ASSESSING THE EFFECT OF A LIGHT INTERVENTION ON SLEEP QUALITY AND PERFORMANCE OF PENTAGON WATCHSTANDERS

Around the world, watchfloors provide information, intelligence, and technical support to operational commands 24 hours a day. Watchstanders often work long shifts surpassing full time 40-hour work weeks, which include night and weekend shifts. Shiftwork has been associated with a decreased amount of sleep in both quantity and quality, which leads to exhaustion and compromised cognitive function. Exposure to high energy visible (HEV) light at appropriate times has the potential to shift the body’s circadian rhythm to align faster to a new shift schedule. Adjusting to shifting work hours quicker could lead to less sleep loss, enhanced sleep quality, and less severe levels of fatigue. This study aims to assess the impact and potential benefits of intentionally introducing HEV light when watchstanders on a shore-based watchfloor are transitioning to a different work shift. The study will consider how the strategic application of HEV light affects circadian entrainment, thereby impacting sleep, performance, mood, and sleepiness. This work will inform recommendations to other shore-based watchfloors at the Pentagon that require non-traditional work schedules to support watchstanding operations.Naval Medical Research Center – Advanced Medical Development Program Silver Spring, MD 20910Lieutenant Commander, United States NavyApproved for public release. Distribution is unlimited

Contribution of Coastal Retrogressive Thaw Slumps to the Nearshore Organic Carbon budget along the Yukon Coast

We describe the evolution of coastal retrogressive thaw slumps (RTSs) between 1952 and 2011 along the Yukon Coast, Canada, and provide the first estimate of the contribution of RTSs to the nearshore organic carbon budget in this area. We 1) monitor the evolution of RTSs during the periods 1952-1972 and 1972-2011; 2) calculate the volume of material eroded and stocks of organic carbon (OC) mobilized through slumping – including soil organic carbon (SOC) and dissolved organic carbon (DOC) – and 3) measure the OC fluxes mobilized through slumping between 1972 and 2011. We identified RTSs using high-resolution satellite imagery from 2011 and geocoded aerial photographs from 1952 and 1972. To estimate the volume of eroded material, we applied a spline interpolation on an airborne LiDAR dataset acquired in July 2013. We inferred the stocks of mobilized SOC and DOC from existing related literature. Our results show a 73% increase in the number of RTSs between 1952 and 2011. In the study area, RTSs displaced at least 8600*103 m^3 of material, with 53% of ice. We estimated that slumping mobilized 81900*10^3 kg of SOC and 156*10^3 kg of DOC. Since 1972, 17% of the RTSs have displaced 8.6*103 m^3/yr of material, with an average OC flux of 82.5*10^3 kg/yr. This flux represents 0.3% of the OC flux released from coastal retreat; however RTSs have a strong impact on the transformation of OC in the coastal fringe

Surface disinfection challenges for Candida auris: an in-vitro study

The emerging pathogenic multidrug-resistant yeast Candida auris is an important source of healthcare-associated infections and of growing global clinical concern. The ability of this organism to survive on surfaces and withstand environmental stressors creates a challenge for eradicating it from hospitals. A panel of C. auris clinical isolates was evaluated on different surface environments against the standard disinfectant sodium hypochlorite and high-level disinfectant peracetic acid. C. auris was shown to selectively tolerate clinically relevant concentrations of sodium hypochlorite and peracetic acid in a surface-dependent manner, which may explain its ability to successfully persist within the hospital environment

Biofilm-stimulated epithelium modulates the inflammatory responses in co-cultured immune cells

The gingival epithelium is a physical and immunological barrier to the microbiota of the oral cavity, which interact through soluble mediators with the immune cells that patrol the tissue at the gingival epithelium. We sought to develop a three-dimensional gingivae-biofilm interface model using a commercially available gingival epithelium to study the tissue inflammatory response to oral biofilms associated with “health”, “gingivitis” and “periodontitis”. These biofilms were developed by sequential addition of microorganisms to mimic the formation of supra- and sub-gingival plaque in vivo. Secondly, to mimic the interactions between gingival epithelium and immune cells in vivo, we integrated peripheral blood mononuclear cells and CD14+ monocytes into our three-dimensional model and were able to assess the inflammatory response in the immune cells cultured with and without gingival epithelium. We describe a differential inflammatory response in immune cells cultured with epithelial tissue, and more so following incubation with epithelium stimulated by “gingivitis-associated” biofilm. These results suggest that gingival epithelium-derived soluble mediators may control the inflammatory status of immune cells in vitro, and therefore targeting of the epithelial response may offer novel therapies. This multi-cellular interface model, both of microbial and host origin, offers a robust in vitro platform to investigate host-pathogens at the epithelial surface

Rapid institutional appraisal

A week-long intensive process of staff development and induction called Rapid Institutional Appraisal (RIA) was conducted in November 2000 in the Systems Discipline, Centre for Complexity and Change (CCC), at the Open University. We report the systemic roots and characteristics of the RIA as designed from traditions of soft systems methodology and rapid rural appraisal. Our experiences arising from our own use of RIA are described and the wider implications for organizational learning in a complex organization discussed. While acknowledging limitations with this RIA event, we argue that RIA offers a potential model for staff development for adaptive use in different contexts and on varying scales. The process builds on principles of "conversation" and "multiple perspectives" as the touchstone for establishing a purposeful community of practice

Functional outcomes following ileal pouch-anal anastomosis (IPAA) in older patients: a systematic review

Aim Ileal pouch-anal anastomosis (IPAA) is performed in ulcerative colitis or familial adenomatous polyposis with a view to restoration of GI continuity and prevention of permanent faecal diversion. Debate exists as to its safety in older patients. This review aims to assess functional outcomes and safety of restorative proctocolectomy (RPC) in older compared to younger patients. Methods Literature search was performed for age-stratified studies which assessed functional outcomes of IPAA. Twelve papers were included overall. Patients were categorized into ‘older’ and ‘younger’ groups. Analysis was split into three separate parts: 1. Age cut-off of 50 ± 5 years (with sensitivity analysis); 2. Age cut-off of 65 ± years; 3. Long-term outcomes (>10 years). Results With an age cut-off of 50 years (4327 versus 513 patients), complication rates were comparable with the exception of an increased rate of small-bowel obstruction in the younger patients (p = 0.034). At 1 year, 24-h stool frequency was significantly higher in the older patient group (p < 0.0001). Daytime (p < 0.0001) and night-time (p < 0.0001) incontinence rates were also significantly higher in older patients. Overall, function deteriorated with time across all ages; however, after 10 years, there was no significant difference in incontinence rates between age groups. Dehydration and electrolyte loss was a significant problem in patients over 65 (p < 0.0001). Despite differences in postoperative function, quality of life was comparable between groups; however, only a few studies reported quality of life data. Conclusion IPAA is safe in older patients, although treating clinicians should bear in mind the increased risk of dehydration. Postoperative function is worse in older patients, but seems to level out with time and does not appear to significantly impact on overall quality of life and patient satisfaction. Assessment for suitability for RPC should not be based on chronological age in isolation. It is imperative that the correct support is given to older patients with worsened postoperative function in order to maintain patient satisfaction and adequate quality of life

A Prospective Surveillance Study of Candidaemia : Epidemiology, Risk Factors, Antifungal Treatment and Outcome in Hospitalized Patients

Funding This work was supported by the Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology 097377/Z/11/Z. Data collection was supported by a grant from Pfizer. GR was also supported by a research fellowship grant from Gilead Sciences. The collection of the isolates was funded by a Gilead Fellowship to GR. Acknowledgments We are grateful to microbiology colleagues throughout Scotland for submitting isolates. Antimicrobial sensitivity testing was performed by the Mycology Reference Laboratory, Public Health England, Bristol.Peer reviewedPublisher PD

Hsp90 governs dispersion and drug resistance of fungal biofilms

Fungal biofilms are a major cause of human mortality and are recalcitrant to most treatments due to intrinsic drug resistance. These complex communities of multiple cell types form on indwelling medical devices and their eradication often requires surgical removal of infected devices. Here we implicate the molecular chaperone Hsp90 as a key regulator of biofilm dispersion and drug resistance. We previously established that in the leading human fungal pathogen, Candida albicans, Hsp90 enables the emergence and maintenance of drug resistance in planktonic conditions by stabilizing the protein phosphatase calcineurin and MAPK Mkc1. Hsp90 also regulates temperature-dependent C. albicans morphogenesis through repression of cAMP-PKA signalling. Here we demonstrate that genetic depletion of Hsp90 reduced C. albicans biofilm growth and maturation in vitro and impaired dispersal of biofilm cells. Further, compromising Hsp90 function in vitro abrogated resistance of C. albicans biofilms to the most widely deployed class of antifungal drugs, the azoles. Depletion of Hsp90 led to reduction of calcineurin and Mkc1 in planktonic but not biofilm conditions, suggesting that Hsp90 regulates drug resistance through different mechanisms in these distinct cellular states. Reduction of Hsp90 levels led to a marked decrease in matrix glucan levels, providing a compelling mechanism through which Hsp90 might regulate biofilm azole resistance. Impairment of Hsp90 function genetically or pharmacologically transformed fluconazole from ineffectual to highly effective in eradicating biofilms in a rat venous catheter infection model. Finally, inhibition of Hsp90 reduced resistance of biofilms of the most lethal mould, Aspergillus fumigatus, to the newest class of antifungals to reach the clinic, the echinocandins. Thus, we establish a novel mechanism regulating biofilm drug resistance and dispersion and that targeting Hsp90 provides a much-needed strategy for improving clinical outcome in the treatment of biofilm infections

Biofilm formation is a risk factor for mortality in patients with Candida albicans bloodstream infection-Scotland, 2012-2013

Acknowledgements This work was supported by the Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology 097377/Z/11/Z. Data collection was supported by a grant from Pfizer. G. Ramage was also supported by a research fellowship grant from Gilead Sciences. We are grateful to microbiology colleagues throughout Scotland for submitting isolates.Peer reviewedPublisher PD

Investigating the biological properties of carbohydrate derived fulvic acid (CHD-FA) as a potential novel therapy for the management of oral biofilm infections.

Background: A number of oral diseases, including periodontitis, derive from microbial biofilms and are associated with increased antimicrobial resistance. Despite the widespread use of mouthwashes being used as adjunctive measures to control these biofilms, their prolonged use is not recommended due to various side effects. Therefore, alternative broad-spectrum antimicrobials that minimise these effects are highly sought after. Carbohydrate derived fulvic acid (CHD-FA) is an organic acid which has previously demonstrated to be microbiocidal against Candida albicans biofilms, therefore, the aims of this study were to evaluate the antibacterial activity of CHD-FA against orally derived biofilms and to investigate adjunctive biological effects.&lt;p&gt;&lt;/p&gt; Methods: Minimum inhibitory concentrations were evaluated for CHD-FA and chlorhexidine (CHX) against a range of oral bacteria using standardised microdilution testing for planktonic and sessile. Scanning electron microscopy was also employed to visualise changes in oral biofilms after antimicrobial treatment. Cytotoxicity of these compounds was assessed against oral epithelial cells, and the effect of CHD-FA on host inflammatory markers was assessed by measuring mRNA and protein expression.&lt;p&gt;&lt;/p&gt; Results: CHD-FA was highly active against all of the oral bacteria tested, including Porphyromonas gingivalis, with a sessile minimum inhibitory concentration of 0.5%. This concentration was shown to kill multi-species biofilms by approximately 90%, levels comparable to that of chlorhexidine (CHX). In a mammalian cell culture model, pretreatment of epithelial cells with buffered CHD-FA was shown to significantly down-regulate key inflammatory mediators, including interleukin-8 (IL-8), after stimulation with a multi-species biofilm.&lt;p&gt;&lt;/p&gt; Conclusions: Overall, CHD-FA was shown to possess broad-spectrum antibacterial activity, with a supplementary function of being able to down-regulate inflammation. These properties offer an attractive spectrum of function from a naturally derived compound, which could be used as an alternative topical treatment strategy for oral biofilm diseases. Further studies in vitro and in vivo are required to determine the precise mechanism by which CHD-FA modulates the host immune response.&lt;p&gt;&lt;/p&gt