TRANSCRIPTIONAL MARKERS OF ORGANIC SUBSTRATE AVAILABILITY IN A COASTAL MARINE BACTERIUM

Microbial activities are essential for the cycling of dissolved organic carbon (DOC) through the ocean. DOC is difficult to measure chemically due to its diversity, low concentrations, and spatial and temporal variability. An alternate method for investigating DOC composition and flux is to examine the transcriptional responses of the bacteria consuming it. However, there is a lack of experimentally validated data linking transcripts to specific carbon sources. In this study, we grew a model marine bacterium, Ruegeria pomeroyi DSS-3, in 42 carbon-limited, continuous cultures to test its transcriptomic response to 12 carbon substrates. Growth on different carbon substrates produced transcriptomic signals unique to each carbon source. Upregulated transcripts included transporters and some members of known substrate degradation pathways; however, many genes not associated with these degradation pathways were also upregulated. In this study, we identify specific transcripts that could be used as indicators of the presence of those carbon substrates.Master of Scienc

Exposure duration modulates the response of Caribbean corals to global change stressors

Global change, including rising temperatures and acidification, threatens corals globally. Although bleaching events reveal fine-scale patterns of resilience, traits enabling persistence under global change remain elusive. We conducted a 95-d controlled-laboratory experiment investigating how duration of exposure to warming (~28, 31°C), acidification (pCO2 ~ 343 [present day], ~663 [end of century], ~3109 [extreme] μatm), and their combination influences physiology of reef-building corals (Siderastrea siderea, Pseudodiploria strigosa) from two reef zones on the Belize Mesoamerican Barrier Reef System. Every 30 d, net calcification rate, host protein and carbohydrate, chlorophyll a, and symbiont density were quantified for the same coral individual to characterize acclimation potential under global change. Coral physiologies of the two species were differentially affected by stressors and exposure duration was found to modulate these responses. Siderastrea siderea exhibited resistance to end of century pCO2 and temperature stress, but calcification was negatively affected by extreme pCO2. However, S. siderea calcification rates remained positive after 95 d of extreme pCO2 conditions, suggesting acclimation. In contrast, P. strigosa was more negatively influenced by elevated temperatures, which reduced most physiological parameters. An exception was nearshore P. strigosa, which maintained calcification rates under elevated temperature, suggesting local adaptation to the warmer environment of their natal reef zone. This work highlights how tracking coral physiology across various exposure durations can capture acclimatory responses to global change stressors.First author draf

Missing children: risks, repeats and responses

Investigating reports of missing children is a major source of demand for the police in the UK. Repeat disappearances are common, can indicate underlying vulnerabilities and have been linked with various forms of exploitation and abuse. Inspired by research on repeat victimisation, this paper examines the prevalence and temporal patterns of repeat missing episodes by children, as well as the characteristics of those involved. Using data on all missing children incidents recorded by one UK police service in 2015 (n = 3,352), we find that: (a) 75% of missing incidents involving children were repeats, i.e. attributed to children who had already been reported missing in 2015; (b) a small proportion of repeatedly missing children (n = 59; 4%) accounted for almost a third of all missing children incidents (n = 952, 28%); (c) over half of all first repeat disappearances occurred within four weeks of an initial police recorded missing episode; and (d) children recorded as missing ten times or more over the one year study period were significantly more likely than those recorded missing once to be teenagers, in the care system or to have drug and/or alcohol dependencies. We conclude by discussing the implications of our findings for future research and the prevention of repeat disappearances by children

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

Correction to: Cluster identification, selection, and description in Cluster randomized crossover trials: the PREP-IT trials

An amendment to this paper has been published and can be accessed via the original article

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat