Preliminary Assessment of Hydrothermal Risks in the Euphrates–Tigris Basin: Droughts in Iraq

This paper presents a temporal and spatial pattern of precipitation, surface air temperature, and drought occurrence in Euphrates–Tigris rivers basin with special emphases on Iraq. Historical records based on 115 years (1900–2014) of monthly precipitation and temperature data has been divided into four sub-periods, each of 30 years (first 1900–1929, second 1930–1959, third 1960–1989 and fourth 1985–2014) and studied separately. The results showed that the mean annual precipitation in Iraq for the four sub-periods is: 218.5, 202.1, 196.4, and 174.9 mm respectively, with an average of 198 mm. This indicates that the mean annual precipitation decreased by 43.6 mm (20 %) in the fourth sub-period compared to the first sub-period. The mean annual temperature for the four sub-periods in Iraq are 22.0, 21.9, 22.0, 22.8 °C respectively, with an average of 22.2 °C. This indicates that the average monthly temperature during the year in Iraq increased by 0.76 °C (3.45 %) in the fourth sub-period compared to the first sub-period. The probability of occurrence of dry (hot) periods in Iraq increased by 345.5 % (147.7 %) in the fourth sub-period compared to the first sub-period. Fortunately, the greatest drought occurrence is observed in western parts of Ira, where agriculture is irrigated, in rain-fed areas in the northern Iraq, there has also been a decrease in precipitation, but not so strong as in the west of the country. A preliminary conclusion about the current climatic desertification and its possible consequences for Iraq was drawn.This paper presents a temporal and spatial pattern of precipitation, surface air temperature, and drought occurrence in Euphrates–Tigris rivers basin with special emphases on Iraq. Historical records based on 115 years (1900–2014) of monthly precipitation and temperature data has been divided into four sub-periods, each of 30 years (first 1900–1929, second 1930–1959, third 1960–1989 and fourth 1985–2014) and studied separately. The results showed that the mean annual precipitation in Iraq for the four sub-periods is: 218.5, 202.1, 196.4, and 174.9 mm respectively, with an average of 198 mm. This indicates that the mean annual precipitation decreased by 43.6 mm (20 %) in the fourth sub-period compared to the first sub-period. The mean annual temperature for the four sub-periods in Iraq are 22.0, 21.9, 22.0, 22.8 °C respectively, with an average of 22.2 °C. This indicates that the average monthly temperature during the year in Iraq increased by 0.76 °C (3.45 %) in the fourth sub-period compared to the first sub-period. The probability of occurrence of dry (hot) periods in Iraq increased by 345.5 % (147.7 %) in the fourth sub-period compared to the first sub-period. Fortunately, the greatest drought occurrence is observed in western parts of Ira, where agriculture is irrigated, in rain-fed areas in the northern Iraq, there has also been a decrease in precipitation, but not so strong as in the west of the country. A preliminary conclusion about the current climatic desertification and its possible consequences for Iraq was drawn

Efficacy and safety of a novel, nebulized glycopyrrolate for the treatment of COPD: effect of baseline disease severity and age; pooled analysis of GOLDEN 3 and GOLDEN 4

Jill Ohar,1 Robert Tosiello,2 Thomas Goodin,2 Shahin Sanjar2 1Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA; 2Sunovion Pharmaceuticals Inc., Marlborough, MA, USA Background: The efficacy and safety of nebulized glycopyrrolate inhalation solution (GLY), administered twice daily (BID) via the innovative eFlow® Closed System nebulizer (PARI Pharma GmbH, Starnberg, Germany), were demonstrated in two replicate, placebo-controlled, 12-week Phase III studies (GOLDEN 3 and GOLDEN 4). This report evaluates the efficacy and safety of GLY by baseline disease severity and age in the pooled GOLDEN 3 and GOLDEN 4 patient population (N=1,294). Methods: Patients were grouped by baseline predicted post-bronchodilator FEV1 (<50%, ≥50%) and age (<65, ≥65, ≥75 years). Results: GLY (25 and 50 µg BID) produced significant improvements in trough FEV1 in FEV1% predicted <50% (0.070 L, 0.079 L) and ≥50% (0.112 L, 0.126 L) subgroups (P<0.01 vs placebo), and in patients aged <65 (0.056 L, 0.086 L), ≥65 (0.140 L, 0.124 L), and ≥75 (0.144 L, 0.120 L) years (P<0.05 vs placebo). St George’s Respiratory Questionnaire (SGRQ) total score was significantly improved with GLY 25 and 50 µg BID (P<0.05 vs placebo) in FEV1% predicted <50% (-3.237, -3.061) and ≥50% (-3.392, -2.322) and in <65 years (-3.447, -2.318) and ≥65 years (-3.053, -3.098) subgroups. In patients aged ≥75 years, GLY 25 µg reduced SGRQ total score by -6.278 units (P<0.01 vs placebo). The incidence of treatment-emergent adverse events was similar between GLY and placebo across all subgroups, and the overall incidence of cardiovascular events was low. Conclusions: Nebulized GLY improved lung function and health status and was well tolerated over 12 weeks in patients with moderate-to-very-severe COPD, irrespective of baseline disease severity and age. Clinical trial registration: NCT02347761, NCT02347774. Keywords: age, COPD, disease severity, long-acting muscarinic antagonist, LAMA, nebulizer, nebulized glycopyrrolat

Loss of epithelial integrity resulting from E-cadherin dysfunction predisposes airway epithelial cells to adenoviral infection

Epithelial intercellular adhesion is fundamental to the formation of the airway epithelial protective barrier. In this respect, cadherins are important because these adhesion molecules regulate formation and maintenance of epithelial intercellular junctions. To study the importance of airway epithelial integrity in determining susceptibility to virus infection, we used a replication-incompetent adenovirus, RAd35, and an E-cadherin specific function-blocking antibody, SHE78-7, to disrupt intercellular contacts in human bronchial epithelial cell line 16HBE14o- and primary bronchial epithelial cells. After exposure of 16HBE14o- cell cultures to SHE78-7, disruption of the transepithelial permeability barrier was indicated by a loss of transepithelial electrical resistance and an associated increase of mannitol, inulin, and dextran paracellular flux. Subsequent exposure of SHE78-7-treated cell cultures to RAd35 showed a remarkable increase in adenoviral infection as assessed by beta-galactosidase reporter gene expression. In cultures exposed to SHE78-7, disruption of E-cadherin function resulted in infection equivalent to that in control cultures using 16-fold lower viral titers. These studies show that manipulation of E-cadherin function provides a specific means of altering epithelial integrity that in turn determines resistance of airway epithelia to adenoviral infection

Effect of background long-acting beta2-agonist therapy on the efficacy and safety of a novel, nebulized glycopyrrolate in subjects with moderate-to-very-severe COPD

Edward M Kerwin,1 Robert Tosiello,2 Barry Price,2 Shahin Sanjar,2 Thomas Goodin2 1Clinical Research Institute of Southern Oregon, Inc., Medford, OR, USA; 2Sunovion Pharmaceuticals Inc., Marlborough, MA, USA Background: Phase III studies demonstrated efficacy and safety of nebulized glycopyrrolate inhalation solution (GLY) in subjects with COPD. Secondary analyses were performed to examine the effect of background long-acting beta2-agonist (LABA) use on the efficacy and safety of nebulized GLY. Methods: In two 12-week placebo-controlled studies (GOLDEN 3 and GOLDEN 4) and one 48-week, open-label active-controlled study (GOLDEN 5), a total of 2,379 subjects were stratified by background LABA use (LABA-yes: n=861; LABA-no: n=1,518) and randomized to placebo vs GLY 25 or 50 µg twice daily, or GLY 50 µg twice daily vs tiotropium (TIO) 18 µg once daily. Lung function, patient-reported outcomes, exacerbations, and safety were assessed. Results: Compared with placebo, pooled data from the 12-week studies showed significant improvements from baseline with GLY 25 and 50 µg across LABA subgroups in trough FEV1 (LABA-yes: 0.101 and 0.110 L; LABA-no: 0.092 and 0.101 L, respectively; P<0.001) and St George’s Respiratory Questionnaire total score (SGRQ; LABA-yes: -2.957 and -3.888; LABA-no: -3.301 and -2.073, respectively; P<0.05). Incidence of treatment-emergent adverse events (TEAEs) was similar in LABA subgroups, and lower in GLY 25 µg vs placebo. In the 48-week active-controlled study, GLY and TIO both showed improvement from baseline across LABA subgroups in FEV1 (LABA-yes: 0.106 and 0.092 L; LABA-no: 0.096 and 0.096 L, respectively) and in SGRQ total score (LABA-yes: -5.190 and -3.094; LABA-no: -4.368 and -4.821, respectively). Incidence of TEAEs was similar between GLY and TIO, and across LABA subgroups. Exacerbation rates were similar across treatments and LABA subgroups, and cardiovascular events of special interest were more frequent in the LABA-no subgroup. Nebulized GLY, combined with LABA, did not generate any additional safety signals. Conclusion: Nebulized GLY demonstrated efficacy and was well tolerated up to 48 weeks in subjects with COPD with/without background LABA. Keywords: COPD, nebulized glycopyrrolate, eFlow® CS, LAMA, background LAB