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

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

Towards an advanced 3D-printed catalyst for hydrogen peroxide decomposition: Development and characterisation

The propellant form of hydrogen peroxide is a non-toxic alternative to hydrazine. However, catalysts used to induce hydrogen peroxide decomposition are often plagued by low melting point, high pressure drop and poor activity. 3D-printing may offer solutions to many of these issues, through the realisation of complex geometries such as triply-periodic minimal surfaces (TPMS). In this work, methods to print and coat such ceramic catalyst supports were developed. A flow reactor was used to quickly screen the catalysts and assess the influence of the chosen active phase, precursor, and support sintering temperature on their intrinsic activity. Platinum prepared from H2PtCl6 emerged as the most active catalyst, with a support sintering temperature of 1200 °C yielding the highest BET surface area. The latter was strongly correlated to catalytic activity. On a per weight basis, the printed Pt catalyst outperformed conventional silver screens and also matched the performance of Pt on a high surface area commercial support, due to its egg-shell distribution. These findings have laid the groundwork for future testing in a thruster configuration, where the proposed advantages of the 3D-printed structures will be evaluated

Low Fidelity Imitation of Atypical Biological Kinematics in Autism Spectrum Disorders Is Modulated by Self-Generated Selective Attention.

We examined whether adults with autism had difficulty imitating atypical biological kinematics. To reduce the impact that higher-order processes have on imitation we used a non-human agent model to control social attention, and removed end-state target goals in half of the trials to minimise goal-directed attention. Findings showed that only neurotypical adults imitated atypical biological kinematics. Adults with autism did, however, become significantly more accurate at imitating movement time. This confirmed they engaged in the task, and that sensorimotor adaptation was self-regulated. The attentional bias to movement time suggests the attenuation in imitating kinematics might be a compensatory strategy due to deficits in lower-level visuomotor processes associated with self-other mapping, or selective attention modulated the processes that represent biological kinematics

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

2-Mercapto-Quinazolinones as Inhibitors of Type II NADH Dehydrogenase and Mycobacterium tuberculosis:Structure-Activity Relationships, Mechanism of Action and Absorption, Distribution, Metabolism, and Excretion Characterization

<i>Mycobacterium tuberculosis</i> (<i>MTb</i>) possesses two nonproton pumping type II NADH dehydrogenase (NDH-2) enzymes which are predicted to be jointly essential for respiratory metabolism. Furthermore, the structure of a closely related bacterial NDH-2 has been reported recently, allowing for the structure-based design of small-molecule inhibitors. Herein, we disclose <i>MTb</i> whole-cell structure–activity relationships (SARs) for a series of 2-mercapto-quinazolinones which target the <i>ndh</i> encoded NDH-2 with nanomolar potencies. The compounds were inactivated by glutathione-dependent adduct formation as well as quinazolinone oxidation in microsomes. Pharmacokinetic studies demonstrated modest bioavailability and compound exposures. Resistance to the compounds in <i>MTb</i> was conferred by promoter mutations in the alternative nonessential NDH-2 encoded by <i>ndhA</i> in <i>MTb</i>. Bioenergetic analyses revealed a decrease in oxygen consumption rates in response to inhibitor in cells in which membrane potential was uncoupled from ATP production, while inverted membrane vesicles showed mercapto-quinazolinone-dependent inhibition of ATP production when NADH was the electron donor to the respiratory chain. Enzyme kinetic studies further demonstrated noncompetitive inhibition, suggesting binding of this scaffold to an allosteric site. In summary, while the initial <i>MTb</i> SAR showed limited improvement in potency, these results, combined with structural information on the bacterial protein, will aid in the future discovery of new and improved NDH-2 inhibitors

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

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