\u3ci\u3eDemocracy and Public Administration\u3c/i\u3e

Chapter 4, A Brief Tour of Public Organization Theory in the United States, authored by Gary S. Marshall, UNO faculty member. The true measure of the successful practice of public service is its ability to remain faithful to the tenets of democratic society. This introductory text links the practice of public administration to the core concepts of American democracy. It covers the nuts and bolts of public administration in the context of delivering democracy in public service--providing what the public really wants as opposed to what self-serving bureaucracies may call for. Chapters in Democracy and Public Administration discuss the functional topics covered in other texts, but from the perspective of this democratic ideal. Each chapter is written by an expert in the area, and summarizes previous research in the area, presents the author\u27s research and thought, and offers ways in which practitioners can apply the concepts discussed to their daily work.https://digitalcommons.unomaha.edu/facultybooks/1249/thumbnail.jp

Corporations' use and misuse of evidence to influence health policy:A case study of sugar-sweetened beverage taxation

Background: Sugar sweetened beverages (SSB) are a major source of sugar in the diet. Although trends in consumption vary across regions, in many countries, particularly LMICs, their consumption continues to increase. In response, a growing number of governments have introduced a tax on SSBs. SSB manufacturers have opposed such taxes, disputing the role that SSBs play in diet-related diseases and the effectiveness of SSB taxation, and alleging major economic impacts. Given the importance of evidence to effective regulation of products harmful to human health, we scrutinised industry submissions to the South African government's consultation on a proposed SSB tax and examined their use of evidence. Results: Corporate submissions were underpinned by several strategies involving the misrepresentation of evidence. First, references were used in a misleading way, providing false support for key claims. Second, raw data, which represented a pliable, alternative evidence base to peer reviewed studies, was misused to dispute both the premise of targeting sugar for special attention and the impact of SSB taxes on SSB consumption. Third, purposively selected evidence was used in conjunction with other techniques, such as selective quoting from studies and omitting important qualifying information, to promote an alternative evidential narrative to that supported by the weight of peer-reviewed research. Fourth, a range of mutually enforcing techniques that inflated the effects of SSB taxation on jobs, public revenue generation, and gross domestic product, was used to exaggerate the economic impact of the tax. This "hyperbolic accounting" included rounding up figures in original sources, double counting, and skipping steps in economic modelling. Conclusions: Our research raises fundamental questions concerning the bona fides of industry information in the context of government efforts to combat diet-related diseases. The beverage industry's claims against SSB taxation rest on a complex interplay of techniques, that appear to be grounded in evidence, but which do not observe widely accepted approaches to the use of either scientific or economic evidence. These techniques are similar, but not identical, to those used by tobacco companies and highlight the problems of introducing evidence-based policies aimed at managing the market environment for unhealthful commodities

Plasma Metabolomic Changes following PI3K Inhibition as Pharmacodynamic Biomarkers: Preclinical Discovery to Phase I Trial Evaluation.

PI3K plays a key role in cellular metabolism and cancer. Using a mass spectrometry-based metabolomics platform, we discovered that plasma concentrations of 26 metabolites, including amino acids, acylcarnitines, and phosphatidylcholines, were decreased in mice bearing PTEN-deficient tumors compared with non-tumor-bearing controls and in addition were increased following dosing with class I PI3K inhibitor pictilisib (GDC-0941). These candidate metabolomics biomarkers were evaluated in a phase I dose-escalation clinical trial of pictilisib. Time- and dose-dependent effects were observed in patients for 22 plasma metabolites. The changes exceeded baseline variability, resolved after drug washout, and were recapitulated on continuous dosing. Our study provides a link between modulation of the PI3K pathway and changes in the plasma metabolome and demonstrates that plasma metabolomics is a feasible and promising strategy for biomarker evaluation. Also, our findings provide additional support for an association between insulin resistance, branched-chain amino acids, and related metabolites following PI3K inhibition. Mol Cancer Ther; 15(6); 1412-24. ©2016 AACR.The Institute of Cancer ResearchThis is the author accepted manuscript. The final version is available from the American Association for Cancer Research via http://dx.doi.org/10.1158/1535-7163.MCT-15-081

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Two For The Road: An Exploratory Study Investigating Driver and Co-Passenger Interactions during Automation and the Transition of Control in a Level 3 Automated Vehicle

To explore the impact of a front-seat passenger during SAE level 3 (L3) automation, eighteen established driver-passenger pairings undertook three 30-minute journeys framed as ‘days-out’ in a L3 driving simulator. Participants were reminded of their responsibilities at L3 (as per SAE lexicon), and were given agency to decide what behaviour was acceptable, but were otherwise free to behave as they wished with the only stipulation that they should resume manual control and exit the motorway at the correct junction to reach a specified destination. Distracting behaviours emerged, in the form of participatory activities, that engaged both vehicle occupants in cooperative tasks, such as watching shared content or playing competitive games on a smartphone, and these delayed or disrupted the resumption of the driving task. Supportive behaviours were also evident amongst more loquacious passengers, who assisted with route-finding and keeping the driver awake/alert. Findings provide empirical evidence regarding permissible activities at L3 and can inform in-vehicle design to promote appropriate behaviour

Orally bioavailable CDK9/2 inhibitor shows mechanism-based therapeutic potential in MYCN-driven neuroblastoma

The undruggable nature of oncogenic Myc transcription factors poses a therapeutic challenge in neuroblastoma, a pediatric cancer in which MYCN amplification is strongly associated with unfavorable outcome. Here, we show that CYC065 (fadraciclib), a clinical inhibitor of CDK9 and CDK2, selectively targeted MYCN-amplified neuroblastoma via multiple mechanisms. CDK9 — a component of the transcription elongation complex P-TEFb — bound to the MYCN-amplicon superenhancer, and its inhibition resulted in selective loss of nascent MYCN transcription. MYCN loss led to growth arrest, sensitizing cells for apoptosis following CDK2 inhibition. In MYCN-amplified neuroblastoma, MYCN invaded active enhancers, driving a transcriptionally encoded adrenergic gene expression program that was selectively reversed by CYC065. MYCN overexpression in mesenchymal neuroblastoma was sufficient to induce adrenergic identity and sensitize cells to CYC065. CYC065, used together with temozolomide, a reference therapy for relapsed neuroblastoma, caused long-term suppression of neuroblastoma growth in vivo, highlighting the clinical potential of CDK9/2 inhibition in the treatment of MYCN-amplified neuroblastoma

Association mapping of spot blotch resistance in wild barley

Spot blotch, caused by Cochliobolus sativus, is an important foliar disease of barley. The disease has been controlled for over 40 years through the deployment of cultivars with durable resistance derived from the line NDB112. Pathotypes of C. sativus with virulence for the NDB112 resistance have been detected in Canada; thus, many commercial cultivars are vulnerable to spot blotch epidemics. To increase the diversity of spot blotch resistance in cultivated barley, we evaluated 318 diverse wild barley accessions comprising the Wild Barley Diversity Collection (WBDC) for reaction to C. sativus at the seedling stage and utilized an association mapping (AM) approach to identify and map resistance loci. A high frequency of resistance was found in the WBDC as 95% (302/318) of the accessions exhibited low infection responses. The WBDC was genotyped with 558 Diversity Array Technology (DArT®) and 2,878 single nucleotide polymorphism (SNP) markers and subjected to structure analysis before running the AM procedure. Thirteen QTL for spot blotch resistance were identified with DArT and SNP markers. These QTL were found on chromosomes 1H, 2H, 3H, 5H, and 7H and explained from 2.3 to 3.9% of the phenotypic variance. Nearly half of the identified QTL mapped to chromosome bins where spot blotch resistance loci were previously reported, offering some validation for the AM approach. The other QTL mapped to unique genomic regions and may represent new spot blotch resistance loci. This study demonstrates that AM is an effective technique for identifying and mapping QTL for disease resistance in a wild crop progenitor