Comparison of Different Strategies for Providing Fecal Microbiota Transplantation to Treat Patients with Recurrent Clostridium difficile Infection in Two English Hospitals: A Review

Fecal microbiota transplant (FMT) has emerged as a highly efficacious treatment for difficult cases of refractory and/or recurrent Clostridium difficile infection (CDI). There have been many well-conducted randomized controlled trials and thousands of patients reported in case series that describe success rates of approximately 90% following one or more FMT. Although the exact mechanisms of FMT have yet to be fully elucidated, replacement or restoration of a ‘normal’ microbiota (or at least a microbiota resembling those who have never had CDI) appears to have a positive effect on the gut dysbiosis that is thought to exist in these patients. Furthermore, despite being aesthetically unappealing, this ‘ultimate probiotic’ is a particularly attractive solution to a difficult problem that avoids repeated courses of antibiotics. The lack of clarity about the exact mechanism of action and the ‘active ingredient’ of FMT (e.g., individual or communities of bacteria, bacteriophage, or bioactive molecules such as bile acids) has hindered the ability to produce a standardized and well-characterized FMT product. There is no standard method to produce material for FMT, and there are a multitude of factors that can vary between institutions that offer this therapy. Only a few studies have directly compared clinical efficacy in groups of patients who have been treated with FMT prepared differently (e.g., fresh vs. frozen) or administered by different route (e.g., by nasojejunal tube, colonoscopy or by oral administration of encapsulated product). More of these studies should be undertaken to clarify the superiority or otherwise of these variables. This review describes the methods and protocols that two English NHS hospitals independently adopted over the same time period to provide FMT for patients with recurrent CDI. There are several fundamental differences in the methods used, including selection and testing of donors, procedures for preparation and storage of material, and route of administration. These methods are described in detail in this review highlighting differing practice. Despite these significant methodological variations, clinical outcomes in terms of cure rate appear to be remarkably similar for both FMT providers. Although both hospitals have treated only modest numbers of patients, these findings suggest that many of the described differences may not be critical factors in influencing the success of the procedure. As FMT is increasingly being proposed for a number of conditions other than CDI, harmonization of methods and techniques may be more critical to the success of FMT, and thus it will be important to standardize these as far as practically possible

Psychosis in autism: comparison of the features of both conditions in a dually affected cohort.

BackgroundThere is limited information on the presentation and characteristics of psychotic illness experienced by people with autism spectrum disorder (ASD).AimsTo describe autistic and psychotic phenomenology in a group of individuals with comorbid ASD and psychosis (ASD-P) and compare this group with populations affected by either, alone.MethodWe studied 116 individuals with ASD-P. We compared features of their ASD with people with ASD and no comorbid psychosis (ASD-NP), and clinical characteristics of psychosis in ASD-P with people with psychosis only.ResultsIndividuals with ASD-P had more diagnoses of atypical psychosis and fewer of schizophrenia compared with individuals with psychosis only. People with ASD-P had fewer stereotyped interests/behaviours compared with those with ASD-NP.ConclusionsOur data show there may be a specific subtype of ASD linked to comorbid psychosis. The results support findings that psychosis in people with ASD is often atypical, particularly regarding affective disturbance.Medical Research Council (PhD studentship, Autism Imaging Multicentre Study (MRC AIMS) Consortium), Baily Thomas Charitable Trust, Health Foundation, University of Cambridge (William Binks Autism Neuroscience Fellowship), Child and Youth Mental Health Collaborative at the Centre for Addiction and Mental Health and The Hospital for Sick Children, Toronto (O’Brien Scholars Program), Autism Research Trust, National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care East of England at the Cambridgeshire & Peterborough NHS Foundation TrustThis is the final version of the article. It first appeared from The Royal College of Psychiatrists via https://doi.org/10.1192/bjp.bp.116.18768

Novel approach to estimate tuberculosis transmission in primary care clinics in sub-Saharan Africa: protocol of a prospective study.

INTRODUCTION Tuberculosis (TB) transmission is difficult to measure, and its drivers are not well understood. The effectiveness of infection control measures at healthcare clinics and the most appropriate intervention strategies to interrupt transmission are unclear. We propose a novel approach using clinical, environmental and position-tracking data to study the risk of TB transmission at primary care clinics in TB and HIV high burden settings in sub-Saharan Africa. METHODS AND ANALYSIS We describe a novel and rapid study design to assess risk factors for airborne TB transmission at primary care clinics in high-burden settings. The study protocol combines a range of different measurements. We will collect anonymous data on the number of patients, waiting times and patient movements using video sensors. Also, we will collect acoustic sound recordings to determine the frequency and intensity of coughing. Environmental data will include indoor carbon dioxide levels (CO2 in parts per million) and relative humidity. We will also extract routinely collected clinical data from the clinic records. The number of Mycobacterium tuberculosis particles in the air will be ascertained from dried filter units using highly sensitive digital droplet PCR. We will calculate rebreathed air volume based on people density and CO2 levels and develop a mathematical model to estimate the risk of TB transmission. The mathematical model can then be used to estimate the effect of possible interventions such as separating patient flows or improving ventilation in reducing transmission. The feasibility of our approach was recently demonstrated in a pilot study in a primary care clinic in Cape Town, South Africa. ETHICS AND DISSEMINATION The study was approved by the University of Cape Town (HREC/REF no. 228/2019), the City of Cape Town (ID-8139) and the Ethics Committee of the Canton Bern (2019-02131), Switzerland. The results will be disseminated in international peer-reviewed journals

The Lyot Project Direct Imaging Survey of Substellar Companions: Statistical Analysis and Information from Nondetections

The Lyot project used an optimized Lyot coronagraph with Extreme Adaptive Optics at the 3.63m Advanced Electro-Optical System telescope (AEOS) to observe 86 stars from 2004 to 2007. In this paper we give an overview of the survey results and a statistical analysis of the observed nondetections around 58 of our targets to place constraints on the population of substellar companions to nearby stars. The observations did not detect any companion in the substellar regime. Since null results can be as important as detections, we analyzed each observation to determine the characteristics of the companions that can be ruled out. For this purpose we use a Monte Carlo approach to produce artificial companions, and determine their detectability by comparison with the sensitivity curve for each star. All the non-detection results are combined using a Bayesian approach and we provide upper limits on the population of giant exoplanets and brown dwarfs for this sample of stars. Our nondetections confirm the rarity of brown dwarfs around solar-like stars and we constrain the frequency of massive substellar companions (M>40Mjup) at orbital separation between and 10 and 50 AU to be <20%.Comment: 32 pages, 11 figures, 2 tables. Published in the Astrophysical Journa

Failure to confirm allelic and haplotypic association between markers at the chromosome 6p22.3 dystrobrevin-binding protein 1 (DTNBP1) locus and schizophrenia

Background: Previous linkage and association studies may have implicated the Dystrobrevin-binding protein 1 (DTNBP1) gene locus or a gene in linkage disequilibrium with DTNBP1 on chromosome 6p22.3 in genetic susceptibility to schizophrenia.Methods: We used the case control design to test for of allelic and haplotypic association with schizophrenia in a sample of four hundred and fifty research subjects with schizophrenia and four hundred and fifty ancestrally matched supernormal controls. We genotyped the SNP markers previously found to be significantly associated with schizophrenia in the original study and also other markers found to be positive in subsequent studies.Results: We could find no evidence of allelic, genotypic or haplotypic association with schizophrenia in our UK sample.Conclusion: The results suggest that the DTNBP1 gene contribution to schizophrenia must be rare or absent in our sample. The discrepant allelic association results in previous studies of association between DTNBP1 and schizophrenia could be due population admixture. However, even positive studies of European populations do not show any consistent DTNBP1 alleles or haplotypes associated with schizophrenia. Further research is needed to resolve these issues. The possible confounding of linkage with association in family samples already showing linkage at 6p22.3 might be revealed by testing genes closely linked to DTNBP1 for allelic association and by restricting family based tests of association to only one case per family

Population screening for colorectal cancer means getting FIT:the past, present, and future of colorectal cancer screening using the fecal immunochemical test for hemoglobin (FIT)

Fecal immunochemical tests for hemoglobin (FIT) are changing the manner in which colorectal cancer (CRC) is screened. Although these tests are being performed worldwide, why is this test different from its predecessors? What evidence supports its adoption? How can this evidence best be used? This review addresses these questions and provides an understanding of FIT theory and practices to expedite international efforts to implement the use of FIT in CRC screening

The stellar halo of the Galaxy

Stellar halos may hold some of the best preserved fossils of the formation history of galaxies. They are a natural product of the merging processes that probably take place during the assembly of a galaxy, and hence may well be the most ubiquitous component of galaxies, independently of their Hubble type. This review focuses on our current understanding of the spatial structure, the kinematics and chemistry of halo stars in the Milky Way. In recent years, we have experienced a change in paradigm thanks to the discovery of large amounts of substructure, especially in the outer halo. I discuss the implications of the currently available observational constraints and fold them into several possible formation scenarios. Unraveling the formation of the Galactic halo will be possible in the near future through a combination of large wide field photometric and spectroscopic surveys, and especially in the era of Gaia.Comment: 46 pages, 16 figures. References updated and some minor changes. Full-resolution version available at http://www.astro.rug.nl/~ahelmi/stellar-halo-review.pd

G Protein Subunit Dissociation and Translocation Regulate Cellular Response to Receptor Stimulation

We examined the role of G proteins in modulating the response of living cells to receptor activation. The response of an effector, phospholipase C-β to M3 muscarinic receptor activation was measured using sensors that detect the generation of inositol triphosphate or diacylglycerol. The recently discovered translocation of Gβγ from plasma membrane to endomembranes on receptor activation attenuated this response. A FRET based G protein sensor suggested that in contrast to translocating Gβγ, non-translocating Gβγ subunits do not dissociate from the αq subunit on receptor activation leading to prolonged retention of the heterotrimer state and an accentuated response. M3 receptors with tethered αq induced differential responses to receptor activation in cells with or without an endogenous translocation capable γ subunit. G protein heterotrimer dissociation and βγ translocation are thus unanticipated modulators of the intensity of a cell's response to an extracellular signal

Discovery and Characterization of a Faint Stellar Companion to the A3V Star Zeta Virginis

Through the combination of high-order Adaptive Optics and coronagraphy, we report the discovery of a faint stellar companion to the A3V star zeta Virginis. This companion is ~7 magnitudes fainter than its host star in the H-band, and infrared imaging spanning 4.75 years over five epochs indicates this companion has common proper motion with its host star. Using evolutionary models, we estimate its mass to be 0.168+/-.016 solar masses, giving a mass ratio for this system q = 0.082. Assuming the two objects are coeval, this mass suggests a M4V-M7V spectral type for the companion, which is confirmed through integral field spectroscopic measurements. We see clear evidence for orbital motion from this companion and are able to constrain the semi-major axis to be greater than 24.9 AU, the period > 124$ yrs, and eccentricity > 0.16. Multiplicity studies of higher mass stars are relatively rare, and binary companions such as this one at the extreme low end of the mass ratio distribution are useful additions to surveys incomplete at such a low mass ratio. Moreover, the frequency of binary companions can help to discriminate between binary formation scenarios that predict an abundance of low-mass companions forming from the early fragmentation of a massive circumstellar disk. A system such as this may provide insight into the anomalous X-ray emission from A stars, hypothesized to be from unseen late-type stellar companions. Indeed, we calculate that the presence of this M-dwarf companion easily accounts for the X-ray emission from this star detected by ROSAT.Comment: 9 pages, 6 figures, Accepted to Ap