/adaptive management occurring in this situation, especially those with authority or influence, should be open to exploring alternate framings of situations. We present this small research project as a practical example of how a focus on revealing and considering discourse can provide interested actors with avenues for co-creation of new understandings and practice

Framing Two Environmental Flow Trials in the Murray-Darling Basin, South-Eastern Australia

We make sense of the world around us through mental knowledge structures called ‘frames’. Frames, and the metaphors that help to form and maintain them, can be studied through examining discourse. In this paper, we aim to understand the framing of two trials with environmental water by analysing interview-derived discourse. Two separate flow trials, involving changes to river operating rules and practices, were undertaken in the Edward/Kolety-Wakool river system in Australia’s Murray-Darling Basin in 2017 and 2018, as part of the adaptive delivery of water for the environment. Semi-structured interviews with 18 actors in the Edward/Kolety-Wakool river system were undertaken in 2019, in which they reflected on the trials and the use of environmental water in the area. Analysis of the interviews suggest four framings of environmental water, which we have labelled business, engineering, science and medical. Each frame privileges expert practice, potentially marginalising other ways of experiencing and knowing the river system. ‘Participants’ in the social learning/adaptive management occurring in this situation, especially those with authority or influence, should be open to exploring alternate framings of situations. We present this small research project as a practical example of how a focus on revealing and considering discourse can provide interested actors with avenues for co-creation of new understandings and practice

Research For A Sustainable Future: Environmental monitoring of variable flow trials conducted at Dartmouth Dam, 2001/02-07/08 - Synthesis of key findings and operational guidelines

Dartmouth and Hume Dams are operated as part of the 'River Murray System' by the River Murray Division of the Murray-Darling Basin Authority (MDBA). Hume Dam was built 1919-36 and is the primary regulating storage in that river system. It was enlarged 1950-61 to accommodate additional water from the Snowy Mountains Scheme. Dartmouth Dam was constructed later (between 1973 and 1979) on the Mitta Mitta River, a major tributary entering Hume Reservoir (Figure 1). Dartmouth Reservoir has a larger capacity (3908 GL) than Hume Reservoir (approx 3000 GL) and is primarily used as "drought reserve" to supplement storage in Hume. Dartmouth Reservoir can take several years to fill because of its large storage capacity relative to its catchment size. Hume typically fills and empties more frequently, sometimes annually. Although the primary purpose of Dartmouth and Hume Reservoirs is to increase the security of water supply for irrigation, stock, domestic and town use, dam operations also mitigate flooding in the valleys below them (Hume and Dartmouth Dams Operations Review Panel 1998)