Alternative project delivery in rural Alaska: experiences, quality and claims

Master's Project (M.S.) University of Alaska Fairbanks, 2015The popularity of alternative project delivery systems has expanded beyond the private sector and into the public sector. Alaska embodies unique challenges that may present obstacles while using alternative project delivery systems. This analysis will provide an understanding of alternative project delivery systems in Alaska and how local experiences, quality and claims are affected. Alaska's unique characteristics present both challenges and opportunities for implementing alternative project delivery systems. This report begins with a discussion of experiences from several rural Alaska projects, and how alternative project delivery systems can be utilized. Some impacts that alternative project delivery systems have on quality are then presented, including a perspective on quality and recommendations for achieving customer satisfaction. A treatment of construction claims is then provided, followed by conclusions and recommendations for stakeholders in selecting an appropriate project delivery system. Alternative project delivery systems were researched by means of scholarly literature reviews, professional interviews and seminars. The report of these findings is intended to provide owners and contractors with a concise presentation of the challenges and advantages for using alternative project delivery systems in Alaska

A Study of Time- and Sex-Dependent Effects of Vortioxetine On Rat Sexual Behavior: Possible Roles of Direct Receptor Modulation

Treatment-related sexual dysfunction is a common side effect of antidepressants and contributes to patient non-compliance or treatment cessation. However, the multimodal antidepressant, vortioxetine, demonstrates low sexual side effects in depressed patients. To investigate the mechanisms involved, sexual behavior was assessed in male and female rats after acute, and repeated (7 and 14 days) treatment with vortioxetine, flesinoxan (a 5-HT1A agonist), CP-94253 (a 5-HT1B agonist), or ondansetron (a 5-HT3 antagonist). These selective ligands were chosen to simulate vortioxetine\u27s direct modulation of these receptors. Paroxetine was also included in the male study. Acute and repeated treatment with vortioxetine at doses corresponding to clinical levels (based on serotonin transporter occupancy) had minimal effects on sexual behavior in male and female rats. High dose vortioxetine plus flesinoxan (to mimic predicted clinical levels of 5-HT1A receptor occupancy by vortioxetine) facilitated male rat sexual behavior (acutely) while inhibiting female rat proceptive behavior (both acutely and after 14 days treatment). The selective serotonin reuptake inhibitor, paroxetine, inhibited male sexual behavior after repeated administration (7 and 14 days). Flesinoxan alone facilitated male sexual behavior acutely while inhibiting female rat proceptive behavior after repeated administration (7 and 14 days). CP-94253 inhibited sexual behavior in both male and female rats after repeated administration. Ondansetron had no effect on sexual behavior. These findings underline the complex serotonergic regulation of sexual behavior and indicate that the low sexual side effects of vortioxetine found in clinical studies are likely associated with its direct modulation of serotonin receptors

Authority fairness for all? Intergroup status and expectations of procedural justice and resource distribution

Authorities such as the police and the government play a vital function in maintaining order in the social systems in which groups exist. Relational models of procedural justice (PJ) state that fair treatment from authority affirms the social standing of those identifying with the authority, communicating inclusion and respect. Previous research suggests that social identity may also inform expectations of authority fairness. Focusing on an intergroup context of authority decision-making, the present research tests a novel hypothesis regarding whether intergroup social status may also inform expectations of authority fairness in terms of fair treatment and favourable outcomes. Operationalising PJ as the extent to which people are provided voice by authorities, three experimental studies showed no effect of intergroup status on expected PJ from authority. A sample weighed internal meta-analysis (N = 704) also provided no support for the hypothesis that relative outgroup status shapes expectations of voice from authority (d = -.02). Intergroup status did, however, influence the extent to which people expected authorities to distribute resources favourably towards the outgroups. Lower status outgroups were expected to receive less favourable outcomes from authorities than equal status outgroups (d = -.23). Thus, outgroup status affects people’s judgements of the resources that outgroups deserve from authority. The present research is among the first to consider how intergroup relations may drive expectations of how authorities will act towards other social groups. Implications for wielding authority and the role of perceived intergroup threat in intergroup settings are discussed

Next-generation sequencing of AV nodal reentrant tachycardia patients identifies broad spectrum of variants in ion channel genes.

Atrioventricular nodal reentry tachycardia (AVNRT) is the most common form of regular paroxysmal supraventricular tachycardia. This arrhythmia affects women twice as frequently as men, and is often diagnosed in patients <40 years of age. Familial clustering, early onset of symptoms and lack of structural anomaly indicate involvement of genetic factors in AVNRT pathophysiology. We hypothesized that AVNRT patients have a high prevalence of variants in genes that are highly expressed in the atrioventricular conduction axis of the heart and potentially involved in arrhythmic diseases. Next-generation sequencing of 67 genes was applied to the DNA profile of 298 AVNRT patients and 10 AVNRT family members using HaloPlex Target Enrichment System. In total, we identified 229 variants in 60 genes; 215 missenses, four frame shifts, four codon deletions, three missense and splice sites, two stop-gain variants, and one start-lost variant. Sixty-five of these were not present in the Exome Aggregation Consortium (ExAC) database. Furthermore, we report two AVNRT families with co-segregating variants. Seventy-five of 284 AVNRT patients (26.4%) and three family members to different AVNRT probands had one or more variants in genes affecting the sodium handling. Fifty-four out of 284 AVNRT patients (19.0%) had variants in genes affecting the calcium handling of the heart. We furthermore find a large proportion of variants in the HCN1-4 genes. We did not detect a significant enrichment of rare variants in the tested genes. This could be an indication that AVNRT might be an electrical arrhythmic disease with abnormal sodium and calcium handling

Angle of Incidence Effects on Far-Field Positive and Negative Phase Blast Parameters

The blast overpressure acting on a rigid target is known to vary between the normally reflected overpressure and the incident overpressure as a function of the angle between the target and the direction of travel of the blast wave. Literature guidance for determining the exact effects of angle of incidence are unclear, particularly when considering the negative phase. This paper presents the results from a series of well controlled experiments where pressure transducers are used to record the pressure-time history acting on the face of a large, rigid target at various angles of incidence for varying sizes of hemispherical PE4 charge and stand-off distances. The test data demonstrated remarkable repeatability, and excellent agreement with semi-empirical predictions for normally reflected overpressures. The oblique results show that peak overpressure, impulse and duration are highly dependent on angle of incidence for the positive phase, and are invariant of angle of incidence for the negative phase

Antiarrhythmic and electrophysiologic effects of flecainide on acutely induced atrial fibrillation in healthy horses

BACKGROUND: Only few pharmacologic compounds have been validated for treatment of atrial fibrillation (AF) in horses. Studies investigating the utility and safety of flecainide to treat AF in horses have produced conflicting results, and the antiarrhythmic mechanisms of flecainide are not fully understood. OBJECTIVES: To study the potential of flecainide to terminate acutely induced AF of short duration (≥15 minutes), to examine flecainide‐induced changes in AF duration and AF vulnerability, and to investigate the in vivo effects of flecainide on right atrial effective refractory period, AF cycle length, and ventricular depolarization and repolarization. ANIMALS: Nine Standardbred horses. Eight received flecainide, 3 were used as time‐matched controls, 2 of which also received flecainide. METHODS: Prospective study. The antiarrhythmic and electrophysiologic effects of flecainide were based on 5 parameters: ability to terminate acute pacing‐induced AF (≥15 minutes), and drug‐induced changes in atrial effective refractory period, AF duration, AF vulnerability, and ventricular depolarization and repolarization times. Parameters were assessed at baseline and after flecainide by programmed electrical stimulation methods. RESULTS: Flecainide terminated all acutely induced AF episodes (n = 7); (AF duration, 21 ± 5 minutes) and significantly decreased the AF duration, but neither altered atrial effective refractory period nor AF vulnerability significantly. Ventricular repolarization time was prolonged between 8 and 20 minutes after initiation of flecainide infusion, but no ventricular arrhythmias were detected. CONCLUSIONS AND CLINICAL IMPORTANCE: Flecainide had clear antiarrhythmic properties in terminating acute pacing‐induced AF, but showed no protective properties against immediate reinduction of AF. Flecainide caused temporary prolongation in the ventricular repolarization, which may be a proarrhythmic effect

Mutant U2AF1-induced alternative splicing of H2afy (macroH2A1) regulates B-lymphopoiesis in mice

Somatic mutations in spliceosome genes are found in ∼50% of patients with myelodysplastic syndromes (MDS), a myeloid malignancy associated with low blood counts. Expression of the mutant splicing factor U2AF1(S34F) alters hematopoiesis and mRNA splicing in mice. Our understanding of the functionally relevant alternatively spliced target genes that cause hematopoietic phenotypes in vivo remains incomplete. Here, we demonstrate that reduced expression of H2afy1.1, an alternatively spliced isoform of the histone H2A variant gene H2afy, is responsible for reduced B cells in U2AF1(S34F) mice. Deletion of H2afy or expression of U2AF1(S34F) reduces expression of Ebf1 (early B cell factor 1), a key transcription factor for B cell development, and mechanistically, H2AFY is enriched at the EBF1 promoter. Induced expression of H2AFY1.1 in U2AF1(S34F) cells rescues reduced EBF1 expression and B cells numbers in vivo. Collectively, our data implicate alternative splicing of H2AFY as a contributor to lymphopenia induced by U2AF1(S34F) in mice and MDS

Observations from Preliminary Experiments on Spatial and Temporal Pressure Measurements from Near-Field Free Air Explosions

It is self-evident that a crucial step in analysing the performance of protective structures is to be able to accurately quantify the blast load arising from a high explosive detonation. For structures located near to the source of a high explosive detonation, the resulting pressure is extremely high in magnitude and highly non-uniform over the face of the target. There exists very little direct measurement of blast parameters in the nearfield, mainly attributed to the lack of instrumentation sufficiently robust to survive extreme loading events yet sensitive enough to capture salient features of the blast. Instead literature guidance is informed largely by early numerical analyses and parametric studies. Furthermore, the lack of an accurate, reliable data set has prevented subsequent numerical analyses from being validated against experimental trials. This paper presents an experimental methodology that has been developed in part to enable such experimental data to be gathered. The experimental apparatus comprises an array of Hopkinson pressure bars, fitted through holes in a target, with the loaded faces of the bars flush with the target face. Thus, the bars are exposed to the normally or obliquely reflected shocks from the impingement of the blast wave with the target. Pressure-time recordings are presented along with associated Arbitary-Langrangian-Eulerian modelling using the LS-DYNA explicit numerical code. Experimental results are corrected for the effects of dispersion of the propagating waves in the pressure bars, enabling accurate characterisation of the peak pressures and impulses from these loadings. The combined results are used to make comments on the mechanism of the pressure load for very near-field blast events

Design and numerical assessment of a rapid-construction corrugated steel-concrete-steel protective structure

A protective structure should be sufficiently resilient to protect its occupants from the harmful effects of an impact or explosion. In many instances, protective structures are also required to be assembled quickly, and be cost-effective. Steel-concrete-steel (SCS) sandwich structures combine the benefits of steel; ductility and anti-scabbing, and concrete; energy absorption and rigidity. Despite these favourable characteristics, the performance of profiled-plate steel-concrete-steel structures under blast and impact loads has yet to be studied in detail. This article presents the results from a numerical study investigating the efficacy of a newly proposed profiled-plate arched steel-concrete-steel structure under the loading from an extremely near-field high explosive detonation. It is observed that as arch thickness (concrete infill depth) increases, a greater proportion of energy is absorbed through concrete crushing and a larger concrete mass is mobilised. It is shown that a 240 mm arch thickness is adequate to resist the blast load from a 5.76 kg TNT charge, therefore proving the suitability of the proposed protective structure