Lung Cancer (internet-based) Delphi (LuCiD): Setting the standard for lung cancer care in Australia and New Zealand - a modified eDelphi consensus to determine clinical quality indicators for lung cancer

Protocol Version 1.1 16 August 202

Tracking Onslow: a community in transition. edition 5, October 2014

This is the fifth edition of Tracking Onslow and the first that is not the result of a visit to the town. In June 2014 we were told that the Shire would not be funding the flights, accommodation or printing for the edition and so the ECU crew looked for other ways to continue documenting the impact of Wheatstone and Macedon on Onslow. Fortunately, our previous visits in July 2012, February 2013, July 2013 and February 2014 had filled our contact books with names and numbers and clued us in to issues that needed to be followed up. After a phone around for updates it was clear that this is not the time to be letting go of the process of documenting the challenges facing the Onslow community. We are very grateful to teacher James Trimble and his students, Amber and Taylor, for helping with the In Your Words section. We’d also like to thank everyone who spoke to us by phone and sent us images. We heard that there were concerns expressed earlier in the year about an image of the Anzac Memorial on our last cover and we would like to clarify that we did nothing to encourage the children to climb on it. We saw them there and snapped the picture. The photo is a true representation of something that happens in Onslow, and as such we reported it. One of the key functions of journalism is operating as a ‘town square’, where the opinions of different members of the community are aired. In this way a publication can help facilitate debate and understanding between different groups. We know that not everyone in Onslow agrees with each other, but we seek to allow everyone a space to speak through our pages. Sometimes opinions are based on misunderstood facts and so some of the things people say may not be true. We can’t vouch for the truth of what the people we spoke to said, but we have faithfully recorded it so that this edition is a true record of what was being said in and about Onslow in mid-late 2014. We hope you enjoy reading it

Haematopoietic SCT in severe autoimmune diseases: updated guidelines of the European Group for Blood and Marrow Transplantation

In 1997, the first consensus guidelines for haematopoietic SCT (HSCT) in autoimmune diseases (ADs) were published, while an international coordinated clinical programme was launched. These guidelines provided broad principles for the field over the following decade and were accompanied by comprehensive data collection in the European Group for Blood and Marrow Transplantation (EBMT) AD Registry. Subsequently, retrospective analyses and prospective phase I/II studies generated evidence to support the feasibility, safety and efficacy of HSCT in several types of severe, treatment-resistant ADs, which became the basis for larger-scale phase II and III studies. In parallel, there has also been an era of immense progress in biological therapy in ADs. The aim of this document is to provide revised and updated guidelines for both the current application and future development of HSCT in ADs in relation to the benefits, risks and health economic considerations of other modern treatments. Patient safety considerations are central to guidance on patient selection and HSCT procedural aspects within appropriately experienced and Joint Accreditation Committee of International Society for Cellular Therapy and EBMT accredited centres. A need for prospective interventional and non-interventional studies, where feasible, along with systematic data reporting, in accordance with EBMT policies and procedures, is emphasized

Staging colorectal cancer with the TNM 7(th): the presumption of innocence when applying the M category

One of the main changes of the current TNM-7 is the elimination of the category MX, since it has been a source of ambiguity and misinterpretation, especially by pathologists. Therefore the ultimate staging would be better performed by the patient's clinician who can classify the disease M0 (no distant metastasis) or M1 (presence of distant metastasis), having access to the completeness of data resulting from clinical examination, imaging workup and pathology report. However this important change doesn't take into account the diagnostic value and the challenge of small indeterminate visceral lesions encountered, in particular, during radiological staging of patients with colorectal cancer. In this article the diagnosis of these lesions with multiple imaging modalities, their frequency, significance and relevance to staging and disease management are described in a multidisciplinary way. In particular the interplay between clinical, radiological and pathological staging, which are usually conducted independently, is discussed. The integrated approach shows that there are both advantages and disadvantages to abandoning the MX category. To avoid ambiguity arising both by applying and interpreting MX category for stage assigning, its abandoning seems reasonable. The recognition of the importance of small lesion characterization raises the need for applying a separate category; therefore a proposal for their categorization is put forward. By using the proposed categorization the lack of consideration for indeterminate visceral lesions with the current staging system will be overcome, also optimizing tailored follow-up

Reduced biological control and enhanced chemical pest management in the evolution of fungus farming in ants

To combat disease, most fungus-growing ants (Attini) use antibiotics from mutualistic bacteria (Pseudonocardia) that are cultured on the ants' exoskeletons and chemical cocktails from exocrine glands, especially the metapleural glands (MG). Previous work has hypothesized that (i) Pseudonocardia antibiotics are narrow-spectrum and control a fungus (Escovopsis) that parasitizes the ants' fungal symbiont, and (ii) MG secretions have broad-spectrum activity and protect ants and brood. We assessed the relative importance of these lines of defence, and their activity spectra, by scoring abundance of visible Pseudonocardia for nine species from five genera and measuring rates of MG grooming after challenging ants with disease agents of differing virulence. Atta and Sericomyrmex have lost or greatly reduced the abundance of visible bacteria. When challenged with diverse disease agents, including Escovopsis, they significantly increased MG grooming rates and expanded the range of targets. By contrast, species of Acromyrmex and Trachymyrmex maintain abundant Pseudonocardia. When challenged, these species had lower MG grooming rates, targeted primarily to brood. More elaborate MG defences and reduced reliance on mutualistic Pseudonocardia are correlated with larger colony size among attine genera, raising questions about the efficacy of managing disease in large societies with chemical cocktails versus bacterial antimicrobial metabolites

An AI-guided screen identifies probucol as an enhancer of mitophagy through modulation of lipid droplets.

Failures in mitophagy, a process by which damaged mitochondria are cleared, results in neurodegeneration, while enhancing mitophagy promotes the survival of dopaminergic neurons. Using an artificial intelligence platform, we employed a natural language processing approach to evaluate the semantic similarity of candidate molecules to a set of well-established mitophagy enhancers. Top candidates were screened in a cell-based mitochondrial clearance assay. Probucol, a lipid-lowering drug, was validated across several orthogonal mitophagy assays. In vivo, probucol improved survival, locomotor function, and dopaminergic neuron loss in zebrafish and fly models of mitochondrial damage. Probucol functioned independently of PINK1/Parkin, but its effects on mitophagy and in vivo depended on ABCA1, which negatively regulated mitophagy following mitochondrial damage. Autophagosome and lysosomal markers were elevated by probucol treatment in addition to increased contact between lipid droplets (LDs) and mitochondria. Conversely, LD expansion, which occurs following mitochondrial damage, was suppressed by probucol and probucol-mediated mitophagy enhancement required LDs. Probucol-mediated LD dynamics changes may prime the cell for a more efficient mitophagic response to mitochondrial damage