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

Wide-field weak lensing by RXJ1347-1145

We present an analysis of weak lensing observations for RXJ1347-1145 over a 43' X 43' field taken in B and R filters on the Blanco 4m telescope at CTIO. RXJ1347-1145 is a massive cluster at redshift z=0.45. Using a population of galaxies with 20<R<26, we detect a weak lensing signal at the p<0.0005 level, finding best-fit parameters of \sigma_v=1400^{+130}_{-140} km s^{-1} for a singular isothermal sphere model and r_{200} = 3.5^{+0.8}_{-0.2} Mpc with c = 15^{+64}_{-10} for a NFW model in an \Omega_m = 0.3, \Omega_\Lambda = 0.7 cosmology. In addition, a mass to light ratio M/L_R =90 \pm 20 M_\odot / L_{R\odot} was determined. These values are consistent with the previous weak lensing study of RXJ1347--1145 by Fischer and Tyson, 1997, giving strong evidence that systemic bias was not introduced by the relatively small field of view in that study. Our best-fit parameter values are also consistent with recent X-ray studies by Allen et al, 2002 and Ettori et al, 2001, but are not consistent with recent optical velocity dispersion measurements by Cohen and Kneib, 2002.Comment: accepted to ApJ, tentative publication 10 May 2005, v624

Probing the Relation Between X-ray-Derived and Weak-Lensing-Derived Masses for Shear-Selected Galaxy Clusters: I. A781

We compare X-ray and weak-lensing masses for four galaxy clusters that comprise the top-ranked shear-selected cluster system in the Deep Lens Survey. The weak-lensing observations of this system, which is associated with A781, are from the Kitt Peak Mayall 4-m telescope, and the X-ray observations are from both Chandra and XMM-Newton. For a faithful comparison of masses, we adopt the same matter density profile for each method, which we choose to be an NFW profile. Since neither the X-ray nor weak-lensing data are deep enough to well constrain both the NFW scale radius and central density, we estimate the scale radius using a fitting function for the concentration derived from cosmological hydrodynamic simulations and an X-ray estimate of the mass assuming isothermality. We keep this scale radius in common for both X-ray and weak-lensing profiles, and fit for the central density, which scales linearly with mass. We find that for three of these clusters, there is agreement between X-ray and weak-lensing NFW central densities, and thus masses. For the other cluster, the X-ray central density is higher than that from weak-lensing by 2 sigma. X-ray images suggest that this cluster may be undergoing a merger with a smaller cluster. This work serves as an additional step towards understanding the possible biases in X-ray and weak-lensing cluster mass estimation methods. Such understanding is vital to efforts to constrain cosmology using X-ray or weak-lensing cluster surveys to trace the growth of structure over cosmic time.Comment: 14 pages, 7 figures, matches version in Ap

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.

Paleoseismological data from a new trench across the El Camp Fault(Catalan Coastal Ranges, NE Iberian Peninsula)

The El Camp Fault (Catalan Coastal Ranges, NE Iberian Peninsula) is a slow slipping normal fault whose seismic potential has only recently been recognised. New geomorphic and trench investigations were carried out during a training course across the El Camp Fault at the La Porquerola alluvial fan site. A new trench (trench 8) was dug close to a trench made previously at this site (trench 4). With the aid of two long topographic profiles across the fault scarp we obtained a vertical slip rate ranging between 0.05 and 0.08 mm/yr. At the trench site, two main faults, which can be correlated between trenches 8 and 4, make up the fault zone. Using trench analysis three paleoseismic events were identified, two between 34.000 and 125.000 years BP (events 3 and 2) and another event younger than 13 500 years BP (event 1), which can be correlated, respectively, with events X (50.000- 125.000 years BP), Y (35.000-50.000 years BP) and Z (3000-25.000 years BP). The last seismic event at the La Porquerola alluvial fan site is described for the first time, but with some uncertainties

Cobalt ions recruit inflammatory cells in vitro through human Toll-like receptor 4

AbstractMetal-on-metal (MoM) hip replacements, often manufactured from a cobalt-chrome alloy, are associated with adverse reactions including soft tissue necrosis and osteolysis. Histopathological analysis of MoM peri-implant tissues reveals an inflammatory cell infiltrate that includes macrophages, monocytes and neutrophils.Toll-like receptor 4 (TLR4) is an innate immune receptor activated by bacterial lipopolysaccharide. Recent studies have demonstrated that cobalt ions from metal-on-metal joints also activate human TLR4, increasing cellular secretion of inflammatory chemokines including interleukin-8 (IL-8, CXCL8) and CCL2. Chemokines recruit immune cells to the site of inflammation, and their overall effect depends on the chemokine profile produced.This study investigated the effect of cobalt on the secretion of inflammatory cytokines CCL20 and IL-6. The chemotactic potential of conditioned media from a cobalt-stimulated human monocyte cell line on primary monocytes and neutrophils was investigated using an in vitro transwell migration assay. The role of TLR4 in observed effects was studied using a small molecule TLR4-specific antagonist.Cobalt ions significantly increased release of CCL2 and IL-6 by MonoMac 6 cells (P<0.001). Conditioned media from cobalt-stimulated cells significantly increased monocyte and neutrophil chemotaxis in vitro (P<0.001). These effects were abrogated by the TLR4 antagonist (P<0.001) suggesting that they occur through cobalt activation of TLR4.This study demonstrates the role of TLR4 in cobalt-mediated immune cell chemotaxis and provides a potential mechanism by which cobalt ions may contribute to the immune cell infiltrate surrounding failed metal hip replacements. It also highlights the TLR4 signalling pathway as a potential therapeutic target in preventing cobalt-mediated inflammation

Hospital-Level Nicu Capacity, Utilization, and 30-Day Outcomes in Texas

IMPORTANCE: Risk-adjusted neonatal intensive care unit (NICU) utilization and outcomes vary markedly across regions and hospitals. The causes of this variation are poorly understood. OBJECTIVE: to assess the association of hospital-level NICU bed capacity with utilization and outcomes in newborn cohorts with differing levels of health risk. DESIGN, SETTING, AND PARTICIPANTS: This population-based retrospective cohort study included all Medicaid-insured live births in Texas from 2010 to 2014 using linked vital records and maternal and newborn claims data. Participants were Medicaid-insured singleton live births (LBs) with birth weights of at least 400 g and gestational ages between 22 and 44 weeks. Newborns were grouped into 3 cohorts: very low birth weight (VLBW; \u3c1500 \u3eg), late preterm (LPT; 34-36 weeks\u27 gestation), and nonpreterm newborns (NPT; ≥37 weeks\u27 gestation). Data analysis was conducted from January 2022 to October 2023. EXPOSURE: Hospital NICU capacity measured as reported NICU beds/100 LBs, adjusted (ie, allocated) for transfers. MAIN OUTCOMES AND MEASURES: NICU admissions and special care days; inpatient mortality and 30-day postdischarge adverse events (ie, mortality, emergency department visit, admission, observation stay). RESULTS: The overall cohort of 874 280 single LBs included 9938 VLBW (5054 [50.9%] female; mean [SD] birth weight, 1028.9 [289.6] g; mean [SD] gestational age, 27.6 [2.6] wk), 63 160 LPT (33 684 [53.3%] female; mean [SD] birth weight, 2664.0 [409.4] g; mean [SD] gestational age, 35.4 [0.8] wk), and 801 182 NPT (407 977 [50.9%] female; mean [SD] birth weight, 3318.7 [383.4] g; mean [SD] gestational age, 38.9 [1.0] wk) LBs. Median (IQR) NICU capacity was 0.84 (0.57-1.30) allocated beds/100 LB/year. For VLBW newborns, NICU capacity was not associated with the risk of NICU admission or number of special care days. For LPT newborns, birth in hospitals with the highest compared with the lowest category of capacity was associated with a 17% higher risk of NICU admission (adjusted risk ratio [aRR], 1.17; 95% CI, 1.01-1.33). For NPT newborns, risk of NICU admission was 55% higher (aRR, 1.55; 95% CI, 1.22-1.97) in the highest- vs the lowest-capacity hospitals. The number of special care days for LPT and NPT newborns was 21% (aRR, 1.21; 95% CI,1.08-1.36) and 37% (aRR, 1.37; 95% CI, 1.08-1.74) higher in the highest vs lowest capacity hospitals, respectively. Among LPT and NPT newborns, NICU capacity was associated with higher inpatient mortality and 30-day postdischarge adverse events. CONCLUSIONS AND RELEVANCE: In this cohort study of Medicaid-insured newborns in Texas, greater hospital NICU bed supply was associated with increased NICU utilization in newborns born LPT and NPT. Higher capacity was not associated with lower risk of adverse events. These findings raise important questions about how the NICU is used for newborns with lower risk

Unusual Intron Conservation near Tissue-Regulated Exons Found by Splicing Microarrays

Alternative splicing contributes to both gene regulation and protein diversity. To discover broad relationships between regulation of alternative splicing and sequence conservation, we applied a systems approach, using oligonucleotide microarrays designed to capture splicing information across the mouse genome. In a set of 22 adult tissues, we observe differential expression of RNA containing at least two alternative splice junctions for about 40% of the 6,216 alternative events we could detect. Statistical comparisons identify 171 cassette exons whose inclusion or skipping is different in brain relative to other tissues and another 28 exons whose splicing is different in muscle. A subset of these exons is associated with unusual blocks of intron sequence whose conservation in vertebrates rivals that of protein-coding exons. By focusing on sets of exons with similar regulatory patterns, we have identified new sequence motifs implicated in brain and muscle splicing regulation. Of note is a motif that is strikingly similar to the branchpoint consensus but is located downstream of the 5′ splice site of exons included in muscle. Analysis of three paralogous membrane-associated guanylate kinase genes reveals that each contains a paralogous tissue-regulated exon with a similar tissue inclusion pattern. While the intron sequences flanking these exons remain highly conserved among mammalian orthologs, the paralogous flanking intron sequences have diverged considerably, suggesting unusually complex evolution of the regulation of alternative splicing in multigene families

Characterization of secreted sphingosine-1-phosphate lyases required for virulence and intracellular survival of <i>Burkholderia pseudomallei</i>

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.Sphingosine-1-phosphate (S1P), a bioactive sphingolipid metabolite, plays a critical role in the orchestration of immune responses. S1P levels within the mammalian host are tightly regulated, in part through the activity of S1P lyase (S1PL) which catalyses its irreversible degradation. Herein we describe the identification and characterization of secreted S1PL orthologues encoded by the facultative intracellular bacteria Burkholderia pseudomallei and Burkholderia thailandensis. These bacterial orthologues exhibited S1PL enzymatic activity, functionally complemented an S1PL-deficient yeast strain, and conferred resistance to the antimicrobial sphingolipid D-erythro-sphingosine. We report that secretion of these bacterial S1PLs is pH-dependent, and is observed during intracellular infection. S1PL-deficient mutants displayed impaired intracellular replication in murine macrophages (associated with an inability to evade the maturing phagosome) and were significantly attenuated in murine and larval infection models. Furthermore, treatment of Burkholderia-infected macrophages with either S1P or a selective agonist of S1P receptor 1 enhanced bacterial colocalisation with LAMP-1 and reduced their intracellular survival. In summary, our studies confirm bacterial-encoded S1PL as a critical virulence determinant of B. pseudomallei and B. thailandensis, further highlighting the pivotal role of S1P in host-pathogen interactions. In addition, our data suggest that S1P pathway modulators have potential for the treatment of intracellular infection.We thank HL Ho & K Haynes (University of Exeter) for provision of strains and relevant vectors for yeast complementation studies. This work was supported by the Defence Science 26 and Technology Laboratory under contract DSTLX-1000060221 (WP1). CJM was funded by the EASTBIO Doctoral Training Partnership. The funders had no role in study design, data collection and analysis, or preparation of the manuscript