Predicting pharmacy naloxone stocking and dispensing following a statewide standing order, Indiana 2016

BACKGROUND: While naloxone, the overdose reversal medication, has been available for decades, factors associated with its availability through pharmacies remain unclear. Studies suggest that policy and pharmacist beliefs may impact availability. Indiana passed a standing order law for naloxone in 2015 to increase access to naloxone. OBJECTIVE: To identify factors associated with community pharmacy naloxone stocking and dispensing following the enactment of a statewide naloxone standing order. METHODS: A 2016 cross-sectional census of Indiana community pharmacists was conducted following a naloxone standing order. Community, pharmacy, and pharmacist characteristics, and pharmacist attitudes about naloxone dispensing, access, and perceptions of the standing order were measured. Modified Poisson and binary logistic regression models attempted to predict naloxone stocking and dispensing, respectively. RESULTS: Over half (58.1%) of pharmacies stocked naloxone, yet 23.6% of pharmacists dispensed it. Most (72.5%) pharmacists believed the standing order would increase naloxone stocking, and 66.5% believed it would increase dispensing. Chain pharmacies were 3.2 times as likely to stock naloxone. Naloxone stocking was 1.6 times as likely in pharmacies with more than one full-time pharmacist. Pharmacies where pharmacists received naloxone continuing education in the past two years were 1.3 times as likely to stock naloxone. The attempted dispensing model yielded no improvement over the constant-only model. CONCLUSIONS: Pharmacies with larger capacity took advantage of the naloxone standing order. Predictors of pharmacist naloxone dispensing should continue to be explored to maximize naloxone access

Subgap anomaly and above-energy-gap structure in chains of diffusive SNS junctions

We present the results of low-temperature transport measurements on chains of superconductor--normal-constriction--superconductor (SNS) junctions fabricated on the basis of superconducting PtSi film. A comparative study of the properties of the chains, consisting of 3 and 20 SNS junctions in series, and single SNS junctions reveals essential distinctions in the behavior of the current-voltage characteristics of the systems: (i) the gradual decrease of the effective suppression voltage for the excess conductivity observed at zero bias as the quantity of the SNS junctions increases, (ii) a rich fine structure on the dependences dV/dI-V at dc bias voltages higher than the superconducting gap and corresponding to some multiples of 2\Delta/e. A model to explain this above-energy-gap structure based on energy relaxation of electron via Cooper-pair-breaking in superconducting island connecting normal metal electrods is proposed.Comment: RevTex, 5 pages, 4 figure

Reference standardization and triglyceride interference of a new homogeneous HDL-cholesterol assay compared with a former chemical precipitation assay

A homogeneous HDL-c assay (HDL-H), which uses polyethylene glycol-modified enzymes and sulfated alpha-cyclodextrin, was assessed for precision, accuracy, and cholesterol and triglyceride interference. In addition, its analytical performance was compared with that of a phosphotungstic acid (PTA)/MgCl2 precipitation method (HDL-P). Within-run CVs were < or = 1.87%; total CVs were < or = 3.08%. Accuracy was evaluated in fresh normotriglyceridemic sera using the Designated Comparison Method (HDL-H = 1.037 Designated Comparison Method + 4 mg/L; n = 63) and in moderately hypertriglyceridemic sera by using the Reference Method (HDL-H = 1.068 Reference Method - 17 mg/L; n = 41). Mean biases were 4.5% and 2.2%, respectively. In hypertriglyceridemic sera (n = 85), HDL-H concentrations were increasingly positively biased with increasing triglyceride concentrations. The method comparison between HDL-H and HDL-P yielded the following equation: HDL-H = 1.037 HDL-P + 15 mg/L; n = 478. We conclude that HDL-H amply meets the 1998 NCEP recommendations for total error; its precision is superior compared with that of HDL-P, and its average bias remains below +/-5% as long as triglyceride concentrations are < or = 10 g/L and in case of moderate hypercholesterolemia

Full Current Statistics in Diffusive Normal-Superconductor Structures

We study the current statistics in normal diffusive conductors in contact with a superconductor. Using an extension of the Keldysh Green's function method we are able to find the full distribution of charge transfers for all temperatures and voltages. For the non-Gaussian regime, we show that the equilibrium current fluctuations are enhanced by the presence of the superconductor. We predict an enhancement of the nonequilibrium current noise for temperatures below and voltages of the order of the Thouless energy E_Th=D/L^2. Our calculation fully accounts for the proximity effect in the normal metal and agrees with experimental data. We demonstrate that the calculation of the full current statistics is in fact simpler than a concrete calculation of the noise.Comment: 4 pages, 2 figures (included

Coherent low-energy charge transport in a diffusive S-N-S junction

We have studied the current voltage characteristics of diffusive mesoscopic Nb-Cu-Nb Josephson junctions with highly-transparent Nb-Cu interfaces. We consider the low-voltage and high-temperature regime eV<\epsilon_{c}<k_{B}T where epsilon_{c} is the Thouless energy. The observed excess current as well as the observed sub-harmonic Shapiro steps under microwave irradiation suggest the occurrence of low-energy coherent Multiple Andreev Reflection (MAR).Comment: 4 pages, 4 figures, final versio

Two-dimensional array of diffusive SNS junctions with high-transparent interfaces

We report the first comparative study of the properties of two-dimensional arrays and single superconducting film - normal wire - superconducting film (SNS) junctions. The NS interfaces of our SNS junctions are really high transparent, for superconducting and normal metal parts are made from the same material (superconducting polycrystalline PtSi film). We have found that the two-dimensional arrays reveal some novel features: (i) the significant narrowing of the zero bias anomaly (ZBA) in comparison with single SNS junctions, (ii) the appearance of subharmonic energy gap structure (SGS), with up to n=16 (eV=\pm 2\Delta/n), with some numbers being lost, (iii) the transition from 2D logarithmic weak localization behavior to metallic one. Our experiments show that coherent phenomena governed by the Andreev reflection are not only maintained over the macroscopic scale but manifest novel pronounced effects as well. The behavior of the ZBA and SGS in 2D array of SNS junctions strongly suggests that the development of a novel theoretical approach is needed which would self-consistently take into account the distribution of the currents, the potentials, and the superconducting order parameter.Comment: RevTex, 5 pages, 5 figure

Full Counting Statistics of Multiple Andreev Reflections in incoherent diffusive superconducting junctions

We present a theory for the full distribution of current fluctuations in incoherent diffusive superconducting junctions, subjected to a voltage bias. This theory of full counting statistics of incoherent multiple Andreev reflections is valid for arbitrary applied voltage. We present a detailed discussion of the properties of the first four cumulants as well as the low and high voltage regimes of the full counting statistics. The work is an extension of the results of Pilgram and the author, Phys. Rev. Lett. 94, 086806 (2005).Comment: Included in special issue Spin Physics of Superconducting heterostructures of Applied Physics A: Materials Science & Processin

GAR22β regulates cell migration, sperm motility, and axoneme structure

© 2016 Gamper et al. Spatiotemporal cytoskeleton remodeling is pivotal for cell adhesion and migration. Here we investigated the function of Gas2-related protein on chromosome 22 (GAR22β), a poorly characterized protein that interacts with actin and microtubules. Primary and immortalized GAR22β-/- Sertoli cells moved faster than wild-type cells. In addition, GAR22β-/- cells showed a more prominent focal adhesion turnover. GAR22β overexpression or its reexpression in GAR22β-/- cells reduced cell motility and focal adhesion turnover. GAR22β-actin interaction was stronger than GAR22β-microtubule interaction, resulting in GAR22β localization and dynamics that mirrored those of the actin cytoskeleton. Mechanistically, GAR22β interacted with the regulator of microtubule dynamics end-binding protein 1 (EB1) via a novel noncanonical amino acid sequence, and this GAR22β-EB1 interaction was required for the ability of GAR22β to modulate cell motility. We found that GAR22β is highly expressed in mouse testes, and its absence resulted in reduced spermatozoa generation, lower actin levels in testes, and impaired motility and ultrastructural disorganization of spermatozoa. Collectively our findings identify GAR22β as a novel regulator of cell adhesion and migration and provide a foundation for understanding the molecular basis of diverse cytoskeleton-dependent processes

Temporal Patterns of Nucleotide Misincorporations and DNA Fragmentation in Ancient DNA

DNA that survives in museum specimens, bones and other tissues recovered by archaeologists is invariably fragmented and chemically modified. The extent to which such modifications accumulate over time is largely unknown but could potentially be used to differentiate between endogenous old DNA and present-day DNA contaminating specimens and experiments. Here we examine mitochondrial DNA sequences from tissue remains that vary in age between 18 and 60,000 years with respect to three molecular features: fragment length, base composition at strand breaks, and apparent C to T substitutions. We find that fragment length does not decrease consistently over time and that strand breaks occur preferentially before purine residues by what may be at least two different molecular mechanisms that are not yet understood. In contrast, the frequency of apparent C to T substitutions towards the 5′-ends of molecules tends to increase over time. These nucleotide misincorporations are thus a useful tool to distinguish recent from ancient DNA sources in specimens that have not been subjected to unusual or harsh treatments

The structure of the tetrasialoganglioside from human brain

Autosomal dominant retinal vasculopathy with cerebral leukodystrophy is a microvascular endotheliopathy with middle- age onset. In nine families, we identified heterozygous C- terminal frameshift mutations in TREX1, which encodes a 3'-5' exonuclease. These truncated proteins retain exonuclease activity but lose normal perinuclear localization. These data have implications for the maintenance of vascular integrity in the degenerative cerebral microangiopathies leading to stroke and dementias