Association of Oral Anticoagulation Prescription with Clinical Events in Patients with an Asymptomatic Unrepaired Abdominal Aortic Aneurysm

Background: Most abdominal aortic aneurysms (AAA) have large volumes of intraluminal thrombus which has been implicated in promoting the risk of major adverse events. The aim of this study was to examine the association of therapeutic anticoagulation with AAA-related events and major adverse cardiovascular events (MACE) in patients with an unrepaired AAA. Methods: Patients with an asymptomatic unrepaired AAA were recruited from four sites in Australia. The primary outcome was the combined incidence of AAA repair or AAA rupture-related mortality (AAA-related events). The main secondary outcome was MACE (the combined incidence of myocardial infarction, stroke, or cardiovascular death). The associations of anticoagulation with these outcomes were assessed using Cox proportional hazard analyses (reporting hazard ratio, HR, and 95% confidence intervals, CI) to adjust for other risk factors. Results: A total of 1161 patients were followed for a mean (standard deviation) of 4.9 (4.0) years. Of them, 536 (46.2%) patients had a least one AAA-related event and 319 (27.5%) at least one MACE. In the sample, 98 (8.4%) patients were receiving long-term therapeutic anticoagulation using warfarin (84), apixaban (7), rivaroxaban (6), or dabigatran (1). Prescription of an anticoagulant was associated with a reduced risk of an AAA-related event (adjusted HR 0.61; 95% CI 0.42, 0.90, p = 0.013), but not MACE (HR 1.16; 95% CI 0.78, 1.72, p = 0.476). Conclusions: These findings suggest that AAA-related events but not MACE may be reduced in patients prescribed an anticoagulant medication. Due to the inherent biases of observational studies, a randomized controlled trial is needed to assess whether anticoagulation reduces the risk of AAA-related events

Immunosuppressive drugs for nontransplant comorbidities are not associated with abdominal aortic aneurysm growth

Background: In the present study, we examined the association of immunosuppressant drug prescriptions with the growth of small abdominal aortic aneurysms (AAAs). Methods: Participants with an AAA measuring between 30 and 50 mm were recruited from four Australian centers. AAA growth was monitored by ultrasound. The immunosuppressant drugs included conventional disease-modifying antirheumatic drugs (eg, methotrexate, sulfasalazine, leflunomide), steroids, hydroxychloroquine, other immunosuppressant drugs (eg, cyclosporine, azacitidine), or a combination of these drugs. Linear mixed effects modeling was performed to examine the independent association of an immunosuppressant prescription with AAA growth. A subanalysis examined the association of steroids with AAA growth. Results: Of the 621 patients, 34 (5.3%) had been prescribed at least one (n = 26) or more (n = 8) immunosuppressant drug and had been followed up for a median period of 2.1 years (interquartile range, 1.1-3.5 years), with a median of three ultrasound scans (interquartile range, two to five ultrasound scans). No significant difference was found in AAA growth when stratified by a prescription of immunosuppressant drugs on either unadjusted (mean difference, 0.2 mm/y; 95% confidence interval [CI], −0.4 to 0.7; P =.589) or risk factor-adjusted (mean difference, 0.2 mm/y; 95% CI, −0.3 to 0.7; P =.369) analyses. The findings were similar for the unadjusted (mean difference, 0.0 mm/y; 95% CI, −0.7 to 0.7; P =.980) and risk factor-adjusted (mean difference, 0.1 mm/y; 95% CI, −0.6 to 0.7; P =.886) subanalyses focused on steroid use. Conclusions: The results from this study suggest that AAA growth is not affected by immunosuppressant drug prescription. Studies with larger sample sizes are needed before reliable conclusions can be drawn

Association between aortic peak wall stress and rupture index with abdominal aortic aneurysm–related events

Objective: The aim of this study was to assess whether aortic peak wall stress (PWS) and peak wall rupture index (PWRI) were associated with the risk of abdominal aortic aneurysm (AAA) rupture or repair (defined as AAA events) among participants with small AAAs. Methods: PWS and PWRI were estimated from computed tomography angiography (CTA) scans of 210 participants with small AAAs (≥ 30 and ≤ 50 mm) prospectively recruited between 2002 and 2016 from two existing databases. Participants were followed for a median of 2.0 (inter-quartile range 1.9, 2.8) years to record the incidence of AAA events. The associations between PWS and PWRI with AAA events were assessed using Cox proportional hazard analyses. The ability of PWS and PWRI to reclassify the risk of AAA events compared to the initial AAA diameter was examined using net reclassification index (NRI) and classification and regression tree (CART) analysis. Results: After adjusting for other risk factors, one standard deviation increase in PWS (hazard ratio, HR, 1.56, 95% confidence intervals, CI 1.19, 2.06; p = 0.001) and PWRI (HR 1.74, 95% CI 1.29, 2.34; p 0.562. PWRI, but not PWS, significantly improved the classification of risk of AAA events compared to the initial AAA diameter alone. Conclusion: PWS and PWRI predicted the risk of AAA events but only PWRI significantly improved the risk stratification compared to aortic diameter alone. Key Points: • Aortic diameter is an imperfect measure of abdominal aortic aneurysm (AAA) rupture risk. • This observational study of 210 participants found that peak wall stress (PWS) and peak wall rupture index (PWRI) predicted the risk of aortic rupture or AAA repair. • PWRI, but not PWS, significantly improved the risk stratification for AAA events compared to aortic diameter alone

Observing protoplanetary discs with the Square Kilometre Array -- I. Characterising pebble substructure caused by forming planets

High angular resolution observations of discs at mm wavelengths (on scales of a few au) are now commonplace, but there is a current lack of a comparable angular resolution for observations at cm wavelengths. This presents a significant barrier to improving our understanding of planet formation, in particular how dust grains grow from mm to cm sizes. In this paper, we examine the ability of the Square Kilometre Array (SKA) to observe dust substructure in a young, planet-forming disc at cm wavelengths. We use dusty hydrodynamics and continuum radiative transfer to predict the distribution and emission of 1 cm dust grains (or pebbles) within the disc, and simulate continuum observations with the current SKA1-MID design baseline at frequencies of 12.5 GHz (Band 5b, ~2.4 cm) on 5-10 au scales. The SKA will provide high-fidelity observations of the cm dust emission substructure in discs for integration times totalling 100's of hours. Radial structure can be obtained at a sufficient resolution and S/N from shorter (10's of hours) integration times by azimuthal averaging in the image plane. By modelling the intensity distribution directly in the visibility plane, it is possible to recover a similar level of (axisymmetric) structural detail from observations with integration times 1-2 orders of magnitude lower than required for high-fidelity imaging. Our results demonstrate that SKA1-MID will provide crucial constraints on the distribution and morphology of the raw material for building planets, the pebbles in protoplanetary discs.Comment: 12 pages, 8 figures, accepted for publication in MNRA

Computer simulations show that Neanderthal facial morphology represents adaptation to cold and high energy demands, but not heavy biting

Three adaptive hypotheses have been forwarded to explain the distinctive Neanderthal face: (i) an improved ability to accommodate high anterior bite forces, (ii) more effective conditioning of cold and/or dry air and, (iii) adaptation to facilitate greater ventilatory demands. We test these hypotheses using three-dimensional models of Neanderthals, modern humans, and a close outgroup (Homo heidelbergensis), applying finite-element analysis (FEA) and computational fluid dynamics (CFD). This is the most comprehensive application of either approach applied to date and the first to include both. FEA reveals few differences between H. heidelbergensis, modern humans, and Neanderthals in their capacities to sustain high anterior tooth loadings. CFD shows that the nasal cavities of Neanderthals and especially modern humans condition air more efficiently than does that of H. heidelbergensis, suggesting that both evolved to better withstand cold and/or dry climates than less derived Homo. We further find that Neanderthals could move considerably more air through the nasal pathway than could H. heidelbergensis or modern humans, consistent with the propositions that, relative to our outgroup Homo, Neanderthal facial morphology evolved to reflect improved capacities to better condition cold, dry air, and, to move greater air volumes in response to higher energetic requirements

The Spitzer survey of interstellar clouds in the Gould Belt. I. IC 5146 observed with IRAC and MIPS

We present observations of two areas totalling 0.57 deg^2 in the IC 5146 star-forming region at 3.6, 4.5, 5.8, 8.0, 24, and 70 μm observed with the Spitzer Space Telescope. We reexamine the issue of the distance to this cloud and conclude a value of 950 ± 80 pc is most likely. We compare source counts, colors, and magnitudes in our observed region to a subset of the SWIRE data that was processed through our pipeline. We identify more than 200 young stellar object (YSO) candidates from color-magnitude and color-color diagrams, many of which were previously unknown. We compare the colors of these YSOs to the models of Robitaille et al. and perform simple fits to the SED's to estimate properties of the circumstellar disks likely to surround the Class II and III sources. We also compare the mid-IR disk excesses to Hα emission-line data where available. We present a quantitative description of the degree of clustering, estimate the star formation efficiency, and discuss the fraction of YSOs in the region with disks relative to an estimate of the diskless YSO population. Finally, we compare the YSO distribution to the cold dust distribution mapped by SCUBA and briefly describe the diffuse emission likely due to PAHs associated with the H II region

Brevi spunti sul d.lgs. n. 150/2009 e sulla sua applicabilità agli Enti locali

© 2014 Taylor & Francis Group, LLC. Gene silencing in cancer frequently involves hypermethylation and dense nucleosome occupancy across promoter regions. How a promoter transitions to this silent state is unclear. Using colorectal adenomas, we investigated nucleosome positioning, DNA methylation, and gene expression in the early stages of gene silencing. Genome-wide gene expression correlated with highly positioned nucleosomes upstream and downstream of a nucleosome-depleted transcription start site (TSS). Hypermethylated promoters displayed increased nucleosome occupancy, specifically at the TSS. We investigated 2 genes, CDH1 and CDKN2B, which were silenced in adenomas but lacked promoter hypermethylation. Instead, silencing correlated with loss of nucleosomes from the -2 position upstream of the TSS relative to normal mucosa. In contrast, permanent CDH1 silencing in carcinoma cells was characterized by promoter hypermethylation and dense nucleosome occupancy. Our findings suggest that silenced genes transition through an intermediary stage involving altered promoter nucleosome positioning, before permanent silencing by hypermethylation and dense nucleosome occupancy.Link_to_subscribed_fulltex

The Spitzer survey of interstellar clouds in the Gould Belt. II. The Cepheus Flare observed with IRAC and MIPS

We present Spitzer IRAC (~2 deg^2) and MIPS (~8 deg^2) observations of the Cepheus Flare which is associated with the Gould Belt, at an approximate distance of ~300 pc. Around 6500 sources are detected in all four IRAC bands, of which ~900 have MIPS 24 micron detections. We identify 133 YSO candidates using color-magnitude diagram techniques, a large number of the YSO candidates are associated with the NGC 7023 reflection nebula. Cross identifications were made with the Guide Star Catalog II and the IRAS Faint Source Catalog, and spectral energy distributions (SED) were constructed. SED modeling was conducted to estimate the degree of infrared excess. It was found that a large majority of disks were optically thick accreting disks, suggesting that there has been little disk evolution in these sources. Nearest-neighbor clustering analysis identified four small protostellar groups (L1228, L1228N, L1251A, and L1251B) with 5-15 members each and the larger NGC 7023 association with 32 YSO members. The star formation efficiency for cores with clusters of protostars and for those without clusters was found to be ~8% and ~1% respectively. The cores L1155, L1241, and L1247 are confirmed to be starless down to our luminosity limit of L_bol=0.06 L_sol.Comment: Submitted to ApJSS. 20 figures, 110 page

The JCMT BISTRO Survey: Studying the Complex Magnetic Field of L43

We present observations of polarized dust emission at 850 μm from the L43 molecular cloud, which sits in the Ophiuchus cloud complex. The data were taken using SCUBA-2/POL-2 on the James Clerk Maxwell Telescope as a part of the BISTRO large program. L43 is a dense (NH 10 22 2 ~ –1023 cm−2) complex molecular cloud with a submillimeter-bright starless core and two protostellar sources. There appears to be an evolutionary gradient along the isolated filament that L43 is embedded within, with the most evolved source closest to the Sco OB2 association. One of the protostars drives a CO outflow that has created a cavity to the southeast. We see a magnetic field that appears to be aligned with the cavity walls of the outflow, suggesting interaction with the outflow. We also find a magnetic field strength of up to ∼160 ± 30 μG in the main starless core and up to ∼90 ± 40 μG in the more diffuse, extended region. These field strengths give magnetically super- and subcritical values, respectively, and both are found to be roughly trans-Alfvénic. We also present a new method of data reduction for these denser but fainter objects like starless cores