Cell-surface signatures of immune dysfunction risk-stratify critically ill patients: INFECT study.

PURPOSE: Cellular immune dysfunctions, which are common in intensive care patients, predict a number of significant complications. In order to effectively target treatments, clinically applicable measures need to be developed to detect dysfunction. The objective was to confirm the ability of cellular markers associated with immune dysfunction to stratify risk of secondary infection in critically ill patients. METHODS: Multi-centre, prospective observational cohort study of critically ill patients in four UK intensive care units. Serial blood samples were taken, and three cell surface markers associated with immune cell dysfunction [neutrophil CD88, monocyte human leucocyte antigen-DR (HLA-DR) and percentage of regulatory T cells (Tregs)] were assayed on-site using standardized flow cytometric measures. Patients were followed up for the development of secondary infections. RESULTS: A total of 148 patients were recruited, with data available from 138. Reduced neutrophil CD88, reduced monocyte HLA-DR and elevated proportions of Tregs were all associated with subsequent development of infection with odds ratios (95% CI) of 2.18 (1.00-4.74), 3.44 (1.58-7.47) and 2.41 (1.14-5.11), respectively. Burden of immune dysfunction predicted a progressive increase in risk of infection, from 14% for patients with no dysfunction to 59% for patients with dysfunction of all three markers. The tests failed to risk stratify patients shortly after ICU admission but were effective between days 3 and 9. CONCLUSIONS: This study confirms our previous findings that three cell surface markers can predict risk of subsequent secondary infection, demonstrates the feasibility of standardized multisite flow cytometry and presents a tool which can be used to target future immunomodulatory therapies. TRIAL REGISTRATION: The study was registered with clinicaltrials.gov (NCT02186522).The study was funded by Innovate UK (Sepsis 2: 101193), BD Biosciences and the National Institute for Academic Anaesthesia. Dr Conway Morris is supported by a Clinical Research Career Development Fellowship from the Wellcome Trust (WT 2055214/Z/16/Z). Dr Shankar-Hari is supported by the National Institute for Health Research Clinician Scientist Award (CS-2016-16- 011)

Early PREdiction of sepsis using leukocyte surface biomarkers: the ExPRES-sepsis cohort study.

PURPOSE: Reliable biomarkers for predicting subsequent sepsis among patients with suspected acute infection are lacking. In patients presenting to emergency departments (EDs) with suspected acute infection, we aimed to evaluate the reliability and discriminant ability of 47 leukocyte biomarkers as predictors of sepsis (Sequential Organ Failure Assessment score ≥ 2 at 24 h and/or 72 h following ED presentation). METHODS: In a multi-centre cohort study in four EDs and intensive care units (ICUs), we standardised flow-cytometric leukocyte biomarker measurement and compared patients with suspected acute infection (cohort-1) with two comparator cohorts: ICU patients with established sepsis (cohort-2), and ED patients without infection or systemic inflammation but requiring hospitalization (cohort-3). RESULTS: Between January 2014 and February 2016, we recruited 272, 59 and 75 patients to cohorts 1, 2, and 3, respectively. Of 47 leukocyte biomarkers, 14 were non-reliable, and 17 did not discriminate between the three cohorts. Discriminant analyses for predicting sepsis within cohort-1 were undertaken for eight neutrophil (cluster of differentiation antigens (CD) CD15; CD24; CD35; CD64; CD312; CD11b; CD274; CD279), seven monocyte (CD35; CD64; CD312; CD11b; HLA-DR; CD274; CD279) and a CD8 T-lymphocyte biomarker (CD279). Individually, only higher neutrophil CD279 [OR 1.78 (95% CI 1.23-2.57); P = 0.002], higher monocyte CD279 [1.32 (1.03-1.70); P = 0.03], and lower monocyte HLA-DR [0.73 (0.55-0.97); P = 0.03] expression were associated with subsequent sepsis. With logistic regression the optimum biomarker combination was increased neutrophil CD24 and neutrophil CD279, and reduced monocyte HLA-DR expression, but no combination had clinically relevant predictive validity. CONCLUSIONS: From a large panel of leukocyte biomarkers, immunosuppression biomarkers were associated with subsequent sepsis in ED patients with suspected acute infection. CLINICAL TRIAL REGISTRATION: NCT02188992.The study was funded by Innovate UK (Sepsis 2: 101193). Dr Shankar-Hari is supported by the National Institute for Health Research Clinician Scientist Award (CS-2016-16-011). Dr Conway Morris is supported by a Clinical Research Career Development Fellowship from the Wellcome Trust (WT 2055214/Z/16/Z)

Arctic climate shifts drive rapid ecosystem responses across the West Greenland landscape

Prediction of high latitude response to climate change is hampered by poor understanding of the role of nonlinear changes in ecosystem forcing and response. While the effects of nonlinear climate change are often delayed or dampened by internal ecosystem dynamics, recent warming events in the Arctic have driven rapid environmental response, raising questions of how terrestrial and freshwater systems in this region may shift in response to abrupt climate change. We quantified environmental responses to recent abrupt climate change in West Greenland using long-term monitoring and paleoecological reconstructions. Using >40 years of weather data, we found that after 1994, mean June air temperatures shifted 2.2 °C higher and mean winter precipitation doubled from 21 to 40 mm; since 2006, mean July air temperatures shifted 1.1 °C higher. Nonlinear environmental responses occurred with or shortly after these abrupt climate shifts, including increasing ice sheet discharge, increasing dust, advancing plant phenology, and in lakes, earlier ice out and greater diversity of algal functional traits. Our analyses reveal rapid environmental responses to nonlinear climate shifts, underscoring the highly responsive nature of Arctic ecosystems to abrupt transitions

Genetic variation and pathogenicity of anastomosis group 2 isolates of Rhizoctonia solani in Australia

Copyright © 2007 The British Mycological Society Published by Elsevier Ltd.A collection of isolates of Rhizoctonia solani anastomosis group (AG) 2 was examined for genetic diversity and pathogenicity. Anastomosis reactions classified the majority of isolates into the known subgroups of AG 2-1 and AG 2-2 but the classification of several isolates was ambiguous. Morphological characters were consistent with the species, with no discriminating characters existing between subgroups. Vertical PAGE of pectic enzymes enabled the separation of zymogram group (ZG) 5 and 6 within AG 2-1, but not the separation of ZG 4 and 10 within AG 2-2. PCR analysis using inter-simple sequence repeats (ISSR) and the intron-splice junction (ISJ) region supported the separation of ZG 5 and 6, while the AG 2-2 isolates were separated by geographic region. A comparison of distance matrices produced by the zymogram analysis and PCR indicated a strong correlation between the marker types. Pathogenicity studies suggested canola (Brassica napus) cultivars were most severely affected by AG 2-1, while cultivars of two species of medic (Medicago truncatula cv. Caliph and M. littoralis cv. Herald) were susceptible to both AG 2-1 and 2-2. The results indicate that AG 2 is a polyphyletic group in which the classification of subtypes is sometimes difficult. Further investigation of the population structure within Australia is required to determine the extent and origin of the observed diversity.Benjamin J. Stodart, Paul R. Harvey, Stephen M. Neate, Dara L. Melanson and Eileen S. Scotthttp://www.elsevier.com/wps/find/journaldescription.cws_home/707043/description#descriptio