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

Notes on Reproduction in the Brownback Salamander (Eurycea aquatica)

Life history data often are lacking for species with an uncertain taxonomic status. As phylogenetic analyses improve and our understanding of species boundaries become more refined, ecological information should likewise keep pace. Here, we report information on the timing of reproduction, clutch size, and nest attendance for the Brownback Salamander (Eurycea aquatica), a species recently documented to be a separate lineage after a long, controversial systematic history. We confirm that this species has the largest clutch size of any lineage within the Eurycea bislineata complex, and suggest that male and male-female nest attendance is not uncommon in this species. We suggest that, in addition to the genetic divergence documented between E. aquatica and other members of the E. bislineata complex, ecological differences also are present and possibly are influenced by the unique springs inhabited by Brownback Salamanders

Notes on Reproduction in the Brownback Salamander (Eurycea aquatica)

Life history data often are lacking for species with an uncertain taxonomic status. As phylogenetic analyses improve and our understanding of species boundaries become more refined, ecological information should likewise keep pace. Here, we report information on the timing of reproduction, clutch size, and nest attendance for the Brownback Salamander (Eurycea aquatica), a species recently documented to be a separate lineage after a long, controversial systematic history. We confirm that this species has the largest clutch size of any lineage within the Eurycea bislineata complex, and suggest that male and male-female nest attendance is not uncommon in this species. We suggest that, in addition to the genetic divergence documented between E. aquatica and other members of the E. bislineata complex, ecological differences also are present and possibly are influenced by the unique springs inhabited by Brownback Salamanders

Nonlocal effects in the shot noise of diffusive superconductor - normal-metal systems

A cross-shaped diffusive system with two superconducting and two normal electrodes is considered. A voltage $eV < \Delta$ is applied between the normal leads. Even in the absence of average current through the superconducting electrodes their presence increases the shot noise at the normal electrodes and doubles it in the case of a strong coupling to the superconductors. The nonequilibrium noise at the superconducting electrodes remains finite even in the case of a vanishingly small transport current due to the absence of energy transfer into the superconductors. This noise is suppressed by electron-electron scattering at sufficiently high voltages.Comment: 4 pages, RevTeX, 2 eps figure

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

Multiple Andreev Reflection and Giant Excess Noise in Diffusive Superconductor/Normal-Metal/Superconductor Junctions

We have studied superconductor/normal metal/superconductor (SNS) junctions consisting of short Au or Cu wires between Nb or Al banks. The Nb based junctions display inherent electron heating effects induced by the high thermal resistance of the NS boundaries. The Al based junctions show in addition subharmonic gap structures in the differential conductance dI/dV and a pronounced peak in the excess noise at very low voltages V. We suggest that the noise peak is caused by fluctuations of the supercurrent at the onset of Josephson coupling between the superconducting banks. At intermediate temperatures where the supercurrent is suppressed a noise contribution ~1/V remains, which may be interpreted as shot noise originating from large multiple charges.Comment: 7 pages, 7 figures, extended 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

MicroRNAs Located in the Hox Gene Clusters Are Implicated in Huntington's Disease Pathogenesis

Transcriptional dysregulation has long been recognized as central to the pathogenesis of Huntington's disease (HD). MicroRNAs (miRNAs) represent a major system of post-transcriptional regulation, by either preventing translational initiation or by targeting transcripts for storage or for degradation. Using next-generation miRNA sequencing in prefrontal cortex (Brodmann Area 9) of twelve HD and nine controls, we identified five miRNAs (miR-10b-5p, miR-196a-5p, miR-196b-5p, miR-615-3p and miR-1247-5p) up-regulated in HD at genome-wide significance (FDR q-value<0.05). Three of these, miR-196a-5p, miR-196b-5p and miR-615-3p, were expressed at near zero levels in control brains. Expression was verified for all five miRNAs using reverse transcription quantitative PCR and all but miR-1247-5p were replicated in an independent sample (8HD/8C). Ectopic miR-10b-5p expression in PC12 HTT-Q73 cells increased survival by MTT assay and cell viability staining suggesting increased expression may be a protective response. All of the miRNAs but miR-1247-5p are located in intergenic regions of Hox clusters. Total mRNA sequencing in the same samples identified fifteen of 55 genes within the Hox cluster gene regions as differentially expressed in HD, and the Hox genes immediately adjacent to the four Hox cluster miRNAs as up-regulated. Pathway analysis of mRNA targets of these miRNAs implicated functions for neuronal differentiation, neurite outgrowth, cell death and survival. In regression models among the HD brains, huntingtin CAG repeat size, onset age and age at death were independently found to be inversely related to miR-10b-5p levels. CAG repeat size and onset age were independently inversely related to miR-196a-5p, onset age was inversely related to miR-196b-5p and age at death was inversely related to miR-615-3p expression. These results suggest these Hox-related miRNAs may be involved in neuroprotective response in HD. Recently, miRNAs have shown promise as biomarkers for human diseases and given their relationship to disease expression, these miRNAs are biomarker candidates in HD

Current noise in long diffusive SNS junctions in the incoherent MAR regime

Spectral density of current fluctuations at zero frequency is calculated for a long diffusive SNS junction with low-resistive interfaces. At low temperature, T << Delta, the subgap shot noise approaches linear voltage dependence, S=(2/ 3R)(eV + 2Delta), which is the sum of the shot noise of the normal conductor and voltage independent excess noise. This result can also be interpreted as the 1/3-suppressed Poisson noise for the effective charge q = e(1+2Delta/eV) transferred by incoherent multiple Andreev reflections (MAR). At higher temperatures, anomalies of the current noise develop at the gap subharmonics, eV = 2Delta/n. The crossover to the hot electron regime from the MAR regime is analyzed in the limit of small applied voltages.Comment: improved version, to be published in Phys. Rev.