First hospital outbreak of the globally emerging Candida auris in a European hospital

Background: Candida auris is a globally emerging multidrug resistant fungal pathogen causing nosocomial transmission. We report an ongoing outbreak of C. auris in a London cardio-thoracic center between April 2015 and July 2016. This is the first report of C. auris in Europe and the largest outbreak so far. We describe the identification, investigation and implementation of control measures. Methods: Data on C. auris case demographics, environmental screening, implementation of infection prevention/control measures, and antifungal susceptibility of patient isolates were prospectively recorded then analysed retrospectively. Speciation of C. auris was performed by MALDI-TOF and typing of outbreak isolates performed by amplified fragment length polymorphism (AFLP). Results: This report describes an ongoing outbreak of 50 C. auris cases over the first 16 month (April 2015 to July 2016) within a single Hospital Trust in London. A total of 44 % (n = 22/50) patients developed possible or proven C. auris infection with a candidaemia rate of 18 % (n = 9/50). Environmental sampling showed persistent presence of the yeast around bed space areas. Implementation of strict infection and prevention control measures included: isolation of cases and their contacts, wearing of personal protective clothing by health care workers, screening of patients on affected wards, skin decontamination with chlorhexidine, environmental cleaning with chorine based reagents and hydrogen peroxide vapour. Genotyping with AFLP demonstrated that C. auris isolates from the same geographic region clustered. Conclusion: This ongoing outbreak with genotypically closely related C. auris highlights the importance of appropriate species identification and rapid detection of cases in order to contain hospital acquired transmission

Optimisation of a high-efficiency solar-driven organic Rankine cycle for applications in the built environment

Recent years have seen a strong increase in the uptake of solar technologies in the built environment. In combined heat and power (CHP) or cogeneration systems, the thermodynamic and economic ‘value’ of the electrical output is usually considered to be greater than that of (an equivalent) thermal output, and therefore the prioritisation of the electrical output in terms of system-level optimisation has been driving much of the research, innovation and technology development in this area. In this work, the potential of a solar CHP technology based on an organic Rankine cycle (ORC) engine is investigated. We present thermodynamic models developed for different collectors, including flat-plate collectors (FPC) and evacuated-tube collectors (ETC) coupled with a non-recuperative sub-critical ORC architecture to deliver power and hot water by using thermal energy rejected from the engine. Results from dynamic 3-D simulations of the solar collectors together with a thermal energy storage (TES) tank are presented. TES offers an important buffering capability during periods of intermittent solar radiation, as well as the potential for demand-side management (DSM). Results are presented of an optimisation analysis to identify the most suitable working fluids for the ORC unit, in which the configuration and operational constraints of the collector array are taken into account. The most suitable working fluids (R245fa and R1233zd) are then chosen for a whole-system optimisation performed in a southern European climate. The system configuration with an ETC array is found to be best-suited for electricity prioritisation, delivering an electrical output of 3,605 kWh/yr from a 60 m2 array. In addition, the system supplies 13,175 kWh/yr in the form of domestic hot water, which is equivalent to more than 6 times the average annual household demand. A brief cost analysis and comparison with photovoltaic (PV) systems are also performed

Analytical method for perturbed frozen orbit around an Asteroid in highly inhomogeneous gravitational fields : A first approach

This article provides a method for nding initial conditions for perturbed frozen orbits around inhomogeneous fast rotating asteroids. These orbits can be used as reference trajectories in missions that require close inspection of any rigid body. The generalized perturbative procedure followed exploits the analytical methods of relegation of the argument of node and Delaunay normalisation to arbitrary order. These analytical methods are extremely powerful but highly computational. The gravitational potential of the heterogeneous body is rstly stated, in polar-nodal coordinates, which takes into account the coecients of the spherical harmonics up to an arbitrary order. Through the relegation of the argument of node and the Delaunay normalization, a series of canonical transformations of coordinates is found, which reduces the Hamiltonian describing the system to a integrable, two degrees of freedom Hamiltonian plus a truncated reminder of higher order. Setting eccentricity, argument of pericenter and inclination of the orbit of the truncated system to be constant, initial conditions are found, which evolve into frozen orbits for the truncated system. Using the same initial conditions yields perturbed frozen orbits for the full system, whose perturbation decreases with the consideration of arbitrary homologic equations in the relegation and normalization procedures. Such procedure can be automated for the first homologic equation up to the consideration of any arbitrary number of spherical harmonics coefficients. The project has been developed in collaboration with the European Space Agency (ESA)

Genomic Context of Azole Resistance Mutations in Aspergillus fumigatus Determined Using Whole-Genome Sequencing.

A rapid and global emergence of azole resistance has been observed in the pathogenic fungus Aspergillus fumigatus over the past decade. The dominant resistance mechanism appears to be of environmental origin and involves mutations in the cyp51A gene, which encodes a protein targeted by triazole antifungal drugs. Whole-genome sequencing (WGS) was performed for high-resolution single-nucleotide polymorphism (SNP) analysis of 24 A. fumigatus isolates, including azole-resistant and susceptible clinical and environmental strains obtained from India, the Netherlands, and the United Kingdom, in order to assess the utility of WGS for characterizing the alleles causing resistance. WGS analysis confirmed that TR34/L98H (a mutation comprising a tandem repeat [TR] of 34 bases in the promoter of the cyp51A gene and a leucine-to-histidine change at codon 98) is the sole mechanism of azole resistance among the isolates tested in this panel of isolates. We used population genomic analysis and showed that A. fumigatus was panmictic, with as much genetic diversity found within a country as is found between continents. A striking exception to this was shown in India, where isolates are highly related despite being isolated from both clinical and environmental sources across >1,000 km; this broad occurrence suggests a recent selective sweep of a highly fit genotype that is associated with the TR34/L98H allele. We found that these sequenced isolates are all recombining, showing that azole-resistant alleles are segregating into diverse genetic backgrounds. Our analysis delineates the fundamental population genetic parameters that are needed to enable the use of genome-wide association studies to identify the contribution of SNP diversity to the generation and spread of azole resistance in this medically important fungus. IMPORTANCE: Resistance to azoles in the ubiquitous ascomycete fungus A. fumigatus was first reported from clinical isolates collected in the United States during the late 1980s. Over the last decade, an increasing number of A. fumigatus isolates from the clinic and from nature have been found to show resistance to azoles, suggesting that resistance is emerging through selection by the widespread usage of agricultural azole antifungal compounds. Aspergillosis is an emerging clinical problem, with high rates of treatment failures necessitating the development of new techniques for surveillance and for determining the genome-wide basis of azole resistance in A. fumigatus

Seeing Tree Structure from Vibration

Humans recognize object structure from both their appearance and motion; often, motion helps to resolve ambiguities in object structure that arise when we observe object appearance only. There are particular scenarios, however, where neither appearance nor spatial-temporal motion signals are informative: occluding twigs may look connected and have almost identical movements, though they belong to different, possibly disconnected branches. We propose to tackle this problem through spectrum analysis of motion signals, because vibrations of disconnected branches, though visually similar, often have distinctive natural frequencies. We propose a novel formulation of tree structure based on a physics-based link model, and validate its effectiveness by theoretical analysis, numerical simulation, and empirical experiments. With this formulation, we use nonparametric Bayesian inference to reconstruct tree structure from both spectral vibration signals and appearance cues. Our model performs well in recognizing hierarchical tree structure from real-world videos of trees and vessels.Comment: ECCV 2018. The first two authors contributed equally to this work. Project page: http://tree.csail.mit.edu

The homotopy type of the loops on (n−1)(n-1)-connected (2n+1)(2n+1)-manifolds

For $n\geq 2$ we compute the homotopy groups of $(n-1)$-connected closed manifolds of dimension $(2n+1)$. Away from the finite set of primes dividing the order of the torsion subgroup in homology, the $p$-local homotopy groups of $M$ are determined by the rank of the free Abelian part of the homology. Moreover, we show that these $p$-local homotopy groups can be expressed as a direct sum of $p$-local homotopy groups of spheres. The integral homotopy type of the loop space is also computed and shown to depend only on the rank of the free Abelian part and the torsion subgroup.Comment: Trends in Algebraic Topology and Related Topics, Trends Math., Birkhauser/Springer, 2018. arXiv admin note: text overlap with arXiv:1510.0519

Better assessment of physical function: item improvement is neglected but essential

INTRODUCTION: Physical function is a key component of patient-reported outcome (PRO) assessment in rheumatology. Modern psychometric methods, such as Item Response Theory (IRT) and Computerized Adaptive Testing, can materially improve measurement precision at the item level. We present the qualitative and quantitative item-evaluation process for developing the Patient Reported Outcomes Measurement Information System (PROMIS) Physical Function item bank. METHODS: The process was stepwise: we searched extensively to identify extant Physical Function items and then classified and selectively reduced the item pool. We evaluated retained items for content, clarity, relevance and comprehension, reading level, and translation ease by experts and patient surveys, focus groups, and cognitive interviews. We then assessed items by using classic test theory and IRT, used confirmatory factor analyses to estimate item parameters, and graded response modeling for parameter estimation. We retained the 20 Legacy (original) Health Assessment Questionnaire Disability Index (HAQ-DI) and the 10 SF-36\u27s PF-10 items for comparison. Subjects were from rheumatoid arthritis, osteoarthritis, and healthy aging cohorts (n = 1,100) and a national Internet sample of 21,133 subjects. RESULTS: We identified 1,860 items. After qualitative and quantitative evaluation, 124 newly developed PROMIS items composed the PROMIS item bank, which included revised Legacy items with good fit that met IRT model assumptions. Results showed that the clearest and best-understood items were simple, in the present tense, and straightforward. Basic tasks (like dressing) were more relevant and important versus complex ones (like dancing). Revised HAQ-DI and PF-10 items with five response options had higher item-information content than did comparable original Legacy items with fewer response options. IRT analyses showed that the Physical Function domain satisfied general criteria for unidimensionality with one-, two-, three-, and four-factor models having comparable model fits. Correlations between factors in the test data sets were \u3e 0.90. CONCLUSIONS: Item improvement must underlie attempts to improve outcome assessment. The clear, personally important and relevant, ability-framed items in the PROMIS Physical Function item bank perform well in PRO assessment. They will benefit from further study and application in a wider variety of rheumatic diseases in diverse clinical groups, including those at the extremes of physical functioning, and in different administration modes

The multiple sclerosis risk sharing scheme monitoring study - early results and lessons for the future

Background: Risk sharing schemes represent an innovative and important approach to the problems of rationing and achieving cost-effectiveness in high cost or controversial health interventions. This study aimed to assess the feasibility of risk sharing schemes, looking at long term clinical outcomes, to determine the price at which high cost treatments would be acceptable to the NHS. Methods: This case study of the first NHS risk sharing scheme, a long term prospective cohort study of beta interferon and glatiramer acetate in multiple sclerosis ( MS) patients in 71 specialist MS centres in UK NHS hospitals, recruited adults with relapsing forms of MS, meeting Association of British Neurologists (ABN) criteria for disease modifying therapy. Outcome measures were: success of recruitment and follow up over the first three years, analysis of baseline and initial follow up data and the prospect of estimating the long term cost-effectiveness of these treatments. Results: Centres consented 5560 patients. Of the 4240 patients who had been in the study for a least one year, annual review data were available for 3730 (88.0%). Of the patients who had been in the study for at least two years and three years, subsequent annual review data were available for 2055 (78.5%) and 265 (71.8%) patients respectively. Baseline characteristics and a small but statistically significant progression of disease were similar to those reported in previous pivotal studies. Conclusion: Successful recruitment, follow up and early data analysis suggest that risk sharing schemes should be able to deliver their objectives. However, important issues of analysis, and political and commercial conflicts of interest still need to be addressed