Understanding physicians’ behavior toward alerts about nephrotoxic medications in outpatients: a cross-sectional analysis

Background: Although most outpatients are relatively healthy, many have chronic renal insufficiency, and high override rates for suggestions on renal dosing have been observed. To better understand the override of renal dosing alerts in an outpatient setting, we conducted a study to evaluate which patients were more frequently prescribed contraindicated medications, to assess providers’ responses to suggestions, and to examine the drugs involved and the reasons for overrides. Methods: We obtained data on renal alert overrides and the coded reasons for overrides cited by providers at the time of prescription from outpatient clinics and ambulatory hospital-based practices at a large academic health care center over a period of 3 years, from January 2009 to December 2011. For detailed chart review, a group of 6 trained clinicians developed the appropriateness criteria with excellent inter-rater reliability (κ = 0.93). We stratified providers by override frequency and then drew samples from the high- and low-frequency groups. We measured the rate of total overrides, rate of appropriate overrides, medications overridden, and the reason(s) for override. Results: A total of 4120 renal alerts were triggered by 584 prescribers in the study period, among which 78.2% (3,221) were overridden. Almost half of the alerts were triggered by 40 providers and one-third was triggered by high-frequency overriders. The appropriateness rates were fairly similar, at 28.4% and 31.6% for high- and low-frequency overriders, respectively. Metformin, glyburide, hydrochlorothiazide, and nitrofurantoin were the most common drugs overridden. Physicians’ appropriateness rates were higher than the rates for nurse practitioners (32.9% vs. 22.1%). Physicians with low frequency override rates had higher levels of appropriateness for metformin than the high frequency overriders (P = 0.005). Conclusion: A small number of providers accounted for a large fraction of overrides, as was the case with a small number of drugs. These data suggest that a focused intervention targeting primarily these providers and medications has the potential to improve medication safety

A variational approach to the stochastic aspects of cellular signal transduction

Cellular signaling networks have evolved to cope with intrinsic fluctuations, coming from the small numbers of constituents, and the environmental noise. Stochastic chemical kinetics equations govern the way biochemical networks process noisy signals. The essential difficulty associated with the master equation approach to solving the stochastic chemical kinetics problem is the enormous number of ordinary differential equations involved. In this work, we show how to achieve tremendous reduction in the dimensionality of specific reaction cascade dynamics by solving variationally an equivalent quantum field theoretic formulation of stochastic chemical kinetics. The present formulation avoids cumbersome commutator computations in the derivation of evolution equations, making more transparent the physical significance of the variational method. We propose novel time-dependent basis functions which work well over a wide range of rate parameters. We apply the new basis functions to describe stochastic signaling in several enzymatic cascades and compare the results so obtained with those from alternative solution techniques. The variational ansatz gives probability distributions that agree well with the exact ones, even when fluctuations are large and discreteness and nonlinearity are important. A numerical implementation of our technique is many orders of magnitude more efficient computationally compared with the traditional Monte Carlo simulation algorithms or the Langevin simulations.Comment: 15 pages, 11 figure

Preparing for a Northwest Passage: A Workshop on the Role of New England in Navigating the New Arctic

Preparing for a Northwest Passage: A Workshop on the Role of New England in Navigating the New Arctic (March 25 - 27, 2018 -- The University of New Hampshire) paired two of NSF\u27s 10 Big Ideas: Navigating the New Arctic and Growing Convergence Research at NSF. During this event, participants assessed economic, environmental, and social impacts of Arctic change on New England and established convergence research initiatives to prepare for, adapt to, and respond to these effects. Shipping routes through an ice-free Northwest Passage in combination with modifications to ocean circulation and regional climate patterns linked to Arctic ice melt will affect trade, fisheries, tourism, coastal ecology, air and water quality, animal migration, and demographics not only in the Arctic but also in lower latitude coastal regions such as New England. With profound changes on the horizon, this is a critical opportunity for New England to prepare for uncertain yet inevitable economic and environmental impacts of Arctic change

The self and others in the experience of pride

Pride is seen as both a self-conscious emotion as well as a social emotion. These categories are not mutually exclusive, but have brought forth different ideas about pride as either revolving around the self or as revolving around one’s relationship with others. Current measures of pride do not include intrapersonal elements of pride experiences. Social comparisons, which often cause experiences of pride, contain three elements: the self, the relationship between the self and another person, and the other person. From the literature on pride, we distilled three related elements; perceptions and feelings of self-inflation, other-distancing, and other-devaluation. In four studies, we explored whether these elements were present in pride experiences. We did so at an implicit (Experiment 1; N = 218) and explicit level (Experiment 2; N = 125), in an academic setting with in vivo (Experiment 3; N = 203) and imagined pride experiences (Experiment 4; N = 126). The data consistently revealed that the experience of pride is characterised by self-inflation, not by other-distancing nor other-devaluation

Nodding syndrome in Tanzania may not be associated with circulating anti-NMDA- and anti-VGKC receptor antibodies or decreased pyridoxal phosphate serum levels-a pilot study

Background: Nodding syndrome (NS) is a seemingly progressive epilepsy disorder of unknown underlying cause. We investigated association of pyridoxal-phosphate serum levels and occurrence of anti-neuronal antibodies against N-methyl-D-aspartate (NMDA) receptor and voltage gated potassium channel (VGKC) complex in NS patients.Methods: Sera of a Tanzanian cohort of epilepsy and NS patients and community controls were tested for the presence of anti-NMDA-receptor and anti-VGKC complex antibodies by indirect immunofluorescence assay. Furthermore pyridoxal-phosphate levels were measured.Results: Auto-antibodies against NMDA receptor or VGKC (LG1 or Caspr2) complex were not detected in sera of patients suffering from NS (n=6), NS plus other seizure types (n=16), primary generalized epilepsy (n=1) and community controls without epilepsy (n=7). Median Pyridoxal-phosphate levels in patients with NS compared to patients with primary generalized seizures and community controls were not significantly different. However, these median pyridoxal-phosphate levels are significantly lower compared to the range considered normal in Europeans.Conclusions: In this pilot study NS was not associated with serum anti-NMDA receptor or anti-VGKC complex antibodies and no association to pyridoxal-phosphate serum levels was found.Key words: nodding syndrome, epilepsy, anti-neuronal antibodies, pyridoxal-phosphat

Cellular and ultrastructural characterization of the grey-morph phenotype in southern right whales (Eubalaena australis)

Southern right whales (SRWs, Eubalena australis) are polymorphic for an X-linked pigmentation pattern known as grey morphism. Most SRWs have completely black skin with white patches on their bellies and occasionally on their backs; these patches remain white as the whale ages. Grey morphs (previously referred to as partial albinos) appear mostly white at birth, with a splattering of rounded black marks; but as the whales age, the white skin gradually changes to a brownish grey color. The cellular and developmental bases of grey morphism are not understood. Here we describe cellular and ultrastructural features of grey-morph skin in relation to that of normal, wild-type skin. Melanocytes were identified histologically and counted, and melanosomes were measured using transmission electron microscopy. Grey-morph skin had fewer melanocytes when compared to wild-type skin, suggesting reduced melanocyte survival, migration, or proliferation in these whales. Grey-morph melanocytes had smaller melanosomes relative to wild-type skin, normal transport of melanosomes to surrounding keratinocytes, and normal localization of melanin granules above the keratinocyte nuclei. These findings indicate that SRW grey-morph pigmentation patterns are caused by reduced numbers of melanocytes in the skin, as well as by reduced amounts of melanin production and/or reduced sizes of mature melanosomes. Grey morphism is distinct from piebaldism and albinism found in other species, which are genetic pigmentation conditions resulting from the local absence of melanocytes, or the inability to synthesize melanin, respectively

Effect of and Acute Bout of Kettlebell Exercise on Glucose Tolerance in Sedentary Men: a Preliminary Study

International Journal of Exercise Science 9(4): 524-535, 2016. Impaired glucose tolerance can have significant health consequences. The purposes of this preliminary study were to examine whether a single session of kettlebell exercise improves acute post-exercise glucose tolerance in sedentary individuals, and whether it was as effective as high-intensity interval running. Six sedentary male subjects underwent a two-hour oral glucose tolerance test following three different conditions: 1) control (no exercise); 2) kettlebell exercise (2 sets of 7 exercises, 15 repetitions per exercise with 30 seconds rest between each exercise); or 3) high-intensity interval running (10 one-minute intervals at a workload corresponding to 90% VO2max interspersed with one-minute active recovery periods). Blood glucose and insulin levels were measured before (0 minutes), and 60 and 120 minutes after glucose ingestion. Both kettlebell and high-intensity interval running exercise significantly lowered blood glucose 60 minutes after glucose ingestion compared with control. However, there was no significant difference in blood glucose between the two exercise conditions at any time point. In addition, there were no significant differences in insulin concentration between high intensity interval running, kettlebell, and control conditions at all time points. Results indicate that an acute bout of kettlebell exercise is as effective as high intensity interval running at improving glucose tolerance in sedentary young men

Dynamic Control of Nanoprecipitation in a Nanopipette

Studying the earliest stages of precipitation at the nanoscale is technically challenging but quite valuable as such phenomena reflect important processes such as crystallization and biomineralization. Using a quartz nanopipette as a nanoreactor, we induced precipitation of an insoluble salt to generate oscillating current blockades. The reversible process can be used to measure both kinetics of precipitation and relative size of the resulting nanoparticles. Counter ions for the highly water-insoluble salt zinc phosphate were separated by the pore of a nanopipette and a potential applied to cause ion migration to the interface. By analyzing the kinetics of pore blockage, two distinct mechanisms were identified: a slower process due to precipitation from solution, and a faster process attributed to voltage-driven migration of a trapped precipitate. We discuss the potential of these techniques in studying precipitation dynamics, trapping particles within a nanoreactor, and electrical sensors based on nanoprecipitation

The authorial delusion: counting lady Macbeth’s children

In 1933, literary critic L. C. Knights published a caustic essay against the notion cultivated by certain of his colleagues, predominantly A. C. Bradley, that Shakespeare is a ‘great creator of characters’. Knights (1973) regarded the examination of isolated particles such as ‘character’ as disorientating, alleging that an analysis of this sort obscures the greater merit of language. Knight’s polemic essentially stands in the threshold of the dissention between formalists and realists: the former consider the examination of the fictional narrative as anything but a textual construct a scholarly faux pas; the latter regard the referential relationship between text and the world as a foundation for the creation of fiction. This is a pseudo-dilemma. The notion that literature is denuded of its artistic merit once it is defined by its constituent artefacts is disorienting, for it completely bypasses the dynamics of its creation. Put differently, a post-event analysis can exist as a standalone act, albeit it cannot challenge or dismiss the foundational principles of the event’s creation process