The Anti-Inflammatory Reliever (AIR) Algorithm Study: a protocol for a single-group study of an AIR stepwise approach to the treatment of adult asthma

Background The stepwise approach to long-term asthma management, which traditionally incorporates short-acting β2-agonist reliever therapy, has been a core feature of asthma guidelines for over 30 years. There have been no studies, however, directly investigating the use of an entire guideline-recommended track. Recently, inhaled corticosteroid–formoterol has been recommended as the preferred reliever therapy in adult asthma, in accordance with a stepwise “Anti-Inflammatory Reliever” (AIR) treatment track. Objective The aim of this study was to evaluate the AIR stepwise approach recommended by the New Zealand adolescent and adult asthma guidelines, in combination with a novel algorithm for transitioning between treatment steps. Methods This 52-week, open-label, single-group study will recruit 100 adults aged 18 to 75 years with mild, moderate and moderate–severe asthma (ACTRN12620001010987). Participants will be allocated to budesonide–formoterol 200/6 µg, one actuation as needed (Step 1), one actuation twice daily and as needed (Step 2), or two actuations twice daily and one as needed (Step 3). Treatment steps will be adjusted throughout the study, in response to reliever use and asthma attacks, according to a stepwise AIR algorithm. Following a 26-week period of investigator-led transitions, participants will adjust their own treatment step. The primary outcome is participant satisfaction as measured by the Global Satisfaction score of the Treatment Satisfaction Questionnaire for Medication. Secondary outcomes will assess efficacy and safety, and describe patterns of medication use and participant flow through the treatment steps. Conclusion This is the first trial to assess the AIR treatment track and algorithm. The results will provide knowledge to guide the clinical use of this approach

The Economic Impact of the Value Chain of a Marcellus Shale Well

The Economic Impact of the Value Chain of a Marcellus Shale Well Site examines the direct economic impact of a Marcellus Shale well located in Southwestern Pennsylvania. This study seeks to fill a critical information gap on the impact of gas drilling and extraction from Marcellus Shale deposits deep underground: an assessment of the economic impacts – emphasizing the direct economic impact, rather than just focusing on the perceived benefits and impacts affecting the region. Our analysis is based on extensive field research, including a site visit and interviews with industry participants. It is further cross-validated by examining similar costs for development of Marcellus Wells by a vertically-integrated exploration and production firm

Changes in the Circadian Rhythm in Patients with Primary Glaucoma

Purpose The current study was undertaken to investigate whether glaucoma affects the sleep quality and whether there is any difference between patients with primary glaucoma (primary open angle glaucoma, POAG and primary angle-closure glaucoma, PACG) and healthy subjects, using a validated self-rated questionnaire, the Pittsburgh Sleep Quality Index (PSQI). Methods The sleep quality of patients with POAG and PACG was tested against normal controls. Subjects were divided into three sub-groups according to age. Differences in the frequency of sleep disturbances (PSQI score >7) were assessed. The differences of sleep quality within the three groups and within the POAG group depending on the patients’ intraocular pressure (IOP) and impairment of visual field (VF) were also studied. Results 92 POAG patients, 48 PACG patients and 199 controls were included. Sleep quality declined with age in control and POAG group (tendency chi-square, P0.05). No significant differences were found in POAG group between patients with a highest IOP in daytime and at nighttime (χ2-test, P>0.05). Conclusions The prevalence of sleep disorders was higher in patients with POAG and PACG than in controls. PACG patients seemed to have a more serious problem of sleep disorders than POAG patients between 61 to 80 years old. No correlation was found between the prevalence of sleep disorders and impairment of VF or the time when POAG patients showed a highest IOP

The relationship between eruptive activity, flank collapse, and sea level at volcanic islands: A long-term (>1 Ma) record offshore Montserrat, Lesser Antilles

Hole U1395B, drilled southeast of Montserrat during Integrated Ocean Drilling Program Expedition 340, provides a long (>1 Ma) and detailed record of eruptive and mass-wasting events (>130 discrete events). This record can be used to explore the temporal evolution in volcanic activity and landslides at an arc volcano. Analysis of tephra fall and volcaniclastic turbidite deposits in the drill cores reveals three heightened periods of volcanic activity on the island of Montserrat (?930 ka to ?900 ka, ?810 ka to ?760 ka, and ?190 ka to ?120 ka) that coincide with periods of increased volcano instability and mass-wasting. The youngest of these periods marks the peak in activity at the Soufrière Hills volcano. The largest flank collapse of this volcano (?130 ka) occurred towards the end of this period, and two younger landslides also occurred during a period of relatively elevated volcanism. These three landslides represent the only large (>0.3 km3) flank collapses of the Soufrière Hills edifice, and their timing also coincides with periods of rapid sea-level rise (>5 m/ka). Available age data from other island arc volcanoes suggests a general correlation between the timing of large landslides and periods of rapid sea-level rise, but this is not observed for volcanoes in intra-plate ocean settings. We thus infer that rapid sea-level rise may modulate the timing of collapse at island arc volcanoes, but not in larger ocean-island settings

The Evolution of the Silver Hills Volcanic Center, and Revised 40Ar/39Ar Geochronology of Montserrat, Lesser Antilles, With Implications for Island Arc Volcanism

Studying the older volcanic centers on Montserrat, Centre Hills and Silver Hills, may reveal how volcanic activity can change over long time periods (≥1 Myr), and whether the recent activity at the Soufrière Hills is typical of volcanism throughout Montserrat's history. Here, we present the first detailed mapping of the Silver Hills, the oldest and arguably least studied volcanic center on Montserrat. Volcanism at the Silver Hills was dominated by episodic andesite lava dome growth and collapse, produced Vulcanian style eruptions, and experienced periodic sector collapse events, similar to the style of volcanic activity that has been documented for the Centre Hills and Soufrière Hills. We also present an updated geochronology of volcanism on Montserrat, by revising existing ages and obtaining new 40Ar/39Ar dates and palaeomagnetic ages from marine tephra layers. We show that the centers of the Silver, Centre, and Soufrière Hills were active during at least ∼2.17–1.03 Ma, ∼1.14–0.38 Ma, and ∼0.45 Ma–present, respectively. Combined with timings of volcanism on Basse-Terre, Guadeloupe these ages suggest that ∼0.5–1 Ma is a common lifespan for volcanic centers in the Lesser Antilles. These new dates identify a previously unrecognized overlap in activity between the different volcanic centers, which appears to be a common phenomenon in island arcs. We also identify an older stage of Soufrière Hills activity ∼450–290 ka characterized by the eruption of hornblende-orthopyroxene-phyric lavas, demonstrating that the petrology of the Soufrière Hills eruptive products has changed at least twice throughout the volcano's development

Selective ablation of VIP interneurons in the rodent prefrontal cortex results in increased impulsivity.

It has been well-established that novelty-seeking and impulsivity are significant risk factors for the development of psychological disorders, including substance use disorder and behavioral addictions. While dysfunction in the prefrontal cortex is at the crux of these disorders, little is known at the cellular level about how alterations in neuron activity can drive changes in impulsivity and novelty seeking. We harnessed a cre-dependent caspase-3 ablation in both male and female mice to selectively ablate vasoactive intestinal peptide (VIP)-expressing interneurons in the prefrontal cortex to better explore how this microcircuit functions during specific behavioral tasks. Caspase-ablated animals had no changes in anxiety-like behaviors or hedonic food intake but had a specific increase in impulsive responding during longer trials in the three-choice serial reaction time test. Together, these data suggest a circuit-level mechanism in which VIP interneurons function as a gate to selectively respond during periods of high expectation

Evaluation of various fluid-film models for use in the analysis of squeeze film dampers with a central groove

Experimental vibration responses of squeeze film dampers (SFDs) are obtained with four different central groove depths, two types of lubricant and various unbalance levels. Highly non-linear fluid stiffness and damping are observed, the damping being sensitively related to oil viscosity and unbalance. Existing oil film models are applied to predict the SFD behaviour. A special groove-two land model is able to predict the vibration behaviour of a very shallow grooved SFD and the conventional two-land theory is applicable to a SFD with a very deep groove. These observations provide useful guidelines for designing a shallow or deep grooved SFD-rotor assembly