Metabolomics and a Breath Sensor Identify Acetone as a Biomarker for Heart Failure.

BACKGROUND: Multi-omics delivers more biological insight than targeted investigations. We applied multi-omics to patients with heart failure with reduced ejection fraction (HFrEF). METHODS: 46 patients with HFrEF and 20 controls underwent metabolomic profiling, including liquid/gas chromatography mass spectrometry (LC-MS/GC-MS) and solid-phase microextraction (SPME) volatilomics in plasma and urine. HFrEF was defined using left ventricular global longitudinal strain, ejection fraction and NTproBNP. A consumer breath acetone (BrACE) sensor validated results in n = 73. RESULTS: 28 metabolites were identified by GCMS, 35 by LCMS and 4 volatiles by SPME in plasma and urine. Alanine, aspartate and glutamate, citric acid cycle, arginine biosynthesis, glyoxylate and dicarboxylate metabolism were altered in HFrEF. Plasma acetone correlated with NT-proBNP (r = 0.59, 95% CI 0.4 to 0.7), 2-oxovaleric and cis-aconitic acid, involved with ketone metabolism and mitochondrial energetics. BrACE > 1.5 ppm discriminated HF from other cardiac pathology (AUC 0.8, 95% CI 0.61 to 0.92, p < 0.0001). CONCLUSION: Breath acetone discriminated HFrEF from other cardiac pathology using a consumer sensor, but was not cardiac specific.

Mine completion criteria defined by best-practice: A global meta-analysis and Western Australian case studies.

In many mining-intensive areas around the world, knowledge-sharing among companies is critical to advance best-practices in mine rehabilitation and closure. The academic literature documents innovative, best-practices options, yet these are often not accessible to field practitioners. Published mine closure plans provide relevant examples of standards accepted by regulators, however, regulations vary with jurisdiction and can change over time, limiting the utility of these plans. There is, therefore, a need for greater transparency and accessibility of practical knowledge to inform the definition of achievable completion criteria. The purpose of this study is to provide an overview of best-practices for the purpose of defining mine completion criteria. The methods comprise: i) a qualitative meta-analysis of the global peer-reviewed literature; and ii) three in-depth case studies in Western Australia. The research identifies ten key best-practices that could be potentially applied by mining proponents to guide the definition of successful completion criteria. These include: multiple references, monitoring and corrective actions, science-informed completion criteria, holistic rehabilitation, dynamic targets, leading indicators, integration of rehabilitation with mine operations, innovation-guided completion criteria, specific objectives and indicators and risk-based completion criteria. These best-practices are further examined through recent mine rehabilitation and closure programs of mid-to-large mining operators in Western Australia. Our findings provide the first comprehensive review of best-practices towards the definition of mine completion criteria, which are relevant to industries requiring rehabilitation of disturbed lands across Australian and international jurisdictions.

A framework for developing completion criteria for mine closure and rehabilitation.

The mining industry is a major contributor to Australia's economy. However, such returns may come at high environmental and social costs, including loss of biodiversity or heritage values. Thus, companies worldwide are required to rehabilitate mine sites to a state that is safe, non-polluting and capable of supporting an agreed post-mining land use. While national and international guidelines on mine rehabilitation and closure exist, there is a lack of guidance on how to define achievable and measurable criteria that reflect rehabilitation success. This often leads to discrepancies between proponents and regulators, which hinder progression towards mine closure and relinquishment. The purpose of this study was to develop a systematic framework for the definition of completion criteria for mine closure and rehabilitation. The study was informed by a global review of the literature and collaborative research with mining stakeholders from Western Australia. The proposed framework consists of six fundamental steps: 1) selection of post mining land use; 2) definition of aspects and closure objectives; 3) selection of reference(s); 4) selection of attributes; 5) definition of completion criteria; and 6) evaluation of performance. This framework is the first to provide a step-by-step guide for defining site-specific completion criteria and applying a risk-based monitoring approach throughout the life of mine. The framework is applicable across jurisdictions and industries, in Australia and internationally, that require similar rehabilitation of disturbed lands.

Medical Management of Inflammatory Bowel Disease.

Inflammatory bowel disease has become a growing concern worldwide. The chronic and progressive nature of inflammatory bowel disease poses significant challenges to the treatment and management of affected patients, straining health care resources. Therapeutic options and optimal management strategies have evolved dramatically. The treat-to-target strategy has shifted focus toward identifiable and attainable treatment targets and with the ability to optimize tight control. Advancements in our understanding of the pathophysiology led to therapeutic mechanisms that have a more narrowed focus toward gut-specific targets, improving safety profiles.

Morphophysiological dormancy in the basal angiosperm order Nymphaeales.

Background and Aims: Substantial evidence supports the hypothesis that morphophysiological dormancy (MPD) is the basal kind of seed dormancy in the angiosperms. However, only physiological dormancy (PD) is reported in seeds of the ANA-grade genus Nymphaea. The primary aim of this study was to determine the kind of dormancy in seeds of six species of Nymphaea from the wet-dry tropics of Australia. Methods: The effects of temperature, light and germination stimulants on germination were tested on multiple collections of seeds of N. immutabilis, N. lukei, N. macrosperma, N. ondinea, N. pubescens and N. violacea. Embryo growth prior to hypocotyl emergence was monitored. Key Results: Germination was generally <10 % after 28 d in control treatments. Germination percentage was highest at 30 or 35 °C for seeds exposed to light and treated with ethylene or in anoxic conditions in sealed vials of water, and it differed significantly between collections of N. lukei, N. macrosperma and N. violacea. Seeds of N. pubescens did not germinate under any of the conditions. Embryo growth (8-37 % in length) occurred before hypocotyl emergence (germination) in seeds of the five species that germinated. Conclusions: Fresh seeds were dormant, and the amount of pregermination embryo growth in seeds of N. lukei and N. immutabilis was relatively small, while in seeds of N. macrosperma, N. ondinea and N. violacea it was relatively large. Thus, seeds of N. lukei and N. immutabilis had PD and those of N. macrosperma, N. ondinea and N. violacea had MPD. Overall, we found that seeds in the most phylogenetically derived clades within Nymphaea have MPD, suggesting that PD is the most likely basal trait within the Nymphaeales. This study also highlights the broad range of dormancy types and germination strategies in the ANA-grade angiosperms.

Short bowel syndrome and Crohn's disease.

Patients with Crohn's disease are at high risk for recurrent disease and often undergo multiple operations. Our aims were to evaluate surgical management and outcome of patients with Crohn's disease who develop short bowel syndrome (SBS) and to identify factors leading to this complication. We reviewed the records of 170 adult patients with SBS evaluated over a 20-year period. Thirty (18%) had Crohn's disease. SBS was defined as an intestinal remnant less than 180 cm with associated malabsorption. There were 20 women and 10 men ranging in age from 18 to 62 years. Eighteen (60%) presented initially with ileocolonic disease, seven (23%) with colonic disease, and five (17%) with small intestinal disease. The interval from initial diagnosis to development of SBS ranged from 2 to 32 years, with 21 patients (71%) having an interval greater than 15 years. The number of resections leading to SBS varied from 2 to 12 with 24 patients (80%) having four or fewer resections. Nineteen patients (63%) had an ostomy. Small intestinal remnant length was less than 60 cm in 10 patients, 60 to 120 cm in six patients, and greater than 120 cm in 14 patients. Only one patient underwent stricturoplasty before developing SBS. Five patients were initially diagnosed as having ulcerative colitis and underwent a pouch procedure, which was subsequently resected. Twenty patients (67%) required parenteral nutrition. Three patients have undergone reversed intestinal segment to slow intestinal transit. Two patients underwent intestinal transplantation. Two patients have died: one from parenteral nutrition-related liver failure and the other after intestinal transplantation. Crohn's disease remains a common cause of SBS. Aggressive resectional therapy, surgical complications, and errors in initial diagnosis contribute to development of SBS in these patients. Selected patients are candidates for surgical therapy for SBS.