Whole-genome sequencing of Klebsiella pneumoniae isolates to track strain progression in a single patient with recurrent urinary tract infection

Klebsiella pneumoniae is an important uropathogen that increasingly harbors broad-spectrum antibiotic resistance determinants. Evidence suggests that some same-strain recurrences in women with frequent urinary tract infections (UTIs) may emanate from a persistent intravesicular reservoir. Our objective was to analyze K. pneumoniae isolates collected over weeks from multiple body sites of a single patient with recurrent UTI in order to track ordered strain progression across body sites, as has been employed across patients in outbreak settings. Whole-genome sequencing of 26 K. pneumoniae isolates was performed utilizing the Illumina platform. PacBio sequencing was used to create a refined reference genome of the original urinary isolate (TOP52). Sequence variation was evaluated by comparing the 26 isolate sequences to the reference genome sequence. Whole-genome sequencing of the K. pneumoniae isolates from six different body sites of this patient with recurrent UTI demonstrated 100% chromosomal sequence identity of the isolates, with only a small P2 plasmid deletion in a minority of isolates. No single nucleotide variants were detected. The complete absence of single-nucleotide variants from 26 K. pneumoniae isolates from multiple body sites collected over weeks from a patient with recurrent UTI suggests that, unlike in an outbreak situation with strains collected from numerous patients, other methods are necessary to discern strain progression within a single host over a relatively short time frame.</p

The 27-28 October 1986 FIRE cirrus case study: Meteorology and clouds

Detailed descriptions of the rawinsonde resolved meteorological conditions (3 hourly soundings) associated with a succession of five distinct mesoscale cirrus cloud regimes, that were intensively observed over a 36 hour period, are given. The synoptic scale systems in which these features were embedded are described and a brief overview of the experiment is given. Regional analyses of the static stability structure and vertical motion are presented and interpreted with respect to the characteristics of the corresponding cloud fields as deduced from satellite and lidar observations. The cloud fields exhibited a high degree of persistent mesoscale organization on scales of 20 to 500 km reflecting corresponding scales of dynamic and thermodynamic structure/variability as on the synoptic scale. Cloud generation was usually confined to layers less than 1 km deep (typically 0.5 km in depth) and cellular organization was evident in most cases irrespective of the thermal stratification. Multilayered development was prevalent (2 to 3 layers) and was associated with vertical structure of the temperature and moisture fields resulting primarily from vertical gradients in horizontal advection

Synoptic conditions producing cirrus during the FIRE cirrus IFO

Although direct observations of cirrus clouds by the FIRE research aircraft were usually confined to the area of Intensive Field Observation (IFO) surface network, these cirrus were generally part of a more extensive zone of upper level cloudiness. It is these large scale patterns of cirriform cloud and their relationship to the corresponding synoptic environment which are the prime focus. Three conceptual models are presented and each of the individual cases are classified into one of these categories. Although the cases manifest significant differences in intensity and small scale structure, it is believed that they are best viewed in this unified context. The descriptions given are mostly qualitative, however, quantitative descriptions of the synoptic control and its relationship to cloud structure for all the IFO cases are summarized. The synoptic situations in which extensive cirriform clouds were observed are classified into three basic types: warm front cases, cold front cases, and closed low aloft cases. A simplified summary of each type of situation is presented

Fluctuation Induced Instabilities in Front Propagation up a Co-Moving Reaction Gradient in Two Dimensions

We study 2D fronts propagating up a co-moving reaction rate gradient in finite number reaction-diffusion systems. We show that in a 2D rectangular channel, planar solutions to the deterministic mean-field equation are stable with respect to deviations from planarity. We argue that planar fronts in the corresponding stochastic system, on the other hand, are unstable if the channel width exceeds a critical value. Furthermore, the velocity of the stochastic fronts is shown to depend on the channel width in a simple and interesting way, in contrast to fronts in the deterministic MFE. Thus, fluctuations alter the behavior of these fronts in an essential way. These affects are shown to be partially captured by introducing a density cutoff in the reaction rate. Some of the predictions of the cutoff mean-field approach are shown to be in quantitative accord with the stochastic results

The fixation probability of rare mutators in finite asexual populations

A mutator is an allele that increases the mutation rate throughout the genome by disrupting some aspect of DNA replication or repair. Mutators that increase the mutation rate by the order of 100 fold have been observed to spontaneously emerge and achieve high frequencies in natural populations and in long-term laboratory evolution experiments with \textit{E. coli}. In principle, the fixation of mutator alleles is limited by (i) competition with mutations in wild-type backgrounds, (ii) additional deleterious mutational load, and (iii) random genetic drift. Using a multiple locus model and employing both simulation and analytic methods, we investigate the effects of these three factors on the fixation probability $P_{fix}$ of an initially rare mutator as a function of population size $N$, beneficial and deleterious mutation rates, and the strength of mutations $s$. Our diffusion based approximation for $P_{fix}$ successfully captures effects (ii) and (iii) when selection is fast compared to mutation ($\mu/s \ll 1$). This enables us to predict the conditions under which mutators will be evolutionarily favored. Surprisingly, our simulations show that effect (i) is typically small for strong-effect mutators. Our results agree semi-quantitatively with existing laboratory evolution experiments and suggest future experimental directions.Comment: 46 pages, 8 figure

Clifford Algebra Decompositions of Conformal Orthogonal Group Elements

Beginning with a finite-dimensional vector space V equipped with a nondegenerate quadratic form Q, we consider the decompositions of elements of the conformal orthogonal group COQ(V), defined as the direct product of the orthogonal group OQ(V) with dilations. Utilizing the correspondence between conformal orthogonal group elements and ``decomposable\u27\u27 elements of the associated Clifford algebra, ClQ(V), a decomposition algorithm is developed. Preliminary results on complexity reductions that can be realized passing from additive to multiplicative representations of invertible elements are also presented with examples. The approach here is based on group actions in the conformal orthogonal group. Algorithms are implemented in Mathematica using the CliffMath package

The Ties that Bind: Citizenship and Civic Engagement in the 21st Century

The creation of a country in which every one of its citizens feels secure, engaged and fulfilled must be a primary objective of a successful modern democratic nation. This would be a country in which everyone feels that they belong, and to which everyone feels they can contribute. Individuals do not learn about governmental and judicial institutions of the United Kingdom through osmosis. The values which underpin our society, which have been tested in recent years by a variety of economic and societal developments, are not self-evident. They need to be learned and understood. Another important step is to understand that the demand for individual rights cannot be divorced from the need for individual responsibility. Finally, whether older or younger, disabled or non-disabled, long established or recently arrived,marginalised or secure, every one of us who together make up the tangled skein of British society has a story to tell and a contribution to make. To try and untangle this complex and sensitive web we have looked at the issue of citizenship and civic engagement through the prism of the civic journey each one of us who lives in Britain will undertake. We have found much that is encouraging, showing British society engaged harmoniously together despite the waves of change that are inexorably rolling over us. But inevitably there are areas where we are less successful. We have tried to identify the barriers which are preventing people from feeling part of our society or contributing to it, together with the steps which must be taken to remove those barriers. So we argue for focusing resources, for reinforcing success rather than reinventing the wheel, and for adopting and seeing through long term strategies. This then is our story. Our first conclusion is that, while a variety of faiths, beliefs and customs can enrich our society, and respect for the values of others is a high priority, respect for the law must come first. There is no place for rules or customs whose effect is to demean or marginalise people or groups—equality before the law is a cornerstone of our society. This is why the rule of law, together with a commitment to democracy, individual liberty and respect for the inherent worth and autonomy of all people, are the shared values of British citizenship from which everything else proceeds. These are “red lines” which have to be defended. As cornerstones these values need to be promoted in their own right rather than simply as an adjunct of counter-extremism policy. We argue that the process we have called the “civic journey” should be a smooth transition in which central and local government provide individuals with a framework for benefiting from and contributing to society, and assist them in overcoming the barriers to engagement. Instead we have found that citizenship education, which should be the first great opportunity for instilling and developing our values, encouraging social cohesion, and creating active citizens has been neglected. Often it is subsumed into individual development which, whilst undoubtedly important, is not the same as learning about the political and social structure of the country, how it is governed, how laws are made and how they are enforced by an independent judiciary. Nor does it offer an opportunity of practising civic engagement in schools, local communities and beyond. The decline in citizenship education has a number of causes: the revision of the national curriculum in 2013, the fact that academies are in any case not required to follow it, the low esteem in which the subject appears to be held, the decrease in the numbers of trained teachers and the corresponding fall in the numbers taking Citizenship GCSE. The Government must re-prioritise the subject, creating a statutory entitlement to citizenship education from primary to the end of secondary education, and set a target which will allow every secondary school to have at least one trained teacher. Chronologically, the next stage of the journey must be to allow children in their late teens further to develop the skills needed to be active and responsible citizens, to mix with people from different backgrounds and to get more involved in their communities. It was with this in mind that the Government announced the National Citizen Service (NCS) in 2010. Its ambition is laudable and its achievements considerable, but it sometimes fails to reach excluded communities in deprived areas. It would be more effective if it reached out to alumni so that it could continue to support them over time; this is the strength of the many longestablished youth organisations. We make recommendations for how this might be achieved, how the NCS should promote active citizenship and how the NCS might do more to work in partnership with schools and colleges. Volunteering is a strength of the UK, but would be helped by more facilities being made available for civic activity. The unemployed should be encouraged to volunteer by having their social security status clarified. More must be done to recognise and reward outstanding contributions made by volunteering. The other distinct limb of civic engagement is democratic involvement and participation. While there has been a dramatic increase in the level of volunteering among the young, democratic engagement remains stagnant. The turnout in general elections, though improving, is still much too low, especially among the socially disadvantaged and the young. We make recommendations for improving the voter registration process, in particular by adopting the scheme which allows voter registration to take place at the same time as registration at universities, further education colleges and, ultimately, perhaps schools. Communication between citizens and government at all levels is often poor, and was a subject frequently raised not just in formal evidence but by those we spoke to on our visits. When seeking people’s views, communication tends to be with the ‘gatekeepers’—those who hold themselves out, not always accurately, as representing their communities. People, especially in deprived areas, must be made to feel that government is speaking directly to them, working with them and for them, and paying attention to their needs and wishes. Contact between the Government and women’s groups is especially important. Communities must also be prepared to open up and bring more voices into the conversation. Forming a single society from different generations, sexes, social and ethnic groups, and those of different faiths requires integration—a word which itself can carry threatening overtones of a requirement to surrender aspects of their way of life. The first requirement must be the ability to speak, read and write in fluent English: an alarming proportion of residents cannot speak English at all, and so cannot communicate outside their communities. This problem is not limited to new arrivals; too many people whose first and only language is English are still functionally illiterate. For them the civic journey barely starts. This huge barrier affects not just them but society as a whole. Extra funds devoted to teaching English would rapidly bring rewards, but we also suggest ways in which the access to such teaching might be made easier. For those already living here who wish to become British citizens by naturalisation,the barriers are particularly steep. They include a “good character” requirement which is undefined, a knowledge test based on materials which are absurd, and a cost which is steeper than it should or need be. We suggest improvements to the whole process. Near the end of our inquiry the Government launched its long-awaited response to the review carried out by Dame Louise Casey. As its title Integrated Communities Strategy Green Paper suggests, this only is a further consultation exercise. Our inquiry into citizenship and civic engagement goes much wider than this; conversely the Green Paper covers areas outside our remit. Nevertheless there is significant overlap. We explain this in our introductory chapter, and in the course of the report we give our views on the relevant parts of the Green Paper. We hope that the evidence we have received, our analysis of that evidence, the conclusions we have drawn and the recommendations we make, some of which are quite hard-edged, will be of value in this consultation exercise. This report should therefore be treated as the response of this Committee to the questions in the Green Paper. But consultation cannot be a substitute for action, either on integration alone or on citizenship as a whole. Moreover for such action to be effective, particularly where it has cross-departmental elements, will require consistent long-term application with defined lines of authority and responsibility. Our evidence suggested that historically there has been no clear co-ordination across Government, no real evaluation to find what works, and no long-term commitment to initiatives—many of which appear not to outlive the minister who initiated them. It is not immediately apparent from the Green Paper that these lessons have been learned in respect of this new Strategy. Austerity is not an excuse for doing nothing. As Dame Louise Casey told us: “You can always do things, and not everything costs money.” We believe that our recommendations, once implemented, will mark a significant step towards a more coherent, confident and inclusive society whose members are encouraged and enabled to participate as active citizens

Response to House of Lords Select Committee for Citizenship and Engagement Call for Evidence (CCE0157)

The following research was carried out by the Applied Policy Sciences Unit at the University of Central Lancashire in collaboration with the Samuel Lindow Foundation, an independent educational charity based in West Cumbria, which has operated since 1992 to advance the education of the public. It is offered as evidence for the proposed implementation in this region of a Connected Communities programme, an evidence-based framework for activity to address the identified research findings

House of Lords Select Committee on Citizenship and Civic Engagement Report

The following research was carried out by the Applied Policy Sciences Unit at the University of Central Lancashire in collaboration with the Samuel Lindow Foundation, an independent educational charity based in West Cumbria, which has operated since 1992 to advance the education of the public. It is offered as evidence for the proposed implementation in this region of a Connected Communities programme, an evidence-based framework for activity to address the identified research findings. The report below responds to the question: Why do so many communities and groups feel “left behind”? Are there any specific factors which act as barriers to active citizenship faced by different communities or groups - white, BME, young,old, rural, urban? How might these barriers be overcome

Analysis and clinical findings of cases positive for the novel synthetic cannabinoid receptor agonist MDMB-CHMICA

Context: MDMB-CHMICA is a synthetic cannabinoid receptor agonist which has caused concern due to its presence in cases of adverse reaction and death. Method: 43 cases of suspected synthetic cannabinoid ingestion were identified from patients presenting at an Emergency Department and from post-mortem casework. These were subjected to liquid-liquid extraction using tertiary-butyl methyl ether and quantitatively analysed by Electospray Ionisation Liquid Chromatography – tandem Mass Spectrometry. For positive samples, case and clinical details were sought and interrogated. Results: 11 samples were found positive for MDMB-CHMICA. Concentrations found ranged from &lt;1 – 22 ng/mL (mean: 6 ng/mL, median: 3 ng/mL). The age range was 15 – 44 years (mean: 26 years, median: 21 years), with the majority (82%) of positive results found in males. Clinical presentations included hypothermia, hypoglycaemia, syncope, recurrent vomiting, altered mental state and serotonin toxicity, with corresponding concentrations of MDMB-CHMICA as low as &lt;1 ng/mL. Duration of hospitalisation ranged from 3 – 24 hours (mean: 12 hours, median: 8 hours). Discussion: The concentration range presented in this case series is indicative of MDMB-CHMICA having a high potency, as is known to be the case for other synthetic cannabinoid receptor agonists. The age range and gender representation were consistent with that reported for users of other drugs of this type. The clinical presentations observed were typical of synthetic cannabinoid receptor agonists and show the difficulties in identifying reactions potentially associated with drugs of this type. Conclusion: The range of MDMB-CHMICA concentrations in Emergency Department presentations (n=9) and post-mortem cases (n=2) was reported. No correlation between the concentration of this drug and clinical presentation or cause of death was reported in this sample. However, the potential for harm associated with low concentrations of MDMB-CHMICA and the symptoms of toxicity being non-specific was highlighted