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Melanoma is the deadliest of skin cancers and has a high tendency to metastasize to distant organs. Calcium and metabolic signals contribute to melanoma invasiveness; however, the underlying molecular details are elusive. The MCU complex is a major route for calcium into the mitochondrial matrix but whether MCU affects melanoma pathobiology was not understood. Here, we show that MCUA expression correlates with melanoma patient survival and is decreased in BRAF kinase inhibitor-resistant melanomas. Knockdown (KD) of MCUA suppresses melanoma cell growth and stimulates migration and invasion. In melanoma xenografts, MCUA_KD reduces tumor volumes but promotes lung metastases. Proteomic analyses and protein microarrays identify pathways that link MCUA and melanoma cell phenotype and suggest a major role for redox regulation. Antioxidants enhance melanoma cell migration, while prooxidants diminish the MCUA_KD-induced invasive phenotype. Furthermore, MCUA_KD increases melanoma cell resistance to immunotherapies and ferroptosis. Collectively, we demonstrate that MCUA controls melanoma aggressive behavior and therapeutic sensitivity. Manipulations of mitochondrial calcium and redox homeostasis, in combination with current therapies, should be considered in treating advanced melanoma.

The Radio Neutrino Observatory Greenland (RNO-G) is scheduled for deployment in the summerof 2021. It will target the detection of astrophysical and cosmogenic neutrinos above 10 PeV. With 35 autonomous stations, it will be the largest implementation of a radio neutrino detector to date.The stations combine best-practice instrumentation from all previous radio neutrino arrays, such as a deep phased-array trigger and surface antennas. These proceedings describe the experimentalconsiderations that have driven the design of RNO-G and the current progress in deployment, aswell as discuss the projected sensitivity of the instrument. RNO-G will provide a unique view ofthe Northern Sky and will also inform the design of the radio component of IceCube-Gen2.

The Askaryan Radio Array (ARA) is a ground-based radio detector at the South Pole designed to capture Askaryan emission from ultra-high energy neutrinos interacting within the Antarctic ice. The newest ARA station has been equipped with a phased array trigger, in which radio signals in multiple antennas are summed in predetermined directions prior to the trigger. In this way, impulsive signals add coherently, while noise likely does not, allowing the trigger threshold to be lower than a traditional ARA station. Early results on just a fraction of available data from this new system prove the feasibility of a low-threshold analysis.

The Askaryan Radio Array (ARA) is an ultra-high energy (UHE) neutrino ($E_{\nu}$ > $10^{17}$ eV) detector at South Pole. ARA aims to utilize radio signals detected from UHE neutrino interactions in the glacial ice to infer properties about the interaction vertex as well as the incident neutrino. To retrieve these properties from experiment data, the first step is to extract timing, amplitude and frequency information from waveforms of different antennas buried in the deep ice. These features can then be utilized in a neural network to reconstruct the neutrino interaction vertex position, incoming neutrino direction and shower energy. So far, vertex can be reconstructed through interferometry while neutrino reconstruction is still under investigation. Here I will present a solution based on multi-task deep neural networks which can perform reconstruction of both vertex and incoming neutrinos with a reasonable precision. After training, this solution is capable of rapid reconstructions (e.g. 0.1 ms/event compared to 10000 ms/event in a conventional routine) useful for trigger and filter decisions, and can be easily generalized to different station configurations for both design and analysis purposes.

Owing to their small interaction cross-section, neutrinos are unparalleled astronomical tracers. Ultra-high energy (UHE; E > 10 PeV) neutrinos probe the most distant, most explosive sources in the Universe, often obscured to optical telescopes. Radio-frequency (RF) detection of Askaryan radiation in cold polar ice is currently regarded as the best experimental measurement technique for UHE neutrinos, provided the RF properties of the ice target can be well-understood. To that end, the Askaryan Radio Array (ARA) experiment at the South Pole has used long-baseline RF propagation to extract information on the index-of-refraction ( n = ϵ r ) in South Polar ice. Owing to the increasing ice density over the upper 150–200 m, rays are measured along two, nearly parallel paths, one of which refracts through an inflection point, with differences in both arrival time and arrival angle that can be used to constrain the neutrino properties. We also observe (first) indications for RF ice birefringence for signals propagating along predominantly horizontal trajectories, corresponding to an asymmetry of order 0.1% between the ordinary and extra-ordinary birefringent axes, numerically compatible with previous measurements of birefringent asymmetries for vertically-propagating radio-frequency signals at South Pole. Qualitatively, these effects offer the possibility of redundantly measuring the range from receiver to a neutrino interaction in Antarctic ice, if receiver antennas are deployed at shallow (z ∼ −25 m) depths. Such range information is essential in determining both the neutrino energy, as well as the incident neutrino direction.

We investigate the use of parabolic equation (PE) methods for solving radio-wave propagation in polar ice. PE methods provide an approximate solution to Maxwell's equations, in contrast to full-field solutions such as finite-difference-time-domain (FDTD) methods, yet provide a more complete model of propagation than simple geometric ray-tracing (RT) methods that are the current state of the art for simulating in-ice radio detection of neutrino-induced cascades. PEs are more computationally efficient than FDTD methods, and more flexible than RT methods, allowing for the inclusion of diffractive effects and modeling of propagation in regions that cannot be modeled with geometric methods. We present a new PE approximation suited to the in-ice case. We conclude that current ray-tracing methods may be too simplistic in their treatment of ice properties, and their continued use could overestimate experimental sensitivity for in-ice neutrino detection experiments. We discuss the implications for current in-ice Askaryan-type detectors and for the upcoming Radar Echo Telescope, two families of experiments for which these results are most relevant. We suggest that PE methods be investigated further for in-ice radio applications., SCOPUS: ar.j, info:eu-repo/semantics/published

The Radar Echo Telescope for Cosmic Rays (RET-CR) is a pathfinder experiment for the Radar Echo Telescope for Neutrinos (RET-N), a next-generation in-ice detection experiment for ultra high energy neutrinos. RET-CR will serve as the testbed for the radar echo method to probe high-energy particle cascades in nature, whereby a transmitted radio signal is reflected from the ionization left in its wake. This method, recently validated at SLAC experiment T576, shows promising preliminary sensitivity to neutrino-induced cascades above the energy range of optical detectors like IceCube. RET-CR intends to use an in-nature test beam: the dense, in-ice cascade produced when the air shower of an ultra high energy cosmic ray impacts a high-elevation ice sheet. This in-ice cascade, orders of magnitude more dense than the in-air shower that preceded it, is similar in profile and density to the expected cascade from a neutrino-induced cascade deep in the ice. RET-CR will be triggered using surface scintillator technology and will be used to develop, test, and deploy the hardware, firmware, and software needed for the eventual RET-N. We present the strategy, status, and design sensitivity of RET-CR, and discuss its application to eventual neutrino detection.

The SLAC T-576 beam test experiment showed the feasibility of the radar detection technique to probe high-energy particle cascades in dense media. Corresponding particle-level simulations indicate that the radar method has very promising sensitivity to probe the $>$PeV cosmic neutrino flux. As such, it is crucial to demonstrate the in-situ feasibility of the radar echo method, which is the main goal of the current RET-CR experiment. Although the final goal of the Radar Echo Telescope is to detect cosmic neutrinos, we seek a proof of principle using cosmic-ray air showers penetrating the (high-altitude) Antarctic ice sheet. When an UHECR particle cascade propagates into a high-elevation ice sheet, it produces a dense in-ice cascade of charged particles which can reflect incoming radio waves. Using a surface cosmic-ray detector, the energy and direction of the UHECR can be reconstructed, and as such this constitutes a nearly ideal in-situ test beam to provide the proof of principle for the radar echo technique. RET-CR will consist of a transmitter array, receiver antennas and a surface scintillator plate array. Here we present the simulation efforts for RET-CR performed to optimise the surface array layout and triggering system, which affords an estimate of the expected event rate.

The Radar Echo Telescope for Cosmic Rays (RET-CR) is a recently initiated experiment designed to detect the englacial cascade of a cosmic-ray initiated air shower via in-ice radar, toward the goal of a full-scale, next-generation experiment to detect ultra high energy neutrinos in polar ice. For cosmic rays with a primary energy greater than 10 PeV, roughly 10% of an air-shower's energy reaches the surface of a high elevation ice-sheet ($\gtrsim$2 km) concentrated into a radius of roughly 10 cm. This penetrating shower core creates an in-ice cascade many orders of magnitude more dense than the preceding in-air cascade. This dense cascade can be detected via the radar echo technique, where transmitted radio is reflected from the ionization deposit left in the wake of the cascade. RET-CR will test the radar echo method in nature, with the in-ice cascade of a cosmic-ray initiated air-shower serving as a test beam. We present the projected event rate and sensitivity based upon a three part simulation using CORSIKA, GEANT4, and RadioScatter. RET-CR expects $\sim$1 radar echo event per day.

The Askaryan Radio Array (ARA) is an ultra-high energy (UHE, $>10^{17}$ eV) neutrino detector designed to observe neutrinos by searching for the radio waves emitted by the relativistic products of neutrino-nucleon interactions in Antarctic ice. In this paper, we present constraints on the diffuse flux of ultra-high energy neutrinos between $10^{16}-10^{21}$ eV resulting from a search for neutrinos in two complementary analyses, both analyzing four years of data (2013-2016) from the two deep stations (A2, A3) operating at that time. We place a 90 % CL upper limit on the diffuse all flavor neutrino flux at $10^{18}$ eV of $EF(E)=5.6\times10^{-16}$ $\textrm{cm}^{-2}$$\textrm{s}^{-1}$$\textrm{sr}^{-1}$. This analysis includes four times the exposure of the previous ARA result, and represents approximately 1/5 the exposure expected from operating ARA until the end of 2022., 12 pages, 7 figures; Accepted to PRD

The observation of electromagnetic radiation from radio to $\gamma$-ray wavelengths has provided a wealth of information about the universe. However, at PeV (10$^{15}$ eV) energies and above, most of the universe is impenetrable to photons. New messengers, namely cosmic neutrinos, are needed to explore the most extreme environments of the universe where black holes, neutron stars, and stellar explosions transform gravitational energy into non-thermal cosmic rays. The discovery of cosmic neutrinos with IceCube has opened this new window on the universe. In this white paper, we present an overview of a next-generation instrument, IceCube-Gen2, which will sharpen our understanding of the processes and environments that govern the universe at the highest energies. IceCube-Gen2 is designed to: 1) Resolve the high-energy neutrino sky from TeV to EeV energies; 2) Investigate cosmic particle acceleration through multi-messenger observations; 3) Reveal the sources and propagation of the highest energy particles in the universe; 4) Probe fundamental physics with high-energy neutrinos. IceCube-Gen2 will increase the annual rate of observed cosmic neutrinos by a factor of ten compared to IceCube, and will be able to detect sources five times fainter than its predecessor. Furthermore, through the addition of a radio array, IceCube-Gen2 will extend the energy range by several orders of magnitude compared to IceCube. Construction will take 8 years and cost about \$350M. The goal is to have IceCube-Gen2 fully operational by 2033. IceCube-Gen2 will play an essential role in shaping the new era of multi-messenger astronomy, fundamentally advancing our knowledge of the high-energy universe. This challenging mission can be fully addressed only in concert with the new survey instruments across the electromagnetic spectrum and gravitational wave detectors which will be available in the coming years., Comment: 56 pages, 29 figures

NuRadioMC is a Monte Carlo framework designed to simulate ultra-high energy neutrino detectors that rely on the radio detection method. This method exploits the radio emission generated in the electromagnetic component of a particle shower following a neutrino interaction. NuRadioMC simulates everything from the neutrino interaction in a medium, the subsequent Askaryan radio emission, the propagation of the radio signal to the detector and finally the detector response. NuRadioMC is designed as a modern, modular Python-based framework, combining flexibility in detector design with user-friendliness. It includes a state-of-the-art event generator, an improved modelling of the radio emission, a revisited approach to signal propagation and increased flexibility and precision in the detector simulation. This paper focuses on the implemented physics processes and their implications for detector design. A variety of models and parameterizations for the radio emission of neutrino-induced showers are compared and reviewed. Comprehensive examples are used to discuss the capabilities of the code and different aspects of instrumental design decisions., SCOPUS: ar.j, info:eu-repo/semantics/published

Background. Ketogenic diet has been used as supportive therapy in a range of conditions including epilepsy, diabetes mellitus, and cancer. Objective. This study aimed to investigate the effects of long-term consumption of ketogenic diet on blood gas, hematological profiles, organ functions, and superoxide dismutase level in a rat model. Materials and Methods. Fifteen male Wistar rats were divided into control (n = 8) and ketogenic (n = 7) groups. Controls received standard diet contained 52.20% of carbohydrates, 7.00% fat, and 15.25% protein; meanwhile, the ketogenic group received a high-fat-low-carbohydrate diet which contained 5.66% of carbohydrate, 86.19% fat, and 8.15% protein. All rats were caged individually and received 30g of either standard or high-fat-low-carbohydrate pellets. The experiment was carried out for 60 days before the blood samples were taken and analyzed to obtain blood gas, cell counts, organ biomarkers, and plasma antioxidant superoxide dismutase (SOD) levels. Results. The rats subjected to ketogenic diet experienced a marked decrease in body weight, blood sugar, and increased blood ketones (p<0.05). The average blood pH was 7.36 ± 0.02 and base excess was −5.57 ± 2.39 mOsm/L, which were significantly lower than controls (p<0.05). Hematological analysis showed significantly lower erythrocyte, hemoglobin, and hematocrit levels. No significant changes were found in alanine aminotransferase, aspartate aminotransferase, urea, and creatinine levels, indicating normal liver and kidney functions. Nevertheless, plasma SOD level significantly reduced with ketogenic diet. Conclusion. Long-term ketogenic diet induces metabolic acidosis, anemia, and reduced antioxidant enzyme level in rats following 60 days of consuming high-fat-low-carbohydrate diet.

Journal of Instrumentation 15(09), P09039 (2020). doi:10.1088/1748-0221/15/09/P09039, The sources of ultra-high energy (UHE) cosmic rays, which can have energies up to 10$^{20}$ eV, remain a mystery. UHE neutrinos may provide important clues to understanding the nature of cosmic-ray sources. ARIANNA aims to detect UHE neutrinos via radio (Askaryan) emission from particle showers when a neutrino interacts with ice, which is an efficient method for neutrinos with energies between 10$^{16}$ eV and 10$^{20}$ eV. The ARIANNA radio detectors are located in Antarctic ice just beneath the surface. Neutrino observation requires that radio pulses propagate to the antennas at the surface with minimum distortion by the ice and firn medium. Using the residual hole from the South Pole Ice Core Project, radio pulses were emitted from a transmitter located up to 1.7 km below the snow surface. By measuring these signals with an ARIANNA surface station, the angular and polarization reconstruction abilities are quantified, which are required to measure the direction of the neutrino. After deconvolving the raw signals for the detector response and attenuation from propagation through the ice, the signal pulses show no significant distortion and agree with a reference measurement of the emitter made in an anechoic chamber. Furthermore, the signal pulses reveal no significant birefringence for our tested geometry of mostly vertical ice propagation. The origin of the transmitted radio pulse was measured with an angular resolution of 0.37�� indicating that the neutrino direction can be determined with good precision if the polarization of the radio-pulse can be well determined. In the present study we obtained a resolution of the polarization vector of 2.7��. Neither measurement show a significant offset relative to expectation., Published by Inst. of Physics, London

The measurement of ultra-high energy (UHE) neutrinos (E $>$ \SI{e16}{eV}) opens a new field of astronomy with the potential to reveal the sources of ultra-high energy cosmic rays especially if combined with observations in the electromagnetic spectrum and gravitational waves. The ARIANNA pilot detector explores the detection of UHE neutrinos with a surface array of independent radio detector stations in Antarctica which allows for a cost-effective instrumentation of large volumes. Twelve stations are currently operating successfully at the Moore's Bay site (Ross Ice Shelf) in Antarctica and at the South Pole. We will review the current state of ARIANNA and its main results. We report on a newly developed wind generator that successfully operates in the harsh Antarctic conditions and powers the station for a substantial time during the dark winter months. The robust ARIANNA surface architecture, combined with environmentally friendly solar and wind power generators, can be installed at any deep ice location on the planet and operated autonomously. We report on the detector capabilities to determine the neutrino direction by reconstructing the signal arrival direction of a \SI{800}{m} deep calibration pulser, and the reconstruction of the signal polarization using the more abundant cosmic-ray air showers. Finally, we describe a large-scale design -- ARIA -- that capitalizes on the successful experience of the ARIANNA operation and is designed sensitive enough to discover the first UHE neutrino., replaced with published version

With the growth of information technologies, E-industry safety has recently become the mutual attention of education and business firms. Digital image watermarking is a technique that refers to the security of multimedia data. It is a process referred to the security and authentication of a digital image, video, and audio by embedding a watermark. Watermarking technique applies a number of variable editions to the host content, where the addition is related to embed information. In the past, researchers develop multiple simple watermarking techniques, today race is to find a region where the watermark is imperceptible and have a high payload. In this paper, an invisible image watermarking technique based on the least significant bit (LSB) and laplacian filter is proposed. The original image is divided into blocks and the laplacian filter is applied on each block. Laplacian is a derivative filter that uses the second derivate to find out the area of rapid changes in the image and the least significant bit is a technique to embed a watermark into the bit positions. Watermark is embedded on these regions which is favourable in achieving high desirable properties. This technique shows strong robustness against image processing and geometrical attacks. In evaluation with state of art methods, the proposed technique shows satisfactory progress.

The Askaryan Radio Array (ARA) experiment at the South Pole is designed to detect high-energy neutrinos which, via in-ice interactions, produce coherent radiation at frequencies up to 1000 MHz. In Dec. 2018, a custom high-amplitude radio-frequency transmitter was lowered into the 1700 m SPICE ice core to provide test sources for ARA receiver stations sensitive to vertical and horizontal polarizations. For these tests, signal geometries correspond to obliquely propagating radio waves from below. The ARA collaboration has recently measured the polarization-dependent time delay variation, and report more significant time delays for trajectories perpendicular to ice flow. Here we use fabric data from the SPICE ice core to construct a bounding model for the ice birefringence and the polarization time delays across ARA. The data-model comparison is consistent with the vertical girdle fabric at the South Pole having the prevailing horizontal crystallographic axis oriented near-perpendicular to ice flow. This study presents the possibility that ice birefringence can be used to constrain the range to a neutrino interaction, and hence aid in neutrino energy reconstruction, for in-ice experiments such as ARA., submitted to Ann. Glac

The detection of astrophysical neutrinos by IceCube has opened a new window for the observation of our universe. The use of antennas for detecting astroparticles has been proven useful and accurate after many years of radio cosmic-ray detections, and will be a valuable asset for increasing the statistics for the detection of neutrinos < 10 PeV and reaching out to the highest energies. The radio technique requires realistic and precise simulations of the electric field created after the neutrino interacts with the detector volume, how it propagates through media, and what measurable signal it produces in the detector. With the goal of providing accurate, fast simulations of neutrino-induced electric fields, we have created the NuRadioMC code. It builds on the experience of software used for current radio neutrino and cosmic ray experiments.

We report the observation of radar echoes from the ionization trails of high-energy particle cascades. These data were taken at the SLAC National Accelerator Laboratory, where the full electron beam ($\sim$10$^9$ e$^-$ at $\sim$10 GeV/e$^-$) was directed into a plastic target to simulate an ultra high-energy neutrino interaction. This target was interrogated with radio waves, and coherent radio reflections from the cascades were detected, with properties consistent with theoretical expectations. This is the first definitive observation of radar echoes from high-energy particle cascades, which may lead to a viable neutrino detection technology for energies $\gtrsim 10^{16}$ eV., Comment: 6 pages, 4 figures

We report on analysis of englacial radio-frequency (RF) pulser data received over horizontal baselines of 1--5 km, based on broadcasts from two sets of transmitters deployed to depths of up to 1500 meters at the South Pole. First, we analyze data collected usingtwo RF bicone transmitters 1400 meters below the ice surface, and frozen into boreholes drilled for the IceCube experiment in 2011. Additionally, in Dec., 2018, a fat-dipole antenna, fed by one of three high-voltage (~1 kV), fast (~(1-5 ns)) signal generators was lowered into the 1700-m deep icehole drilled for the South Pole Ice Core Experiment (SPICE), approximately 3 km from the geographic South Pole. Signals from transmitters were recorded on the five englacial multi-receiver ARA stations, with receiver depths between 60--200 m. We confirm the long, >1 km RF electric field attenuation length, test our observed signal arrival timing distributions against models, and measure birefringent asymmetries at the 0.15% level.

Ongoing experimental efforts in Antarctica seek to detect ultra-high energy neutrinos by measurement of radio-frequency (RF) Askaryan radiation generated by the collision of a neutrino with an ice molecule. An array of RF antennas, deployed either in-ice or in-air, is used to infer the properties of the neutrino. To evaluate their experimental sensitivity, such experiments require a refractive index model for ray tracing radio-wave trajectories from a putative in-ice neutrino interaction point to the receiving antennas; this gives the degree of signal absorption or ray bending from source to receiver. The gradient in the density profile over the upper 200 meters of Antarctic ice, coupled with Fermat's least-time principle, implies ray "bending" and the existence of "forbidden" zones for predominantly horizontal signal propagation at shallow depths. After re-deriving the formulas describing such shadowing, we report on experimental results that, somewhat unexpectedly, demonstrate the existence of electromagnetic wave transport modes from nominally shadowed regions. The fact that this shadow-signal propagation is observed both at South Pole and the Ross Ice Shelf in Antarctica suggests that the effect may be a generic property of polar ice, with potentially important implications for experiments seeking to detect neutrinos., Comment: 33 pages, 14 figures, accepted for publication in JCAP

Ultra-high energy neutrinos are detectable through impulsive radio signals generated through interactions in dense media, such as ice. Subsurface in-ice radio arrays are a promising way to advance the observation and measurement of astrophysical high-energy neutrinos with energies above those discovered by the IceCube detector ($\geq$1 PeV) as well as cosmogenic neutrinos created in the GZK process ($\geq$100 PeV). Here we describe the $\textit{NuPhase}$ detector, which is a compact receiving array of low-gain antennas deployed 185 m deep in glacial ice near the South Pole. Signals from the antennas are digitized and coherently summed into multiple beams to form a low-threshold interferometric phased array trigger for radio impulses. The NuPhase detector was installed at an Askaryan Radio Array (ARA) station during the 2017/18 Austral summer season. $\textit{In situ}$ measurements with an impulsive, point-source calibration instrument show a 50% trigger efficiency on impulses with voltage signal-to-noise ratios (SNR) of $\le$2.0, a factor of $\sim$1.8 improvement in SNR over the standard ARA combinatoric trigger. Hardware-level simulations, validated with $\textit{in situ}$ measurements, predict a trigger threshold of an SNR as low as 1.6 for neutrino interactions that are in the far field of the array. With the already-achieved NuPhase trigger performance included in ARASim, a detector simulation for the ARA experiment, we find the trigger-level effective detector volume is increased by a factor of 1.8 at neutrino energies between 10 and 100 PeV compared to the currently used ARA combinatoric trigger. We also discuss an achievable near term path toward lowering the trigger threshold further to an SNR of 1.0, which would increase the effective single-station volume by more than a factor of 3 in the same range of neutrino energies., Comment: 19 pages, 19 figures, submitted to Nuclear Instruments and Methods in Physics Research A

Recently the radar scattering technique to probe neutrino induced particle cascades above PeV energies in ice was investigated. The feasibility of the radar detection method was shown to crucially depend on several up to now unknown plasma properties, such as the plasma lifetime and the free charge collision rate. To determine these parameters, a radar scattering experiment was performed at the Telescope Array Electron Light Source facility, where a beam of high-energy electrons was directed in a block of ice. The induced ionization plasma was consequently probed using a radar detection set-up detecting over a wide frequency range from 200 MHz up to 2 GHz. First qualitative results of this experiment will be presented.

Little is known about risk factors for biliary pancreatitis in children. We characterized cases of pediatric biliary pancreatitis, compared biliary with nonbiliary cases, examined differences in presentation between younger and older children, and studied features distinguishing gallstone- from sludge-induced pancreatitis.We evaluated 76 episodes of biliary pancreatitis from 271 cases of acute pancreatitis in children admitted to a tertiary care hospital from 1994 to 2007.Of the 76 cases, 55% had gallstones, 21% had sludge, and 24% had structural defects. Hispanic children had 2.85 (P = 0.01) and 5.59 (P = 0.003) times higher probability for biliary pancreatitis than white and black children, respectively. Median serum amylase and lipase in children with biliary pancreatitis were 64% and 49% higher, respectively, compared with other causes (P0.05). In multiple logistic regression, aspartate aminotransferase was an independent predictor of biliary pancreatitis (odds ratio 6.69, P = 0.001). When comparing gallstone- with sludge-induced causes, obesity was an independent predictor (38% more prevalent, P0.01) of gallstone cases.Hispanic ethnicity is a risk factor and aspartate aminotransferase is a biomarker for biliary pancreatitis over other causes. Furthermore, obesity can distinguish gallstone- from sludge-induced pancreatitis. These findings may spur prospective studies to determine the optimal evaluation and management of children with biliary pancreatitis.

INTRODUCTION Renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancies and is responsible for over 13,000 deaths in the U.S. annually. The fatalities are largely due to distant metastasis, with lung, liver, bone and brain being most commonly affected organs. Gastric metastasis from RCC is a rare event (less than 20 cases reported in the English language literature) and usually presents as a large, solitary mass or ulcer (average size of 4.8 cm) resembling primary gastric cancer. Here we report the first case of metastatic RCC presenting as small gastric polyps. PRESENTATION OF CASE The patient was a 60-year-old African American woman with a history of clear cell RCC (pT1bNX). She underwent esophagogastroduodenoscopy and colonoscopy 5 months after nephrectomy due to anemia. Two non-ulcerated, 0.6-cm benign-appearing polyps were found at the greater curvature of the gastric body, which were subsequently removed endoscopically. Unexpectedly, histopathologic examination of the gastric polyps revealed nested collections of vacuolated epithelioid cells in a background of delicate, arborizing vasculature, immediately beneath the congested and hyperplastic foveolar epithelium. A diagnosis of metastatic RCC was rendered after confirming the renal epithelial origin by immunohistochemical stains. DISCUSSION Gastric metastasis from RCC usually presents as a large, solitary mass or ulcer, but it can be subtle and present as multiple, small benign-appearing polyps. CONCLUSION A careful follow up and thorough endoscopic and histopathologic examinations should be conducted in patients with a history of RCC who present with gastrointestinal manifestations.

The aim of this study was to assess for any trend in management of pancreatic fluid collections (PFCs) and identify impacting factors. The endoscopy and surgical databases were queried for PFC patients. PFCs were categorized as pseudocysts (PP) or complex collections (CC) that included abscess/necrosis. The outcome measures were to compare the utilization of surgery and endoscopy from 2004 to 2007 (group I) and from 2008 to 2010 (group II) and identify factors impacting practice patterns. A total of 285 patients were treated: group I included 119 and group II 166. Of 119 group I patients, 29 per cent were treated by surgery and 71 per cent by endoscopy. Of 85 endoscopy patients, 42 per cent were drained by conventional transmural drainage and 58 per cent by endoscopic ultrasound (EUS). Of 166 group II patients, 31 per cent were treated surgically and 69 per cent endoscopically. Of the 115 endoscopy patients, 17 per cent were drained by conventional transmural drainage and 83 per cent by EUS. Compared with group I, all pseudocysts in group II were treated by endoscopy (84% vs 100%, P = 0.001). There was no difference in the rate of CC treated by endoscopy between both groups (57.7% vs 56.8%, P = 0.9). PFCs not causing luminal compression ( P < 0.0001) or measuring

Medications are a major cause of acute pancreatitis; however, little is known about their influence in children. Our primary aims were to identify common comorbidities and concomitant pancreatitis etiologies in children with drug-associated pancreatitis. Our secondary aims were to identify the most commonly associated drugs in the different age groups, evaluate management practices, and compare drug-associated cases with non-drug-associated cases.In the present study, we examined children (ages 0-20 years) admitted to Yale-New Haven Children's Hospital with pancreatitis between 1994 and 2007.Of a total of 271 pediatric cases, drugs were associated with pancreatitis in 25.6% (55). The 3 most common comorbidities in children with drug-associated pancreatitis were seizure disorders, acute lymphocytic leukemia, and Crohn disease. One third of drug-associated cases had an additional pancreatitis etiology. The most commonly associated drugs were valproic acid and corticosteroids. Compared with non-drug-associated cases, children with drug-associated cases were more likely to undergo CT scanning (54.5% vs 28.4%; P0.001), stay in the hospital longer (10 vs 4 days; P0.001), and transition to parenteral nutrition from a nil per os status (37.5% vs 21.2%; P0.05). There was a higher frequency of valproic acid-associated cases in children younger than 11 years (29.4% vs 9.5% in the 11- to 20-year-old age group).Our study underscores the importance of considering drugs as a cause and a contributor to pancreatitis in children, particularly valproic acid in young children.

Objectives: Acute pancreatitis is a necroinflammatory disease that leads to 210,000 hospitalizations in the United States annually. Recent reports suggest that there may be important differences in clinical features between infants/toddlers and older children. Thus, in this study we make a direct comparison between the pediatric age groups in presentation and management trends of acute pancreatitis. Patients and Methods: We examined all children (ages 0 to 20 years) admitted to Yale-New Haven Children’s Hospital with pancreatitis between 1994 and 2007. Results: Two hundred seventy-one cases met inclusion criteria for acute pancreatitis. Infants and toddlers manifested fewer signs and symptoms of abdominal pain, epigastric tenderness, and nausea compared with older children (43% vs 93%; 57% vs 90%; and 29% vs 76%, respectively; P

Acute pancreatitis is a painful inflammatory disorder with a major health impact (1,2). It accounts for more than 230,000 adult hospitalizations annually in the United States at an estimated cost of $4.6 to 4.8 billion/year (3). Even mild disease may require analgesia, nutritional support, and hospital stay ranging from 3 to 10 days (4). Data in children with acute pancreatitis are limited, but they suggest important differences vis-a-vis adults (1,5). Although alcohol and biliary tract disease cause most cases in adults, etiologies in children are more variable. Adult pancreatitis has been increasing in the last 4 decades (6). This has been attributed to the increasing incidence of gallstone pancreatitis. In children, recent reports indicate an increase of acute pancreatitis within the last decade (7–9). However, these data are confined to limited series from specific geographic locations. It is unclear whether the increase is attributable to local factors or a general shift in the epidemiology of this disease. Our primary objective was to analyze the frequency of pediatric pancreatitis in the last 12 years at Yale-New Haven Children’s Hospital. Our secondary objective was to perform detailed analysis on etiologies of pancreatitis in children. If changes in frequency were present, then we sought to attribute causes for observed trends by analyzing shifts in etiologies, body mass index (BMI), or referral patterns during the study period.

Role-based access control (RBAC) models have generated a great interest in the security community as a powerful and generalized approach to security management. In many practical scenarios, users may be restricted to assume roles only at predefined time periods. Furthermore, roles may only be invoked on prespecified intervals of time depending upon when certain actions are permitted. To capture such dynamic aspects of a role, a temporal RBAC (TRBAC) model has been recently proposed. However, the TRBAC model addresses the role enabling constraints only. In This work, we propose a generalized temporal role-based access control (GTRBAC) model capable of expressing a wider range of temporal constraints. In particular, the model allows expressing periodic as well as duration constraints on roles, user-role assignments, and role-permission assignments. In an interval, activation of a role can further be restricted as a result of numerous activation constraints including cardinality constraints and maximum active duration constraints. The GTRBAC model extends the syntactic structure of the TRBAC model and its event and trigger expressions subsume those of TRBAC. Furthermore, GTRBAC allows expressing role hierarchies and separation of duty (SoD) constraints for specifying fine-grained temporal semantics.

Fully covered esophageal self-expandable metal stents (SEMSs) are potentially removable but can be associated with high migration rates. For precise positioning, non-foreshortening SEMSs are preferred. Recently, a new fully covered non-foreshortening SEMS with anti-migration features was introduced.To evaluate the efficacy and safety of this new esophageal SEMS.Retrospective study.Single, tertiary-care center.Consecutive patients with malignant and benign strictures with dysphagia grade of ≥3 and patients with fistulas/leaks were studied.Stent placement and removal.Technical success in stent deployment/removal, efficacy in relieving dysphagia and sealing fistulas/leaks, and adverse events.Forty-three stents were placed in 35 patients (mean [± standard deviation] age 65 ± 11 years; 31 male), 24 for malignant and 11 for benign (5 strictures, 6 leaks) indications. Technical success in precise SEMS placement was 100%. The after-stent dysphagia grade improved significantly (at 1 week: 1.5 ± 0.7; at 4 weeks: 1.2 ± 0.4; baseline: 3.8 ± 0.4; P .0001). Twenty stents were removed for clinical indications, with technical success of 100%. All leaks sealed after SEMS placement and did not recur after stent removal. All benign strictures recurred after stent removal. Adverse events included migration (14%), chest pain (11%), and dysphagia from tissue hyperplasia (6%). There was no stent-related mortality.Nonrandomized, single-center study.The new esophageal SEMS was effective in relieving malignant dysphagia, allowed for precise placement, and was easily removable. It was effective in treating benign esophageal fistulas and leaks. Stent-related adverse events were acceptable.

Hypercalcemia is an important etiology to consider in the evaluation of acute pancreatitis. Not only is it a treatable cause, but understanding the basis for this etiology may provide new insight into the common biochemical mechanisms involved in the pathogenesis of pancreatitis. We report a case of an 11-year-old girl with hypercalcemia due to primary hyperparathyroidism who developed recurrent pancreatitis. We review clinical and experimental data that implicate hypercalcemia as the cause and discuss mechanisms for the association.