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Pathway-specific Polygenic Risk Scores (PRS) identify OSA-related pathways differentially moderating genetic susceptibility to CAD
No full textBackground—Obstructive sleep apnea (OSA) and its features, such as chronic intermittent hypoxia (IH), may differentially affect specific molecular pathways and processes in the pathogenesis of coronary artery disease (CAD) and influence the subsequent risk and severity of CAD events. In particular, competing adverse (e.g. inflammatory) and protective (e.g. increased coronary collateral blood flow) mechanisms may operate, but remain poorly understood. We hypothesize that common genetic variation in selected molecular pathways influences the likelihood of CAD events differently in individuals with and without OSA, in a pathway-dependent manner. Methods—We selected a cross-sectional sample of 471,877 participants from the UK Biobank, among whom we ascertained 4,974 to have OSA, 25,988 to have CAD, and 711 to have both. We calculated pathway-specific polygenic risk scores (PS-PRS) for CAD, based on 6.6 million common variants evaluated in the CARDIoGRAMplusC4D genome-wide association study (GWAS), annotated tospecific genes and pathways using functional genomics databases. Based on evidence of involvement with IH and CAD, we tested PS-PRS for the HIF-1, VEGF, NFkB and TNF signaling pathways. Results—In a multivariable-adjusted logistic generalized additive model, elevated PS-PRSs for the KEGG VEGF pathway (39 genes) associated with protection for CAD in OSA (interaction odds ratio 0.86, p = 6E-04). By contrast, the genome-wide CAD PRS did not show evidence of statistical interaction with OSA.Conclusions—We find evidence that pathway-specific genetic risk of CAD differs between individuals with and without OSA in a qualitatively pathway-dependent manner, consistent with the previously studied phenomena whereby features of OSA may have both positive and negative effects on CAD. These results provide evidence that gene-by-environment interaction influences CAD riskin certain pathways among people with OSA, an effect that is not well-captured by the genome-wise wide PRS. These results can be followed up to study how OSA interacts with genetic risk at the molecular level, and potentially to personalize OSA treatment and reduce CAD risk according to individual pathway-specific genetic risk profiles
Stitches and patches: The Franciscan habit in an engraving by Lucas Vorsterman
No full textAn early seventeenth century engraving by Lucas Vorsterman held by the National Gallery of Victoria and catalogued as the ‘Death of Saint Francis’ depicts the saint in a habit which shows clear wear and repair: there are frayed edges at the ends of the sleeves and several patches have been added. Focusing on Vorsterman’s engraving, this article explores the importance ascribed to the making and mending of the Franciscan habit - and the ways in which this could be indicated in prints from the late sixteenth to mid seventeenth century - with particular reference to the value placed on stitching
Direct propylene epoxidation with molecular oxygen over cobalt-containing zeolites
No full textDirect propylene epoxidation with molecular oxygen is a dream reaction with 100 % atom economy, but the aerobic epoxidation is challenging due to the undesired over-oxidation and isomerization of epoxide product. Herein, we report the construction of uniform cobalt ions confined in faujasite zeolite, namely Co@Y, which exhibits unprecedented catalytic performance in the aerobic epoxidation of propylene. Propylene conversion of 24.6 % is achieved at propylene oxide selectivity of 57 % at 773 K, giving a state-of-the-art propylene oxide production rate of 4.7 mmol/gcat/h. The catalytic performance of Co@Y is very stable and no activity loss can be observed for over 200 h. Spectroscopic analyses reveal the details of molecular oxygen activation on isolated cobalt ions followed by interaction with propylene to produce epoxide, in which the Co2+-Coδ+-Co2+ (2<δ<3) redox cycle is involved. The reaction pathway of propylene oxide and byproduct acrolein formation from propylene epoxidation is investigated by density functional theory calculations, and the unique catalytic performance of Co@Y is interpreted. This work presents an explicit example of constructing specific transition metal ions within zeolite matrix toward selective catalytic oxidations.<br/
Formation-containment tracking and scaling for multiple quadcopters with an application to choke-point navigation
No full textThis paper investigates the cooperative control problem of choke-point navigation for multiple quadcopters when only their subgroup is equipped with obstacle detecting sensors. We define a quadcopter as a leader if it is equipped with an obstacle detecting sensor; otherwise, it is a follower. In addition, we introduce a virtual leader agent to create the group motion. First, we apply the leader-follower approach and propose a formation-containment tracking controller for multiple quadcopters to track the time-varying velocity of the virtual leader agent. At the same time, the leader quadcopters form the prescribed formation while the follower quadcopters converge inside a safe region, which is the convex hull spanned by those leaders. Then, we introduce a scaling vector into the displacement-based formation constraints. When the leader quadcopters identify the choke-point via their obstacle detecting sensors, they update the scaling variable to adjust the size of the formation (i.e. the safe region) and guide all quadcopters to safely pass through the choke-point. The proposed cooperative controllers are distributed because each quadcopter’s control command only relies on the information states from its neighbours. Finally, two autonomous flight experiments, including formation-containment tracking and choke-point navigation, are provided to validate the effectiveness of the proposed cooperative control laws
Governance choice misfit and firm performance in offshoring innovation: The role of institutional environment
No full textIn this paper, we analyse the effect of institutional factors on the relationship between governance choices and business outcomes when offshoring innovation. Grounded in an institutional theory perspective, we use survey data from the ORN database to estimate regression models and identify governance modes related to specific drivers of offshore innovation. We then analyse the effect on firm performance of choosing a governance mode not in line with the one predicted by the model. We find that choosing a fully owned offshoring operation when theory would predict selecting offshore outsourcing has a negative effect on performance, but not vice versa. We also find that institutional factors of rule of law and IPR protection strength in host countries negatively affect firm performance when offshoring innovation activities
ADBSat: Verification and validation of a novel panel method for quick aerodynamic analysis of satellites
No full textWe present the validation of ADBSat, a novel implementation of the panel method including a fast pseudo-shading algorithm, that can quickly and accurately determine the forces and torques on satellites in free-molecular flow. Our main method of validation is comparing test cases between ADBSat, the current de facto standard of direct simulation Monte Carlo (DSMC), and published literature. ADBSat exhibits a significantly shorter runtime than DSMC and performs well, except where deep concavities are present in the satellite models. The shading algorithm also experiences problems when a large proportion of the satellite surface area is oriented parallel to the flow, but this can be mitigated by examining the body at small angles to this configuration (± 0.1◦). We recommend that an error interval on ADBSat outputs of up to 3% is adopted. Therefore, ADBSat is a suitable tool for quickly determining the aerodynamic characteristics of a wide range of satellite geometries in different environmental conditions in VLEO. It can also be used in a complementary manner to identify cases that warrant further investigation using other numerical-based methods.<br/
Ageing in Place over time::The making and unmaking of home
No full text‘Ageing in place’ is a key component of UK policy, aimed at supporting older people to remain living in their own homes and communities for as long as possible. Although wide-ranging, the scholarly literature in this field has not sufficiently examined the interconnections between ageing in place and the changing experience of ‘home’ over time. This paper addresses this gap in a novel way by bringing together qualitative secondary analysis of longitudinal data with critical literature on ‘home’ and Mason’s (2018) cutting-edge theories of ‘affinities’ to understand the multi-dimensionality of home in relation to ageing in place. The paper makes significant methodological, empirical, and theoretical contributions to the field of scholarship on home, by demonstrating how homes are made and unmade over time. Discussions of home emerged organically in the longitudinal data that focused on people’s travel and transport use, allowing our qualitative secondary analysis approach to look anew at how experiences of home are dynamically shaped by people’s potent connections inside and outside the dwelling. Presenting an empirical analysis of four case studies, the paper suggests that future discussions in the field of ageing in place should pay closer attention to the factors which shape experiences of the un/making of home over time, such as how deteriorating physical and mental health can shape how people experience their dwelling and neighbourhood as well as their relationships across these settings.<br/
Bias-Variance Decompositions for Margin Losses
No full textWe introduce a novel bias-variance decomposition for a range of strictly convex margin losses, including the logistic loss (minimized by the classic LogitBoost algorithm), as well as the squared margin loss and canonical boosting loss. Furthermore, we show that, for all strictly convex margin losses, the expected risk decomposes into the risk of a “central” model and a term quantifying variation in the functional margin with respect to variations in the training data. These decompositions provide a diagnostic tool for practitioners to understand model overfitting/underfitting, and have implications for additive ensemble models—for example, when our bias-variance decomposition holds, there is a corresponding “ambiguity” decomposition, which can be used to quantify model diversity.<br/
Combined statistical decision limits based on two GH-2000 scores for the detection of growth hormone misuse
No full textThe GH-2000 biomarker method, based on the measurements of insulin-like growth factor-I (IGF-I) and the amino-terminal pro-peptide of type III collagen (P-III-NP), has been developed as a powerful technique for the detection of growth hormone (GH) misuse by athletes. IGF-I and P-III-NP are combined in gender specific formulas to create the GH-2000 score, which is used to determine whether GH has been administered. To comply with World Anti-Doping Agency regulations, each analyte must be measured by two methods. IGF-I and P-III-NP can be measured by a number of approved methods, each leading to its own GH-2000 score. Single decision limits for each GH-2000 score have been introduced and developed by Bassett, Erotokritou-Mulligan, Holt, Boehning and their co-authors in a series of papers. These have been incorporated into the guidelines of the World Anti-Doping Agency. A joint decision limit was constructed based on the sample correlation between the two GH-2000 scores generated from an available sample in order to increase the sensitivity of the biomarker method. This paper takes this idea further into a fully developed statistical approach. It constructs combined decision limits when two GH-2000 scores from different assay combinations are used to decide whether an athlete has been misusing GH. The combined decision limits are directly related to tolerance regions and constructed using a Bayesian approach. It is also shown to have highly satisfactory frequentist properties. The new approach meets the required false-positive rate with a pre-specified level of certainty