Virus-virus interactions impact the population dynamics of influenza and the common cold

The human respiratory tract hosts a diverse community of cocirculating viruses that are responsible for acute respiratory infections. This shared niche provides the opportunity for virus–virus interactions which have the potential to affect individual infection risks and in turn influence dynamics of infection at population scales. However, quantitative evidence for interactions has lacked suitable data and appropriate analytical tools. Here, we expose and quantify interactions among respiratory viruses using bespoke analyses of infection time series at the population scale and coinfections at the individual host scale. We analyzed diagnostic data from 44,230 cases of respiratory illness that were tested for 11 taxonomically broad groups of respiratory viruses over 9 y. Key to our analyses was accounting for alternative drivers of correlated infection frequency, such as age and seasonal dependencies in infection risk, allowing us to obtain strong support for the existence of negative interactions between influenza and noninfluenza viruses and positive interactions among noninfluenza viruses. In mathematical simulations that mimic 2-pathogen dynamics, we show that transient immune-mediated interference can cause a relatively ubiquitous common cold-like virus to diminish during peak activity of a seasonal virus, supporting the potential role of innate immunity in driving the asynchronous circulation of influenza A and rhinovirus. These findings have important implications for understanding the linked epidemiological dynamics of viral respiratory infections, an important step towards improved accuracy of disease forecasting models and evaluation of disease control interventions

HI Clouds Beyond the Galactic Disk

Recent observations in the 21cm line with the Green Bank Telescope have changed our view of the neutral interstellar medium (ISM) in several ways. The new data show that in the inner parts of the Milky Way the disk-halo interface is composed of many discrete HI clouds. The clouds lie in a layer more than one kpc thick and follow Galactic rotation. Their origin and evolution is unknown. In the outer Galaxy, the new data show that the high-velocity cloud Complex H is likely a satellite on a retrograde orbit interacting with some extended component of the Milky Way's ISM. These observations place new constraints on models of the ISM and are directly related to the work of Don Cox and Ron Reynolds.Comment: 8 pages includes 2 figures. To appear in "How Does the Galaxy Work?", eds. E.J. Alfaro, E. Perez, & J. Franco, Kluwer, Proceedings of a Conference held 23-27 June 2003 in Granada, Spai

The relationship between individual differences in spontaneous self-affirmation and affect associated with self-weighing

We investigate whether the tendency to self-affirm in response to threat is associated with how people feel when they weigh themselves. People who were preoccupied with their weight anticipated feeling less negative (Studies 1a and 1b) and felt less negative (Study 2) when self-weighing if they typically affirmed their strengths. Study 3 experimentally manipulated self-affirmation. Although this intervention prompted affirmation of strengths it did not influence how participants felt when they subsequently weighed themselves. Together, the findings suggest that the tendency to spontaneously affirm strengths, but not values or social relations, is associated with the psychological outcomes of self-weighing and thus provide the basis for understanding how such individual differences might moderate how people respond in other self-evaluative contexts

Multimodality treatment for esophageal adenocarcinoma: Multi-center propensity-score matched study

Background: The primary aim of this study was to compare survival from neoadjuvant chemoradiotherapy plus surgery (NCRS) versus neoadjuvant chemotherapy plus surgery (NCS) for the treatment of esophageal or junctional adenocarcinoma. The secondary aims were to compare pathological effects, short-term mortality and morbidity, and to evaluate the effect of lymph node harvest upon survival in both treatment groups. Methods: Data were collected from 10 European centers from 2001 to 2012. Six hundred and eight patients with stage II or III oesophageal or oesophago-gastric junctional adenocarcinoma were included; 301 in the NCRS group and 307 in the NCS group. Propensity score matching and Cox regression analyses were used to compensate for

Complementary methods to investigate the development of clogging within a horizontal sub-surface flow tertiary treatment wetland

A combination of experimental methods was applied at a clogged, horizontal subsurface flow (HSSF) municipal wastewater tertiary treatment wetland (TW) in the UK, to quantify the extent of surface and subsurface clogging which had resulted in undesirable surface flow. The three dimensional hydraulic conductivity profile was determined, using a purpose made device which recreates the constant head permeameter test in-situ. The hydrodynamic pathways were investigated by performing dye tracing tests with Rhodamine WT and a novel multi-channel, data-logging, flow through Fluorimeter which allows synchronous measurements to be taken from a matrix of sampling points. Hydraulic conductivity varied in all planes, with the lowest measurement of 0.1 md1 corresponding to the surface layer at the inlet, and the maximum measurement of 1550 md1 located at a 0.4m depth at the outlet. According to dye tracing results, the region where the overland flow ceased received five times the average flow, which then vertically short-circuited below the rhizosphere. The tracer break-through curve obtained from the outlet showed that this preferential flow-path accounted for approximately 80% of the flow overall and arrived 8 h before a distinctly separate secondary flow-path. The overall volumetric efficiencyof the clogged system was 71% and the hydrology was simulated using a dual-path, dead-zone storage model. It is concluded that uneven inlet distribution, continuous surface loading and high rhizosphere resistance is responsible for the clog formation observed in this system. The average inlet hydraulic conductivity was 2 md1, suggesting that current European design guidelines, which predict that the system will reach an equilibrium hydraulic conductivity of 86 md1, do not adequately describe the hydrology of mature systems

Shift work, clinically significant sleep disorders and mental health in a representative, cross-sectional sample of young working adults

Mental health conditions confer considerable global disease burden in young adults, who are also the highest demographic to work shifts, and of whom 20% meet criteria for a sleep disorder. We aimed to establish the relationship between the combined effect of shift work and sleep disorders, and mental health. The Raine Study is the only longitudinal, population-based birth cohort in the world with gold-standard, Level 1 measurement of sleep (polysomnography, PSG) collected in early adulthood. Participants (aged 22y) underwent in-laboratory PSG and completed detailed sleep questionnaires. Multivariable adjusted robust linear regression models were conducted to explore associations with anxiety (GAD7) and depression (PHQ9), adjusted for sex, health comorbidities, and work hours/week. Data were from 660 employed young adults (27.3% shift workers). At least one clinically significant sleep disorder was present in 18% of shift workers (day, evening and night shifts) and 21% of non-shift workers (p = 0.51); 80% were undiagnosed. Scores for anxiety and depression were not different between shift and non-shift workers (p = 0.29 and p = 0.82); but were higher in those with a sleep disorder than those without (Md(IQR) anxiety: 7.0(4.0-10.0) vs 4.0(1.0-6.0)), and depression: (9.0(5.0-13.0) vs 4.0(2.0-6.0)). Considering evening and night shift workers only (i.e. excluding day shift workers) revealed an interaction between shift work and sleep disorder status for anxiety (p = 0.021), but not depression (p = 0.96), with anxiety scores being highest in those shift workers with a sleep disorder (Md(IQR) 8.5(4.0-12.2). We have shown that clinical sleep disorders are common in young workers and are largely undiagnosed. Measures of mental health do not appear be different between shift and non-shift workers. These findings indicate that the identification and treatment of clinical sleep disorders should be prioritised for young workers as these sleep disorders, rather than shift work per se, are associated with poorer mental health. These negative mental health effects appear to be greatest in those who work evening and/or night shift and have a sleep disorder.Amy C. Reynolds, Bastien Lechat, Yohannes Adama Melaku, Kelly Sansom, Brandon W. J. Brown, Meagan E. Crowther, Sian Wanstall, Kathleen J. Maddison, Jennifer H. Walsh, Leon Straker, Robert J. T. Adams, Nigel McArdle, Peter R. Eastwoo

Gene and environmental risk factors: interplay between CNR1 genetic variants cannabis use, childhood trauma and psychosis [abstract only]

Background: Cannabis use and childhood trauma have been proposed as environmental risk factors for psychosis and its known that gene-environment (G×E) interactions increase the risk of psychosis [1]. In particular, a recent finding suggests a link between genetic variants in the cannabinoid receptor type 1 (CNR1) gene, which encodes CB1 receptors and is expressed widely in the central and peripheral systems, and cannabis playing a role in the multifactorial pathogenesis of psychosis [2]. However, how the genetic variants interact with lifetime cannabis use and other environmental risk factors, such as childhood trauma, underlying psychosis remains challenging. Objective: To investigate whether there are associations of gene and environmental factors with psychosis, as well as G×E interactions in the relationship between lifetime cannabis use, childhood trauma, and single nucleotide variants (SNVs) of CNR1 and psychosis in a Brazilian sample. Methods: In a population-based case-control study nested in an incident study (STREAM, Brazil) [3], part of the WP2 EU-GEI consortium, 143 first-episode psychosis patients (FEPp) and 286 community-based controls of both sexes, aged between 16 and 64 years, were included over a period of three years. Thirteen SNVs of CNR1 gene (rs806380, rs806379, rs1049353, rs6454674, rs1535255, rs2023239, rs12720071, rs6928499, rs806374, rs7766029, rs806378, rs10485170, rs9450898), were genotyped from peripheral blood DNA using a custom Illumina HumanCoreExome-24 BeadChip genotyping arrays (GWAS Cardiff chip). Environmental adversities were evaluated using the Cannabis Experience and the Childhood Trauma Questionnaires. Data were analysed using a binary logistic regression model (Adj OR, 95% CI), including a binary outcome (community-based controls and FEPp), adjusted by sex, age, skin colour, years of education and tobacco smoking. Genotype frequencies were analysed under the dominant model (homozygous ancestral x heterozygous + homozygous variant). The significance level was set at α≤0.05. Results: Lifetime cannabis use and childhood trauma increased the risk for psychosis (OR=3.7; 2.6-6.195% CI, p<0.001; OR=3.0; 1.9-4.7 95% CI, p<0.001, respectively). We also showed that the presence of CNR1 rs12720071-T-allele moderated the association between lifetime cannabis use and psychosis (OR=6.0; 2.0-17.5 95% CI; p=0.001). Moreover, the combination of CNR1 rs12720071-T-allele carriers with childhood trauma also suggests a change in the risk of psychosis (OR=3.6; 1.4-9.0 95% CI; p=0.006). No significant associations between the environmental factors and other SNVs were found. Conclusions: We demonstrated a significant interaction between CNR1 rs12720071 SNV and two important environmental risk factors in their association with psychosis. T allele carriers of CNR1 rs12720071 had a higher risk of psychosis when lifetime cannabis use or childhood trauma were present. Our results suggest a G×E interaction involving the CNR1 gene, trauma and cannabis in psychosis. We will explore the associations between genetic and epigenetic markers of the CNR1 gene with environmental factors in larger and longer follow-up cohorts to better understand the mechanisms of endocannabinoid system dysfunction in the etiology of psychosis

Effect of D2R, NMDAR and CB1R genetic variants associated with cannabis use and childhood trauma in first-episode psychosis in a Brazilian population [abstract only]

Introduction Gene-environment interactions increase psychosis risk (Gayer-Anderson et al. Soc Psychiatry Psychiatr Epidemiol 2020; 55(5):645-657). However, identifying the genetic variants involved and how they interact with environmental risk factors underlying psychosis remains challenging. Objectives To investigate whether there are gene-environment interactions in the relationships of childhood trauma, lifetime cannabis use, and single nucleotide variants (SNVs) of dopamine D2 receptor (D2R: DRD2), N-methyl-d-aspartate receptor (NMDAR: GRIN1, GRIN2A and GRIN2B) and cannabinoid receptor type 1 (CB1R: CNR1) with psychosis. Methods In a population-based case-control study nested in an incident study (STREAM, Brazil) (Del-Ben et al. Br J of Psychiatry 2019; 215(6):726-729), part of the EU-GEI consortium (Gayer-Anderson et al. Soc Psychiatry Psychiatr Epidemiol 2020; 55(5):645-657), 143 first-episode psychosis patients and 286 community-based controls of both sexes aged between 16 and 64 years were included over a period of 3 years. Twenty-three SNVs of D2R (rs1799978, rs7131056, rs6275), NMDAR (GRIN1: rs4880213, rs11146020; GRIN2A: rs1420040, rs11866328; GRIN2B: rs890, rs2098469, rs7298664), and CB1R genes (CNR1: rs806380, rs806379, rs1049353, rs6454674, rs1535255, rs2023239, rs12720071, rs6928499, rs806374, rs7766029, rs806378, rs10485170, rs9450898), were genotyped from peripheral blood DNA using a custom Illumina HumanCoreExome-24 BeadChip. Environmental adversities were evaluated using the Cannabis Experience Questionnaire (Di Forti et al. The Lancet Psychiatry 2009; 6(5):427–436) and the Childhood Trauma Questionnaire (Grassi-Oliveira et al. Rev Saude Publica 2006; 40(2):249-55). Associations between SNVs and environmental risk factors were performed using the nonparametric multifactor dimensionality reduction software (version 3.0.2). Results Single locus analysis showed no association among the 23 SNVs with psychosis; however, gene-environment analysis was significant for the polymorphic loci rs12720071 and rs7766029 in CNR1. The best association models were the two-factor representing by the combination of CNR1 rs12720071 with lifetime cannabis use (p<0.001), and CNR1 rs12720071 with childhood trauma (p<0.05), both suggesting an increased risk of psychosis. Additionally, when considering the interaction of both environmental factors in the same model, we found CNR1 rs7766029 to be associated with psychosis (p<0.001). Conclusions Our study supports the hypothesis of gene-environment interactions for psychosis involving the T allele carriers of CNR1 SNVs (rs12720071 and rs7766029), childhood trauma and lifetime cannabis use in psychosis

A High Statistics Search for Ultra-High Energy Gamma-Ray Emission from Cygnus X-3 and Hercules X-1

We have carried out a high statistics (2 Billion events) search for ultra-high energy gamma-ray emission from the X-ray binary sources Cygnus X-3 and Hercules X-1. Using data taken with the CASA-MIA detector over a five year period (1990-1995), we find no evidence for steady emission from either source at energies above 115 TeV. The derived upper limits on such emission are more than two orders of magnitude lower than earlier claimed detections. We also find no evidence for neutral particle or gamma-ray emission from either source on time scales of one day and 0.5 hr. For Cygnus X-3, there is no evidence for emission correlated with the 4.8 hr X-ray periodicity or with the occurrence of large radio flares. Unless one postulates that these sources were very active earlier and are now dormant, the limits presented here put into question the earlier results, and highlight the difficulties that possible future experiments will have in detecting gamma-ray signals at ultra-high energies.Comment: 26 LaTeX pages, 16 PostScript figures, uses psfig.sty to be published in Physical Review

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types