Engagement in Hepatitis C and HIV Prevention: Community Pharmacists’ Knowledge and Attitudes Regarding Non-Prescription Syringe Dispensing Legislation

Since 2010, the incidence of acute Hepatitis C Virus (HCV) infections in the U.S. has nearly quadrupled. Re-use and sharing of syringes among people who inject drugs (PWID) is a significant contributor to increased rates of HCV transmission and a risk factor for HIV infection. Community pharmacists are uniquely positioned to offer harm reduction services that lower the transmission of HCV/HIV by providing sterile syringes to PWID. However, legislation on non-prescription syringe dispensing varies by state and differences in individual pharmacists’ interpretation and attitudes regarding these laws may impact their willingness to participate in harm reduction services. Little is known about the impact of these factors on pharmacist engagement with harm reduction services in central Appalachia, a region particularly hard-hit by the opioid epidemic. The objective of this project is to qualitatively evaluate open-ended responses collected as part of a survey administered to community pharmacists in three central Appalachian states in order to determine: 1) pharmacists’ knowledge and attitudes regarding their state’s non-prescription syringe dispensing laws; and 2) the correlation of attitudes about state legislation to pharmacists’ intent to sell syringes to PWID. A telephonic community pharmacist survey on non-prescription syringe attitudes and behaviors was conducted between April and June 2018 in Northeast Tennessee, Western North Carolina, and Southwest Virginia. Survey responses were obtained from pharmacists practicing in 391 community pharmacies (51% response rate) in the study region. Transcribed responses to open-ended survey questions were extracted from the dataset and a qualitative analysis was completed using a generalized inductive approach. A single investigator coded all qualitative data and a second investigator coded data from a random selection of 10% of the respondents in order to develop themes through consensus. Descriptive analysis was conducted using SPSS version 25 to compare syringe law attitude thematic categories to respondents’ intent to sell syringes to PWID. Preliminary analysis identified discrepancies in pharmacists’ non-prescription syringe law knowledge, state-specific differences in pharmacists’ non-prescription syringe law attitudes, and underlying differences in willingness to sell syringes to PWID based on attitudes. The findings may encourage pharmacists to reflect on personal attitudes and interpretation of state-specific legislation as factors that may influence participation in an evidence-based harm reduction strategy for prevention of HCV/HIV transmission. This study offers preliminary results that will serve as a basis for larger studies and interventions aimed at reducing ambiguity in pharmacists’ interpretation of non-prescription syringe dispensing laws and encouraging pharmacists to counter the spread of HCV/HIV in an evidence-based manner

Analogue Modelling of Inverted Oblique Rift Systems

The geometric evolution of brittle fault systems in inverted oblique and offset rift systems has been simulated using scaled sandbox analogue models. Dry fine-grained quartz sand was used to represent the brittle upper crust. Extensional faults geometries in the models were governed by the geometry and orientation of a stretching zone at the base of the models. Oblique rift models were characterized by segmented en-echelon border fault systems trending parallel to the rift axis and the underlying zone of basement stretching. Offset rift models promoted highly-segmented border faults as well as offset sub-basins within the rift. In both types of models, intra-rift fault arrays were oriented sub-perpendicular to the extension direction. Inversion of the oblique and offset extensional models was achieved by horizontal shortening. This resulted in partial inversion of the border and intra-rift faults as well as the formation of new reverse faults. The geometries, distribution, orientations and number of these new reverse faults were strongly controlled by the earlier-formed fault extensional architectures. At the margins of the rift zone, shortening was mainly accommodated by partial inversion of the border faults together with the formation of hanging-wall bypass faults and footwall shortcut thrusts. Inversion of the offset rift models produced reactivation of the extensional accommodation zones as soft-linked transfer zones between new thrust faults. The analogue model results have been compared with natural inversion structures in the Atlas Mountains of Morocco and the Ukrainian Donbas fold belt. The analogue modelling results suggest that the High Atlas formed as the result of oblique inversion of an oblique rift system, and the contractional structures in the Ukranian Donbas belt were generated by partial inversion of the earlier-formed Donbas extensional graben via two major newly developed short-cuts that uplifted and exhumed the basin

Structural control of inherited salt structures during inversion of a domino basement-fault system from an analogue modelling approach

The geometries of inverted rift systems are different depending on a large variety of factors that include, among others, the presence of decoupling layers, the thickness of the pre- and syn-extension successions, or structural inheritances. Our study focuses on the inversion of an extensional domino-style basement-fault system with a pre-extension salt layer using analogue models to understand the role of pre-existing structural features during inversion. Models investigate how different overburden and salt thicknesses, inherited extensional structures, and salt distributions condition the evolution during inversion. The experimental results show that models with thick salt can partially or totally preserve the extensional ramp–syncline basin geometry independently of the overburden thickness. In contrast, models with a thin salt layer result in a total inversion of the ramp–syncline basins with the development of crestal collapse grabens and extensional faults affecting the overburden. Inversion also triggered the growth or reactivation of salt-related structures such as primary weld reopening and/or obliteration, diapir rejuvenation, salt thickening, or thrust emplacement. The use of analogue modelling allowed us to address the processes that controlled the growth and evolution of these structural elements during the inversion. Experimental results also provide a template of different structural styles resulting from the positive inversion of basins with a pre-extensional salt layer that can help subsurface interpretation in areas with poor seismic imaging.</p

Weld kinematics of syn-rift salt during basement-involved extension and subsequent inversion: Results from analog models

Scaled analog models based on extensional basins with synrift salt show how basement topography exerts a control factor on weld kinematics during the extension and inversion phases. In the case of basement-involved extension, syn-rift salt thickness differences may lead to variable degrees of extensional decoupling between basement topography and overburden, which in turn have a strong impact on the development of salt structures. With ongoing extension and after welding, the basin kinematics evolves toward a coupled deformation style. The basin architecture of our experimental results record the halokinetic activity related to growing diapirs and the timing of weld formationduring extension. Moreover, the structures that result from anysubsequent inversion of these basins strongly depends on the inherited welds and salt structures. While those basins are uplifted,the main contractional deformation during inversion is absorbed by the pre-existing salt structures, whose are squeezed developing secondary welds that often evolve into thrust welds. The analysis of our analog models shows that shortening of diapirs is favored by: i) basement topography changes that induce reactivation of primary welds as thrust welds; ii) reactivation of the salt unit as a contractional detachment and iii) synkinematic sedimentation during basin inversion. Finally, in this article, we also compare two natural examples from the southern North Sea that highlight deformation patterns very similar to those observed in our analog models

Phase II study of second-line therapy with DTIC, BCNU, cisplatin and tamoxifen (Dartmouth regimen) chemotherapy in patients with malignant melanoma previously treated with dacarbazine

This study assessed response rates to combination dacarbazine (DTIC), BCNU (carmustine), cisplatin and tamoxifen (DBPT) chemotherapy in patients with progressive metastatic melanoma previously treated with DTIC, as an evaluation of DBPT as a second-line regimen, and as an indirect comparison of DBPT with DTIC. Thirty-five consecutive patients received DBPT. The patients were divided into two groups. Group 1 comprised 17 patients with progressive disease (PD) on DTIC + tamoxifen therapy who were switched directly to DBPT. Group 2 comprised 18 patients not immediately switched to DBPT and included patients who had either a partial response (PR; one patient) or developed stable disease (SD; four patients) with DTIC, or received adjuvant DTIC (nine patients). All except four patients had received tamoxifen at the time of initial DTIC treatment. Median times since stopping DTIC were 22 days (range 20–41) and 285 days (range 50–1240) in Groups 1 and 2 respectively. In Group 1, one patient developed SD for 5 months and the remainder had PD. In Group 2, there were two PRs, four patients with SD (4, 5, 6, and 6 months), and 11 with PD. These results indicate that the DBPT regimen is not of value in melanoma primarily refractory to DTIC. There were responses in patients not directly switched from DTIC to DBPT, suggesting combination therapy may be of value in a small subgroup of melanoma patients. © 2000 Cancer Research Campaig

Gene regulatory network subcircuit controlling a dynamic spatial pattern of signaling in the sea urchin embryo

We dissect the transcriptional regulatory relationships coordinating the dynamic expression patterns of two signaling genes, wnt8 and delta, which are central to specification of the sea urchin embryo endomesoderm. cis-Regulatory analysis shows that transcription of the gene encoding the Notch ligand Delta is activated by the widely expressed Runx transcription factor, but spatially restricted by HesC-mediated repression through a site in the delta 5′UTR. Spatial transcription of the hesC gene, however, is controlled by Blimp1 repression. Blimp1 thus represses the repressor of delta, thereby permitting its transcription. The blimp1 gene is itself linked into a feedback circuit that includes the wnt8 signaling ligand gene, and we showed earlier that this circuit generates an expanding torus of blimp1 and wnt8 expression. The finding that delta expression is also controlled at the cis-regulatory level by the blimp1-wnt8 torus-generating subcircuit now explains the progression of Notch signaling from the mesoderm to the endoderm of the developing embryo. Thus the specific cis-regulatory linkages of the gene regulatory network encode the coordinated spatial expression of Wnt and Notch signaling as they sweep outward across the vegetal plate of the embryo

Vasa Protein Expression is Restricted to the Small Micromeres of the Sea Urchin, but is Inducible in Other Lineages Early in Development

Vasa is a DEAD-box RNA helicase that functions in translational regulation of specific mRNAs. In many animals it is essential for germ line development and may have a more general stem cell role. Here we identify vasa in two sea urchin species and analyze the regulation of its expression. We find that vasa protein accumulates in only a subset of cells containing vasa mRNA. In contrast to vasa mRNA, which is present uniformly throughout all cells of the early embryo, vasa protein accumulates selectively in the 16-cell stage micromeres, and then is restricted to the small micromeres through gastrulation to larval development. Manipulating early embryonic fate specification by blastomere separations, exposure to lithium, and dominant-negative cadherin each suggest that, although vasa protein accumulation in the small micromeres is fixed, accumulation in other cells of the embryo is inducible. Indeed, we find that embryos in which micromeres are removed respond by significant up-regulation of vasa protein translation, followed by spatial restriction of the protein late in gastrulation. Overall, these results support the contention that sea urchins do not have obligate primordial germ cells determined in early development, that vasa may function in an early stem cell population of the embryo, and that vasa expression in this embryo is restricted early by translational regulation to the small micromere lineage.Organismic and Evolutionary Biolog

Evidence for the influence of conspecific chemical cues on Aphthona nigriscutis (Coleoptera: Chrysomelidae) behaviour and distribution.

Abstract. Although the distribution of biological control agents may have a significant effect upon their impacts, the mechanisms regulating these distributions are often unknown. Such is the case with Aphthona nigriscutis, a classical biological control agent of leafy spurge in North America. These beetles assume aggregated distributions at some sites but disperse rapidly at others. The potential influence of plant and insect-factors upon aggregation and dispersal was investigated to try to explain these observations. Male beetles produce a putative aggregation pheromone. Responses of conspecifics to male-associated cues are greater when beetles are feeding on host plants. Densities of beetle groups greatly impact their attractiveness. Males are more sensitive to dispersal cues and females are more sensitive to congregation cues