Whole-genome sequencing shows that patient-to-patient transmission rarely accounts for acquisition of Staphylococcus aureus in an intensive care unit

BACKGROUND  Strategies to prevent Staphylococcus aureus infection in hospitals focus on patient-to-patient transmission. We used whole-genome sequencing to investigate the role of colonized patients as the source of new S. aureus acquisitions, and the reliability of identifying patient-to-patient transmission using the conventional approach of spa typing and overlapping patient stay. METHODS Over 14 months, all unselected patients admitted to an adult intensive care unit (ICU) were serially screened for S. aureus. All available isolates (n = 275) were spa typed and underwent whole-genome sequencing to investigate their relatedness at high resolution. RESULTS Staphylococcus aureus was carried by 185 of 1109 patients sampled within 24 hours of ICU admission (16.7%); 59 (5.3%) patients carried methicillin-resistant S. aureus (MRSA). Forty-four S. aureus (22 MRSA) acquisitions while on ICU were detected. Isolates were available for genetic analysis from 37 acquisitions. Whole-genome sequencing indicated that 7 of these 37 (18.9%) were transmissions from other colonized patients. Conventional methods (spa typing combined with overlapping patient stay) falsely identified 3 patient-to-patient transmissions (all MRSA) and failed to detect 2 acquisitions and 4 transmissions (2 MRSA). CONCLUSIONS Only a minority of S. aureus acquisitions can be explained by patient-to-patient transmission. Whole-genome sequencing provides the resolution to disprove transmission events indicated by conventional methods and also to reveal otherwise unsuspected transmission events. Whole-genome sequencing should replace conventional methods for detection of nosocomial S. aureus transmission

Sublimation properties of x,y-dihydroxybenzoic acid isomers as model matrix assisted laser desorption ionisation (MALDI) matrices

Abstract The enthalpies of sublimation of the six isomers of dihydroxybenzoic acid were determined by thermogravimetry as part of a study to investigate their performance as model matrices in matrix assisted laser desorption/ionisation-mass spectrometry. The enthalpy of sublimation could be determined to within an error of AE7%. In the MALDI mechanism, sublimation is thought to play an important part, however in the present study no positive correlation between this parameter and the performance of the material as a matrix was found.

Stellar intensity interferometry: Experimental steps toward long-baseline observations

Experiments are in progress to prepare for intensity interferometry with arrays of air Cherenkov telescopes. At the Bonneville Seabase site, near Salt Lake City, a testbed observatory has been set up with two 3-m air Cherenkov telescopes on a 23-m baseline. Cameras are being constructed, with control electronics for either off- or online analysis of the data. At the Lund Observatory (Sweden), in Technion (Israel) and at the University of Utah (USA), laboratory intensity interferometers simulating stellar observations have been set up and experiments are in progress, using various analog and digital correlators, reaching 1.4 ns time resolution, to analyze signals from pairs of laboratory telescopes.Comment: 12 pages, 3 figur

Experimental study of the reactions e(+)e(-)→e(+)e(-) and e(+)e(-)→γγ at 29 GeV

This is the publisher's version, also available electronically from http://journals.aps.org/prd/abstract/10.1103/PhysRevD.34.3286.This paper reports measurements of the differential cross sections for the reactions e(+)e(-)→e(+)e(-) (Bhabha scattering) and e(+)e(-)→γγ (γ-pair production). The reactions are studied at a center-of-mass energy of 29 GeV and in the polar-angular region ‖costheta‖154 GeV and Λ->220 GeV for Bhabha scattering, and Λ+>59 GeV and Λ->59 GeV for γ-pair production

The Inherited Intestinal Microbiota from Myeloid-Specific ZIP8KO Mice Impairs Pulmonary Host Defense against Pneumococcal Pneumonia

Intestinal dysbiosis increases susceptibility to infection through the alteration of metabolic profiles, which increases morbidity. Zinc (Zn) homeostasis in mammals is tightly regulated by 24 Zn transporters. ZIP8 is unique in that it is required by myeloid cells to maintain proper host defense against bacterial pneumonia. In addition, a frequently occurring ZIP8 defective variant (SLC39A8 rs13107325) is strongly associated with inflammation-based disorders and bacterial infection. In this study, we developed a novel model to study the effects of ZIP8-mediated intestinal dysbiosis on pulmonary host defense independent of the genetic effects. Cecal microbial communities from a myeloid-specific Zip8 knockout mouse model were transplanted into germ-free mice. Conventionalized ZIP8KO-microbiota mice were then bred to produce F1 and F2 generations of ZIP8KO-microbiota mice. F1 ZIP8KO-microbiota mice were also infected with S. pneumoniae, and pulmonary host defense was assessed. Strikingly, the instillation of pneumococcus into the lung of F1 ZIP8KO-microbiota mice resulted in a significant increase in weight loss, inflammation, and mortality when compared to F1 wild-type (WT)-microbiota recipients. Similar defects in pulmonary host defense were observed in both genders, although consistently greater in females. From these results, we conclude that myeloid Zn homeostasis is not only critical for myeloid function but also plays a significant role in the maintenance and control of gut microbiota composition. Further, these data demonstrate that the intestinal microbiota, independent of host genetics, play a critical role in governing host defense in the lung against infection. Finally, these data strongly support future microbiome-based interventional studies, given the high incidence of zinc deficiency and the rs13107325 allele in humans

Characterization of neutrino signals with radiopulses in dense media through the LPM effect

We discuss the possibilities of detecting radio pulses from high energy showers in ice, such as those produced by PeV and EeV neutrino interactions. It is shown that the rich radiation pattern structure in the 100 MHz to few GHz allows the separation of electromagnetic showers induced by photons or electrons above 100 PeV from those induced by hadrons. This opens up the possibility of measuring the energy fraction transmitted to the electron in a charged current electron neutrino interaction with adequate sampling of the angular distribution of the signal. The radio technique has the potential to complement conventional high energy neutrino detectors with flavor information.Comment: 5 pages, 4 ps figures. Submitted to Phys. Rev. Let

Human Alcohol-Microbiota Mice have Increased Susceptibility to Bacterial Pneumonia

Preclinical studies have shown that chronic alcohol abuse leads to alterations in the gastrointestinal microbiota that are associated with behavior changes, physiological alterations, and immunological effects. However, such studies have been limited in their ability to evaluate the direct effects of alcohol-associated dysbiosis. To address this, we developed a humanized alcoholmicrobiota mouse model to systematically evaluate the immunological effects of chronic alcohol abuse mediated by intestinal dysbiosis. Germ-free mice were colonized with human fecal microbiota from individuals with high and low Alcohol Use Disorders Identification Test (AUDIT) scores and bred to produce human alcohol-associated microbiota or human control-microbiota F1 progenies. F1 offspring colonized with fecal microbiota from individuals with high AUDIT scores had increased susceptibility to Klebsiella pneumoniae and Streptococcus pneumoniae pneumonia, as determined by increased mortality rates, pulmonary bacterial burden, and post-infection lung damage. These findings highlight the importance of considering both the direct effects of alcohol and alcohol-induced dysbiosis when investigating the mechanisms behind alcohol-related disorders and treatment strategies

Self-supervised machine learning to characterise step counts from wrist-worn accelerometers in the UK Biobank

Purpose: Step count is an intuitive measure of physical activity frequently quantified in health-related studies; however, accurate step counting is difficult in the free-living environment, with error routinely above 20% in wrist-worn devices against camera-annotated ground truth. This study aims to describe the development and validation of step count derived from a wrist-worn accelerometer and assess its association with cardiovascular and all-cause mortality in a large prospective cohort. Methods: We developed and externally validated a self-supervised machine learning step detection model, trained on an open-source and step-annotated free-living dataset. 39 individuals will free-living ground-truth annotated step counts were used for model development. An open-source dataset with 30 individuals was used for external validation. Epidemiological analysis was performed using 75,263 UK Biobank participants without prevalent cardiovascular disease (CVD) or cancer. Cox regression was used to test the association of daily step count with fatal CVD and all-cause mortality after adjustment for potential confounders. Results: The algorithm substantially outperformed reference models (free-living mean absolute percent error of 12.5%, versus 65-231%). Our data indicate an inverse dose-response association, where taking 6,430-8,277 daily steps was associated with 37% [25-48%] and 28% [20-35%] lower risk of fatal CVD and all-cause mortality up to seven years later, compared to those taking fewer steps each day. Conclusions: We have developed an open and transparent method that markedly improves the measurement of steps in large-scale wrist-worn accelerometer datasets. The application of this method demonstrated expected associations with CVD and all-cause mortality, indicating excellent face validity. This reinforces public health messaging for increasing physical activity and can help lay the groundwork for the inclusion of target step counts in future public health guidelines

Transmission of Staphylococcus aureus between health-care workers, the environment, and patients in an intensive care unit: a longitudinal cohort study based on whole-genome sequencing

Background: Health-care workers have been implicated in nosocomial outbreaks of Staphylococcus aureus, but the dearth of evidence from non-outbreak situations means that routine health-care worker screening and S aureus eradication are controversial. We aimed to determine how often S aureus is transmitted from health-care workers or the environment to patients in an intensive care unit (ICU) and a high-dependency unit (HDU) where standard infection control measures were in place. Methods: In this longitudinal cohort study, we systematically sampled health-care workers, the environment, and patients over 14 months at the ICU and HDU of the Royal Sussex County Hospital, Brighton, England. Nasal swabs were taken from health-care workers every 4 weeks, bed spaces were sampled monthly, and screening swabs were obtained from patients at admission to the ICU or HDU, weekly thereafter, and at discharge. Isolates were cultured and their whole genome sequenced, and we used the threshold of 40 single-nucleotide variants (SNVs) or fewer to define subtypes and infer recent transmission. Findings: Between Oct 31, 2011, and Dec 23, 2012, we sampled 198 health-care workers, 40 environmental locations, and 1854 patients; 1819 isolates were sequenced. Median nasal carriage rate of S aureus in health-care workers at 4-weekly timepoints was 36·9% (IQR 35·7–37·3), and 115 (58%) health-care workers had S aureus detected at least once during the study. S aureus was identified in 8–50% of environmental samples. 605 genetically distinct subtypes were identified (median SNV difference 273, IQR 162–399) at a rate of 38 (IQR 34–42) per 4-weekly cycle. Only 25 instances of transmission to patients (seven from health-care workers, two from the environment, and 16 from other patients) were detected. Interpretation: In the presence of standard infection control measures, health-care workers were infrequently sources of transmission to patients. S aureus epidemiology in the ICU and HDU is characterised by continuous ingress of distinct subtypes rather than transmission of genetically related strains. Funding: UK Medical Research Council, Wellcome Trust, Biotechnology and Biological Sciences Research Council, UK National Institute for Health Research, and Public Health England

Injury epidemiology in professional ballet: a five-season prospective study of 1596 medical attention injuries and 543 time-loss injuries

OBJECTIVES: To describe the incidence rate, severity, burden and aetiology of medical attention and time-loss injuries across five consecutive seasons at a professional ballet company. METHODS: Medical attention injuries, time-loss injuries and dance exposure hours of 123 professional ballet dancers (women: n=66, age: 28.0+/-8.3 years; men: n=57, age: 27.9+/-8.5 years) were prospectively recorded between the 2015/2016 and 2019/2020 seasons. RESULTS: The incidence rate (per 1000 hours) of medical attention injury was 3.9 (95% CI 3.3 to 4.4) for women and 3.1 (95% CI 2.6 to 3.5) for men. The incidence rate (per 1000 hours) of time-loss injury was 1.2 (95% CI 1.0 to 1.5) for women and 1.1 (95% CI 0.9 to 1.3) for men. First Soloists and Principals experienced between 2.0-2.2 additional medical attention injuries per 1000 hours and 0.9-1.1 additional time-loss injuries per 1000 hours compared with Apprentices (p</=0.025). Further, intraseason differences were observed in medical attention, but not time-loss, injury incidence rates with the highest incidence rates in early (August and September) and late (June) season months. Thirty-five per cent of time-loss injuries resulted in over 28 days of modified dance training. A greater percentage of time-loss injuries were classified as overuse (women: 50%; men: 51%) compared with traumatic (women: 40%; men: 41%). CONCLUSION: This is the first study to report the incidence rate of medical attention and time-loss injuries in professional ballet dancers. Incidence rates differed across company ranks and months, which may inform targeted injury prevention strategies