Association of inferior vena cava filter placement for venous thromboembolic disease and a contraindication to anticoagulation with 30-day mortality

Importance: Despite the absence of data from randomized clinical trials, professional societies recommend inferior vena cava (IVC) filters for patients with venous thromboembolic disease (VTE) and a contraindication to anticoagulation therapy. Prior observational studies of IVC filters have suggested a mortality benefit associated with IVC filter insertion but have often failed to adjust for immortal time bias, which is the time before IVC filter insertion, during which death can only occur in the control group. Objective: To determine the association of IVC filter placement with 30-day mortality after adjustment for immortal time bias. Design, Setting, and Participants: This comparative effectiveness, retrospective cohort study used a population-based sample of hospitalized patients with VTE and a contraindication to anticoagulation using the State Inpatient Database and the State Emergency Department Database, part of the Healthcare Cost and Utilization Project of the Agency for Healthcare Research and Quality, from hospitals in California (January 1, 2005, to December 31, 2011), Florida (January 1, 2005, to December 31, 2013), and New York (January 1, 2005, to December 31, 2012). Data analysis was conducted from September 15, 2015, to March 14, 2018. Exposure: Inferior vena cava filter placement. Main Outcomes and Measures: Multivariable Cox proportional hazard models were constructed with IVC filters as a time-dependent variable that adjusts for immortal time bias. The Cox model was further adjusted using the propensity score as an adjustment variable. Results: Of 126 030 patients with VTE, 61 281 (48.6%) were male and the mean (SD) age was 66.9 (16.6) years. In this cohort, 45 771 (36.3%) were treated with an IVC filter, whereas 80 259 (63.7%) did not receive a filter. In the Cox model with IVC filter status analyzed as a time-dependent variable to account for immortal time bias, IVC filter placement was associated with a significantly increased hazard ratio of 30-day mortality (1.18; 95% CI, 1.13-1.22; P \u3c .001). When the propensity score was included in the Cox model, IVC filter placement remained associated with an increased hazard ratio of 30-day mortality (1.18; 95% CI, 1.13-1.22; P \u3c .001). Conclusions and Relevance: After adjustment for immortal time bias, IVC filter placement was associated with increased 30-day mortality in patients with VTE and a contraindication to anticoagulation. Randomized clinical trials are needed to determine the efficacy of IVC filter placement in patients with VTE and a contraindication to anticoagulation

Direct Detection and Sequencing of Damaged DNA Bases

Products of various forms of DNA damage have been implicated in a variety of important biological processes, such as aging, neurodegenerative diseases, and cancer. Therefore, there exists great interest to develop methods for interrogating damaged DNA in the context of sequencing. Here, we demonstrate that single-molecule, real-time (SMRT®) DNA sequencing can directly detect damaged DNA bases in the DNA template - as a by-product of the sequencing method - through an analysis of the DNA polymerase kinetics that are altered by the presence of a modified base. We demonstrate the sequencing of several DNA templates containing products of DNA damage, including 8-oxoguanine, 8-oxoadenine, O6-methylguanine, 1-methyladenine, O4-methylthymine, 5-hydroxycytosine, 5-hydroxyuracil, 5-hydroxymethyluracil, or thymine dimers, and show that these base modifications can be readily detected with single-modification resolution and DNA strand specificity. We characterize the distinct kinetic signatures generated by these DNA base modifications

Detection of weak gravitational lensing distortions of distant galaxies by cosmic dark matter at large scales

Most of the matter in the universe is not luminous and can be observed directly only through its gravitational effect. An emerging technique called weak gravitational lensing uses background galaxies to reveal the foreground dark matter distribution on large scales. Light from very distant galaxies travels to us through many intervening overdensities which gravitationally distort their apparent shapes. The observed ellipticity pattern of these distant galaxies thus encodes information about the large-scale structure of the universe, but attempts to measure this effect have been inconclusive due to systematic errors. We report the first detection of this ``cosmic shear'' using 145,000 background galaxies to reveal the dark matter distribution on angular scales up to half a degree in three separate lines of sight. The observed angular dependence of this effect is consistent with that predicted by two leading cosmological models, providing new and independent support for these models.Comment: 18 pages, 5 figures: To appear in Nature. (This replacement fixes tex errors and typos.

Testing the Cosmological Constant as a Candidate for Dark Energy

It may be difficult to single out the best model of dark energy on the basis of the existing and planned cosmological observations, because many different models can lead to similar observational consequences. However, each particular model can be studied and either found consistent with observations or ruled out. In this paper, we concentrate on the possibility to test and rule out the simplest and by far the most popular of the models of dark energy, the theory described by general relativity with positive vacuum energy (the cosmological constant). We evaluate the conditions under which this model could be ruled out by the future observations made by the Supernova/Acceleration Probe SNAP (both for supernovae and weak lensing) and by the Planck Surveyor cosmic microwave background satellite.Comment: 6 pages, 2 figures, revtex

Organizational evolution and the Olympic Games: the case of sport climbing

This paper discusses the processes underpinning the evolutionary development of sport climbing in recent decades, with a particular focus on the impact of its inclusion in the Olympic Games. New institutionalism and resource-dependence theory provide an analytical and explanatory framework for this study. The research adopted a qualitative method strategy comprising a series of interviews and the analysis of documents, reports, press and social media. The recent inclusion of the sport in the Tokyo 2020 Olympic programme has created challenges, primarily because of strong values inherent within the sport. The research, however, shows that the values of a sport can expand and develop in order to fit the regulatory legitimacy required by inclusion in the Olympic Games. Nonetheless, the research also shows that involvement with the IOC raises questions about who ‘owns’ the sport

Modified-Source Gravity and Cosmological Structure Formation

One way to account for the acceleration of the universe is to modify general relativity, rather than introducing dark energy. Typically, such modifications introduce new degrees of freedom. It is interesting to consider models with no new degrees of freedom, but with a modified dependence on the conventional energy-momentum tensor; the Palatini formulation of $f(R)$ theories is one example. Such theories offer an interesting testing ground for investigations of cosmological modified gravity. In this paper we study the evolution of structure in these ``modified-source gravity'' theories. In the linear regime, density perturbations exhibit scale dependent runaway growth at late times and, in particular, a mode of a given wavenumber goes nonlinear at a higher redshift than in the standard $\Lambda$CDM model. We discuss the implications of this behavior and why there are reasons to expect that the growth will be cut off in the nonlinear regime. Assuming that this holds in a full nonlinear analysis, we briefly describe how upcoming measurements may probe the differences between the modified theory and the standard $\Lambda$CDM model.Comment: 22 pages, 6 figures, uses iopart styl

Multitrophic Interactions in the Sea: Assessing the Effect of Infochemical-Mediated Foraging in a 1-d Spatial Model

The release of chemicals following herbivore grazing on primary producers may provide feeding cues to carnivorous predators, thereby promoting multitrophic interactions. In particular, chemicals released following grazing on phytoplankton by microzooplankton herbivores have been shown to elicit a behavioural foraging response in carnivorous copepods, which may use this chemical information as a mechanism to locate and remain within biologically productive patches of the ocean. In this paper, we use a 1D spatial reaction-diffusion model to simulate a tri-trophic planktonic system in the water column, where predation at the top trophic level (copepods) is affected by infochemicals released by the primary producers forming the bottom trophic level. The effect of the infochemical-mediated predation is investigated by comparing the case where copepods forage randomly to the case where copepods adjust their vertical position to follow the distribution of grazing-induced chemicals. Results indicate that utilization of infochemicals for foraging provides fitness benefits to copepods and stabilizes the system at high nutrient load, whilst also forming a possible mechanism for phytoplankton bloom formation. We also investigate how the copepod efficiency to respond to infochemicals affects the results, and show that small increases (2%) in the ability of copepods to sense infochemicals can promote their persistence in the system. Finally we argue that effectively employing infochemicals for foraging can be an evolutionarily stable strategy for copepods