Taxonomic studies of micrococci and staphylococci

In the course of 3 years, 274 strains of micrococci and staphylococci were isolated from a variety of habitats, and 132 strains were obtained as pure cultures, mainly from culture collections; this gave a total of 406 strains for taxonomic studies. All 406 strains were examined for a total of 49 morphological and physiological characters, and the strains were compared for characters in common. It would found that strains with practically all combinations of characters existed, from the coagulase positive, biochemically active staphylococci, through many intermediate groupings to the biochemically weak yellow and red micrococci; a classification scheme based on a few arbitrarily ohosen main characters, as is the tradition in this group of bacteria, would be entirely artificial. After discussing some of these main characters, and finding practically all of them unsuitable as important criteria for classifying the 406 strains of micrococci and staphylococci, I decided to adopt the Adansonian approach to classification, and treated 49 morphological and physiological character as being equal. As I expected, the results of this Adansonian classification demonstrated that there was no clear division of the 406 strains into 2 main groups, equivalent to the genera Microcccus and Staphylococous, but there was a division into very many small groupings, the majority of which contained only one strain. The most important conclusion drawn from this scheme was that all micrococcus and staphylococci should be placed into one genus - Micrococcus, and it seemed unlikely that further division of this genus into natural groupings by morphological and physiological characters was possible. Consequently, other characters, in particular those demonstrated by electrophoretic methods, were examined for their suitability in classification. I studied the isozyme bands, detected by specific colour reactions in acrylamide gol slices, which contained electrophoresed cell contents of the 406 micrococcal and staphylococcal bacterial strains, and I found that only 3 types of isozymes - esterase isozymes, used in classifications of other bacteria, and 2 previously unreported isozyme systems, blood band isozymes and starch hydrolysing isozymes - were of use in classifying' my strains. These strains showed great variety in the number and mobility of the isozyme bands; the strains produced between 0 and 6 of 87 esterase bands between 0 and 7 of 40 blood bands, and between 0 and 3 of 12 starch hydrolysing isozyme bands. With the 139 electrophoretic characters of these 3 isozyme systems, the 406 strains were classified by Adansonian means, and it was found that all but 2 of the strains fell into a large group, the genus Micrococcus and within this genus it was possible to detect natural groupings - 28 Micrococcus Groups. In addition, there were 2 other Electrophoretic Groups (25 and 30), which possessed electrophoretic characters, completely unrelated to the other Electrophoretic Groups, and these were excluded from the genus Micrococcus. The electrophoretic grouping does not compare well with my own Scheme 1, and published morphological and physiological classifications, but it does fit in closely with DAN base ratio analysis groupings. The classification scheme of micrococci and staphylococci, based on eleotrophoretic characters, seems to have certain advantages over schemes based on morphological and physiological characters, since electrophoretic analysis clearly shows the existence of natural groupings within one large group. Taxonomists have not been previously aware of the existence of Groups like Micrococcus Group 3, which, apart from a unique electrophoretic pattern of characters, contains strains which oxidise and ferment mannitol, and yet are coagulase negative. An important contribution to the taxonomy of micrococci and staphylococci has been made by the creation of the electrophoretic classification scheme since 1) coagulaso positive staphylococci have been shown to be closely related to certain coagulase negative strains (strains of Micrococcus Group 1). In addition, strains of Micrococci and staphylococci, other than those producing coagulase, have been shown to cause disease. The character of coagulase production, therefore, can no longer be regarded as the sole criterion for classifying, a unique group of pathogenic staphylococci, although it is a useful identification character. 2) the yellow and red pigmented biochemically weak micrococci - Electrophoretic Micrococcus Groups 24 and 27 respectively - have been classified on positive characters i.e. on electrophoretic characters which the strains possess, instead of the almost complete lack of physiological characters, except pigmentation, which have been previously used to classify these organisms. An identification scheme, based on the electrophoretic classification scheme, is proposed which would identify any unknown micrococcus or staphylococcus

A Robust Compositional Architecture for Autonomous Systems

Space exploration applications can benefit greatly from autonomous systems. Great distances, limited communications and high costs make direct operations impossible while mandating operations reliability and efficiency beyond what traditional commanding can provide. Autonomous systems can improve reliability and enhance spacecraft capability significantly. However, there is reluctance to utilizing autonomous systems. In part this is due to general hesitation about new technologies, but a more tangible concern is that of reliability of predictability of autonomous software. In this paper, we describe ongoing work aimed at increasing robustness and predictability of autonomous software, with the ultimate goal of building trust in such systems. The work combines state-of-the-art technologies and capabilities in autonomous systems with advanced validation and synthesis techniques. The focus of this paper is on the autonomous system architecture that has been defined, and on how it enables the application of validation techniques for resulting autonomous systems

TTCF4LAMMPS: A toolkit for simulation of the non-equilibrium behaviour of molecular fluids at experimentally accessible shear rates

Program summary: Program title: TTCF4LAMMPS CPC Library link to program files: https://doi.org/10.17632/hh2rkcxbrf.1 Developer's repository link: https://github.com/edwardsmith999/TTCF4LAMMPS Licensing provisions: GNU General Public License 3 Programming language: Python 3 Nature of problem: Measuring the nonequilibrium behaviour of bulk and confined fluids under experimentally accessible strain rates in non-equilibrium molecular dynamics (NEMD) simulations. Solution method: Creating a Python-based code that utilises the transient-time correlation function method and the LAMMPS software to enable the bulk fluid properties (e.g. viscosity) and confined fluid interfacial properties (e.g. shear stress and slip velocity) to be computed at low shear rates with NEMD.Data availability: All data used in this work are freely reproducible using the program provided. The source files are also available at the link https://github.com/edwardsmith999/TTCF4LAMMPS.We present TTCF4LAMMPS, a toolkit for performing non-equilibrium molecular dynamics (NEMD) simulations to study the fluid behaviour at low shear rates using the LAMMPS software. By combining direct NEMD simulations and the transient-time correlation function (TTCF) technique, we study the fluid response to shear rates spanning 15 orders of magnitude. We present two examples for simple monatomic systems: one consisting of a bulk liquid and another with a liquid layer confined between two solid walls. The small bulk system is suitable for testing on personal computers, while the larger confined system requires high-performance computing (HPC) resources. We demonstrate that the TTCF formalism can successfully detect the system response for arbitrarily weak external fields. We provide a brief mathematical explanation for this feature. Although we showcase the method for simple monatomic systems, TTCF can be readily extended to study more complex molecular fluids. Moreover, in addition to shear flows, the method can be extended to investigate elongational or mixed flows as well as thermal or electric fields. The high computational cost needed for the method is offset by the two following benefits: i) the cost is independent of the magnitude of the external field, and ii) the simulations can be made highly efficient on HPC architectures by exploiting the parallel design of the algorithm. We expect the toolkit to be useful for computational researchers striving to study the nonequilibrium behaviour of fluids under experimentally-accessible conditions.We thank the Australian Research Council for a grant obtained through the Discovery Projects Scheme (Grant No. DP200100422) and The Royal Society for support via International Exchanges, Grant No. IES/R3/170/233. J.P.E. was supported by the Royal Academy of Engineering (RAEng) through their Research Fellowships scheme. D.D. was supported through a Shell/RAEng Research Chair in Complex Engineering Interfaces. The authors acknowledge the Swinburne OzSTAR Supercomputing facility and the Imperial College London Research Computing Service (DOI:https://doi.org/10.14469/hpc/2232) for providing computational resources for this work. We thank Debra Bernhardt and Stephen Sanderson (University of Queensland) for useful discussions regarding the implementation of SLLOD in LAMMPS

Clinical characteristics, risk factors and outcomes in patients with severe COVID-19 registered in the International Severe Acute Respiratory and Emerging Infection Consortium WHO clinical characterisation protocol: a prospective, multinational, multicentre, observational study

Due to the large number of patients with severe coronavirus disease 2019 (COVID-19), many were treated outside the traditional walls of the intensive care unit (ICU), and in many cases, by personnel who were not trained in critical care. The clinical characteristics and the relative impact of caring for severe COVID-19 patients outside the ICU is unknown. This was a multinational, multicentre, prospective cohort study embedded in the International Severe Acute Respiratory and Emerging Infection Consortium World Health Organization COVID-19 platform. Severe COVID-19 patients were identified as those admitted to an ICU and/or those treated with one of the following treatments: invasive or noninvasive mechanical ventilation, high-flow nasal cannula, inotropes or vasopressors. A logistic generalised additive model was used to compare clinical outcomes among patients admitted or not to the ICU. A total of 40 440 patients from 43 countries and six continents were included in this analysis. Severe COVID-19 patients were frequently male (62.9%), older adults (median (interquartile range (IQR), 67 (55-78) years), and with at least one comorbidity (63.2%). The overall median (IQR) length of hospital stay was 10 (5-19) days and was longer in patients admitted to an ICU than in those who were cared for outside the ICU (12 (6-23) days versus 8 (4-15) days, p<0.0001). The 28-day fatality ratio was lower in ICU-admitted patients (30.7% (5797 out of 18 831) versus 39.0% (7532 out of 19 295), p<0.0001). Patients admitted to an ICU had a significantly lower probability of death than those who were not (adjusted OR 0.70, 95% CI 0.65-0.75; p<0.0001). Patients with severe COVID-19 admitted to an ICU had significantly lower 28-day fatality ratio than those cared for outside an ICU

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Increasing frailty is associated with higher prevalence and reduced recognition of delirium in older hospitalised inpatients: results of a multi-centre study

Purpose: Delirium is a neuropsychiatric disorder delineated by an acute change in cognition, attention, and consciousness. It is common, particularly in older adults, but poorly recognised. Frailty is the accumulation of deficits conferring an increased risk of adverse outcomes. We set out to determine how severity of frailty, as measured using the CFS, affected delirium rates, and recognition in hospitalised older people in the United Kingdom. Methods: Adults over 65 years were included in an observational multi-centre audit across UK hospitals, two prospective rounds, and one retrospective note review. Clinical Frailty Scale (CFS), delirium status, and 30-day outcomes were recorded. Results: The overall prevalence of delirium was 16.3% (483). Patients with delirium were more frail than patients without delirium (median CFS 6 vs 4). The risk of delirium was greater with increasing frailty [OR 2.9 (1.8–4.6) in CFS 4 vs 1–3; OR 12.4 (6.2–24.5) in CFS 8 vs 1–3]. Higher CFS was associated with reduced recognition of delirium (OR of 0.7 (0.3–1.9) in CFS 4 compared to 0.2 (0.1–0.7) in CFS 8). These risks were both independent of age and dementia. Conclusion: We have demonstrated an incremental increase in risk of delirium with increasing frailty. This has important clinical implications, suggesting that frailty may provide a more nuanced measure of vulnerability to delirium and poor outcomes. However, the most frail patients are least likely to have their delirium diagnosed and there is a significant lack of research into the underlying pathophysiology of both of these common geriatric syndromes

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Food-Borne Disease Prevention and Risk Assessment

&ldquo;Food-borne Disease Prevention and Risk Assessment&rdquo; is a Special Issue of the International Journal of Environmental Research and Public Health on understanding how food-borne disease is still a global threat to health today and to be able to target strategies to reduce its prevalence [...

EMERGING ISSUES/ GLOBAL MARKETS (PowerPoint Presentation)

POWERPOINT PRESENTATIO