Integrability of SLE via conformal welding of random surfaces

We demonstrate how to obtain integrable results for the Schramm-Loewner evolution (SLE) from Liouville conformal field theory (LCFT) and the mating-of-trees framework for Liouville quantum gravity (LQG). In particular, we prove an exact formula for the law of a conformal derivative of a classical variant of SLE called $\mathrm{SLE}_\kappa(\rho_-;\rho_+)$. Moreover, we prove that the SLE loop measure constructed by Zhan (2020) arises naturally from the conformal welding of two quantum disks in LQG. Our proofs are built on two connections between SLE, LCFT, and mating-of-trees. Firstly, LCFT and mating-of-trees provide equivalent but complementary methods to describe natural random surfaces in LQG. We extend earlier equivalence results in two directions, namely by allowing fewer marked points and more generic singularities. Secondly, the conformal welding of these random surfaces produces SLE curves as their interfaces. In particular, we rely on the conformal welding results proved in our companion paper [AHS20]. Our paper is an essential part of a program proving integrability results for SLE, LCFT, and mating-of-trees based on these two connections.Comment: 57 pages, 4 figure

Conformal welding of quantum disks and multiple SLE: the non-simple case

Two-pointed quantum disks with a weight parameter $W>0$ is a canonical family of finite-volume random surfaces in Liouville quantum gravity. We extend the conformal welding of quantum disks in [AHS23] to the non-simple regime, and give a construction of the multiple SLE associated with any given link pattern for $\kappa\in(4,8)$. Our proof is based on connections between SLE and Liouville conformal field theory (LCFT), where we show that in the conformal welding of multiple forested quantum disks, the surface after welding can be described in terms of LCFT, and the random conformal moduli contains the SLE partition function for the interfaces as a multiplicative factor. As a corollary, for $\kappa\in(4,8)$, we prove the existence of the multiple SLE partition functions, which are smooth functions satisfying a system of PDEs and conformal covariance.Comment: 43 pages, 7 figure

Chlorhexidine and octenidine use, qac genes carriage, and reduced antiseptic susceptibility in methicillin-resistant Staphylococcus aureus isolates from a healthcare network

Funding: This research was supported by the Small Innovative Grant (SIG/15033) and Communicable Diseases – Public Health Research Grant (CDPHRG/0008/2014) awarded by the National Healthcare Group and Ministry of Health Singapore respectively.Objectives With the widespread use of antiseptics in healthcare facilities for the prevention of methicillin-resistant Staphylococcus aureus (MRSA) transmission, there are concerns for antiseptic tolerance and resistance. We sought to understand the use of chlorhexidine and octenidine, qac genes carriage and reduced antiseptic susceptibilities. Methods A serial cross-sectional study was conducted in an acute care hospital and three extended-care facilities of a healthcare network in June-July, 2014-2016. Two of the extended-care facilities were exposed to intranasal octenidine and universal daily chlorhexidine/octenidine bathing. The minimum inhibitory concentration (MIC) levels and qac genes were determined by broth microdilution tests and whole genome sequencing respectively. Multivariable logistic regression was used to assess for the independent associations between antiseptic exposures, qac genes and reduced antiseptic susceptibilities. Results A total of 878 MRSA isolates were obtained. There were associations between qacA/B carriage and chlorhexidine (adjusted odds ratio [aOR]: 7.80; 95% confidence interval [CI]: 3.25-18.71) and octenidine (aOR: 11.79; 95%CI: 5.14-27.04) exposures. Chlorhexidine exposure was associated with reduced chlorhexidine susceptibility (MIC≥4mg/L) (aOR: 3.15; 95%CI: 1.14-8.74). Carriage of qacA/B (aOR: 10.65: 95%CI: 4.14-27.40) or qacC (aOR: 2.55; 95%CI: 1.22-5.32) had an association with reduced chlorhexidine susceptibility; while MRSA sequence type modified the association. However, we found no direct association between (i) antiseptics use and qacC carriage, (ii) octenidine exposure and reduced susceptibility and (iii) reduced octenidine susceptibility and qacA/B or qacC carriage. Conclusions Antiseptic exposures were associated with qac genes carriage. Chlorhexidine exposure was associated with reduced chlorhexidine susceptibility, requiring continued surveillance for the emergence of resistance.PostprintPeer reviewe

Comparative epidemiology and factors associated with major healthcare-associated methicillin-resistant Staphylococcus aureus clones among interconnected acute-, intermediate- and long-term healthcare facilities in Singapore

Funding: Bioinformatics and Computational Biology analyses were supported by the University of St Andrews Bioinformatics Unit that is funded by a Wellcome Trust ISSF award (grant 097831/Z/11/Z). M.T.G.H is supported by the Scottish Infection Research Network and Chief Scientist Office through the Scottish Healthcare Associated Infection Prevention Institute consortium funding (CSO Reference: SIRN10).Objectives Methicillin-resistant Staphylococcus aureus(MRSA) has spread across countries and healthcare settings, with different ecological niches for different clones. It is crucial to understand the comparative epidemiology of MRSA clones between healthcare settings, and independent factors associated with colonization of specific clones. Methods We conducted annual cross-sectional surveillance studies in a network comprising an acute-care hospital and six closely-affiliated intermediate- and long-term care facilities in Singapore, in June-July, 2014-2016. 5,394 patients contributed 16,045 nasal, axillary and groin samples for culture and MRSA isolates for whole genome sequencing. Multivariable multilevel multinomial regression models were constructed to assess for independent factors associated with MRSA colonization. Results MRSA clonal complex(CC) 22 was more prevalent in the acute-care hospital(n=256/493; 51.9%) and intermediate-care(n=348/634; 54.9%) than long-term care(n=88/351; 25.1%) facilities, with clones besides CC22 and CC45 being more prevalent in long-term care facilities(n=144/351; 41.0%) (P<0.001). Groin colonization with CC45 was 6 times that of nasal colonization(aOR 6.21, 95%CI 4.26-9.01). Prior MRSA carriage was associated with increased odds of current MRSA colonization in all settings, with a stronger association with CC22(aOR 6.45, 95%CI 3.85-10.87) than CC45(aOR 4.15, 95%CI 2.26-7.58). Conclusions Colonization of MRSA clones differed between anatomic sites and across healthcare settings. With CC22 having a predilection for the nares and CC45 the groin, MRSA screening should include both sites. Prior MRSA carriage is a risk factor for colonization with predominant MRSA clones in the acute-care hospital and intermediate- and long-term care facilities. Contact precautions for prior MRSA-carriers on admission to any healthcare facility could prevent intra- and inter-institutional MRSA transmission.PostprintPeer reviewe

The Basilicata Wealth Fund: Resource Policy and Long-Run Economic Development in Southern Italy

This paper contributes to the growing political economy literature of within-country natural resources management, by proposing a new resource policy for the oil-rich southern Italian region of Basilicata. The policy proposal is to establish a (regional) wealth fund in which all the royalty revenues from non-renewable natural resource exploitation in Basilicata would be stored and fully converted into low-risk financial assets. The scope is to give priority to long-run investments as to better exploit revenues from large-scale extraction of natural capital. Establishing a wealth fund at the regional sub-national level is a novel approach that can be applied to other resource-rich regions in the world. I label the fund as the Basilicata Wealth Fund (BWF). The BWF would be a regionally owned investment fund, however independently administered from national authorities (for instance, as an independent legal entity under the jurisdiction of the Bank of Italy). In addition, the paper posits a transparent and clear-cut spending fiscal rule in order to let regional authorities use the resource revenues to finance economic policy. The clear advantage from the BWF would be the stronger focus on long-run economic development and the higher accountability, hence avoiding misuse of resource revenues for myopic fiscal spending

MRSA transmission dynamics among interconnected acute, intermediate-term, and long-term healthcare facilities in Singapore

This work was supported by the Ministry of Health, Singapore (Communicable Diseases–Public Health Research Grant), the Wellcome Trust (Institutional Strategic Support Fund award [grant 097831/Z/11/Z] to the University of St Andrews Bioinformatics Unit), and the Scottish Infection Research Network and Chief Scientist Office (Scottish Healthcare Associated Infection Prevention Institute consortium funding [Chief Scientist Office reference SIRN10] to K. P. and M. T. G. H.).Background: Methicillin-resistant Staphylococcus aureus (MRSA) is the most common healthcare-associated multidrug-resistant organism. Despite the interconnectedness between acute care hospitals (ACHs) and intermediate- and long-term care facilities (ILTCFs), the transmission dynamics of MRSA between healthcare settings is not well understood. Methods: We conducted a cross-sectional study in a network comprising an ACH and 5 closely affiliated ILTCFs in Singapore. A total of 1700 inpatients were screened for MRSA over a 6-week period in 2014. MRSA isolates underwent whole-genome sequencing, with a pairwise single-nucleotide polymorphism (Hamming distance) cutoff of 60 core genome single-nucleotide polymorphisms used to define recent transmission clusters (clades) for the 3 major clones. Results: MRSA prevalence was significantly higher in intermediate-term (29.9%) and long-term (20.4%) care facilities than in the ACH (11.8%) (P < .001). The predominant clones were sequence type [ST] 22 (n = 183; 47.8%), ST45 (n = 129; 33.7%), and ST239 (n = 26; 6.8%), with greater diversity of STs in ILTCFs relative to the ACH. A large proportion of the clades in ST22 (14 of 21 clades; 67%) and ST45 (7 of 13; 54%) included inpatients from the ACH and ILTCFs. The most frequent source of the interfacility transmissions was the ACH (n = 28 transmission events; 36.4%). Conclusions: MRSA transmission dynamics between the ACH and ILTCFs were complex. The greater diversity of STs in ILTCFs suggests that the ecosystem in such settings might be more conducive for intrafacility transmission events. ST22 and ST45 have successfully established themselves in ILTCFs. The importance of interconnected infection prevention and control measures and strategies cannot be overemphasized.PostprintPeer reviewe

The evolution of new enzyme function: lessons from xenobiotic metabolizing bacteria versus insecticide-resistant insects

Here, we compare the evolutionary routes by which bacteria and insects have evolved enzymatic processes for the degradation of four classes of synthetic chemical insecticide. For insects, the selective advantage of such degradative activities is survival on exposure to the insecticide, whereas for the bacteria the advantage is simply a matter of access to additional sources of nutrients. Nevertheless, bacteria have evolved highly efficient enzymes from a wide variety of enzyme families, whereas insects have relied upon generalist esterase-, cytochrome P450- and glutathione-S-transferase-dependent detoxification systems. Moreover, the mutant insect enzymes are less efficient kinetically and less diverged in sequence from their putative ancestors than their bacterial counterparts. This presumably reflects several advantages that bacteria have over insects in the acquisition of new enzymatic functions, such as a broad biochemical repertoire from which new functions can be evolved, large population sizes, high effective mutation rates, very short generation times and access to genetic diversity through horizontal gene transfer. Both the insect and bacterial systems support recent theory proposing that new biochemical functions often evolve from ‘promiscuous’ activities in existing enzymes, with subsequent mutations then enhancing those activities. Study of the insect enzymes will help in resistance management, while the bacterial enzymes are potential bioremediants of insecticide residues in a range of contaminated environments

An outbreak of Streptococcus pyogenes in a mental health facility : advantage of well-timed whole-genome sequencing over emm typing

Financial support: The outbreak investigation was supported by Institute of Mental Health.OBJECTIVE:  We report the utility of whole-genome sequencing (WGS) conducted in a clinically relevant time frame (ie, sufficient for guiding management decision), in managing a Streptococcus pyogenes outbreak, and present a comparison of its performance with emm typing. SETTING:  A 2,000-bed tertiary-care psychiatric hospital. METHODS:  Active surveillance was conducted to identify new cases of S. pyogenes. WGS guided targeted epidemiological investigations, and infection control measures were implemented. Single-nucleotide polymorphism (SNP)-based genome phylogeny, emm typing, and multilocus sequence typing (MLST) were performed. We compared the ability of WGS and emm typing to correctly identify person-to-person transmission and to guide the management of the outbreak. RESULTS:  The study included 204 patients and 152 staff. We identified 35 patients and 2 staff members with S. pyogenes. WGS revealed polyclonal S. pyogenes infections with 3 genetically distinct phylogenetic clusters (C1-C3). Cluster C1 isolates were all emm type 4, sequence type 915 and had pairwise SNP differences of 0-5, which suggested recent person-to-person transmissions. Epidemiological investigation revealed that cluster C1 was mediated by dermal colonization and transmission of S. pyogenes in a male residential ward. Clusters C2 and C3 were genomically diverse, with pairwise SNP differences of 21-45 and 26-58, and emm 11 and mostly emm120, respectively. Clusters C2 and C3, which may have been considered person-to-person transmissions by emm typing, were shown by WGS to be unlikely by integrating pairwise SNP differences with epidemiology. CONCLUSIONS:  WGS had higher resolution than emm typing in identifying clusters with recent and ongoing person-to-person transmissions, which allowed implementation of targeted intervention to control the outbreak.PostprintPeer reviewe