Fiber optic reference frequency distribution to remote beam waveguide antennas

In the NASA/JPL Deep Space Network (DSN), radio science experiments (probing outer planet atmospheres, rings, gravitational waves, etc.) and very long-base interferometry (VLBI) require ultra-stable, low phase noise reference frequency signals at the user locations. Typical locations for radio science/VLBI exciters and down-converters are the cone areas of the 34 m high efficiency antennas or the 70 m antennas, located several hundred meters from the reference frequency standards. Over the past three years, fiber optic distribution links have replaced coaxial cable distribution for reference frequencies to these antenna sites. Optical fibers are the preferred medium for distribution because of their low attenuation, immunity to EMI/IWI, and temperature stability. A new network of Beam Waveguide (BWG) antennas presently under construction in the DSN requires hydrogen maser stability at tens of kilometers distance from the frequency standards central location. The topic of this paper is the design and implementation of an optical fiber distribution link which provides ultra-stable reference frequencies to users at a remote BWG antenna. The temperature profile from the earth's surface to a depth of six feet over a time period of six months was used to optimize the placement of the fiber optic cables. In-situ evaluation of the fiber optic link performance indicates Allan deviation on the order of parts in 10(exp -15) at 1000 and 10,000 seconds averaging time; thus, the link stability degradation due to environmental conditions still preserves hydrogen maser stability at the user locations. This paper reports on the implementation of optical fibers and electro-optic devices for distributing very stable, low phase noise reference signals to remote BWG antenna locations. Allan deviation and phase noise test results for a 16 km fiber optic distribution link are presented in the paper

Target template guidance of eye movements during real-world search

Humans must regularly locate task-relevant objects when interacting with the world around them. Previous research has identified different types of information that the visual system can use to help locate objects in real-world scenes, including low-level image features and scene context. However, previous research using object arrays suggest that there may be another type of information that can guide real-world search: target knowledge. When a participant knows what a target looks like they generate and store a visual representation, or template, of it. This template then facilitates the search process. A complete understanding of real-world search needs to identify how a target template guides search through scenes. Three experiments in Chapter 2 confirmed that a target template facilitates realworld search. By using an eye-tracker target knowledge was found to facilitate both scanning and verification behaviours during search, but not the search initiation process. Within the scanning epoch a target template facilitated gaze directing and shortened fixation durations. These results suggest that target knowledge affects both the activation map, which selects which regions of the scene to fixate, and the evaluation process that compares a fixated object to the internal representation of the target. With the exact behaviours that a target template facilitates now identified, Chapter 3 investigated the role that target colour played in template-guided search. Colour is one of the more interesting target features as it has been shown to be preferred by the visual system over other features when guiding search through object arrays. Two real-world search experiments in Chapter 3 found that colour information had its strongest effect on the gaze directing process, suggesting that the visual system relies heavily on colour information when searching for target-similar regions in the scene percept. Although colour was found to facilitate the evaluation process too, both when rejecting a fixated object as a distracter and accepting it as the target, this behaviour was found to be influenced comparatively less. This suggests that the two main search behaviours – gaze directing and region evaluation – rely on different sets of template features. The gaze directing process relies heavily on colour information, but knowledge of other target features will further facilitate the evaluation process. Chapter 4 investigated how target knowledge combined with other types of information to guide search. This is particularly relevant in real-world search where several sources of guidance information are simultaneously available. A single experiment investigated how target knowledge and scene context combined to facilitate search. Both information types were found to facilitate scanning and verification behaviours. During the scanning epoch both facilitated the eye guidance and object evaluation processes. When both information sources were available to the visual system simultaneously, each search behaviour was facilitated additively. This suggests that the visual system processes target template and scene context information independently. Collectively, the results indicate not only the manner in which a target template facilitates real-world search but also updates our understanding of real-world search and the visual system. These results can help increase the accuracy of future realworld search models by specifying the manner in which our visual system utilises target template information, which target features are predominantly relied upon and how target knowledge combines with other types of guidance information

Integrating genome-wide polygenic risk scores and non-genetic risk to predict colorectal cancer diagnosis: a cohort study in UK Biobank

OBJECTIVE: To evaluate the benefit of combining polygenic risk scores with the QCancer-10 (colorectal cancer) prediction model for non-genetic risk to identify people at highest risk of colorectal cancer. DESIGN: Population based cohort study. SETTING: Data from the UK Biobank study, collected between March 2006 and July 2010. PARTICIPANTS: 434 587 individuals with complete data for genetics and QCancer-10 predictions were included in the QCancer-10 plus polygenic risk score modelling and validation cohorts. MAIN OUTCOME MEASURES: Prediction of colorectal cancer diagnosis by genetic, non-genetic, and combined risk models. Using data from UK Biobank, six different polygenic risk scores for colorectal cancer were developed using LDpred2 polygenic risk score software, clumping, and thresholding approaches, and a model based on genome-wide significant polymorphisms. The top performing genome-wide polygenic risk score and the score containing genome-wide significant polymorphisms were combined with QCancer-10 and performance was compared with QCancer-10 alone. Case-control (logistic regression) and time-to-event (Cox proportional hazards) analyses were used to evaluate risk model performance in men and women. RESULTS: Polygenic risk scores derived using the LDpred2 program performed best, with an odds ratio per standard deviation of 1.584 (95% confidence interval 1.536 to 1.633), and top age and sex adjusted C statistic of 0.733 (95% confidence interval 0.710 to 0.753) in logistic regression models in the validation cohort. Integrated QCancer-10 plus polygenic risk score models out-performed QCancer-10 alone. In men, the integrated LDpred2 model produced a C statistic of 0.730 (0.720 to 0.741) and explained variation of 28.2% (26.3 to 30.1), compared with 0.693 (0.682 to 0.704) and 21.0% (18.9 to 23.1) for QCancer-10 alone. In women, the C statistic for the integrated LDpred2 model was 0.687 (0.673 to 0.702) and explained variation was 21.0% (18.7 to 23.7), compared with 0.645 (0.631 to 0.659) and 12.4% (10.3 to 14.6) for QCancer-10 alone. In the top 20% of individuals at highest absolute risk, the sensitivity and specificity of the integrated LDpred2 models for predicting colorectal cancer diagnosis was 47.8% and 80.3% respectively in men, and 42.7% and 80.1% respectively in women, with increases in absolute risk in the top 5% of risk in men of 3.47-fold and in women of 2.77-fold compared with the median. Illustrative decision curve analysis indicated a small incremental improvement in net benefit with QCancer-10 plus polygenic risk score models compared with QCancer-10 alone. CONCLUSIONS: Integrating polygenic risk scores with QCancer-10 modestly improves risk prediction over use of QCancer-10 alone. Given that QCancer-10 data can be obtained relatively easily from health records, use of polygenic risk score in risk stratified population screening for colorectal cancer currently has no clear justification. The added benefit, cost effectiveness, and acceptability of polygenic risk scores should be carefully evaluated in a real life screening setting before implementation in the general population

Phenome-wide association study (PheWAS) of colorectal cancer risk SNP effects on health outcomes in UK Biobank

BACKGROUND: Associations between colorectal cancer (CRC) and other health outcomes have been reported, but these may be subject to biases, or due to limitations of observational studies. METHODS: We set out to determine whether genetic predisposition to CRC is also associated with the risk of other phenotypes. Under the phenome-wide association study (PheWAS) and tree-structured phenotypic model (TreeWAS), we studied 334,385 unrelated White British individuals (excluding CRC patients) from the UK Biobank cohort. We generated a polygenic risk score (PRS) from CRC genome-wide association studies as a measure of CRC risk. We performed sensitivity analyses to test the robustness of the results and searched the Danish Disease Trajectory Browser (DTB) to replicate the observed associations. RESULTS: Eight PheWAS phenotypes and 21 TreeWAS nodes were associated with CRC genetic predisposition by PheWAS and TreeWAS, respectively. The PheWAS detected associations were from neoplasms and digestive system disease group (e.g. benign neoplasm of colon, anal and rectal polyp and diverticular disease). The results from the TreeWAS corroborated the results from the PheWAS. These results were replicated in the observational data within the DTB. CONCLUSIONS: We show that benign colorectal neoplasms share genetic aetiology with CRC using PheWAS and TreeWAS methods. Additionally, CRC genetic predisposition is associated with diverticular disease

The essential value of long-term experimental data for hydrology and water management

We would like to thank the European Research Council ERC for funding the VeWa project and most of Tetzlaff's time (project GA 335910 VeWa). No data were used in producing this manuscript.Peer reviewedPublisher PD

Alcohol consumption, DNA methylation and colorectal cancer risk:Results from pooled cohort studies and Mendelian randomization analysis

Alcohol consumption is thought to be one of the modifiable risk factors for colorectal cancer (CRC). However, the causality and mechanisms by which alcohol exerts its carcinogenic effect are unclear. We evaluated the association between alcohol consumption and CRC risk by analyzing data from 32 cohort studies and conducted two-sample Mendelian randomization (MR) analysis to examine for casual relationship. To explore the effect of alcohol related DNA methylation on CRC risk, we performed an epigenetic MR analysis with data from an epigenome-wide association study (EWAS). We additionally performed gene-alcohol interaction analysis nested in the UK Biobank to assess effect modification between alcohol consumption and susceptibility genes. We discovered distinct effects of alcohol on CRC incidence and mortality from the meta-analyses, and genetic predisposition to alcohol drinking was causally associated with an increased CRC risk (OR = 1.79, 95% CI: 1.23-2.61) using two-sample MR approaches. In epigenetic MR analysis, two alcohol-related CpG sites (cg05593667 and cg10045354 mapped to COLCA1/COLCA2 gene) were identified causally associated with an increased CRC risk (P < 8.20 × 10-4 ). Gene-alcohol interaction analysis revealed that carriage of the risk allele of the eQTL (rs3087967) and mQTL (rs11213823) polymorphism of COLCA1/COLCA2 would interact with alcohol consumption to increase CRC risk (PInteraction  = .027 and PInteraction  = .016). Our study provides comprehensive evidence to elucidate the role of alcohol in CRC and highlights that the pathogenic effect of alcohol on CRC could be partly attributed to DNA methylation by regulating the expression of COLCA1/COLCA2 gene

Precipitation instruments at Rothera Station, Antarctic Peninsula: a comparative study

Direct measurement of precipitation in the Antarctic using ground-based instruments is important to validate the results from climate models, reanalyses and satellite observations. Quantifying precipitation in Antarctica faces many unique challenges such as wind and other technical difficulties due to the harsh environment. This study compares a variety of precipitation measurements in Antarctica, including satellite data and reanalysis fields atRothera Station, Antarctica Peninsula. The tipping bucket gauges (TBGs) were less sensitive than laser-based sensors (LBSs). The most sensitive LBS (Visibility and Present Weather Sensor, VPF-730) registered 276 precipitation days, while the most sensitive TBG (Universal Precipitation Gauge, UPG-1000) detected 152 precipitation days. Case studies of the precipitation and seasonal accumulation results show the VPF-730 to be the most reliable precipitation sensor of the evaluated instruments. The precipitation amounts given by the reanalyses were positively correlated with wind speed. The precipitation from the Japanese 55-year Reanalysis was most affected by wind speed. Case studies also show that during low wind periods, precipitation measurements from the instruments were very close to the precipitation measurement given by the Global Precipitation Climatology Project (GPCP) 1-degree-daily (1DD) data. During strong wind events, the GPCP 1DD did not fully capture the effect of wind, accounting for the relatively small precipitation amount. The Laser Precipitation Monitor (LPM) and Campbell Scientific-700 (CS700H) experienced instrumental errors during the study, which caused the precipitation readings to become exceedingly high and low, respectively. Installing multiple LBSs in different locations (in close proximity) can help identify inconsistency in the readings

Exploring the complex relationship between gut microbiota and risk of colorectal neoplasia using bidirectional Mendelian Randomization analysis

Background: Human gut microbiome has complex relation-ships with the host, contributing to metabolism, immunity, and carcinogenesis. Methods: Summary-level data for gut microbiota and metabo-lites were obtained from MiBioGen, FINRISK and human meta-bolome consortia. Summary-level data for colorectal cancer were derived from a genome-wide association study meta-analysis. In forward Mendelian randomization (MR), we employed genetic instrumental variables (IV) for 24 gut microbiota taxa and six bacterial metabolites to examine their causal relationship with colorectal cancer. We also used a lenient threshold for nine apriori gut microbiota taxa as secondary analyses. In reverse MR, we explored association between genetic liability to colorectal neoplasia and abundance of microbiota studied above using 95, 19, and 7 IVs for colorectal cancer, adenoma, and polyps, respectively. Results: Forward MR did not find evidence indicating causal relationship between any of the gut microbiota taxa or six bacterial metabolites tested and colorectal cancer risk. However, reverse MR supported genetic liability to colorectal adenomas was causally related with increased abundance of two taxa: Gammaproteobacteria (b = 0.027, which represents a 0.027 increase in log-transformed relative abundance values of Gam-maproteobacteria for per one-unit increase in log OR of adenoma risk; P = 7.06x10-8), Enterobacteriaceae (b = 0.023, P = 1.29x10-5). Conclusions: We find genetic liability to colorectal neoplasia may be associated with abundance of certain microbiota taxa. It is more likely that subset of colorectal cancer genetic liability variants changes gut biology by influencing both gut microbiota and colo-rectal cancer risk.Impact: This study highlights the need of future complemen-tary studies to explore causal mechanisms linking both host genetic variation with gut microbiome and colorectal cancer susceptibility

Modifiable pathways for colorectal cancer : a mendelian randomisation analysis

Background Epidemiological studies have linked lifestyle, cardiometabolic, reproductive, developmental, and inflammatory factors to the risk of colorectal cancer. However, which specific factors affect risk and the strength of these effects are unknown. We aimed to examine the relationship between potentially modifiable risk factors and colorectal cancer. Methods We used a random-effects model to examine the relationship between 39 potentially modifiable risk factors and colorectal cancer in 26 397 patients with colorectal cancer and 41 481 controls (ie, people without colorectal cancer). These population data came from a genome-wide association study of people of European ancestry, which was amended to exclude UK BioBank data. In the model, we used genetic variants as instruments via two-sample mendelian randomisation to limit bias from confounding and reverse causation. We calculated odds ratios per genetically predicted SD unit increase in each putative risk factor (OR SD) for colorectal cancer risk. We did mendelian randomisation Egger regressions to identify evidence of potential violations of mendelian randomisation assumptions. A Bonferroni-corrected threshold of p=1.3 x 10(-3) was considered significant, and p values less than 0.05 were considered to be suggestive of an association. Findings No putative risk factors were significantly associated with colorectal cancer risk after correction for multiple testing. However, suggestive associations with increased risk were noted for genetically predicted body fat percentage (OR SD 1.14 [95% CI 1.03-1.25]; p=0.0086), body-mass index (1.09 [1.01-1.17]; p=0.023), waist circumference (1.13 [1.02-1.26]; p=0.018), basal metabolic rate (1.10 [1.03-1.18]; p=0.0079), and concentrations of LDL cholesterol (1.14 [1.04-1.25]; p=0.0056), total cholesterol (1.09 [1.01-1.18]; p=0.025), circulating serum iron (1.17 [1.00-1.36]; p=0.049), and serum vitamin B12 (1.21 [1.04-1.42]; p=0.016), although potential pleiotropy among genetic variants used as instruments for vitamin B12 constrains the finding. A suggestive association was also noted between adult height and increased risk of colorectal cancer (OR SD 1.04 [95% CI 1.00-1.08]; p=0.032). Low blood selenium concentration had a suggestive association with decreased risk of colorectal cancer (OR SD 0.85 [95% CI 0.75-0.96]; p=0.0078) based on a single variant, as did plasma concentrations of interleukin-6 receptor subunit a (also based on a single variant; 0.98 [0.96-1.00]; p=0.035). Risk of colorectal cancer was not associated with any sex hormone or reproductive factor, serum calcium, or circulating 25-hydroxyvitamin D concentrations. Interpretation This analysis identified several modifiable targets for primary prevention of colorectal cancer, including lifestyle, obesity, and cardiometabolic factors, that should inform public health policy. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe

Patient emergency health-care use before hospital admission for COVID-19 and long-term outcomes in Scotland: a national cohort study

BackgroundIt is unclear what effect the pattern of health-care use before admission to hospital with COVID-19 (index admission) has on the long-term outcomes for patients. We sought to describe mortality and emergency readmission to hospital after discharge following the index admission (index discharge), and to assess associations between these outcomes and patterns of health-care use before such admissions.MethodsWe did a national, retrospective, complete cohort study by extracting data from several national databases and linking the databases for all adult patients admitted to hospital in Scotland with COVID-19. We used latent class trajectory modelling to identify distinct clusters of patients on the basis of their emergency admissions to hospital in the 2 years before the index admission. The primary outcomes were mortality and emergency readmission up to 1 year after index admission. We used multivariable regression models to explore associations between these outcomes and patient demographics, vaccination status, level of care received in hospital, and previous emergency hospital use.FindingsBetween March 1, 2020, and Oct 25, 2021, 33 580 patients were admitted to hospital with COVID-19 in Scotland. Overall, the Kaplan-Meier estimate of mortality within 1 year of index admission was 29·6% (95% CI 29·1-30·2). The cumulative incidence of emergency hospital readmission within 30 days of index discharge was 14·4% (95% CI 14·0-14·8), with the number increasing to 35·6% (34·9-36·3) patients at 1 year. Among the 33 580 patients, we identified four distinct patterns of previous emergency hospital use: no admissions (n=18 772 [55·9%]); minimal admissions (n=12 057 [35·9%]); recently high admissions (n=1931 [5·8%]), and persistently high admissions (n=820 [2·4%]). Patients with recently or persistently high admissions were older, more multimorbid, and more likely to have hospital-acquired COVID-19 than patients with no or minimal admissions. People in the minimal, recently high, and persistently high admissions groups had an increased risk of mortality and hospital readmission compared with those in the no admissions group. Compared with the no admissions group, mortality was highest in the recently high admissions group (post-hospital mortality HR 2·70 [95% CI 2·35-2·81]; pInterpretationLong-term mortality and readmission rates for patients hospitalised with COVID-19 were high; within 1 year, one in three patients had died and a third had been readmitted as an emergency. Patterns of hospital use before index admission were strongly predictive of mortality and readmission risk, independent of age, pre-existing comorbidities, and COVID-19 vaccination status. This increasingly precise identification of individuals at high risk of poor outcomes from COVID-19 will enable targeted support.FundingChief Scientist Office Scotland, UK National Institute for Health Research, and UK Research and Innovation