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Oceanic Anoxic Event 2 (OAE-2) occurred at the Cenomanian-Turonian boundary (∼94.1 Ma) and was a time of profound global changes in ocean chemistry and the carbon cycle. This event was characterized by a positive carbon isotope excursion (CIE) caused by massive organic carbon burial, global greenhouse temperatures, ocean deoxygenation, and changes in ocean life driven by large igneous province (LIP) activity. LIPs throughout the Phanerozoic have had dynamic magma flux, with episodes of major eruptions interspersed with periods of relatively less intense eruptions. A possible trigger for LIP activity throughout the Phanerozoic has been attributed to extraterrestrial impacts because there are multiple contemporaneous occurrences of large craters, LIP activity, and mass extinctions in the geologic record. At the Cenomanian-Turonian boundary, there is a 25 km diameter (rim-to-rim) complex crater in NW Alberta, Canada known as the Steen River impact structure dated at 91 ± 7 Ma (Carrigy and Short, 1968). An alternative explanation for those craters found contemporaneous with LIP activity and mass extinctions is that they were created by large explosive events related to LIP activity. Explosive events associated with mantle plume incubation beneath cratonic lithosphere have been suggested to create geologic features commonly attributed to impacts (e.g., shocked quartz, microspherules, etc.). Currently, the trigger for LIP activity during OAE-2, as well as the duration of LIP activity and the temporal variation and magnitude of eruption rates are not well constrained. To address the issue of LIP eruption rates and the trigger for LIP activity, we examined osmium (Os) abundances and isotopes as well as highly siderophile element (HSE; for this study: Re, Ru, Pd, Os, Ir, Pt) abundance data from a continuous sedimentary section spanning OAE-2. The section is from the Eagle Ford Group in the Iona-1 core, deposited in the Cretaceous Western Interior Seaway (KWIS). We found three high Os concentration intervals with mantle-like initial Osi isotope (initial 187Os/188Os) values of ∼0.16. These intervals are interpreted to reflect high-flux LIP magmatic pulses. Between the pulses, lower Os abundances with more radiogenic Osi values of ∼0.20 are observed, which we interpret as low-flux LIP activity between the high-flux periods. This trend of high-and-low flux Os concentration pulses with mantle-like Osi values during the high flux periods is found in another KWIS core (USGS Portland #1) deposited to the north of Iona-1, and in core Deep Sea Drilling Project (DSDP) Site 530 Hole A (hereafter DSDP 530A; drilled off-shore Namibia in the Angola Basin) deposited in the Southern Hemisphere. Before and throughout the Iona-1 core OAE-2 interval, HSE abundance patterns indicate a mantle source for the unradiogenic Os, and are not consistent with an extraterrestrial impact trigger or contribution to LIP activity during OAE-2. This evidence for multiple high-flux pulses of LIP activity driving ocean deoxygenation has implications for the modern ocean, which is currently experiencing deoxygenation. These results provide new constraints on subsequent high-flux periods that extended the event. The first high-flux period started ∼60 Kyr after our selection of the onset of the CIE. The second and third high-flux periods started ∼270 and ∼400 Kyr after the onset of the CIE, respectively. After the third high-flux period, δ13Corg and Os isotope ratios shifted back to pre-excursion values over ∼585 kyr. In the Iona-1 core, OAE-2 lasted for 1.04 ± 0.12 Myr based on our selection of the CIE.

Rationale: This is the first multicenter randomized controlled trial to evaluate the effectiveness and safety of Zephyr Endobronchial Valve (EBV) in patients with little to no collateral ventilation out to 12 months.Objectives: To evaluate the effectiveness and safety of Zephyr EBV in heterogeneous emphysema with little to no collateral ventilation in the treated lobe.Methods: Subjects were enrolled with a 2:1 randomization (EBV/standard of care [SoC]) at 24 sites. Primary outcome at 12 months was the Delta EBV-SoC of subjects with a post-bronchodilator FEV1 improvement from baseline of greater than or equal to 15%. Secondary endpoints included absolute changes in post-bronchodilator FEV1, 6-minute-walk distance, and St. George's Respiratory Questionnaire scores.Measurements and Main Results: A total of 190 subjects (128 EBV and 62 SoC) were randomized. At 12 months, 47.7% EBV and 16.8% SoC subjects had a Delta FEV1 greater than or equal to 15% (P Conclusions: Zephyr EBV provides clinically meaningful benefits in lung function, exercise tolerance, dyspnea, and quality of life out to at least 12 months, with an acceptable safety profile in patients with little or no collateral ventilation in the target lobe.

Rationale: Bronchoscopic lung volume reduction with Zephyr Valves improves lung function, exercise tolerance, and quality of life of patients with hyperinflated emphysema and little to no collateral ventilation. Objectives: Post hoc analysis of patient-reported outcomes (PROs), including multidimensional measures of dyspnea, activity, and quality of life, in the LIBERATE (Lung Function Improvement after Bronchoscopic Lung Volume Reduction with Pulmonx Endobronchial Valves used in Treatment of Emphysema) study are reported. Methods: A total of 190 patients with severe heterogeneous emphysema and little to no collateral ventilation in the target lobe were randomized 2:1 to the Zephyr Valve or standard of care. Changes in PROs at 12 months in the two groups were compared: dyspnea with the Transitional Dyspnea Index (TDI), focal score; the Chronic Obstructive Pulmonary Disease Assessment Test (CAT; breathlessness on hill/stairs); Borg; the EXAcerbations of Chronic pulmonary disease Tool–PRO, dyspnea domain; activity with the TDI, magnitude of task/effort/functional impairment, CAT (limited activities), and the St. George’s Respiratory Questionnaire (SGRQ), activity domain; and psychosocial status with the SGRQ, impacts domain, and CAT (confidence and energy). Results: At 12 months, patients using the Zephyr Valve achieved statistically significant and clinically meaningful improvements in the SGRQ; CAT; and the TDI, focal score, compared with standard of care. Improvements in the SGRQ were driven by the impacts and activity domains (P

Introduction: Zephyr® Endobronchial Valve (EBV®) treatment in severe emphysema patients, improves lung function, exercise capacity and quality of life. Objective: Evaluate effectiveness and safety of EBV treatment in severe emphysema. Methods: 190 severe heterogeneous emphysema subjects (M47%/F53%) with hyperinflation (FEV1 27.4 %pred; RV 224.5 %pred) and absent collateral ventilation (Chartis®) were randomized 2:1 (EBV:Standard-of-Care (SoC). Responders were classified according to established Minimal Clinically Important Differences for outcome measures. Results: At 12-months 84.2% EBV subjects had a target lobe volume reduction ≥350mL. Between group differences (ΔEBV–SoC) for mean changes from baseline were significant (p

Rationale: Single-center randomized controlled trials of the Zephyr endobronchial valve (EBV) treatment have demonstrated benefit in severe heterogeneous emphysema. This is the first multicenter study evaluating this treatment approach.Objectives: To evaluate the efficacy and safety of Zephyr EBVs in patients with heterogeneous emphysema and absence of collateral ventilation.Methods: This was a prospective, multicenter 2:1 randomized controlled trial of EBVs plus standard of care or standard of care alone (SoC). Primary outcome at 3 months post-procedure was the percentage of subjects with FEV1 improvement from baseline of 12% or greater. Changes in FEV1, residual volume, 6-minute-walk distance, St. George's Respiratory Questionnaire score, and modified Medical Research Council score were assessed at 3 and 6 months, and target lobe volume reduction on chest computed tomography at 3 months.Measurements and Main Results: Ninety seven subjects were randomized toEBV(n = 65) or SoC(n = 32). At 3 months, 55.4% of EBV and 6.5% of SoC subjects had an FEV1 improvement of 12% or more (P Conclusions: EBV treatment in hyperinflated patients with heterogeneous emphysema without collateral ventilation resulted in clinically meaningful benefits in lung function, dyspnea, exercise tolerance, and quality of life, with an acceptable safety profile.

Care of the long-term tracheostomy patient is changing. By moving the initiation of tracheostomy out of the operating room and shifting responsibility for the procedure to the medical specialist, more patients are undergoing tracheostomy for a wider spectrum of diagnoses. With much of the aftercare now directed by the medical specialist, successful reintegration of the long-term tracheostomy patient into a productive life is dependent upon the collaborative care of several disciplines directed by the specialist. To effectively care for these challenging patients, it is critical for the physician who performs tracheostomy to be aware of the new caregiving role that is now theirs.

Disulfiram (Antabuse) (DSF) has been reported to protect rats and other animals from the effects of hyperbaric hyperoxia at 4 to 6 ATA (atmospheres). In contrast, DSF and diethyldithiocarbamate (DDC), its metabolite, accelerate the toxic effects in rats of 100% oxygen at 1 to 2 ATA. We have examined the effects of DSF and DDC on glutathione (GSH) levels in bovine pulmonary artery endothelial cells and Chinese hamster ovary cells. Increases in intracellular GSH occurred 8 to 24 h after addition of DSF to the culture media. These increases in intracellular GSH were associated with increases in the rate of uptake of cystine into the cells. DDC was a less effective inducer of cystine uptake and increased intracellular GSH levels than was DSF. At the concentrations used, neither DDC nor DSF caused significant decreases in intracellular superoxide dismutase levels. Exogenous sulfhydryl compounds including GSH and cysteine partially blocked the induction of cystine transport by DSF or DDC, suggesting that the induction might be mediated through a sulfhydryl reaction between DSF and some cellular components. The increases in GSH in the cultured cells were not significant by 4 h of exposure. In contrast, other stress proteins including heme oxygenase are induced by 2 to 4 h after DSF addition. In previously reported in vivo studies, DSF treatment protected against hyperbaric oxygen damage after as little as 1 to 4 h pre-exposure. This suggests that effects of DSF exposure other than GSH augmentation may be responsible for the protective effects seen in vivo.

The Center for Humanistic Change offers programs that allow participants to develop an awareness and understanding of the requisites of healthy growth. Licensed as a drug and alcohol prevention agency, the Center uses humanistic principles to develop and implement life skills programs which invite participant involvement on many levels.

Both glutathione (γ-glutamylcysteinylglycine; GSH) and the metalloprotein metallothionein (MT) are composed of approximately one-third cysteine. Both have antioxidant activity and are induced by oxidant stresses and heavy metals. Intracellular cysteine levels may depend on uptake and reduction of extracellular cystine. GSH synthesis can be limited by the activity of the [Formula: see text] cystine transport system, which is induced by oxidants and other stresses. MT is induced by treatments that also increase GSH levels and may compete with GSH for intracellular cysteine. We investigated the induction of MT and GSH and cystine transport in NIH/3T3 cells and bovine pulmonary artery endothelial cells exposed to cadmium (Cd) or arsenite. Cd and arsenite increased MT and GSH in both cells. Increases in MT and GSH were accompanied by increases in cystine uptake. Inhibition of cystine transport by glutamate decreased GSH levels and blocked Cd-induced GSH increases in both cell types. MT levels were not significantly affected, suggesting that MT synthesis is less sensitive to intracellular cysteine levels than GSH synthesis.