Thrombocytosis: Diagnostic Evaluation, Thrombotic Risk Stratification, and Risk-Based Management Strategies

Thrombocytosis is a commonly encountered clinical scenario, with a large proportion of cases discovered incidentally. The differential diagnosis for thrombocytosis is broad and the diagnostic process can be challenging. Thrombocytosis can be spurious, attributed to a reactive process or due to clonal disorder. This distinction is important as it carries implications for evaluation, prognosis, and treatment. Clonal thrombocytosis associated with the myeloproliferative neoplasms, especially essential thrombocythemia and polycythemia vera, carries a unique prognostic profile, with a markedly increased risk of thrombosis. This risk is the driving factor behind treatment strategies in these disorders. Clinical trials utilizing targeted therapies in thrombocytosis are ongoing with new therapeutic targets waiting to be explored. This paper will outline the mechanisms underlying thrombocytosis, the diagnostic evaluation of thrombocytosis, complications of thrombocytosis with a special focus on thrombotic risk as well as treatment options for clonal processes leading to thrombocytosis, including essential thrombocythemia and polycythemia vera

Effect of improving representation of horizontal and vertical cloud structure on the Earth's global radiation budget. Part II: The global effects

Reliably representing both horizontal cloud inhomogeneity and vertical cloud overlap is fundamentally important for the radiation budget of a general circulation model. Here, we build on the work of Part One of this two-part paper by applying a pair of parameterisations that account for horizontal inhomogeneity and vertical overlap to global re-analysis data. These are applied both together and separately in an attempt to quantify the effects of poor representation of the two components on radiation budget. Horizontal inhomogeneity is accounted for using the “Tripleclouds” scheme, which uses two regions of cloud in each layer of a gridbox as opposed to one; vertical overlap is accounted for using “exponential-random” overlap, which aligns vertically continuous cloud according to a decorrelation height. These are applied to a sample of scenes from a year of ERA-40 data. The largest radiative effect of horizontal inhomogeneity is found to be in areas of marine stratocumulus; the effect of vertical overlap is found to be fairly uniform, but with larger individual short-wave and long-wave effects in areas of deep, tropical convection. The combined effect of the two parameterisations is found to reduce the magnitude of the net top-of-atmosphere cloud radiative forcing (CRF) by 2.25 W m−2, with shifts of up to 10 W m−2 in areas of marine stratocumulus. The effects of the uncertainty in our parameterisations on radiation budget is also investigated. It is found that the uncertainty in the impact of horizontal inhomogeneity is of order ±60%, while the uncertainty in the impact of vertical overlap is much smaller. This suggests an insensitivity of the radiation budget to the exact nature of the global decorrelation height distribution derived in Part One

Recurrent glomerular disease after kidney transplantation diagnostic and management dilemmas

Recurrent glomerular disease after kidney transplant remains an important cause of allograft failure. Many of the different entities post-transplant still suffer from incomplete knowledge on pathophysiology, and therefore lack targeted and effective therapies. In this review, we focus on specific clinical dilemmas encountered by physicians in managing recurrent glomerular disease by highlighting new insights into the understanding and treatment of post-transplant focal segmental glomerulosclerosis, membranous nephropathy, atypical hemolytic uremic syndrome, C3 glomerulopathy, amyloid light-chain (AL) amyloidosis, and IgA nephropathy

Timing of Deformation along the Iron Springs Thrust, Southern Sevier Fold-and-Thrust Belt, Utah: Evidence for an Extensive Thrusting Event in the mid-Cretaceous

The temporal and spatial distribution of strain associated with the Sevier orogeny in western North America is significantly different in the southern end of the belt, at the latitude of Las Vegas, Nevada, than farther to the north at the latitude of Salt Lake City, Utah. Reasons for these differences have been speculative as a lack of temporal constraints on thrusting in the intervening region hindered along-strike correlation across the belt. We determined a crystallization age of 100.18 ± 0.04 Ma for zircons extracted from a recently recognized dacite lapilli ash-fall tuff near the base of the synorogenic Iron Springs Formation. We propose the name “Three Peaks Tuff Member” for this unit, and identify a type stratigraphic section on the western flank of the “Three Peaks,” a topographic landmark in Iron County, Utah. Field relationships and this age constrain movement on the Iron Springs thrust and the end of the sub-Cretaceous unconformity in the critical intervening area to latest Albian/earliest Cenomanian. Movement on the Iron Springs thrust was synchronous with movement on multiple Sevier thrusts at ~100 Ma, indicating that the mid-Cretaceous was a period of extensive thrust-fault movement. This mid-Cretaceous thrusting event coincided with a period of global plate reorganization and increased convergence, and hence an increased subduction rate for the Farallon Plate beneath North America. The accelerated subduction contributed to a Cordilleran arc flare-up event and steepening of the orogenic wedge, which triggered widespread thrusting across the retroarc Sevier deformation belts. Additionally, based on temporal constraints and the strong spatial connection of mid-Cretaceous thrusts to lineaments interpreted as pre-orogenic transform faults, we suggest that temporal and spatial variations along the strike of the orogenic belt reflect tectonic inheritance of basement structures associated with the edge of the rifted Precambrian craton

Interferometric Constraints on Quantum Geometrical Shear Noise Correlations

Final measurements and analysis are reported from the first-generation Holometer, the first instrument capable of measuring correlated variations in space-time position at strain noise power spectral densities smaller than a Planck time. The apparatus consists of two co-located, but independent and isolated, 40 m power-recycled Michelson interferometers, whose outputs are cross-correlated to 25 MHz. The data are sensitive to correlations of differential position across the apparatus over a broad band of frequencies up to and exceeding the inverse light crossing time, 7.6 MHz. By measuring with Planck precision the correlation of position variations at spacelike separations, the Holometer searches for faint, irreducible correlated position noise backgrounds predicted by some models of quantum space-time geometry. The first-generation optical layout is sensitive to quantum geometrical noise correlations with shear symmetry---those that can be interpreted as a fundamental noncommutativity of space-time position in orthogonal directions. General experimental constraints are placed on parameters of a set of models of spatial shear noise correlations, with a sensitivity that exceeds the Planck-scale holographic information bound on position states by a large factor. This result significantly extends the upper limits placed on models of directional noncommutativity by currently operating gravitational wave observatories.Comment: Matches the journal accepted versio

Foot care education and self management behaviors in diverse veterans with diabetes

The objective of this study was to examine differences in self-reported diabetes foot care education, self management behaviors, and barriers to good foot care among veterans with diabetes by race and ethnicity. Data was collected using the Veterans Health Administration Footcare Survey, a validated tool that assessed demographic, general health, diabetes and foot self-care information, barriers to foot self-care, receipt of professional foot care, and satisfaction with current care. We mailed surveys to a random sample of patients with diabetes from eight VA medical centers. Study participants were 81% White; 13% African American; 4% Asian, and 2% American Indian and Pacific Islanders. The majority of respondents felt that they did not know enough about foot self-care. There were large gaps between self-reported knowledge and actual foot care practices, even among those who reported “knowing enough” on a given topic. There were significant differences in self-reported foot care behaviors and education by race and ethnicity. These findings document the need for culturally-specific self-management education to address unique cultural preferences and barriers to care

Impact of improved representation of horizontal and vertical cloud structure in a climate model

Abstract Many studies have investigated the effects that misrepresentation of sub-grid cloud structure can have on the radiation budget. In this study, we perform 20-year simulations of the current climate using an atmosphere-only version of the Met Office Unified Model to investigate the effects of cloud approximation on model climate. We apply the ''Tripleclouds'' scheme for representing horizontal cloud inhomogeneity and ''exponential-random'' overlap, both separately and in combination, in place of a traditional plane-parallel representation with maximum-random overlap, to the clouds within the radiation scheme. The resulting changes to both the radiation budget and other meteorological variables, averaged over the 20 years, are compared. The combined global effect of the parameterizations on topof-atmosphere short-wave and long-wave radiation budget is less than 1 W m -2 , but changes of up to 10 W m -2 are identified in marine stratocumulus regions. A cooling near the surface over the winter polar regions of up to 3°C is also identified when horizontal cloud inhomogeneity is represented, and a warming of similar magnitude is found when exponential-random overlap is implemented. Corresponding changes of the same sign are also found in zonally averaged temperature, with maximum changes in the upper tropical troposphere of up to 0.5°C. Changes in zonally averaged cloud fraction in this location were of opposite sign and up to 0.02. The individual effects on tropospheric temperature of improving the two components of cloud structure are of similar magnitudes to about 2% of the warming created by a quadrupling of carbon dioxide

Cost Estimating Using a New Learning Curve Theory for Non-Constant Production Rates

Traditional learning curve theory assumes a constant learning rate regardless of the number of units produced. However, a collection of theoretical and empirical evidence indicates that learning rates decrease as more units are produced in some cases. These diminishing learning rates cause traditional learning curves to underestimate required resources, potentially resulting in cost overruns. A diminishing learning rate model, namely Boone’s learning curve, was recently developed to model this phenomenon. This research confirms that Boone’s learning curve systematically reduced error in modeling observed learning curves using production data from 169 Department of Defense end-items. However, high amounts of variability in error reduction precluded concluding the degree to which Boone’s learning curve reduced error on average. This research further justifies the necessity of a diminishing learning rate forecasting model and assesses a potential solution to model diminishing learning rates

Computational Tracking of Shear-Mediated Platelet Interactions with von Willebrand Factor

The imaging of shear-mediated dynamic platelet behavior interacting with surface-immobilized von Willebrand factor (vWF) has tremendous potential in characterizing changes in platelet function for clinical diagnostics purposes. However, the imaging output, a series of images representing platelets adhering and rolling on the surface, poses unique, non-trivial challenges for software algorithms that reconstruct the positional trajectories of platelets. We report on an algorithm that tracks platelets using the output of such flow run experiments, taking into account common artifacts encountered by previously-published methods, and we derive seven key metrics of platelet dynamics that can be used to characterize platelet function. Extensive testing of our method using simulated platelet flow run data was carried out to validate our tracking method and derived metrics in capturing key platelet-vWF interaction-dynamics properties. Our results show that while the number of platelets present on the imaged area is the leading cause of errors, flow run data from two experiments using whole blood samples showed that our method and metrics can detect platelet property changes/differences that are concordant with the expected biological outcome, such as inhibiting key platelet receptors such as P2Y1, glycoprotein (GP)Ib and GPIIb/IIIa. These findings support the use of our methodologies to characterize platelet function among a wide range of healthy and disease cohorts

Active Control of Plasmonic–Photonic Interactions in a Microbubble Cavity

Active control of light–matter interactions using nanophotonic structures is critical for new modalities for solar energy production, cavity quantum electrodynamics (QED), and sensing, particularly at the single-particle level, where it underpins the creation of tunable nanophotonic networks. Coupled plasmonic–photonic systems show great promise toward these goals because of their subwavelength spatial confinement and ultrahigh-quality factors inherited from their respective components. Here, we present a microfluidic approach using microbubble whispering-gallery mode cavities to actively control plasmonic–photonic interactions at the single-particle level. By changing the solvent in the interior of the microbubble, control can be exerted on the interior dielectric constant and, thus, on the spatial overlap between the photonic and plasmonic modes. Qualitative agreement between experiment and simulation reveals the competing roles mode overlap and mode volume play in altering coupling strengths.journal articl