The radio source 3C 264, hosted by the giant elliptical galaxy NGC 3862, was observed with the Very Energetic Radiation Imaging Telescope Array System (VERITAS) between 2017 February and 2019 May. ...These deep observations resulted in the discovery of very high energy (VHE; E > 100 GeV) γ-ray emission from this active galaxy. An analysis of ∼57 hr of quality-selected live time yields a detection at the position of the source, corresponding to a statistical significance of 7.8 standard deviations above background. The observed VHE flux is variable on monthly timescales, with an elevated flux seen in 2018 observations. The VHE emission during this elevated state is well characterized by a power-law spectrum with a photon index Γ = 2.20 0.27 and flux F(>315 GeV) = ( cm−2 s−1, or approximately 0.7% of the Crab Nebula flux above the same threshold. 3C 264 (z = 0.0217) is the most distant radio galaxy detected at VHE, and the elevated state is thought to be similar to that of the famously outbursting jet in M87. Consequently, extensive contemporaneous multiwavelength data were acquired in 2018 at the time of the VHE high state. An analysis of these data, including Very Long Baseline Array, Very Large Array, Hubble Space Telescope, Chandra, and Swift observations in addition to the VERITAS data, is presented, along with a discussion of the resulting spectral energy distribution.
Diabetes increases oxidant stress and doubles the risk of dying after myocardial infarction, but the mechanisms underlying increased mortality are unknown. Mice with streptozotocin-induced diabetes ...developed profound heart rate slowing and doubled mortality compared with controls after myocardial infarction. Oxidized Ca(2+)/calmodulin-dependent protein kinase II (ox-CaMKII) was significantly increased in pacemaker tissues from diabetic patients compared with that in nondiabetic patients after myocardial infarction. Streptozotocin-treated mice had increased pacemaker cell ox-CaMKII and apoptosis, which were further enhanced by myocardial infarction. We developed a knockin mouse model of oxidation-resistant CaMKIIδ (MM-VV), the isoform associated with cardiovascular disease. Streptozotocin-treated MM-VV mice and WT mice infused with MitoTEMPO, a mitochondrial targeted antioxidant, expressed significantly less ox-CaMKII, exhibited increased pacemaker cell survival, maintained normal heart rates, and were resistant to diabetes-attributable mortality after myocardial infarction. Our findings suggest that activation of a mitochondrial/ox-CaMKII pathway contributes to increased sudden death in diabetic patients after myocardial infarction.
Objective
To compare the incidence of hospitalized bacterial infections among children with and children without juvenile idiopathic arthritis (JIA) and to examine the effects of selected ...medications.
Methods
Using national Medicaid data from 2000 through 2005, we identified a cohort of children with JIA and a comparator cohort of children with attention deficit hyperactivity disorder (ADHD). Exposures to methotrexate (MTX), TNF inhibitors, and oral glucocorticoids (GCs) were determined using pharmacy claims. Patients hospitalized with bacterial infections were identified using coded discharge diagnoses. We calculated adjusted hazard ratios (HRadj) to compare infection incidence rates while adjusting for relevant covariates.
Results
We identified 8,479 JIA patients with 13,003 person‐years of followup; 36% took MTX and 16% took TNF inhibitors. Compared with ADHD patients, JIA patients who were not currently taking MTX or TNF inhibitors had an increased rate of infection (HRadj 2.0 95% confidence interval (95% CI) 1.5, 2.5). Among JIA patients not receiving TNF inhibitor therapy, MTX users had a similar rate of infection as those not currently taking MTX (HRadj 1.2 95% CI 0.9, 1.7). TNF inhibitor use (irrespective of MTX) resulted in a similar rate of infection as use of MTX without a TNF inhibitor (HRadj 1.2 95% CI 0.8, 1.8). Use of high‐dose GCs (≥10 mg/day of prednisone or equivalent) increased the rate of infection as compared with no GC use, after adjustment for MTX and TNF inhibitor use (HRadj 3.1 95% CI 2.0, 4.7).
Conclusion
Children with JIA had an increased rate of infection compared to children with ADHD. Among children with JIA, the rate of infection was not increased with MTX or TNF inhibitor use, but was significantly increased with high‐dose GC use.
We present the analysis of Hubble Space Telescope (HST) J- and H-band imaging for 29 galaxies on the star-forming main sequence at z ~ 2, which have adaptive optics Very Large Telescope SINFONI ...integral field spectroscopy from our SINS/zC-SINF program. The SINFONI H alpha data resolve the ongoing star formation and the ionized gas kinematics on scales of 1-2 kpc; the near-IR images trace the galaxies' rest-frame optical morphologies and distributions of stellar mass in old stellar populations at a similar resolution. The global light profiles of most galaxies show disk-like properties well described by a single Sersic profile with n ~ 1, with only ~ 15% requiring a high n > 3 Sersic index, all more massive than 10 super(10) M sub(middot in circle). This is attributed to differences in sample selection and definitions of size and/or mass measurements.
Historically, gelatinous zooplankton have been considered important consumers or predators in marine food webs, but more recently they have also been recognized as important prey for many marine ...species. Here, we summarized data obtained from >100 Northeast Pacific fish predators based on extensive gut content analysis (~450000 stomachs examined) from broad-scale demersal trawl surveys ranging from the Bering Sea to Southern California. In the Bering Sea, we identified 27 predators on jellyfish and 23 on urochordates. In the Aleutian Islands, 14 and 18 predators were identified, respectively, and for the Gulf of Alaska, a total of 23 and 32 such predators were documented. Off the West Coast of the contiguous USA, we identified 16 coelenterate predators and 7 urochordate predators. Many of these predators were not previously known to prey on gelatinous zooplankton. Dominant consumers of coelenterates include prowfish, rockfishes, walleye pollock, sablefish, and grenadiers, and primary consumers of urochordates included rockfishes, Atka mackerel, and sablefish. Pronounced seasonal and interannual variability in gelatinous taxa occurrence was observed in several dominant fish predators. The occurrence of jellyfish prey was generally much higher in diets of fishes examined fresh at sea when compared with diets of the same species examined in the laboratory following preservation. Differences in occurrence were less pronounced with the more durable urochordate prey. We suggest that many existing estimates of predation on easily dissolved gelatinous prey may underestimate the true predation rate and the importance of these organisms in marine food webs.
CONTEXT Based on limited data, the live attenuated herpes zoster (HZ) vaccine is contraindicated in patients taking anti–tumor necrosis factor (anti-TNF) therapies or other biologics commonly used to ...treat immune-mediated diseases. The safety and effectiveness of the vaccine are unclear for these patients. OBJECTIVE To examine the association between HZ vaccination and HZ incidence within and beyond 42 days after vaccination in patients with selected immune-mediated diseases and in relation to biologics and other therapies used to treat these conditions. DESIGN, SETTING, AND PATIENTS Retrospective cohort study of 463 541 Medicare beneficiaries 60 years and older with rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis, or inflammatory bowel disease using Medicare claims data from January 1, 2006, through December 31, 2009. MAIN OUTCOME MEASURES Herpes zoster incidence rate within 42 days after vaccination (a safety concern) and beyond 42 days; hazard ratios estimated using Cox proportional hazards models for HZ comparing vaccinated vs unvaccinated patients. RESULTS Median duration of follow-up was 2.0 years (interquartile range, 0.8-3.0); 4.0% of patients received HZ vaccine. The overall crude HZ incidence rate was 7.8 cases per 1000 person-years (95% CI, 3.7-16.5) within 42 days after vaccination. The rate among the unvaccinated was 11.6 cases per 1000 person-years (95% CI, 11.4-11.9). Among 633 patients exposed to biologics at the time of vaccination or within the subsequent 42 days, no case of HZ or varicella occurred. After multivariable adjustment, HZ vaccination was associated with a hazard ratio of 0.61 (95% CI, 0.52-0.71) for HZ risk after 42 days. CONCLUSIONS Receipt of HZ vaccine was not associated with a short-term increase in HZ incidence among Medicare beneficiaries with selected immune-mediated diseases, including those exposed to biologics. The vaccine was associated with a lower HZ incidence over a median of 2 years of follow-up.
Cylindrospermopsin (CYN) is a toxin associated with numerous species of freshwater cyanobacteria throughout the world. It is postulated to have caused an episode of serious illnesses in Australia ...through treated drinking water, as well as lethal effects in livestock exposed to water from farm ponds. Toxicity included effects indicative of both hepatic and renal dysfunction. In humans, symptoms progressed from initial hepatomegaly, vomiting, and malaise to acidosis and hypokalemia, bloody diarrhea, and hyperemia in mucous membranes. Laboratory animal studies predominantly involved the intraperitoneal (i.p.) route of administration and confirmed this pattern of toxicity with changes in liver enzyme activities and histopathology consistent with hepatic injury and adverse renal effects. The aim of this study was designed to assess subchronic oral exposure (90 d) of purified CYN from 75 to 300 µg/kg/d in mouse. At the end of the dosing period, examinations of animals noted (1) elevated organ to body weight ratios of liver and kidney at all dose levels, (2) treatment-related increases in serum alanine aminotransferase (ALT) activity, (3) decreased blood urea nitrogen (BUN) and cholesterol concentrations in males, and (4) elevated monocyte counts in both genders. Histopathological alterations included hepatocellular hypertrophy and cord disruption in the liver, as well as renal cellular hypertrophy, tubule dilation, and cortical tubule lesions that were more prominent in males. A series of genes were differentially expressed including Bax (apoptosis), Rpl6 (tissue regeneration), Fabp4 (fatty acid metabolism), and Proc (blood coagulation). Males were more sensitive to many renal end points suggestive of toxicity. At the end of exposure, toxicity was noted at all dose levels, and the 75 µg/kg group exhibited significant effects in liver and kidney/body weight ratios, reduced BUN, increased serum monocytes, and multiple signs of histopathology indicating that a no-observed-adverse-effect level could not be determined for any dose level.
Robotic radiosurgery using more than one circular collimator can improve treatment plan quality and reduce total monitor units (MU). The rationale for an iris collimator that allows the field size to ...be varied during treatment delivery is to enable the benefits of multiple-field-size treatments to be realized with no increase in treatment time due to collimator exchange or multiple traversals of the robotic manipulator by allowing each beam to be delivered with any desired field size during a single traversal. This paper describes the Iris variable aperture collimator (Accuray Incorporated, Sunnyvale, CA, USA), which incorporates 12 tungsten-copper alloy segments in two banks of six. The banks are rotated by 30 degrees with respect to each other, which limits the radiation leakage between the collimator segments and produces a 12-sided polygonal treatment beam. The beam is approximately circular, with a root-mean-square (rms) deviation in the 50% dose radius of <0.8% (corresponding to <0.25 mm at the 60 mm field size) and an rms variation in the 20-80% penumbra width of about 0.1 mm at the 5 mm field size increasing to about 0.5 mm at 60 mm. The maximum measured collimator leakage dose rate was 0.07%. A commissioning method is described by which the average dose profile can be obtained from four profile measurements at each depth based on the periodicity of the isodose line variations with azimuthal angle. The penumbra of averaged profiles increased with field size and was typically 0.2-0.6 mm larger than that of an equivalent fixed circular collimator. The aperture reproducibility is < or =0.1 mm at the lower bank, diverging to < or =0.2 mm at a nominal treatment distance of 800 mm from the beam focus. Output factors (OFs) and tissue-phantom-ratio data are identical to those used for fixed collimators, except the OFs for the two smallest field sizes (5 and 7.5 mm) are considerably lower for the Iris Collimator. If average collimator profiles are used, the assumption of circular symmetry results in dose calculation errors that are <1 mm or <1% for single beams across the full range of field sizes; errors for multiple non-coplanar beam treatment plans are expected to be smaller. Treatment plans were generated for 19 cases using the Iris Collimator (12 field sizes) and also using one and three fixed collimators. The results of the treatment planning study demonstrate that the use of multiple field sizes achieves multiple plan quality improvements, including reduction of total MU, increase of target volume coverage and improvements in conformality and homogeneity compared with using a single field size for a large proportion of the cases studied. The Iris Collimator offers the potential to greatly increase the clinical application of multiple field sizes for robotic radiosurgery.
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