The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridioides difficile infection and other potential indications: second edition of joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines.

The first British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS)-endorsed faecal microbiota transplant (FMT) guidelines were published in 2018. Over the past 5 years, there has been considerable growth in the evidence base (including publication of outcomes from large national FMT registries), necessitating an updated critical review of the literature and a second edition of the BSG/HIS FMT guidelines. These have been produced in accordance with National Institute for Health and Care Excellence-accredited methodology, thus have particular relevance for UK-based clinicians, but are intended to be of pertinence internationally. This second edition of the guidelines have been divided into recommendations, good practice points and recommendations against certain practices. With respect to FMT for Clostridioides difficile infection (CDI), key focus areas centred around timing of administration, increasing clinical experience of encapsulated FMT preparations and optimising donor screening. The latter topic is of particular relevance given the COVID-19 pandemic, and cases of patient morbidity and mortality resulting from FMT-related pathogen transmission. The guidelines also considered emergent literature on the use of FMT in non-CDI settings (including both gastrointestinal and non-gastrointestinal indications), reviewing relevant randomised controlled trials. Recommendations are provided regarding special areas (including compassionate FMT use), and considerations regarding the evolving landscape of FMT and microbiome therapeutics.

Deformation versus Sphericity in the Ground States of the Lightest Gold Isotopes.

The changes in mean-squared charge radii of neutron-deficient gold nuclei have been determined using the in-source, resonance-ionization laser spectroscopy technique, at the ISOLDE facility (CERN). From these new data, nuclear deformations are inferred, revealing a competition between deformed and spherical configurations. The isotopes ^{180,181,182}Au are observed to possess well-deformed ground states and, when moving to lighter masses, a sudden transition to near-spherical shapes is seen in the extremely neutron-deficient nuclides, ^{176,177,179}Au. A case of shape coexistence and shape staggering is identified in ^{178}Au which has a ground and isomeric state with different deformations. These new data reveal a pattern in ground-state deformation unique to the gold isotopes, whereby, when moving from the heavy to light masses, a plateau of well-deformed isotopes exists around the neutron midshell, flanked by near-spherical shapes in the heavier and lighter isotopes-a trend hitherto unseen elsewhere in the nuclear chart. The experimental charge radii are compared to those from Hartree-Fock-Bogoliubov calculations using the D1M Gogny interaction and configuration mixing between states of different deformation. The calculations are constrained by the known spins, parities, and magnetic moments of the ground states in gold nuclei and show a good agreement with the experimental results.

Patient-Centred Outcomes Following Tracheostomy in Critical Care.

INTRODUCTION: Around 20% of intensive care unit (ICU) patients undergo tracheostomy insertion and expect high-quality care concentrating on patient-centered outcomes including communication, oral intake, and mobilization. The majority of data has focused on timing, mortality, and resource utilization, with a paucity of information on quality of life following tracheostomy. METHODS: Single center retrospective study including all patients requiring tracheostomy from 2017 to 2019. Information collected on demographics, severity of illness, ICU and hospital length of stay (LOS), ICU and hospital mortality, discharge disposition, sedation, time to vocalization, swallow and mobilization. Outcomes were compared for early versus late tracheostomy (early =

The PERCIVAL detector: first user experiments.

The PERCIVAL detector is a CMOS imager designed for the soft X-ray regime at photon sources. Although still in its final development phase, it has recently seen its first user experiments: ptychography at a free-electron laser, holographic imaging at a storage ring and preliminary tests on X-ray photon correlation spectroscopy. The detector performed remarkably well in terms of spatial resolution achievable in the sample plane, owing to its small pixel size, large active area and very large dynamic range; but also in terms of its frame rate, which is significantly faster than traditional CCDs. In particular, it is the combination of these features which makes PERCIVAL an attractive option for soft X-ray science.

Large Shape Staggering in Neutron-Deficient Bi Isotopes.

The changes in the mean-square charge radius (relative to ^{209}Bi), magnetic dipole, and electric quadrupole moments of ^{187,188,189,191}Bi were measured using the in-source resonance-ionization spectroscopy technique at ISOLDE (CERN). A large staggering in radii was found in ^{187,188,189}Bi^{g}, manifested by a sharp radius increase for the ground state of ^{188}Bi relative to the neighboring ^{187,189}Bi^{g}. A large isomer shift was also observed for ^{188}Bi^{m}. Both effects happen at the same neutron number, N=105, where the shape staggering and a similar isomer shift were observed in the mercury isotopes. Experimental results are reproduced by mean-field calculations where the ground or isomeric states were identified by the blocked quasiparticle configuration compatible with the observed spin, parity, and magnetic moment.

Laser Spectroscopy of Neutron-Rich

The mean-square charge radii of ^{207,208}Hg (Z=80, N=127, 128) have been studied for the first time and those of ^{202,203,206}Hg (N=122, 123, 126) remeasured by the application of in-source resonance-ionization laser spectroscopy at ISOLDE (CERN). The characteristic kink in the charge radii at the N=126 neutron shell closure has been revealed, providing the first information on its behavior below the Z=82 proton shell closure. A theoretical analysis has been performed within relativistic Hartree-Bogoliubov and nonrelativistic Hartree-Fock-Bogoliubov approaches, considering both the new mercury results and existing lead data. Contrary to previous interpretations, it is demonstrated that both the kink at N=126 and the odd-even staggering (OES) in its vicinity can be described predominately at the mean-field level and that pairing does not need to play a crucial role in their origin. A new OES mechanism is suggested, related to the staggering in the occupation of the different neutron orbitals in odd- and even-A nuclei, facilitated by particle-vibration coupling for odd-A nuclei.

H3K9 methyltransferases and demethylases control lung tumor-propagating cells and lung cancer progression.

Epigenetic regulators are attractive anticancer targets, but the promise of therapeutic strategies inhibiting some of these factors has not been proven in vivo or taken into account tumor cell heterogeneity. Here we show that the histone methyltransferase G9a, reported to be a therapeutic target in many cancers, is a suppressor of aggressive lung tumor-propagating cells (TPCs). Inhibition of G9a drives lung adenocarcinoma cells towards the TPC phenotype by de-repressing genes which regulate the extracellular matrix. Depletion of G9a during tumorigenesis enriches tumors in TPCs and accelerates disease progression metastasis. Depleting histone demethylases represses G9a-regulated genes and TPC phenotypes. Demethylase inhibition impairs lung adenocarcinoma progression in vivo. Therefore, inhibition of G9a is dangerous in certain cancer contexts, and targeting the histone demethylases is a more suitable approach for lung cancer treatment. Understanding cellular context and specific tumor populations is critical when targeting epigenetic regulators in cancer for future therapeutic development.

The conformation and dynamics of P-glycoprotein in a lipid bilayer investigated by atomic force microscopy.

The membrane-bound P-glycoprotein (Pgp) transporter plays a major role in human disease and drug disposition because of its ability to efflux a chemically diverse range of drugs through ATP hydrolysis and ligand-induced conformational changes. Deciphering these structural changes is key to understanding the molecular basis of transport and to developing molecules that can modulate efflux. Here, atomic force microscopy (AFM) is used to directly image individual Pgp transporter molecules in a lipid bilayer under physiological pH and ambient temperature. Analysis of the Pgp AFM images revealed "small" and "large" protrusions from the lipid bilayer with significant differences in protrusion height and volume. The geometry of these "small" and "large" protrusions correlated to the predicted extracellular (EC) and cytosolic (C) domains of the Pgp X-ray crystal structure, respectively. To assign these protrusions, simulated AFM images were produced from the Pgp X-ray crystal structures with membrane planes defined by three computational approaches, and a simulated 80 ŠAFM cantilever tip. The theoretical AFM images of the EC and C domains had similar heights and volumes to the "small" and "large" protrusions in the experimental AFM images, respectively. The assignment of the protrusions in the AFM images to the EC and C domains was confirmed by changes in protrusion volume by Pgp-specific antibodies. The Pgp domains showed a considerable degree of conformational dynamics in time resolved AFM images. With this information, a model of Pgp conformational dynamics in a lipid bilayer is proposed within the context of the known Pgp X-ray crystal structures.

Precision Mass Measurements of

The neutron-rich isotopes ^{58-63}Cr were produced for the first time at the ISOLDE facility and their masses were measured with the ISOLTRAP spectrometer. The new values are up to 300 times more precise than those in the literature and indicate significantly different nuclear structure from the new mass-surface trend. A gradual onset of deformation is found in this proton and neutron midshell region, which is a gateway to the second island of inversion around N=40. In addition to comparisons with density-functional theory and large-scale shell-model calculations, we present predictions from the valence-space formulation of the ab initio in-medium similarity renormalization group, the first such results for open-shell chromium isotopes.

Multiple intra-hospital transports during relocation to a new critical care unit.

OBJECTIVE: Intra-hospital transport (IHT) of critically ill patients is associated with morbidity and mortality. Mass transfer of patients, as happens with unit relocation, is poorly described. We outline the process and adverse events associated with the relocation of a critical care unit. DESIGN: Extensive planning of the relocation targeted patient and equipment transfer, reduction in clinical pressure prior to the event and patient care during the relocation phase. SETTING: The setting was a 30-bed, tertiary referral, combined medical and surgical critical care unit, located in a 570-bed hospital that serves as the national referral centre for cardiothoracic surgery and spinal injuries. PARTICIPANTS: All stakeholders relevant to the critical care unit relocation were involved, including nursing and medical staff, porters, information technology services, laboratory staff, project development managers, pharmacy staff and building contractors. MAIN OUTCOME MEASURES: Mortality at discharge from critical care unit and discharge from hospital were the main outcome measures. A wide range of adverse events were prospectively recorded, as were transfer times. RESULTS: Twenty-one patients underwent IHT, with a median transfer time of 10 min. Two transfers were complicated by equipment failure and three patients experienced an episode of hypotension requiring intervention. There were no cases of central venous or arterial catheter or endotracheal tube dislodgement, and hospital mortality at 30 days was 14%. CONCLUSION: Although IHT is associated with morbidity and mortality, careful logistical planning allows for efficient transfer with low complication rates.

The Inability to Screen Exhibition Swine for Influenza A Virus Using Body Temperature.

Agricultural fairs create an unconventional animal-human interface that has been associated with swine-to-human transmission of influenza A virus (IAV) in recent years. Early detection of IAV-infected pigs at agricultural fairs would allow veterinarians to better protect swine and human health during these swine exhibitions. This study assessed the use of swine body temperature measurement, recorded by infrared and rectal thermometers, as a practical method to detect IAV-infected swine at agricultural fairs. In our first objective, infrared thermometers were used to record the body surface temperature of 1,092 pigs at the time of IAV nasal swab collection at the end of the exhibition period of 55 agricultural fairs. IAV was recovered from 212 (19.4%) pigs, and the difference in mean infrared body temperature measurement of IAV-positive and IAV-negative pigs was 0.83°C. In a second objective, snout wipes were collected from 1,948 pigs immediately prior to the unloading of the animals at a single large swine exhibition. Concurrent to the snout wipe collection, owners took the rectal temperatures of his/her pigs. In this case, 47 (2.4%) pigs tested positive for IAV before they entered the swine barn. The mean rectal temperatures differed by only 0.19°C between IAV-positive and IAV-negative pigs. The low prevalence of IAV among the pigs upon entry to the fair in the second objective provides evidence that limiting intraspecies spread of IAV during the fairs will likely have significant impacts on the zoonotic transmission. However, in both objectives, the high degree of similarity in the body temperature measurements between the IAV-positive and IAV-negative pigs made it impossible to set a diagnostically meaningful cut point to differentiate IAV status of the individual animals. Unfortunately, body temperature measurement cannot be used to accurately screen exhibition swine for IAV.

Use of a Continuous Wave Laser and Pockels Cell for Sensitive High-Resolution Collinear Resonance Ionization Spectroscopy.

New technical developments have led to a 2 orders of magnitude improvement of the resolution of the collinear resonance ionization spectroscopy (CRIS) experiment at ISOLDE, CERN, without sacrificing the high efficiency of the CRIS technique. Experimental linewidths of 20(1) MHz were obtained on radioactive beams of francium, allowing us for the first time to determine the electric quadrupole moment of the short lived [t_{1/2}=22.0(5) ms] ^{219}Fr Q_{s}=-1.21(2) eb, which would not have been possible without the advantages offered by the new method. This method relies on a continuous-wave laser and an external Pockels cell to produce narrow-band light pulses, required to reach the high resolution in two-step resonance ionization. Exotic nuclei produced at rates of a few hundred ions/s can now be studied with high resolution, allowing detailed studies of the anchor points for nuclear theories.

Resonance ionization laser ion sources for on-line isotope separators (invited).

A Resonance Ionization Laser Ion Source (RILIS) is today considered an essential component of the majority of Isotope Separator On Line (ISOL) facilities; there are seven laser ion sources currently operational at ISOL facilities worldwide and several more are under development. The ionization mechanism is a highly element selective multi-step resonance photo-absorption process that requires a specifically tailored laser configuration for each chemical element. For some isotopes, isomer selective ionization may even be achieved by exploiting the differences in hyperfine structures of an atomic transition for different nuclear spin states. For many radioactive ion beam experiments, laser resonance ionization is the only means of achieving an acceptable level of beam purity without compromising isotope yield. Furthermore, by performing element selection at the location of the ion source, the propagation of unwanted radioactivity downstream of the target assembly is reduced. Whilst advances in laser technology have improved the performance and reliability of laser ion sources and broadened the range of suitable commercially available laser systems, many recent developments have focused rather on the laser/atom interaction region in the quest for increased selectivity and/or improved spectral resolution. Much of the progress in this area has been achieved by decoupling the laser ionization from competing ionization processes through the use of a laser/atom interaction region that is physically separated from the target chamber. A new application of gas catcher laser ion source technology promises to expand the capabilities of projectile fragmentation facilities through the conversion of otherwise discarded reaction fragments into high-purity low-energy ion beams. A summary of recent RILIS developments and the current status of laser ion sources worldwide is presented.

Collinear resonance ionization spectroscopy of neutron-deficient francium isotopes.

The magnetic moments and isotope shifts of the neutron-deficient francium isotopes (202-205)Fr were measured at ISOLDE-CERN with use of collinear resonance ionization spectroscopy. A production-to-detection efficiency of 1% was measured for (202)Fr. The background from nonresonant and collisional ionization was maintained below one ion in 10(5) beam particles. Through a comparison of the measured charge radii with predictions from the spherical droplet model, it is concluded that the ground-state wave function remains spherical down to (205)Fr, with a departure observed in (203)Fr (N=116).

Measurement of the first ionization potential of astatine by laser ionization spectroscopy.

The radioactive element astatine exists only in trace amounts in nature. Its properties can therefore only be explored by study of the minute quantities of artificially produced isotopes or by performing theoretical calculations. One of the most important properties influencing the chemical behaviour is the energy required to remove one electron from the valence shell, referred to as the ionization potential. Here we use laser spectroscopy to probe the optical spectrum of astatine near the ionization threshold. The observed series of Rydberg states enabled the first determination of the ionization potential of the astatine atom, 9.31751(8) eV. New ab initio calculations are performed to support the experimental result. The measured value serves as a benchmark for quantum chemistry calculations of the properties of astatine as well as for the theoretical prediction of the ionization potential of superheavy element 117, the heaviest homologue of astatine.

Dietary treatment of hypoglycaemia: should the Australian recommendation be increased?

Australian recommendations for treatment of hypoglycaemia are 15 g of carbohydrate repeated at 10-15 min if hypoglycaemia persists. Cited evidence is expert opinion or older studies not pertinent to current insulin regimens. This study aimed to determine the effect of increasing initial treating carbohydrate and decreasing wait-time to retreatment on resolution of hypoglycaemia in 92 free-living adults on current insulin regimens. The results support an initial treatment of 20-g carbohydrate, with a 10-min wait to repeat treatment as an optimal recommendation for the insulin-treated individual self-treating hypoglycaemia.

Upgrade of the resonance ionization laser ion source at ISOLDE on-line isotope separation facility: new lasers and new ion beams.

The resonance ionization laser ion source (RILIS) produces beams for the majority of experiments at the ISOLDE on-line isotope separator. A substantial improvement in RILIS performance has been achieved through a series of upgrade steps: replacement of the copper vapor lasers by a Nd:YAG laser; replacement of the old homemade dye lasers by new commercial dye lasers; installation of a complementary Ti:Sapphire laser system. The combined dye and Ti:Sapphire laser system with harmonics is capable of generating beams at any wavelength in the range of 210-950 nm. In total, isotopes of 31 different elements have been selectively laser-ionized and separated at ISOLDE, including recently developed beams of samarium, praseodymium, polonium, and astatine.

Sustained reduction in tuberculosis incidence following a community-based participatory intervention.

BACKGROUND: Rates of latent tuberculosis infection (LTBI) and tuberculosis (TB) disease are elevated in the rural southeastern United States and among US- and foreign-born Black residents. To prevent TB and reduce TB transmission, community-based strategies are essential. OBJECTIVE: To describe a community-based participatory intervention for improving the detection and treatment of LTBI and TB and reducing TB incidence. DESIGN: In rural Florida, we carried out a community educational TB campaign from 1997 to 2000, including presentations at community events, a media campaign and working with local community groups to develop culturally appropriate prevention messages. The campaign was implemented concurrently with a population-based LTBI survey. RESULTS: The annual TB incidence rate in the intervention area decreased from 81 per 100 000 in 1994-1997, to 42/ 100 000 in 1998-2001, and to 25/100 000 in 2002-2005 (P = 0.001). This decrease was not observed in communities where the intervention was not implemented. There was no decrease in the TB incidence rate ratio between Blacks and non-Blacks in either region during the study period. CONCLUSIONS: We conclude that community participation in LTBI screening and TB education was associated with a substantial reduction in TB rates. Although the TB incidence rate ratio did not decrease between Blacks and non-Blacks, TB incidence fell in all racial groups.

Dual skin tests with Mycobacterium avium sensitin and PPD to detect misdiagnosis of latent tuberculosis infection.

BACKGROUND: A positive tuberculin skin test (TST) may indicate cross-reacting immunity to non-tuberculous mycobacteria (NTM) and not latent tuberculosis infection (LTBI). OBJECTIVES: To assess misclassification of LTBI, as assessed by skin testing with Mycobacterium avium sensitin (MaS), and to determine how this misclassification affects the analysis of risk factors for LTBI. METHODS: In a population-based survey, participants underwent skin testing with M. tuberculosis purified protein derivative (PPD) and MaS. A PPD-dominant skin test was a reaction that was ≥ 3 mm larger than the MaS reaction; a MaS-dominant skin test was a reaction that was ≥ 3 mm larger than the PPD reaction. RESULTS: Of 447 randomly selected persons, 135 (30%) had a positive PPD test. Of these, 21 (16%) were MaS- dominant, and were therefore attributable to NTM and misclassified as LTBI. PPD reactions of 5-14 mm were more likely to be misclassified than those ≥ 15 mm (OR = 5.0, 95%CI 1.9-13.2). Adjusting for misclassification had only a small impact on the analysis of risk factors for LTBI. CONCLUSIONS: A substantial number of individuals who are diagnosed with LTBI are actually sensitized to NTM. Using dual skin testing would reduce misdiagnosis and prevent unnecessary treatment.

Early onset of ground state deformation in neutron deficient polonium isotopes.

In-source resonant ionization laser spectroscopy of the even-A polonium isotopes (192-210,216,218)Po has been performed using the 6p(3)7s (5)S(2) to 6p(3)7p (5)P(2) (λ=843.38 nm) transition in the polonium atom (Po-I) at the CERN ISOLDE facility. The comparison of the measured isotope shifts in (200-210)Po with a previous data set allows us to test for the first time recent large-scale atomic calculations that are essential to extract the changes in the mean-square charge radius of the atomic nucleus. When going to lighter masses, a surprisingly large and early departure from sphericity is observed, which is only partly reproduced by beyond mean field calculations.