Development and validation of a machine learning-based, point-of-care risk calculator for post-ERCP pancreatitis and prophylaxis selection.

BACKGROUND AND AIMS: A robust model of post-ERCP pancreatitis (PEP) risk is not currently available. We aimed to develop a machine learning-based tool for PEP risk prediction to aid in clinical decision making related to periprocedural prophylaxis selection and postprocedural monitoring. METHODS: Feature selection, model training, and validation were performed using patient-level data from 12 randomized controlled trials. A gradient-boosted machine (GBM) model was trained to estimate PEP risk, and the performance of the resulting model was evaluated using the area under the receiver operating curve (AUC) with 5-fold cross-validation. A web-based clinical decision-making tool was created, and a prospective pilot study was performed using data from ERCPs performed at the Johns Hopkins Hospital over a 1-month period. RESULTS: A total of 7389 patients were included in the GBM with an 8.6% rate of PEP. The model was trained on 20 PEP risk factors and 5 prophylactic interventions (rectal nonsteroidal anti-inflammatory drugs [NSAIDs], aggressive hydration, combined rectal NSAIDs and aggressive hydration, pancreatic duct stenting, and combined rectal NSAIDs and pancreatic duct stenting). The resulting GBM model had an AUC of 0.70 (65% specificity, 65% sensitivity, 95% negative predictive value, and 15% positive predictive value). A total of 135 patients were included in the prospective pilot study, resulting in an AUC of 0.74. CONCLUSIONS: This study demonstrates the feasibility and utility of a novel machine learning-based PEP risk estimation tool with high negative predictive value to aid in prophylaxis selection and identify patients at low risk who may not require extended postprocedure monitoring.

Convergence of marine megafauna movement patterns in coastal and open oceans.

The extent of increasing anthropogenic impacts on large marine vertebrates partly depends on the animals' movement patterns. Effective conservation requires identification of the key drivers of movement including intrinsic properties and extrinsic constraints associated with the dynamic nature of the environments the animals inhabit. However, the relative importance of intrinsic versus extrinsic factors remains elusive. We analyze a global dataset of ∼2.8 million locations from >2,600 tracked individuals across 50 marine vertebrates evolutionarily separated by millions of years and using different locomotion modes (fly, swim, walk/paddle). Strikingly, movement patterns show a remarkable convergence, being strongly conserved across species and independent of body length and mass, despite these traits ranging over 10 orders of magnitude among the species studied. This represents a fundamental difference between marine and terrestrial vertebrates not previously identified, likely linked to the reduced costs of locomotion in water. Movement patterns were primarily explained by the interaction between species-specific traits and the habitat(s) they move through, resulting in complex movement patterns when moving close to coasts compared with more predictable patterns when moving in open oceans. This distinct difference may be associated with greater complexity within coastal microhabitats, highlighting a critical role of preferred habitat in shaping marine vertebrate global movements. Efforts to develop understanding of the characteristics of vertebrate movement should consider the habitat(s) through which they move to identify how movement patterns will alter with forecasted severe ocean changes, such as reduced Arctic sea ice cover, sea level rise, and declining oxygen content.

Tracking apex marine predator movements in a dynamic ocean.

Pelagic marine predators face unprecedented challenges and uncertain futures. Overexploitation and climate variability impact the abundance and distribution of top predators in ocean ecosystems. Improved understanding of ecological patterns, evolutionary constraints and ecosystem function is critical for preventing extinctions, loss of biodiversity and disruption of ecosystem services. Recent advances in electronic tagging techniques have provided the capacity to observe the movements and long-distance migrations of animals in relation to ocean processes across a range of ecological scales. Tagging of Pacific Predators, a field programme of the Census of Marine Life, deployed 4,306 tags on 23 species in the North Pacific Ocean, resulting in a tracking data set of unprecedented scale and species diversity that covers 265,386 tracking days from 2000 to 2009. Here we report migration pathways, link ocean features to multispecies hotspots and illustrate niche partitioning within and among congener guilds. Our results indicate that the California Current large marine ecosystem and the North Pacific transition zone attract and retain a diverse assemblage of marine vertebrates. Within the California Current large marine ecosystem, several predator guilds seasonally undertake north-south migrations that may be driven by oceanic processes, species-specific thermal tolerances and shifts in prey distributions. We identify critical habitats across multinational boundaries and show that top predators exploit their environment in predictable ways, providing the foundation for spatial management of large marine ecosystems.

The lakes of Titan.

The surface of Saturn's haze-shrouded moon Titan has long been proposed to have oceans or lakes, on the basis of the stability of liquid methane at the surface. Initial visible and radar imaging failed to find any evidence of an ocean, although abundant evidence was found that flowing liquids have existed on the surface. Here we provide definitive evidence for the presence of lakes on the surface of Titan, obtained during the Cassini Radar flyby of Titan on 22 July 2006 (T16). The radar imaging polewards of 70 degrees north shows more than 75 circular to irregular radar-dark patches, in a region where liquid methane and ethane are expected to be abundant and stable on the surface. The radar-dark patches are interpreted as lakes on the basis of their very low radar reflectivity and morphological similarities to lakes, including associated channels and location in topographic depressions. Some of the lakes do not completely fill the depressions in which they lie, and apparently dry depressions are present. We interpret this to indicate that lakes are present in a number of states, including partly dry and liquid-filled. These northern-hemisphere lakes constitute the strongest evidence yet that a condensable-liquid hydrological cycle is active in Titan's surface and atmosphere, in which the lakes are filled through rainfall and/or intersection with the subsurface 'liquid methane' table.

Titan Radar Mapper observations from Cassini's T3 fly-by.

Cassini's Titan Radar Mapper imaged the surface of Saturn's moon Titan on its February 2005 fly-by (denoted T3), collecting high-resolution synthetic-aperture radar and larger-scale radiometry and scatterometry data. These data provide the first definitive identification of impact craters on the surface of Titan, networks of fluvial channels and surficial dark streaks that may be longitudinal dunes. Here we describe this great diversity of landforms. We conclude that much of the surface thus far imaged by radar of the haze-shrouded Titan is very young, with persistent geologic activity.

Of mice and men: comparative proteomics of bronchoalveolar fluid.

We hypothesised that comparing the protein mixture in bronchoalveolar lavage fluid (BALF) between humans and mice may lead to mechanistic insights into common and divergent pathways that evolved in each species. BALF from four humans and six mice was pooled separately and underwent identical shotgun proteomic analysis. Functional and network analysis was applied to identify overlapping and distinct pathways enriched in the BALF. Follow-up experiments using Western analysis in unpooled BALF samples were performed. We identified 91 unique proteins in human and 117 unique proteins in mouse BALF samples. Functional analysis of the proteins revealed conservation of several key processes between the species, including defence response. Oxidative stress response, however, was selectively enriched only in mouse BALF. Differences in the expression of peroxiredoxin-1, a key member of the defence pathway against oxidative injury, were confirmed between normal human and mouse BALF and in models of lung injury. A computational proteomics approach of mouse and human BALF confirms the conservation of immune and defence-mediated pathways while highlighting differences in response to oxidative stress. These observations suggest that the use of mice models to study human lung disorders should be undertaken with an appreciation of interspecies variability.

Technical comment on "Synovial fibroblast-neutrophil interactions promote pathogenic adaptive immunity in rheumatoid arthritis".

Reassessment of citrullinome cargo in neutrophil extracellular traps confirms the presence of citrullinated peptides.

"Atmospheric" Epoxidation of Benzo[a]pyrene by Ozone: Formation of the Metabolite Benzo[a]pyrene-4,5-Oxide.

Benzo[a]pyrene deposited on a glass fiber filter reacts rapidly in the dark or light with ambient levels of ozone to yield a mixture of products that display strong direct mutagenicity in the Ames assay. The major stable contributor to this activity has been identified as benzo[a]pyrene-4,5-oxide, a DNA-binding metabolite in biological systems, known to be a strong direct mutagen with Salmonella typhimurium strain TA98.

Impact of meteorological conditions on noise propagation from freeway corridors.

This paper examines the impact of meteorological conditions on the propagation of vehicular noise from urban freeways. A parabolic equation model coupled to an analytical Green's function solution close to the source field is used to compute the refracted sound field up to half a mile from the freeway to predict the noise exposure of residential areas nearby. The model was used in conjunction with meteorological and sound-level measurements taken at two freeway sites over the course of four days in Phoenix, AZ. From the data collected, three test cases of varying levels of atmospheric stratification and wind shear are presented and discussed. The model demonstrates that atmospheric effects are able to raise sound levels by 10-20 dB at significant distances away from the highway, causing violations of acceptable limits imposed by the Federal Highway Administration in residential areas that are normally in compliance.

Tropical seabirds sample broadscale patterns of marine contaminants.

Contaminants in the marine environment are widespread, but ship-based sampling routines are much narrower. We evaluated the utility of seabirds, highly-mobile marine predators, as broad samplers of contaminants throughout three tropical ocean regions. Our aim was to fill a knowledge gap in the distributions of, and processes that contribute to, tropical marine contaminants; and explore how species-specific foraging ecologies could inform or bias our understanding of contaminant distributions. Mercury and persistent organic pollutant (POPs) concentrations were measured in adults of five seabird species from four colonies in the central Pacific (Laysan and Tern Islands, Hawaii; Palmyra Atoll) and the eastern Caribbean (Barbuda). Blood-based total mercury (THg) and 89 POPs were measured in two seabird families: surface-foraging frigatebirds (Fregata spp.) and plunge-diving boobies (Sula spp.). Overall, largescale contaminant differences between colonies were more informative of contaminant distributions than inter-specific foraging ecology. Model selection results indicated that proximity to human populations was the best predictor of THg and POPs. Regional differences in contaminants were distinct: Barbudan Magnificent Frigatebirds had more compounds (n=52/89 POP detected) and higher concentrations (geometric mean THg=0.97µgg-1; mean ΣPOP53=26.6ngmL-1) than the remote colonies (34-42/89 POP detected; range of THg geometric means=0.33-0.93µgg-1; range of mean ΣPOP53:7.3-17.0ngmL-1) and had the most recently-synthesized POPs. Moderate differences in foraging ecologies were somewhat informative of inter-specific differences in contaminant types and concentrations between nearshore and offshore foragers. Across species, contaminant concentrations were higher in frigatebirds (THg=0.87µgg-1; ΣPOP53=17.5ngmL-1) compared to boobies (THg=0.48µgg-1; ΣPOP53=9.8). Ocean currents and contaminants' physiochemical properties provided additional insight into the scales of spatial and temporal contaminant exposure. Seabirds are excellent, broad samplers with which we can understand contaminant distributions in the marine environment. This is especially important for tropical remote regions that are under-sampled.

A slow-cycling subpopulation of melanoma cells with highly invasive properties.

Melanoma is a heterogeneous tumor with different subpopulations showing different proliferation rates. Slow-cycling cells were previously identified in melanoma, but not fully biologically characterized. Using the label-retention method, we identified a subpopulation of slow-cycling cells, defined as label-retaining cells (LRC), with strong invasive properties. We demonstrate through live imaging that LRC are leaving the primary tumor mass at a very early stage and disseminate to peripheral organs. Through global proteome analyses, we identified the secreted protein SerpinE2/protease nexin-1 as causative for the highly invasive potential of LRC in melanomas.

Different oligomeric forms of protein phosphatase 2A activate and inhibit simian virus 40 DNA replication.

The ability of simian virus 40 (SV40) large T antigen to catalyze the initiation of viral DNA replication is regulated by its phosphorylation state. Previous studies have identified the free catalytic subunit of protein phosphatase 2A (PP2Ac) as the cellular phosphatase which can remove inhibitory phosphoryl groups from serines 120 and 123. The catalytic C subunit exists in the cell complexed with a 65-kDa A subunit and one of several B subunits. To determine if any of the holoenzymes could activate T antigen, we tested the ability of the heterodimeric AC and two heterotrimeric ABC forms to stimulate T-antigen function in unwinding the origin of SV40 DNA replication. Only free catalytic subunit C and the heterotrimeric form with a 72-kDa B subunit (PP2A-T72) could stimulate T-antigen-dependent origin unwinding. Both the dimeric form (PP2A-D) and the heterotrimer with a 55-kDa B subunit (PP2A-T55) actively inhibited T-antigen function. We found that PP2A-T72 activated T antigen by dephosphorylating serines 120 and 123, while PP2A-D and PP2A-T55 inactivated T antigen by dephosphorylating the p34cdc2 target site, threonine 124. Thus, alterations in the subunit composition of PP2A holoenzymes have significant functional consequences for the initiation of in vitro SV40 DNA replication. The regulatory B subunits of PP2A may play a role in regulating SV40 DNA replication in infected cells as well.

Effects of El Niño-driven changes in wind patterns on North Pacific albatrosses.

Changes to patterns of wind and ocean currents are tightly linked to climate change and have important implications for cost of travel and energy budgets in marine vertebrates. We evaluated how El Niño-Southern Oscillation (ENSO)-driven wind patterns affected breeding Laysan and black-footed albatross across a decade of study. Owing to latitudinal variation in wind patterns, wind speed differed between habitat used during incubation and brooding; during La Niña conditions, wind speeds were lower in incubating Laysan (though not black-footed) albatross habitat, but higher in habitats used by brooding albatrosses. Incubating Laysan albatrosses benefited from increased wind speeds during El Niño conditions, showing increased travel speeds and mass gained during foraging trips. However, brooding albatrosses did not benefit from stronger winds during La Niña conditions, instead experiencing stronger cumulative headwinds and a smaller proportion of trips in tailwinds. Increased travel costs during brooding may contribute to the lower reproductive success observed in La Niña conditions. Furthermore, benefits of stronger winds in incubating habitat may explain the higher reproductive success of Laysan albatross during El Niño conditions. Our findings highlight the importance of considering habitat accessibility and cost of travel when evaluating the impacts of climate-driven habitat change on marine predators.

Clinical relevance of culture versus screens for the detection of microbial pathogens in urine specimens.

The use of screens to detect "significant levels" of pathogenic microorganisms in urine specimens offers the advantages of both rapidly reporting results and controlling costs. Many of these screens, however, are insensitive at microbial counts below 10(5) colony-forming units (CFU)/ml of urine. It is increasingly apparent that patients with almost any type of urinary tract infection (except for most patients who are asymptomatic or who have pyelonephritis) may have urine concentrations of pathogens as low as 10(2) to 10(3) CFU/ml. This review documents factors that can contribute to diminished concentrations of microorganisms in urine, lists patient populations in whose urine microorganisms in concentrations well below 10(5) CFU/ml have been associated with infection, and makes recommendations for selection of laboratory tests, including rapid screens, for the diagnosis and management of urinary tract infections.

Postnatal weight changes in low birth weight infants.

Postnatal body weight changes were assessed in 385 surviving infants with birth weights of less than 2,500 g. Body weight was measured daily between birth and 45 days of age. Infants were grouped according to 100-g birth weight categories, and mean body weight changes for each group were compared. Initial postnatal weight loss occurred in each group and ranged between 7.9% and 14.6% of birth weight. Mean postnatal weight loss was greater in the lowest birth weight groups, but considerable variability was observed among individual infants. Duration of postnatal weight loss was similar among all birth weight groups. Weight gain usually began between four and six days of age, and the rate of weight gain expressed as grams per kilogram per day was similar in all birth weight groups.

Fast and fuel efficient? Optimal use of wind by flying albatrosses.

The influence of wind patterns on behaviour and effort of free-ranging male wandering albatrosses (Diomedea exulans) was studied with miniaturized external heart-rate recorders in conjunction with satellite transmitters and activity recorders. Heart rate was used as an instantaneous index of energy expenditure. When cruising with favourable tail or side winds, wandering albatrosses can achieve high flight speeds while expending little more energy than birds resting on land. In contrast, heart rate increases concomitantly with increasing head winds, and flight speeds decrease. Our results show that effort is greatest when albatrosses take off from or land on the water. On a larger scale, we show that in order for birds to have the highest probability of experiencing favourable winds, wandering albatrosses use predictable weather systems to engage in a stereotypical flight pattern of large looping tracks. When heading north, albatrosses fly in anticlockwise loops, and to the south, movements are in a clockwise direction. Thus, the capacity to integrate instantaneous eco-physiological measures with records of large-scale flight and wind patterns allows us to understand better the complex interplay between the evolution of morphological, physiological and behavioural adaptations of albatrosses in the windiest place on earth.

Hydrogen bonding in transient bifunctional hypervalent radicals by neutralization-reionization mass spectrometry.

Neutralization-reionization mass spectrometry is used to generate hypervalent 9-N-4 (ammonium) and 9-O-3 (oxonium) radicals derived from protonated α,ω-bis-(dimethylamino)alkanes and α,ω-dimethoxyalkanes, which exist as cyclic hydrogen-bonded structures in the gas phase. Collisional neutralization with dimethyl disulfide, trimethylamine, and xenon of the hydrogen-bonded onium cations followed by reionization with oxygen results in complete dissociation. Bond cleavages at the hypervalent nitrogen atoms are found to follow the order CH2-N>CH3-N>N-H, which differs from that in the monofunctional hydrogen-n-heptyldimethylammonium radical, which gives CH2-N>N-H>CH3-N. No overall stabilization through hydrogen bonding of the bifunctional hypervalent ammonium and oxonium radicals is observed. Subtle effects of ring size are found that tend to stabilize large ring structures and are attributed to intramolecular hydrogen bonding.

Novel tandem quadrupole-acceleration-deceleration mass spectrometer for neutralization-reionization studies.

A new tandem mass spectrometer of the quadrupole-acceleration lens-deceleration. lens-quadrupole (QADQ) configuration is described. The instrument is designed for neutralization-reionization studies and consists of a 2000-u quadrupole mass analyzer as MS-I, an acceleration electrostatic lens, a series of three differentially pumped collision cells, and an electrostatic deceleration lens, energy filter, and another 2000-u quadrupole mass analyzer as MS-II. The ion optical system achieves high total ion transmission for 5-9-keV ions. Unit mass resolution in neutralization-reionization mass spectra of aromatic compounds is demonstrated. Mass, kinetic energy, and linked scans at various levels of mass resolution and sensitivity are described.

Effect of human hydrosalpinx fluid on murine embryo development and implantation.

OBJECTIVE: To determine the effect of hydrosalpinx fluid-containing medium on murine embryo development and implantation. DESIGN: The development of one-, two-, and four-cell mouse embryos in medium containing 5%, 10%, and 20% of human hydrosalpinx fluid was observed. Implantation rates of mouse embryos transferred into the uterine horn with hydrosalpinx fluid-containing media were determined. SETTING: Private hospital-based fertility center and IVF program. MAIN OUTCOME MEASURE(S): Percentage of embryos continuing cell division and implantation rates after ET. RESULT(S): Hydrosalpinx fluid in culture medium affected embryo development in a dose-dependent fashion. The injection of hydrosalpinx fluid-containing medium into the uterine horn did not affect embryo implantation. CONCLUSION(S): Hydrosalpinx fluid negatively affects murine embryo development, but its presence in the uterine horn at ET did not affect implantation.

Effects of learned flavor cues on single meal and daily food intake in humans.

This study examined the effects of learned flavor cues on lunch-meal and daily food intake in 39, normal-weight, free-living adults. Subjects were fed distinctly flavored high-calorie (HC) and low-calorie (LC) milkshake preloads. Following the repeated flavor-calorie pairings, the flavors of the milkshakes were covertly switched. Twenty-three percent of the participants were classified as sensory responders. That is, their lunch intake reflected the anticipated caloric content of the preloads based on the sensory properties rather than the true energy value. Short-term sensory learning did not reliably alter 24-h energy intake in these subjects. The remaining subjects (i.e., sensory nonresponders) ignored the flavor cues and consumed the same size lunches across all phases of the study. Compensation for the preloads was examined during the training period (i.e., before the flavors were switched). Sensory responders accurately adjusted lunch intakes on the first day of exposure to both preloads, demonstrating unlearned compensation for energy density. Compensation continued to be accurate across training days for the HC (85%) but not the LC preload (65%). Sensory nonresponders did not compensate accurately for either of the preloads. Thus, sensory responders were initially more responsive to the caloric density of the preloads and continued to make accurate adjustments when the flavor cue matched the caloric load (i.e., during training) but were misled by the flavor cue when it did not match the caloric consequence (i.e., when the flavors were switched). Sensory nonresponders ignored the sensory cues and ate the same size lunches regardless of the caloric value of the preload.(ABSTRACT TRUNCATED AT 250 WORDS)