Systematic versus opportunistic risk assessment for the primary prevention of cardiovascular disease

Background Screening programmes can potentially identify people at high cardiovascular risk and reduce cardiovascular disease (CVD) morbidity and mortality. However, there is currently not enough evidence showing clear clinical or economic benefits of systematic screening-like programmes over the widely practised opportunistic risk assessment of CVD in primary care settings. Objectives The primary objective of this review was to assess the effectiveness, costs and adverse effects of systematic risk assessment compared to opportunistic risk assessment for the primary prevention of CVD. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) on the Cochrane Library, MEDLINE, EMBASE on 30 January 2015, and Web of Science Core Collection and additional databases on the Cochrane Library on 4 December 2014. We also searched two clinical trial registers and checked reference lists of relevant articles. We applied no language restrictions. Selection criteria We selected randomised controlled trials (RCTs) that assessed the effects of systematic risk assessment, defined as a screening-like programme involving a predetermined selection process of people, compared with opportunistic risk assessment which ranged from no risk assessment at all to incentivised case finding of CVD and related risk factors. Participants included healthy adults from the general population, including those who are at risk of CVD. Data collection and analysis Two review authors independently selected studies. One review author extracted data and assessed them for risk of bias and a second checked them. We assessed evidence quality using the GRADE approach and present this in a ’Summary of findings’ table. Main results Nine completed RCTs met the inclusion criteria, of which four were cluster-randomised. We also identified five ongoing trials. The included studies had a high or unclear risk of bias, and the GRADE ratings of overall quality were low or very low. The length of follow-up varied from one year in four studies, three years in one study, five or six years in two studies, and ten years in two studies. Eight studies recruited participants from the general population, although there were differences in the age ranges targeted. One study recruited family members of cardiac patients (high risk assessment). There were considerable differences between the studies in the interventions received by the intervention and control groups. There was insufficient evidence to stratify by the types of risk assessment approaches. Limited data were available on all-cause mortality (risk ratio (RR) 0.97, 95% confidence interval (CI) 0.92 to 1.02; 3 studies,103,571 participants, I² = 0%; low-quality evidence) and cardiovascular mortality (RR 1.00, 95% CI 0.90 to 1.11; 2 studies, 43,955 participants, I² = 0%), and suggest that screening has no effect on these outcomes. Data were also limited for combined non-fatal endpoints; overall, evidence indicates no difference in total coronary heart disease (RR 1.01, 95% CI 0.95 to 1.07; 4 studies, 5 comparisons, 110,168 participants, I² = 0%; low-quality evidence), non-fatal coronary heart disease (RR 0.98, 95% CI 0.89 to 1.09; 2 studies, 43,955 participants, I² = 39%), total stroke (RR 0.99, 95% CI 0.90 to 1.10; 2 studies, 79,631 participants, I² = 0%, low-quality evidence), and non-fatal stroke (RR 1.17, 95% CI 0.94 to 1.47; 1 study, 20,015 participants). Overall, systematic risk assessment appears to result in lower total cholesterol levels (mean difference (MD) -0.11 mmol/l, 95% CI -0.17 to -0.04, 6 studies, 7 comparisons, 12,591 participants, I² = 57%; very low-quality evidence), lower systolic blood pressure (MD -3.05 mmHg, 95% CI -4.84 to -1.25, 6 studies, 7 comparisons, 12,591 participants, I² = 82%; very low-quality evidence) and lower diastolic blood pressure (MD -1.34 mmHg, 95% CI -1.76 to -0.93, 6 studies, 7 comparisons, 12,591 participants, I² = 0%; low-quality evidence). One study assessed adverse effects and found no difference in psychological distress at five years (1126 participants). Authors' conclusions The results are limited by the heterogeneity between trials in terms of participants recruited, interventions and duration of follow-up. Limited data suggest that systematic risk assessment for CVD has no statistically significant effects on clinical endpoints. There is limited evidence to suggest that CVD systematic risk assessment may have some favourable effects on cardiovascular risk factors. The completion of the five ongoing trials will add to the evidence base

An extension theorem for conformal gauge singularities

We analyse conformal gauge, or isotropic, singularities in cosmological models in general relativity. Using the calculus of tractors, we find conditions in terms of tractor curvature for a local extension of the conformal structure through a cosmological singularity and prove a local extension theorem.Comment: 43 pages, no figures, version as published in JMP, small changes, updated reference

Analysis of microtubule movement on isolated Xenopus egg cortices provides evidence that the cortical rotation involves dynein as well as Kinesin Related Proteins and is regulated by local microtubule polymerisation

AbstractIn amphibians, the cortical rotation, a translocation of the egg cortex relative to the cytoplasm, specifies the dorsoventral axis. The cortical rotation involves an array of subcortical microtubules whose alignment is mediated by Kinesin–related proteins (KRPs), and stops as M-phase promoting factor (MPF) activation propagates across the egg. To dissect the role of different motor proteins in the cortical rotation and to analyse their regulation, we have developed an open cell assay system involving reactivation of microtubule movement on isolated cortices. Microtubule movements were dependent on ATP and consisted mainly of wriggling and flailing without net displacement, consistent with a tethering of microtubules to the cortex. Reactivated movements were inhibited by anti-KRP and anti-dynein antibodies perfused together but not separately, the KRP antibody alone becoming fixed to the cortex. Neither antibody could inhibit movement in the presence of MPF, indicating that arrest of the cortical rotation is not due to MPF-dependent inhibition of motor molecules. In contrast, D2O treatment of live eggs to protect microtubules from progressive depolymerisation prolonged the cortical rotation. We conclude that the cortical rotation probably involves cytoplasmic dynein as well as cortical KRPs and terminates as a result of local MPF-dependent microtubule depolymerisation

Systematic versus opportunistic risk assessment for the primary prevention of cardiovascular disease: Cochrane systematic review protocol

A large number of people, considered at increased risk of vascular disease, remainunidentified, untreated and not reached by lifestyle advice or intervention, despite publichealth and clinical efforts. This has prompted the initiation of national  screening/systematic risk assessment programmes for vascular disease in healthy populations. These exist in addition to the more ad hoc opportunistic risk assessment initiatives undertaken worldwide. There is currently not enough indisputable evidence either showing clear clinical or economic benefits of systematic screening-like programmes over opportunistic risk assessment of cardiovascular disease (CVD) in primary care. We present the rationale and methodology of a Cochrane systematic review, assessing the effectiveness, costs and adverse effects of systematic risk assessment compared to opportunistic risk assessment for the primary prevention of CVD

Integrated Structure and Semantics for Reo Connectors and Petri Nets

In this paper, we present an integrated structural and behavioral model of Reo connectors and Petri nets, allowing a direct comparison of the two concurrency models. For this purpose, we introduce a notion of connectors which consist of a number of interconnected, user-defined primitives with fixed behavior. While the structure of connectors resembles hypergraphs, their semantics is given in terms of so-called port automata. We define both models in a categorical setting where composition operations can be elegantly defined and integrated. Specifically, we formalize structural gluings of connectors as pushouts, and joins of port automata as pullbacks. We then define a semantical functor from the connector to the port automata category which preserves this composition. We further show how to encode Reo connectors and Petri nets into this model and indicate applications to dynamic reconfigurations modeled using double pushout graph transformation

Chemical Structure and Upconversion Enhancement of NaYF₄ Nanocrystals and Nanosheets

University of Technology Sydney. Faculty of Science.The ability of lanthanide ions to convert lower energy photons to higher energy photons through the process known as upconversion presents as an opportunity to overcome limitations in sensitivity, efficiency and selectivity present for a wide variety of applications such as bio-imaging, photovoltaics and anti-counterfeiting. Sodium Yttrium Fluoride (NaYF₄) is an inorganic insulator with low phonon energy (360 cm⁻¹ ≈ 45 meV), wide band gap (8.5 eV) and high chemical stability. These properties make NaYF₄ an ideal optical host crystal for lanthanide dopants to produce upconversion nanoparticles (UCNPs). The shape, size and structure of UCNPs can be highly controlled allowing them to be tailored to the requirements of specific applications. Key challenges of concentration quenching and low quantum yield still confront UCNPs before their potential can be fully realised. Accordingly, enhancing the efficiency of UCNPs and their brightness has been the focus of numerous studies. In this project these challenges facing UCNPs are addressed by material characterisation and optimisation based on a comprehensive understanding of the chemical and optical properties of the material. Firstly, synchrotron-based XPS and NEXAFS along with EDS and ICP-MS characterisation techniques were employed on a range of UCNPs with sizes from 13 nm - 51 nm and different lanthanide (Ln³⁺) concentrations of 20% - 60% to determine how lanthanides are distributed within each nanocrystal. This analysis reveals a radial gradient distribution of Yb³⁺ and Tb³⁺ exists from the core to the surface of the NaYF₄ UCNPs, regardless of their size or lanthanide dopant concentration. The active core structure of this distribution was then systematically correlated to the optical properties of UCNPs with different sizes revealing a trend of increased optical upconversion emission efficiency by smaller sized UCNPs. Secondly, surface plasmon coupling was achieved between core-shell UCNPs and dewetted gold nanoparticles by precisely growing NaYF₄ shell coatings of varied thickness from 5 nm - 15 nm around the optically active core UCNPs. The local surface plasmon of the gold nanoparticles could be controlled and coupled with the internal transitions of the Er³⁺ ions. Combining these inert shelled UCNPs and plasmonic gold nanoparticles produced a shell thickness dependent enhancement with five times enhanced upconversion emission from the core-shell UCNPs with a shell thickness of 10 nm. Thirdly, bulk NaYF₄ microparticles were successfully exfoliated to make 2D NaYF₄ nanosheets. By using a simple soft exfoliation method without the need for intensive ultrasonication atomically flat optically active nanosheets down to a single monolayer were produced. Extensive characterisation of the nanosheets supported by DFT calculations reveals a phase change and 1 eV band gap reduction for this new 2D material compared to the bulk. Finally, in an appendix to demonstrate a massive three orders of magnitude increase in emission from ultra-small Tm³⁺ doped UCNPs an anti-counterfeiting mark was designed and fabricated. This enhancement only occurs at high temperature as activated surface phonons become efficient energy pathways for energy migration. The temperature dependence of the enhancement allowed the anti-counterfeiting mark to be temperature responsive