Metagenome-assembled genomes from High Arctic glaciers highlight the vulnerability of glacier-associated microbiota and their activities to habitat loss.

The rapid warming of the Arctic is threatening the demise of its glaciers and their associated ecosystems. Therefore, there is an urgent need to explore and understand the diversity of genomes resident within glacial ecosystems endangered by human-induced climate change. In this study we use genome-resolved metagenomics to explore the taxonomic and functional diversity of different habitats within glacier-occupied catchments. Comparing different habitats within such catchments offers a natural experiment for understanding the effects of changing habitat extent or even loss upon Arctic microbiota. Through binning and annotation of metagenome-assembled genomes (MAGs) we describe the spatial differences in taxon distribution and their implications for glacier-associated biogeochemical cycling. Multiple taxa associated with carbon cycling included organisms with the potential for carbon monoxide oxidation. Meanwhile, nitrogen fixation was mediated by a single taxon, although diverse taxa contribute to other nitrogen conversions. Genes for sulphur oxidation were prevalent within MAGs implying the potential capacity for sulphur cycling. Finally, we focused on cyanobacterial MAGs, and those within cryoconite, a biodiverse microbe-mineral granular aggregate responsible for darkening glacier surfaces. Although the metagenome-assembled genome of Phormidesmis priestleyi, the cyanobacterium responsible for forming Arctic cryoconite was represented with high coverage, evidence for the biosynthesis of multiple vitamins and co-factors was absent from its MAG. Our results indicate the potential for cross-feeding to sustain P. priestleyi within granular cryoconite. Taken together, genome-resolved metagenomics reveals the vulnerability of glacier-associated microbiota to the deletion of glacial habitats through the rapid warming of the Arctic.

Global variability and controls on the accumulation of fallout radionuclides in cryoconite.

The accumulation of fallout radionuclides (FRNs) from nuclear weapons testing and nuclear accidents has been evaluated for over half a century in natural environments; however, until recently their distribution and abundance within glaciers have been poorly understood. Following a series of individual studies of FRNs, specifically 137Cs, 241Am and 210Pb, deposited on the surface of glaciers, we now understand that cryoconite, a material commonly found in the supraglacial environment, is a highly efficient accumulator of FRNs, both artificial and natural. However, the variability of FRN activity concentrations in cryoconite across the global cryosphere has never been assessed. This study thus aims to both synthesize current knowledge on FRNs in cryoconite and assess the controls on variability of activity concentrations. We present a global database of new and previously published data based on gamma spectrometry of cryoconite and proglacial sediments, and assess the extent to which a suite of environmental and physical factors can explain spatial variability in FRN activity concentrations in cryoconite. We show that FRNs are not only found in cryoconite on glaciers within close proximity to specific sources of radioactivity, but across the global cryosphere, and at activity concentrations up to three orders of magnitude higher than those found in soils and sediments in the surrounding environment. We also show that the organic content of cryoconite exerts a strong control on accumulation of FRNs, and that activity concentrations in cryoconite are some of the highest ever described in environmental matrices outside of nuclear exclusion zones, occasionally in excess of 10,000 Bq kg-1. These findings highlight a need for significant improvements in the understanding of the fate of legacy contaminants within glaciated catchments. Future interdisciplinary research is required on the mechanisms governing their accumulation, storage, and mobility, and their potential to create time-dependent impacts on downstream water quality and ecosystem sustainability.

Evidence-practice gaps in P2Y12 inhibitor use after hospitalisation for acute myocardial infarction: findings from a new population-level data linkage in Australia.

BACKGROUND: P2Y12 inhibitor therapy is recommended for 12 months in patients hospitalised for acute myocardial infarction (AMI) unless the bleeding risk is high. AIMS: To describe real-world use of P2Y12 inhibitor therapy following AMI hospitalisation. METHODS: We used population-level linked hospital data to identify all patients discharged from a public hospital with a primary diagnosis of AMI between July 2011 and June 2013 in New South Wales and Victoria, Australia. We used dispensing claims to examine dispensing of a P2Y12 inhibitor (clopidogrel, prasugrel or ticagrelor) within 30 days of discharge and multilevel models to identify predictors of post-discharge dispensing and persistence of therapy to 1 year. RESULTS: We identified 31 848 patients hospitalised for AMI, of whom 56.8% were dispensed a P2Y12 inhibitor within 30 days of discharge. The proportion of patients with post-discharge dispensing varied between hospitals (interquartile range: 25.0-56.5%), and significant between-hospital variation remained after adjusting for patient characteristics. Patient factors associated with the lowest likelihood of post-discharge dispensing were: having undergone coronary artery bypass grafting (odds ratio (OR): 0.17; 95% confidence intervals (CI): 0.15-0.20); having oral anticoagulants dispensed 180 days before or 30 days after discharge (OR: 0.39, 95% CI: 0.35-0.44); major bleeding (OR: 0.68, 95% CI: 0.61-0.76); or being aged ≥85 years (OR: 0.68, 95% CI: 0.62-0.75). A total of 26.8% of patients who were dispensed a P2Y12 inhibitor post-discharge discontinued therapy within 1 year. CONCLUSION: Post-hospitalisation use of P2Y12 inhibitor therapy in AMI patients is low and varies substantially by hospital of discharge. Our findings suggest strategies addressing both health system (hospital and physician) and patient factors are needed to close this evidence-practice gap.

Microbial genomics amidst the Arctic crisis.

The Arctic is warming - fast. Microbes in the Arctic play pivotal roles in feedbacks that magnify the impacts of Arctic change. Understanding the genome evolution, diversity and dynamics of Arctic microbes can provide insights relevant for both fundamental microbiology and interdisciplinary Arctic science. Within this synthesis, we highlight four key areas where genomic insights to the microbial dimensions of Arctic change are urgently required: the changing Arctic Ocean, greenhouse gas release from the thawing permafrost, 'biological darkening' of glacial surfaces, and human activities within the Arctic. Furthermore, we identify four principal challenges that provide opportunities for timely innovation in Arctic microbial genomics. These range from insufficient genomic data to develop unifying concepts or model organisms for Arctic microbiology to challenges in gaining authentic insights to the structure and function of low-biomass microbiota and integration of data on the causes and consequences of microbial feedbacks across scales. We contend that our insights to date on the genomics of Arctic microbes are limited in these key areas, and we identify priorities and new ways of working to help ensure microbial genomics is in the vanguard of the scientific response to the Arctic crisis.

Evidence-Practice Gaps in Postdischarge Initiation With Oral Anticoagulants in Patients With Atrial Fibrillation.

Background Oral anticoagulant (OAC) therapy reduces the risk of stroke in people with atrial fibrillation (AF), and is considered best practice; however, there is little Australian evidence around the uptake of OACs in this population. Methods and Results We used linked hospital admissions, pharmaceutical dispensing claims, medical services, and mortality data for people in Australia's 2 most populous states (July 2010 to June 2015). Among OAC-naïve people hospitalized with AF, we estimated initiation of OAC therapy within 30 days of discharge, and persistence with therapy in the first year. We analyzed both outcomes using multivariable Cox regression. In 71 184 people with AF (median age 78 years, 49% female), 22.7% initiated OAC therapy. Initiation was lowest in July to December 2011 (17.0%) and highest in July to December 2014 (30.1%) after subsidy of the direct OACs. In adjusted analyses, initiation was most likely in people with a CHA2DS2-VA score ≥7 (versus 0) (hazard ratio=6.25, 95% CI 5.08-7.69), and a history of venous thromboembolism (hazard ratio=2.65, 95% CI 2.49-2.83). Of the people who initiated OAC therapy, 39.9% discontinued within 1 year; a lower risk of discontinuation was associated with a CHA2DS2-VA score ≥7 (versus 0) (hazard ratio=0.22, 95% CI 0.14-0.35), or initiation on a direct OAC (versus warfarin) (hazard ratio=0.55, 95% CI 0.50-0.60). Conclusions We found that OAC therapy was severely underutilized in people hospitalized with AF, even among high-risk individuals. Reasons for this underuse, whether patient, prescriber, or hospital related, should be identified and addressed to reduce stroke-related morbidity and mortality in people with AF.

What is the impact of systems of care for heart failure on patients diagnosed with heart failure: a systematic review.

BACKGROUND: Hospital admissions for heart failure are predicted to rise substantially over the next decade placing increasing pressure on the health care system. There is an urgent need to redesign systems of care for heart failure to improve evidence-based practice and create seamless transitions through the continuum of care. The aim of the review was to examine systems of care for heart failure that reduce hospital readmissions and/or mortality. METHOD: Electronic databases searched were: Ovid MEDLINE, EMBASE, CINAHL, grey literature, reviewed bibliographies and Cochrane Central Register of Controlled Trials for randomised controlled trials, non-randomised trials and cohort studies from 1st January 2008 to 4th August 2015. Inclusion criteria for studies were: English language, randomised controlled trials, non-randomised trials and cohort studies of systems of care for patients diagnosed with heart failure and aimed at reducing hospital readmissions and/or mortality. Three reviewer authors independently assessed articles for eligibility based on title and abstract and then full-text. Quality of evidence was assessed using Newcastle-Ottawa Scale for non-randomised trials and GRADE rating tool for randomised controlled trials. RESULTS: We included 29 articles reporting on systems of care in the workforce, primary care, in-hospital, transitional care, outpatients and telemonitoring. Several studies found that access to a specialist heart failure team/service reduced hospital readmissions and mortality. In primary care, a collaborative model of care where the primary physician shared the care with a cardiologist, improved patient outcomes compared to a primary physician only. During hospitalisation, quality improvement programs improved the quality of inpatient care resulting in reduced hospital readmissions and mortality. In the transitional care phase, heart failure programs, nurse-led clinics, and early outpatient follow-up reduced hospital readmissions. There was a lack of evidence as to the efficacy of telemonitoring with many studies finding conflicting evidence. CONCLUSION: Redesigning systems of care aimed at improving the translation of evidence into clinical practice and transitional care can potentially improve patient outcomes in a cohort of patients known for high readmission rates and mortality.

Association of type XI collagen genes with chronic Achilles tendinopathy in independent populations from South Africa and Australia.

BACKGROUND: Type XI collagen, which is expressed in developing tendons and is encoded by the COL11A1, COL11A2 and COL2A1 genes, shares structural and functional homology with type V collagen, which plays an important role in collagen fibril assembly. We investigated the association of these three polymorphisms with Achilles tendinopathy (AT) and whether these polymorphisms interact with COL5A1 to modulate the risk of AT. METHODS: 184 participants diagnosed with chronic AT (TEN) and 338 appropriately matched asymptomatic controls (CON) were genotyped for the three polymorphisms. RESULTS: Although there were no independent associations with AT, the TCT pseudohaplotype constructed from rs3753841 (T/C), rs1676486 (C/T) and rs1799907 (T/A) was significantly over-represented (p=0.006) in the TEN (25.9%) compared with the CON (17.1%) group. The TCT(AGGG) pseudohaplotypes constructed using these type XI collagen polymorphisms and the functional COL5A1 rs71746744 (-/AGGG) polymorphism were also significantly over-represented (p<0.001) in the TEN (25.2%) compared with the CON (9.1%) group. DISCUSSION: The genes encoding structural and functionally related type XI (COL11A1 and COL11A2) and type V (COL5A1) collagens interact with one another to collectively modulate the risk for AT. Although there are no immediate clinical applications, the results of this study provide additional evidence that interindividual variations in collagen fibril assembly might be an important molecular mechanism in the aetiology of chronic AT.