Which indicators of early cancer diagnosis from population-based data sources are associated with short-term mortality and survival?

BACKGROUND: A key component of recent English cancer policy is the monitoring of trends in early diagnosis of cancer. Early diagnosis can be defined by the disease stage at diagnosis or by other indicators derived from electronic health records. We evaluate the association between different early diagnosis indicators and survival, and discuss the implementation of the indicators in surveillance of early diagnosis. METHODS: We searched the PubMed database and grey literature to identify early diagnosis indicators and evaluate their association with survival. We analysed cancer registrations for 355,502 cancer patients diagnosed in England during the period 2009-2013, and quantified the association between each early diagnosis indicator and 30-day mortality and five-year net survival. RESULTS: Each incremental difference in stage (I-IV) predicts lower 5-year survival, so prognostic information is lost in comparisons which use binary stage indicators. Patients without a recorded stage have high risk of death shortly following diagnosis and lower 5-year survival. Emergency presentation is independently associated with lower five-year survival. Shorter intervals between first symptoms and diagnosis are not consistently associated with improved survival, potentially due to confounding from tumour characteristics. INTERPRETATION: Contrary to current practice, we recommend that all the stage information should be used in surveillance. Patients missing stage should also be included to minimise bias. Combined data on stage and emergency presentation could be used to create summary prognostic measures. More work is needed to create statistics based on the diagnostic interval that will be useful for surveillance

Mécanique de l'arbre sur pied : les relevés dendrométriques classiques pour quantifier les efforts gravitationnels supportés par un tronc - leurs limites

Le fût d'un arbre sur pied est soumis à l'action de la pesanteur, qui induit un effet de flexion sur un arbre déséquilibré. La qualification de cette action réclame donc d'évaluer non seulement la masse de l'arbre, mais aussi son déséquilibre, c'est-à-dire la position de son centre de gravité dans un plan horizontal. Une méthode d'estimation de cette position à partir de relevés dendrométriques simples (mesure d'une inclinaison du fût, de huit rayons de la projection au sol du houppier) est proposée. Appliquée à 9 peupliers, elle permet de classer les individus en trois groupes : droits, inclinés, flexueux. Confrontée aux résultats d'un essai mécanique de suppression de la masse supportée, elle apparaît suffisante pour estimer la direction de l'effort de flexion sur les individus de conformation simple, droits ou inclinés, mais doit être affinée dans les cas plus complexes. L'essai comme la modélisation confirment en outre la prépondérance des effets de flexion sur ceux de compression, même sur des individus apparemment équilibrés. (Résumé d'auteur

Importance of Genotypic and Phenotypic Tolerance in the Treatment of Experimental Endocarditis Due to Streptococcus gordonii

Genotypic and phenotypic tolerance was studied in penicillin treatment of experimental endocarditis due to nontolerant and tolerant Streptococcus gordonii and to their backcross transformants. The organisms were matched for in vitro and in vivo growth rates. Rats with aortic endocarditis were treated for 3 or 5 days, starting 12, 24, or 48 h after inoculation. When started at 12 h, during fast intravegetation growth, 3 days of treatment cured 80% of the nontolerant parent compared with <30% of the tolerant derivative (P < .005). When started at 24 or 48 h and if intravegetation growth had reached a plateau, 3 days of treatment failed against both bacteria. However, a significant difference between the 2 organisms was restored when treatment was extended to 5 days. Thus, genotypic tolerance conferred a survival advantage in both fast- and slow-growing bacteria, demonstrating that the in vitro-defined tolerant phenotype also carried the risk of treatment failure in viv

Acute ascending aortic dissection complicating open heart surgery: cerebral perfusion defines the outcome

Objective: This retrospective study was designed to assess the risks of acute ascending aorta dissection (AAD) as a rare but potentially fatal complication of open heart surgery. Method: Among 8624 cardiac surgical procedures under cardiopulmonary bypass (CPB) and cardioplegic myocardial protection from 1978 to 1997, 10 patients (0.12%) presented with a secondary or so called ‘iatrogenic' AAD. There were seven men and three women, mean age 64±9 years, ranging from 47 to 79. The original procedures involved five coronary artery bypass grafts (CABG), one repeat CABG, one aortic valve replacement (AVR), one AVR and CABG, one mitral valvuloplasty (MVP) and CABG and one ascending aorta replacement. We retrospectively analyzed their hospital records. Results: Group I consisted of seven patients with AAD intraoperatively and group II consisted of three patients who developed acute AAD 8-32 days after cardiac surgery. In group I, treatment consisted of the original procedure, plus grafting of the ascending aorta in six patients and closed plication and aortic wrapping in one. In group II, two patients received a dacron graft and one patient developed lethal tamponnade due to aortic rupture before surgery. Postoperatively, six patients responded well and three died (33%), two patients from group I on the 2nd postoperative day with severe post-anoxic encephalopathy, and one from group II with severe peroperative cardiogenic shock. Conclusion: Preventing AAD with the appropriate means remains standard practice in cardiac surgery. If AAD occurs, it requires prompt diagnosis and interposition graft to allow a better prognosis. Intraoperative AAD happens at the beginning of CPB jeopardizing perfusion of the supra-aortic arterie

Creep stability of the proposed AIDA mission target 65803 Didymos: I. Discrete cohesionless granular physics model

As the target of the proposed Asteroid Impact & Deflection Assessment (AIDA) mission, the near-Earth binary asteroid 65803 Didymos represents a special class of binary asteroids, those whose primaries are at risk of rotational disruption. To gain a better understanding of these binary systems and to support the AIDA mission, this paper investigates the creep stability of the Didymos primary by representing it as a cohesionless self-gravitating granular aggregate subject to rotational acceleration. To achieve this goal, a soft-sphere discrete element model (SSDEM) capable of simulating granular systems in quasi-static states is implemented and a quasi-static spin-up procedure is carried out. We devise three critical spin limits for the simulated aggregates to indicate their critical states triggered by reshaping and surface shedding, internal structural deformation, and shear failure, respectively. The failure condition and mode, and shear strength of an aggregate can all be inferred from the three critical spin limits. The effects of arrangement and size distribution of constituent particles, bulk density, spin-up path, and interparticle friction are numerically explored. The results show that the shear strength of a spinning self-gravitating aggregate depends strongly on both its internal configuration and material parameters, while its failure mode and mechanism are mainly affected by its internal configuration. Additionally, this study provides some constraints on the possible physical properties of the Didymos primary based on observational data and proposes a plausible formation mechanism for this binary system. With a bulk density consistent with observational uncertainty and close to the maximum density allowed for the asteroid, the Didymos primary in certain configurations can remain geo-statically stable without including cohesion.Comment: 66 pages, 24 figures, submitted to Icarus on 25/Aug/201

High-fidelity single-shot readout for a spin qubit via an enhanced latching mechanism

The readout of semiconductor spin qubits based on spin blockade is fast but suffers from a small charge signal. Previous work suggested large benefits from additional charge mapping processes, however uncertainties remain about the underlying mechanisms and achievable fidelity. In this work, we study the single-shot fidelity and limiting mechanisms for two variations of an enhanced latching readout. We achieve average single-shot readout fidelities > 99.3% and > 99.86% for the conventional and enhanced readout respectively, the latter being the highest to date for spin blockade. The signal amplitude is enhanced to a full one-electron signal while preserving the readout speed. Furthermore, layout constraints are relaxed because the charge sensor signal is no longer dependent on being aligned with the conventional (2, 0) - (1, 1) charge dipole. Silicon donor-quantum-dot qubits are used for this study, for which the dipole insensitivity substantially relaxes donor placement requirements. One of the readout variations also benefits from a parametric lifetime enhancement by replacing the spin-relaxation process with a charge-metastable one. This provides opportunities to further increase the fidelity. The relaxation mechanisms in the different regimes are investigated. This work demonstrates a readout that is fast, has one-electron signal and results in higher fidelity. It further predicts that going beyond 99.9% fidelity in a few microseconds of measurement time is within reach.Comment: Supplementary information is included with the pape

GWIPS-viz: 2018 update

The GWIPS-viz browser (http://gwips.ucc.ie/) is an on-line genome browser which is tailored for exploring ribosome profiling (Ribo-seq) data. Since its publication in 2014, GWIPS-viz provides Ribo-seq data for an additional 14 genomes bringing the current total to 23. The integration of new Ribo-seq data has been automated thereby increasing the number of available tracks to 1792, a 10-fold increase in the last three years. The increase is particularly substantial for data derived from human sources. Following user requests, we added the functionality to download these tracks in bigWig format. We also incorporated new types of data (e.g. TCP-seq) as well as auxiliary tracks from other sources that help with the interpretation of Ribo-seq data. Improvements in the visualization of the data have been carried out particularly for bacterial genomes where the Ribo-seq data are now shown in a strand specific manner. For higher eukaryotic datasets, we provide characteristics of individual datasets using the RUST program which includes the triplet periodicity, sequencing biases and relative inferred A-site dwell times. This information can be used for assessing the quality of Ribo-seq datasets. To improve the power of the signal, we aggregate Ribo-seq data from several studies into Global aggregate tracks for each genome

Point vortices on the sphere: a case with opposite vorticities

We study systems formed of 2N point vortices on a sphere with N vortices of strength +1 and N vortices of strength -1. In this case, the Hamiltonian is conserved by the symmetry which exchanges the positive vortices with the negative vortices. We prove the existence of some fixed and relative equilibria, and then study their stability with the ``Energy Momentum Method''. Most of the results obtained are nonlinear stability results. To end, some bifurcations are described.Comment: 35 pages, 9 figure

Constraints on the perturbed mutual motion in Didymos due to impact-induced deformation of its primary after the DART impact

Binary near-Earth asteroid (65803) Didymos is the target of the proposed NASA Double Asteroid Redirection Test (DART), part of the Asteroid Impact & Deflection Assessment (AIDA) mission concept. In this mission, the DART spacecraft is planned to impact the secondary body of Didymos, perturbing mutual dynamics of the system. The primary body is currently rotating at a spin period close to the spin barrier of asteroids, and materials ejected from the secondary due to the DART impact are likely to reach the primary. These conditions may cause the primary to reshape, due to landslides, or internal deformation, changing the permanent gravity field. Here, we propose that if shape deformation of the primary occurs, the mutual orbit of the system would be perturbed due to a change in the gravity field. We use a numerical simulation technique based on the full two-body problem to investigate the shape effect on the mutual dynamics in Didymos after the DART impact. The results show that under constant volume, shape deformation induces strong perturbation in the mutual motion. We find that the deformation process always causes the orbital period of the system to become shorter. If surface layers with a thickness greater than ~0.4 m on the poles of the primary move down to the equatorial region due to the DART impact, a change in the orbital period of the system and in the spin period of the primary will be detected by ground-based measurement.Comment: 8 pages, 7 figures, 2 tables, accepted for publication in MNRA