OSSOS III - Resonant Trans-Neptunian Populations: Constraints from the first quarter of the Outer Solar System Origins Survey

The first two observational sky "blocks" of the Outer Solar System Origins Survey (OSSOS) have significantly increased the number of well-characterized observed trans-Neptunian objects (TNOs) in Neptune's mean motion resonances. We describe the 31 securely resonant TNOs detected by OSSOS so far, and we use them to independently verify the resonant population models from the Canada-France Ecliptic Plane Survey (CFEPS; Gladman et al. 2012), with which we find broad agreement. We confirm that the 5:2 resonance is more populated than models of the outer Solar System's dynamical history predict; our minimum population estimate shows that the high eccentricity (e>0.35) portion of the resonance is at least as populous as the 2:1 and possibly as populated as the 3:2 resonance. One OSSOS block was well-suited to detecting objects trapped at low libration amplitudes in Neptune's 3:2 resonance, a population of interest in testing the origins of resonant TNOs. We detected three 3:2 objects with libration amplitudes below the cutoff modeled by CFEPS; OSSOS thus offers new constraints on this distribution. The OSSOS detections confirm that the 2:1 resonance has a dynamically colder inclination distribution than either the 3:2 or 5:2 resonances. Using the combined OSSOS and CFEPS 2:1 detections, we constrain the fraction of 2:1 objects in the symmetric mode of libration to be 0.2-0.85; we also constrain the fraction of leading vs. trailing asymmetric librators, which has been theoretically predicted to vary depending on Neptune's migration history, to be 0.05-0.8. Future OSSOS blocks will improve these constraints.Comment: Accepted for publication in A

Perseveration and Shifting in Obsessive-Compulsive Disorder as a Function of Uncertainty, Punishment, and Serotonergic Medication

© 2023 The Author(s). Published by Elsevier Inc on behalf of the Society of Biological Psychiatry. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/Background The nature of cognitive flexibility deficits in obsessive-compulsive disorder (OCD), which historically have been tested with probabilistic reversal learning tasks, remains elusive. Here, a novel deterministic reversal task and inclusion of unmedicated patients in the study sample illuminated the role of fixed versus uncertain rules/contingencies and of serotonergic medication. Additionally, our understanding of probabilistic reversal was enhanced through theoretical computational modeling of cognitive flexibility in OCD. Methods We recruited 49 patients with OCD, 21 of whom were unmedicated, and 43 healthy control participants matched for age, IQ, and gender. Participants were tested on 2 tasks: a novel visuomotor deterministic reversal learning task with 3 reversals (feedback rewarding/punishing/neutral) measuring accuracy/perseveration and a 2-choice visual probabilistic reversal learning task with uncertain feedback and a single reversal measuring win-stay and lose-shift. Bayesian computational modeling provided measures of learning rate, reinforcement sensitivity, and stimulus stickiness. Results Unmedicated patients with OCD were impaired on the deterministic reversal task under punishment only at the first and third reversals compared with both control participants and medicated patients with OCD, who had no deficit. Perseverative errors were correlated with OCD severity. On the probabilistic reversal task, unmedicated patients were only impaired at reversal, whereas medicated patients were impaired at both the learning and reversal stages. Computational modeling showed that the overall change was reduced feedback sensitivity in both OCD groups. Conclusions Both perseveration and increased shifting can be observed in OCD, depending on test conditions including the predictability of reinforcement. Perseveration was related to clinical severity and remediated by serotonergic medication.Peer reviewe

Natural Language Processing markers in first episode psychosis and people at clinical high-risk.

Funder: MQ: Transforming Mental Health; Grant(s): MQF17_24Recent work has suggested that disorganised speech might be a powerful predictor of later psychotic illness in clinical high risk subjects. To that end, several automated measures to quantify disorganisation of transcribed speech have been proposed. However, it remains unclear which measures are most strongly associated with psychosis, how different measures are related to each other and what the best strategies are to collect speech data from participants. Here, we assessed whether twelve automated Natural Language Processing markers could differentiate transcribed speech excerpts from subjects at clinical high risk for psychosis, first episode psychosis patients and healthy control subjects (total N = 54). In-line with previous work, several measures showed significant differences between groups, including semantic coherence, speech graph connectivity and a measure of whether speech was on-topic, the latter of which outperformed the related measure of tangentiality. Most NLP measures examined were only weakly related to each other, suggesting they provide complementary information. Finally, we compared the ability of transcribed speech generated using different tasks to differentiate the groups. Speech generated from picture descriptions of the Thematic Apperception Test and a story re-telling task outperformed free speech, suggesting that choice of speech generation method may be an important consideration. Overall, quantitative speech markers represent a promising direction for future clinical applications.SEM was supported by the Accelerate Programme for Scientific Discovery, funded by Schmidt Futures, a Fellowship from The Alan Turing Institute, London, and a Henslow Fellowship at Lucy Cavendish College, University of Cambridge, funded by the Cambridge Philosophical Society. PEV is supported by a fellowship from MQ: Transforming Mental Health (MQF17_24). This work was supported by The Alan Turing Institute under the EPSRC grant EP/N510129/1, the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014), the UK Medical Research Council (MRC) and the National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London

Natural Language Processing markers in first episode psychosis and people at clinical high-risk.

Funder: MQ: Transforming Mental Health; Grant(s): MQF17_24Recent work has suggested that disorganised speech might be a powerful predictor of later psychotic illness in clinical high risk subjects. To that end, several automated measures to quantify disorganisation of transcribed speech have been proposed. However, it remains unclear which measures are most strongly associated with psychosis, how different measures are related to each other and what the best strategies are to collect speech data from participants. Here, we assessed whether twelve automated Natural Language Processing markers could differentiate transcribed speech excerpts from subjects at clinical high risk for psychosis, first episode psychosis patients and healthy control subjects (total N = 54). In-line with previous work, several measures showed significant differences between groups, including semantic coherence, speech graph connectivity and a measure of whether speech was on-topic, the latter of which outperformed the related measure of tangentiality. Most NLP measures examined were only weakly related to each other, suggesting they provide complementary information. Finally, we compared the ability of transcribed speech generated using different tasks to differentiate the groups. Speech generated from picture descriptions of the Thematic Apperception Test and a story re-telling task outperformed free speech, suggesting that choice of speech generation method may be an important consideration. Overall, quantitative speech markers represent a promising direction for future clinical applications.SEM was supported by the Accelerate Programme for Scientific Discovery, funded by Schmidt Futures, a Fellowship from The Alan Turing Institute, London, and a Henslow Fellowship at Lucy Cavendish College, University of Cambridge, funded by the Cambridge Philosophical Society. PEV is supported by a fellowship from MQ: Transforming Mental Health (MQF17_24). This work was supported by The Alan Turing Institute under the EPSRC grant EP/N510129/1, the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014), the UK Medical Research Council (MRC) and the National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London

Demographic and Spatiotemporal Patterns of Avian Influenza Infection at the Continental Scale, and in Relation to Annual Life Cycle of a Migratory Host

Since the spread of highly pathogenic avian influenza (HPAI) H5N1 in the eastern hemisphere, numerous surveillance programs and studies have been undertaken to detect the occurrence, distribution, or spread of avian influenza viruses (AIV) in wild bird populations worldwide. To identify demographic determinants and spatiotemporal patterns of AIV infection in long distance migratory waterfowl in North America, we fitted generalized linear models with binominal distribution to analyze results from 13,574 blue-winged teal (Anas discors, BWTE) sampled in 2007 to 2010 year round during AIV surveillance programs in Canada and the United States. Our analyses revealed that during late summer staging (July-August) and fall migration (September-October), hatch year (HY) birds were more likely to be infected than after hatch year (AHY) birds, however there was no difference between age categories for the remainder of the year (winter, spring migration, and breeding period), likely due to maturing immune systems and newly acquired immunity of HY birds. Probability of infection increased non-linearly with latitude, and was highest in late summer prior to fall migration when densities of birds and the proportion of susceptible HY birds in the population are highest. Birds in the Central and Mississippi flyways were more likely to be infected compared to those in the Atlantic flyway. Seasonal cycles and spatial variation of AIV infection were largely driven by the dynamics of AIV infection in HY birds, which had more prominent cycles and spatial variation in infection compared to AHY birds. Our results demonstrate demographic as well as seasonal, latitudinal and flyway trends across Canada and the US, while illustrating the importance of migratory host life cycle and age in driving cyclical patterns of prevalence

Species-specific differences in the Pro-Ala rich region of cardiac myosin binding protein-C

Cardiac myosin binding protein-C (cMyBP-C) is an accessory protein found in the A-bands of vertebrate sarcomeres and mutations in the cMyBP-C gene are a leading cause of familial hypertrophic cardiomyopathy. The regulatory functions of cMyBP-C have been attributed to the N-terminus of the protein, which is composed of tandem immunoglobulin (Ig)-like domains (C0, C1, and C2), a region rich in proline and alanine residues (the Pro-Ala rich region) that links C0 and C1, and a unique sequence referred to as the MyBP-C motif, or M-domain, that links C1 and C2. Recombinant proteins that contain various combinations of the N-terminal domains of cMyBP-C can activate actomyosin interactions in the absence of Ca2+, but the specific sequences required for these effects differ between species; the Pro-Ala region has been implicated in human cMyBP-C whereas the C1 and M-domains appear important in mouse cMyBP-C. To investigate whether species-specific differences in sequence can account for the observed differences in function, we compared sequences of the Pro-Ala rich region in cMyBP-C isoforms from different species. Here we report that the number of proline and alanine residues in the Pro-Ala rich region varies significantly between different species and that the number correlates directly with mammalian body size and inversely with heart rate. Thus, systematic sequence differences in the Pro-Ala rich region of cMyBP-C may contribute to observed functional differences in human versus mouse cMyBP-C isoforms and suggest that the Pro-Ala region may be important in matching contractile speed to cardiac function across species

Impact of vaccination on the association of COVID-19 with cardiovascular diseases: An OpenSAFELY cohort study

Infection with SARS-CoV-2 is associated with an increased risk of arterial and venous thrombotic events, but the implications of vaccination for this increased risk are uncertain. With the approval of NHS England, we quantified associations between COVID-19 diagnosis and cardiovascular diseases in different vaccination and variant eras using linked electronic health records for ~40% of the English population. We defined a ‘pre-vaccination’ cohort (18,210,937 people) in the wild-type/Alpha variant eras (January 2020-June 2021), and ‘vaccinated’ and ‘unvaccinated’ cohorts (13,572,399 and 3,161,485 people respectively) in the Delta variant era (June-December 2021). We showed that the incidence of each arterial thrombotic, venous thrombotic and other cardiovascular outcomes was substantially elevated during weeks 1-4 after COVID-19, compared with before or without COVID-19, but less markedly elevated in time periods beyond week 4. Hazard ratios were higher after hospitalised than non-hospitalised COVID-19 and higher in the pre-vaccination and unvaccinated cohorts than the vaccinated cohort. COVID-19 vaccination reduces the risk of cardiovascular events after COVID-19 infection. People who had COVID-19 before or without being vaccinated are at higher risk of cardiovascular events for at least two years

Characterization of Inhibitory Anti-Duffy Binding Protein II Immunity: Approach to Plasmodium vivax Vaccine Development in Thailand

Plasmodium vivax Duffy binding protein region II (DBPII) is an important vaccine candidate for antibody-mediated immunity against vivax malaria. A significant challenge for vaccine development of DBPII is its highly polymorphic nature that alters sensitivity to neutralizing antibody responses. Here, we aim to characterize naturally-acquired neutralizing antibodies against DBPII in individual Thai residents to give insight into P. vivax vaccine development in Thailand. Anti-DBPII IgG significantly increased in acute vivax infections compared to uninfected residents and naive controls. Antibody titers and functional anti-DBPII inhibition varied widely and there was no association between titer and inhibition activity. Most high titer plasmas had only a moderate to no functional inhibitory effect on DBP binding to erythrocytes, indicating the protective immunity against DBPII binding is strain specific. Only 5 of 54 samples were highly inhibitory against DBP erythrocyte-binding function. Previously identified target epitopes of inhibitory anti-DBPPII IgG (H1, H2 and H3) were localized to the dimer interface that forms the DARC binding pocket. Amino acid polymorphisms (monomorphic or dimorphic) in H1 and H3 protective epitopes change sensitivity of immune inhibition by alteration of neutralizing antibody recognition. The present study indicates Thai variant H1.T1 (R308S), H3.T1 (D384G) and H3.T3 (K386N) are the most important variants for a DBPII candidate vaccine needed to protect P. vivax in Thai residents

Impact of vaccination on the association of COVID-19 with cardiovascular diseases:An OpenSAFELY cohort study

Infection with SARS-CoV-2 is associated with an increased risk of arterial and venous thrombotic events, but the implications of vaccination for this increased risk are uncertain. With the approval of NHS England, we quantified associations between COVID-19 diagnosis and cardiovascular diseases in different vaccination and variant eras using linked electronic health records for ~40% of the English population. We defined a 'pre-vaccination' cohort (18,210,937 people) in the wild-type/Alpha variant eras (January 2020-June 2021), and 'vaccinated' and 'unvaccinated' cohorts (13,572,399 and 3,161,485 people respectively) in the Delta variant era (June-December 2021). We showed that the incidence of each arterial thrombotic, venous thrombotic and other cardiovascular outcomes was substantially elevated during weeks 1-4 after COVID-19, compared with before or without COVID-19, but less markedly elevated in time periods beyond week 4. Hazard ratios were higher after hospitalised than non-hospitalised COVID-19 and higher in the pre-vaccination and unvaccinated cohorts than the vaccinated cohort. COVID-19 vaccination reduces the risk of cardiovascular events after COVID-19 infection. People who had COVID-19 before or without being vaccinated are at higher risk of cardiovascular events for at least two years.</p