The acute respiratory distress syndrome (ARDS) remains a common and highly morbid condition despite advances in the understanding and management of this complex critical illness. Recent work has ...illuminated the heterogeneity within ARDS and demonstrated the likely impact of heterogeneity on the identification of effective therapeutic interventions. Despite these challenges, new data have also informed the standard of care for ARDS and have resulted in the re-evaluation of previously established therapies, including ventilation strategies, pharmacologic interventions, and rescue therapies. As the field of ARDS continues to evolve, innovative approaches will be needed to further define phenotypes within ARDS and design targeted clinical trials.
Summary In this Series paper, we review the current evidence for the use of high-flow oxygen therapy, inhaled gases, and aerosols in the care of critically ill patients. The available evidence ...supports the use of high-flow nasal cannulae for selected patients with acute hypoxaemic respiratory failure. Heliox might prevent intubation or improve gas flow in mechanically ventilated patients with severe asthma. Additionally, it might improve the delivery of aerosolised bronchodilators in obstructive lung disease in general. Inhaled nitric oxide might improve outcomes in a subset of patients with postoperative pulmonary hypertension who had cardiac surgery; however, it has not been shown to provide long-term benefit in patients with acute respiratory distress syndrome (ARDS). Inhaled prostacyclins, similar to inhaled nitric oxide, are not recommended for routine use in patients with ARDS, but can be used to improve oxygenation in patients who are not adequately stabilised with traditional therapies. Aerosolised bronchodilators are useful in mechanically ventilated patients with asthma and chronic obstructive pulmonary disease, but are not recommended for those with ARDS. Use of aerosolised antibiotics for ventilator-associated pneumonia and ventilator-associated tracheobronchitis shows promise, but the delivered dose can be highly variable if proper attention is not paid to the delivery method.
Circadian rhythms are daily oscillations that, in mammals, are driven by both a master clock, located in the brain, and peripheral clocks in cells and tissues. Approximately 10% of the transcriptome, ...including extracellular matrix components, is estimated to be under circadian control. Whilst it has been established that certain collagens and extracellular matrix proteases are diurnally regulated (for example in tendon, cartilage and intervertebral disc) the role played by circadian rhythms in mediating elastic fiber homeostasis is poorly understood. Skin, arteries and lungs are dynamic, resilient, elastic fiber-rich organs and tissues. In skin, circadian rhythms influence cell migration and proliferation, wound healing and susceptibility of the tissues to damage (from protease activity, oxidative stress and ultraviolet radiation). In the cardiovascular system, blood pressure and heart rate also follow age-dependent circadian rhythms whilst the lungs exhibit diurnal variations in immune response. In order to better understand these processes it will be necessary to characterise diurnal changes in extracellular matrix biology. In particular, given the sensitivity of peripheral clocks to external factors, the timed delivery of interventions (chronotherapy) has the potential to significantly improve the efficacy of treatments designed to repair and regenerate damaged cutaneous, vascular and pulmonary tissues.
•In mammals, circadian rhythms are controlled by a master clock in the brain and by peripheral clocks in cells and tissues.•Approximately 10% of transcripts appear to be under tissue-specific circadian control.•The influence of circadian rhythms on elastin and elastic fiber-associated proteins is poorly understood.•Chronotherapy, the timed application of treatment, has the potential to improve the efficacy of existing interventions.
Hot subdwarfs represent a group of low-mass helium-burning stars formed through binary-star interactions and include some of the most chemically peculiar stars in the Galaxy. Stellar evolution theory ...suggests that they should have helium-rich atmospheres but, because radiation causes hydrogen to diffuse upwards, a majority are extremely helium poor. Questions posed include: when does the atmosphere become chemically stratified and at what rate?
The existence of several helium-rich subdwarfs suggests further questions: are there distinct subgroups of hot subdwarf, or do hot subdwarfs change their surface composition in the course of evolution? Recent analyses have revealed remarkable surface chemistries amongst the helium-rich subgroup. In this paper, we analyse high-resolution spectra of nine intermediate helium-rich hot subdwarfs. We report the discovery that two stars, HE 2359−2844 and HE 1256−2738, show an atmospheric abundance of lead which is nearly 10 000 times that seen in the Sun. This is measured from optical Pb iv absorption lines never previously seen in any star. The lead abundance is 10 to 100 times that measured in normal hot-subdwarf atmospheres from ultraviolet spectroscopy. HE 2359−2844 also shows zirconium and yttrium abundances similar to those in the zirconium star LS IV−14°116. The new discoveries are interpreted in terms of heavily stratified atmospheres and the general picture of a surface chemistry in transition from a new-born helium-rich subdwarf to a normal helium-poor subdwarf.
This paper explores the dialogical dimensions of discursive legitimation in social media sites to understand how organisations produce knowledge of legitimacy in concert with their stakeholders. ...Drawing on the dialogical theories of Bakhtin and Nikulin, we consider the potential for conceptualising discursive legitimation as a product of dissent: an ongoing ‘allosensual’ dialogue comprising different voices and competing knowledge claims. We explore this through a micro-level analysis of organisation-led social media sites, wherein organisational practices are increasingly subjected to public scrutiny and where knowledge of legitimacy can be significantly shaped. Our dialogical lens highlights three interrelated functions of discursive legitimation. Discursive authorisation represents attempts to assume a credible ‘voice’ in-relation-to ‘other’ voices, within the dialogue. Discursive validation represents attempts to subject truth claims about legitimacy to rational, normative and moral verification. Finally, discursive finalisation represents attempts to harmonise dissent, by either co-opting or antagonising stakeholders towards consensus. Primarily, this paper unpacks the role of social media in legitimation processes, while also elaborating on organisational attempts to control stakeholder dialogue in online contexts.
Aims. We present rates for all E1, E2, M1, and M2 transitions among the 295 fine-structure levels of the configurations 3d9, 3d84s, 3d74s2, 3d84p, and 3d74s4p, determined through an extensive ...configuration interaction calculation. Methods. The CIV3 code developed by Hibbert and coworkers is used to determine for these levels configuration interaction wave functions with relativistic effects introduced through the Breit-Pauli approximation. Results. Two different sets of calculations have been undertaken with different 3d and 4d functions to ascertain the effect of such variation. The main body of the text includes a representative selection of data, chosen so that key points can be discussed. Some analysis to assess the accuracy of the present data has been undertaken, including comparison with earlier calculations and the more limited range of experimental determinations. The full set of transition data is given in the supplementary material as it is very extensive. Conclusions. We believe that the present transition data are the best currently available.
Objectives
To describe the effect of low‐dose (111MBq) radioiodine therapy on thyroid and renal function in hyperthyroid cats over a 12‐month follow‐up period.
Materials and Methods
Client‐owned ...hyperthyroid cats underwent low‐dose radioiodine therapy and were followed‐up for 12 months. Immediately before radioiodine treatment, and at 1, 6 and 12 months afterwards, total thyroxine, thyroid stimulating hormone, serum creatinine and glomerular filtration rate were measured.
Results
Fifteen of the 24 (63%) cats achieved euthyroidism following low‐dose radioiodine treatment. The incidence of overt hypothyroidism was six of 24 (25%) cats. Of the six cats developing overt hypothyroidism, three had decreased renal function, with decreased glomerular filtration rate preceding azotaemia in two of these individuals. Transient overt or subclinical hypothyroidism before restoration of euthyroidism was not observed.
Clinical Significance
Low‐dose radioiodine is effective treatment for hyperthyroidism in most cats but overt hypothyroidism may develop in some. Concurrent early decline in renal function may only be detected by measuring glomerular filtration rate rather than serum creatinine in some cats. Monitoring following radioiodine treatment should include total thyroxine and thyroid stimulating hormone and measurement of glomerular filtration rate should be considered in non‐azotaemic cats.
ABSTRACT Helium-rich subdwarf B (He-sdB) stars represent a small group of low-mass hot stars with luminosities greater than those of conventional sdB stars, and effective temperatures lower than ...those of subdwarf O (sdO) stars. By measuring their surface chemistry, we aim to explore the connection between He-sdB stars, He-rich sdO stars and normal sdB stars. LSIV-14°116 is a relatively intermediate He-sdB star, also known to be a photometric variable. High-resolution blue-optical spectroscopy was obtained with the Anglo-Australian Telescope. Analysis of the spectrum shows LSIV-14°116 to have effective temperature Teff= 34000 ± 500K, surface gravity logg= 5.6 ± 0.2 and surface helium abundance nHe= 0.16 ± 0.03 by number. This places the star slightly above the standard extended horizontal branch, as represented by normal sdB stars. The magnesium and silicon abundances indicate the star to be metal poor relative to the Sun. A number of significant but unfamiliar absorption lines were identified as being due to germanium, strontium, yttrium and zirconium. After calculating oscillator strengths (for Ge, Y and Zr), the photospheric abundances of these elements were established to range from 3 dex (Ge) to 4 dex (Sr, Y and Zr) above solar. The most likely explanation is that these overabundances are caused by radiatively driven diffusion forming a chemical cloud layer in the photosphere. It is conjectured that this cloud formation could be mediated by a strong magnetic field. PUBLICATION ABSTRACT
Aims. We report electric quadrupole and magnetic dipole transitions among the levels belonging to 3d64s, 3d7 and 3d54s2 configurations of Fe II in a large scale configuration interaction (CI) ...calculation. Methods. The CIV3 code developed by Hibbert and coworkers is used to determine configuration interaction wave functions for these levels: for the optimisation of two different sets of orbitals based on alternative choices of the 3d function, for creating and diagonalising the Hamiltonian matrices and finally for calculating transition probabilities. Results. Where possible, we have used experimental energies, not only for transition energies but also to enhance the accuracy of our ab initio CI expansions. We compare our results with those of other authors, and discuss differences between them. The good agreement between our results obtained for the same transitions but with different d-functions indicates that we have treated the state dependence of the d-functions sufficiently well. Most of our results are available in electronic form as an appendix to the paper. Conclusions. Our analysis of our own results and those of others suggests that many of our transition rates are more accurate than the rather conservative 20−30% we have stated in the text, though in a small proportion of transitions, we could not justify an accuracy greater than this.
Background
Sepsis is the leading cause of death in US hospitals. Compliance with bundled care, specifically serial lactates, blood cultures, and antibiotics, improves outcomes but is often delayed or ...missed altogether in a busy practice environment.
Objective
This study aims to design, implement, and validate a novel monitoring and alerting platform that provides real-time feedback to frontline emergency department (ED) providers regarding adherence to bundled care.
Methods
This single-center, prospective, observational study was conducted in three phases: the design and technical development phase to build an initial version of the platform; the pilot phase to test and refine the platform in the clinical setting; and the postpilot rollout phase to fully implement the study intervention.
Results
During the design and technical development, study team members and stakeholders identified the criteria for patient inclusion, selected bundle measures from the Center for Medicare and Medicaid Sepsis Core Measure for alerting, and defined alert thresholds, message content, delivery mechanisms, and recipients. Additional refinements were made based on 70 provider survey results during the pilot phase, including removing alerts for vasopressor initiation and modifying text in the pages to facilitate patient identification. During the 48 days of the postpilot rollout phase, 15,770 ED encounters were tracked and 711 patient encounters were included in the active monitoring cohort. In total, 634 pages were sent at a rate of 0.98 per attending physician shift. Overall, 38.3% (272/711) patients had at least one page. The missing bundle elements that triggered alerts included: antibiotics 41.6% (136/327), repeat lactate 32.4% (106/327), blood cultures 20.8% (68/327), and initial lactate 5.2% (17/327). Of the missing Sepsis Core Measures elements for which a page was sent, 38.2% (125/327) were successfully completed on time.
Conclusions
A real-time sepsis care monitoring and alerting platform was created for the ED environment. The high proportion of patients with at least one alert suggested the significant potential for such a platform to improve care, whereas the overall number of alerts per clinician suggested a low risk of alarm fatigue. The study intervention warrants a more rigorous evaluation to ensure that the added alerts lead to better outcomes for patients with sepsis.
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