FORENSIC PAIN MEDICINE SECTION Original Research Article Societal Costs of Prescription Opioid Abuse, Dependence, and Misuse in the United Statesp me_1075 657..667

Abstract Objectives. The objective of this study was to estimate the societal costs of prescription opioid abuse, dependence, and misuse in the United States. Methods. Costs were grouped into three categories: health care, workplace, and criminal justice. Costs were estimated by 1) quantity method, which multiplies the number of opioid abuse patients by cost per opioid abuse patient; and 2) apportionment method, which begins with overall costs of drug abuse per component and apportions the share associated with prescription opioid abuse based on relative prevalence of prescription opioid to overall drug abuse. Excess health care costs per patient were based on claims data analysis of privately insured and Medicaid beneficiaries. Other data/ information were derived from publicly available survey and other secondary sources. Conclusions. The costs of prescription opioid abuse represent a substantial and growing economic burden for the society. The increasing prevalence of abuse suggests an even greater societal burden in the future

Coronary calcium mass scores measured by identical 64-slice MDCT scanners are comparable: a cardiac phantom study

To assess whether absolute mass scores are comparable or differ between identical 64-slice MDCT scanners of the same manufacturer and to compare absolute mass scores to the physical mass and between scan modes using a calcified phantom. A non-moving anthropomorphic phantom with nine calcifications of three sizes and three densities was scanned 30 times on three 64-slice MDCT scanners of manufacturer A and on three 64-slice MDCT scanners of manufacturer B in both sequential and spiral scan mode. The mean mass scores and mass score variabilities of seven calcifications were determined for all scanners; two non-detectable calcifications were omitted. It was analyzed whether identical scanners yielded similar or significantly different mass scores. Furthermore mass scores were compared to the physical mass and mass scores were compared between scan modes. The mass score calibration factor was determined for all scanners. Mass scores obtained on identical scanners were similar for almost all calcifications. Overall, mass score differences between the scanners were small ranging from 1.5 to 3.4% for the total mass scores, and most differences between scanners were observed for high density calcifications. Mass scores were significantly different from the physical mass for almost all calcifications and all scanners. In sequential mode the total physical mass (167.8 mg) was significantly overestimated (+2.3%) for 4 out of 6 scanners. In spiral mode a significant overestimation (+2.5%) was found for system B and a significant underestimation (−1.8%) for two scanners of system A. Mass scores were dependent on the scan mode, for manufacturer A scores were higher in sequential mode and for manufacturer B in spiral mode. For system A using spiral scan mode no differences were found between identical scanners, whereas a few differences were found using sequential mode. For system B the scan mode did not affect the number of different mass scores between identical scanners. Mass scores obtained in the same scan mode are comparable between identical 64-slice CT scanners and identical 64-slice CT scanners on different sites can be used in follow-up studies. Furthermore, for all systems significant differences were found between mass scores and the physical calcium mass; however, the differences were relatively small and consistent

Bridging the legitimacy gap—translating theory into practical signposts for legitimate flood risk governance

Legitimacy is widely regarded as a founding principle of ‘good’ and effective governance, yet despite intense academic debate and policy discourse, the concept remains conceptually confusing and poorly articulated in practice. To bridge this gap, this research performed an interpretive thematic analysis of academic scholarship across public administration, public policy, law, political science and geography. Three core themes were identified in relation to representative deliberation, procedural and distributive equity and justice, and socio-political acceptability, with numerous sub-themes therein. In an attempt to clarify conceptual confusion, this paper grounds these theoretical debates in the context of flood risk governance where numerous legitimacy dilemmas exist. A number of questions are presented as conceptual ‘sign posts’ to encourage reflexive governance in the future. Thus, more broadly, we assert the importance of bringing legitimacy to the forefront of contemporary flood risk governance discourse and practice, moving beyond the realm of academic reflection

Over-expression of AhR (aryl hydrocarbon receptor) induces neural differentiation of Neuro2a cells: neurotoxicology study

BACKGROUND: Dioxins and related compounds are suspected of causing neurological disruption in human and experimental animal offspring following perinatal exposure during development and growth. The molecular mechanism(s) of the actions in the brain, however, have not been fully investigated. A major participant in the process of the dioxin-toxicity is the dioxin receptor, namely the aryl hydrocarbon receptor (AhR). AhR regulates the transcription of diverse genes through binding to the xenobiotic-responsive element (XRE). Since the AhR has also been detected in various regions of the brain, the AhR may play a key role in the developmental neurotoxicity of dioxins. This study focused on the effect of AhR activation in the developing neuron. METHODS: The influence of the AhR on the developing neuron was assessed using the Neuro2a-AhR transfectant. The undifferentiated murine neuroblastoma Neuro2a cell line (ATCC) was stably transfected with AhR cDNA and the established cell line was named N2a-Rα. The activation of exogenous AhR in N2a-Rα cells was confirmed using RNAi, with si-AhR suppressing the expression of exogenous AhR. The neurological properties of N2a-Rα based on AhR activation were evaluated by immunohistochemical analysis of cytoskeletal molecules and by RT-PCR analysis of mRNA expression of neurotransmitter-production related molecules, such as tyrosine hydroxylase (TH). RESULTS: N2a-Rα cells exhibited constant activation of the exogenous AhR. CYP1A1, a typical XRE-regulated gene, mRNA was induced without the application of ligand to the culture medium. N2a-Rα cells exhibited two significant functional features. Morphologically, N2a-Rα cells bore spontaneous neurites exhibiting axon-like properties with the localization of NF-H. In addition, cdc42 expression was increased in comparison to the control cell line. The other is the catecholaminergic neuron-like property. N2a-Rα cells expressed tyrosine hydroxylase (TH) mRNA as a functional marker of catecholaminergic neurotransmitter production. Thus, exogenous AhR induced catecholaminergic differentiation in N2a-Rα cells. CONCLUSION: The excessive activation of AhR resulted in neural differentiation of Neuro2a cells. This result revealed that dioxins may affect the nervous system through the AhR-signaling pathway. Activated AhR may disrupt the strictly regulated brain formation with irregular differentiation occurring rather than cell death

Evidence of gene-environment interaction for two genes on chromosome 4 and environmental tobacco smoke in controlling the risk of nonsyndromic cleft palate

Nonsyndromic cleft palate (CP) is one of the most common human birth defects and both genetic and environmental risk factors contribute to its etiology. We conducted a genome-wide association study (GWAS) using 550 CP case-parent trios ascertained in an international consortium. Stratified analysis among trios with different ancestries was performed to test for GxE interactions with common maternal exposures using conditional logistic regression models. While no single nucleotide polymorphism (SNP) achieved genome-wide significance when considered alone, markers in SLC2A9 and the neighboring WDR1 on chromosome 4p16.1 gave suggestive evidence of gene-environment interaction with environmental tobacco smoke (ETS) among 259 Asian trios when the models included a term for GxE interaction. Multiple SNPs in these two genes were associated with increased risk of nonsyndromic CP if the mother was exposed to ETS during the peri-conceptual period (3 months prior to conception through the first trimester). When maternal ETS was considered, fifteen of 135 SNPs mapping to SLC2A9 and 9 of 59 SNPs in WDR1 gave P values approaching genome-wide significance (10-6<P<10-4) in a test for GxETS interaction. SNPs rs3733585 and rs12508991 in SLC2A9 yielded P = 2.26×10-7 in a test for GxETS interaction. SNPs rs6820756 and rs7699512 in WDR1 also yielded P = 1.79×10-7 and P = 1.98×10-7 in a 1 df test for GxE interaction. Although further replication studies are critical to confirming these findings, these results illustrate how genetic associations for nonsyndromic CP can be missed if potential GxE interaction is not taken into account, and this study suggest SLC2A9 and WDR1 should be considered as candidate genes for CP. © 2014 Wu et al

Negative Priming Under Rapid Serial Visual Presentation

Negative priming (NP) was examined under a new paradigm wherein a target and distractors were temporally separated using rapid serial visual presentation (RSVP). The results from the two experiments revealed that (a) NP was robust under RSVP, such that the responses to a target were slower when the target served as a distractor in a previous trial than when it did not; (b) NP was found regardless of whether the distractors appeared before or after the targets; and (c) NP was stronger when the distractor was more distinctive. These findings are generally similar to those on NP in the spatial search task. The implications for the processes causing NP under RSVP are discussed in the current paper

Global genome expression analysis of rice in response to drought and high-salinity stresses in shoot, flag leaf, and panicle

To elucidate genome-level responses to drought and high-salinity stress in rice, a 70mer oligomer microarray covering 36,926 unique genes or gene models was used to profile genome expression changes in rice shoot, flag leaf and panicle under drought or high-salinity conditions. While patterns of gene expression in response to drought or high-salinity stress within a particular organ type showed significant overlap, comparison of expression profiles among different organs showed largely organ-specific patterns of regulation. Moreover, both stresses appear to alter the expression patterns of a significant number of genes involved in transcription and cell signaling in a largely organ-specific manner. The promoter regions of genes induced by both stresses or induced by one stress in more than one organ types possess relative enrichment of two cis-elements (ABRE core and DRE core) known to be associated with water stress. An initial computational analysis indicated that novel promoter motifs are present in the promoters of genes involved in rehydration after drought. This analysis suggested that rice might possess a mechanism that actively detects rehydration and facilitates rapid recovery. Overall, our data supports a notion that organ-specific gene regulation in response to the two abiotic stresses may primarily be mediated by organ-specific transcription responses. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11103-006-9111-1) contains supplementary material, which is available to authorized users