It is demonstrated that using HSE06 gives a much more accurate electronic description of the vacancy and

yields an excellent estimate of the activation energy of self-diffusion in Ge consistent with experimental data. The migration energies of the vacancy in different charge states calculated with the HSE06 approach agree well with the results of low-temperature infrared-absorption measurements. In contrast selleck products to previous results, the HSE06 calculations suggest that vacancies in Ge are multiple-level acceptors with levels located in the upper half of the bandgap. This can explain the observed high density of acceptor-like interface traps near the conduction band, pinning the Fermi level and inhibiting the formation of an inversion layer in n-channel devices in Ge. (C) 2011 American Institute of Physics. [doi: 10.1063/1.3642953]“
“Tuberous sclerosis complex (TSC) is an autosomal dominant disease caused by mutations in either the TSC1 (encodes hamartin) or TSC2 (encodes tuberin) genes. Patients with TSC have hamartomas in various organs throughout the whole body, most notably in the brain, skin, eye, heart, kidney and lung. To study the development of hamartomas, we generated a zebrafish model of TSC featuring a nonsense mutation (vu242) in the tsc2 CCI-779 mouse gene. This tsc(2vu242) allele

encodes a truncated Tuberin protein lacking the GAP domain, which is required for inhibition of Rheb and of the TOR kinase within TORC1. We show that tsc(2vu242) is a recessive larval-lethal mutation that causes increased cell size in the brain and liver. Greatly elevated TORC1 signaling is observed in tsc2(vu242/vu242) homozygous zebrafish, and is moderately increased in tsc2(vu242/+) heterozygotes. Forebrain neurons are poorly organized in tsc2(vu242/vu242) homozygous mutants, which have extensive gray and white matter disorganization and ectopically positioned cells. Genetic https://www.selleckchem.com/products/birinapant-tl32711.html mosaic analyses demonstrate that tsc2 limits TORC1 signaling in a cell-autonomous manner. However, in

chimeric animals, tsc2(vu242/vu242) mutant cells also mislocalize wild-type host cells in the forebrain in a non-cell-autonomous manner. These results demonstrate a highly conserved role of tsc2 in zebrafish and establish a new animal model for studies of TSC. The finding of a non-cell-autonomous function of mutant cells might help explain the formation of brain hamartomas and cortical malformations in human TSC.”
“Refsum disease is a genetic progressive neurological disorder caused by neurotoxic phytanic acid, a nutritional component patients are unable to metabolize. Symptoms include retinopathy, polyneuropathy, ataxia, and deafness. They are variable and rarely recognized before adulthood. The authors report the case of a 14-year-old girl diagnosed because of night blindness. They treated her with a phytanic acid-poor diet and extracorporeal lipid apheresis. They used different methods over a 30-month period.

Such a strategy would incorporate proven treatments specifically targeting Thiazovivin concentration the under lying disease process. A vast number of strokes could be prevented by optimal treatment of modifiable vascular risk factors.

This paper presents current evidence-based management

of conventional and novel vascular risk factors in patients with ischemic stroke whose underlying pathophysiologic mechanism is accelerated atherosclerosis. Therapies discussed include antithrombotics, statins, antihypertensives, and surgical/endovascular treatments.”
“We synthesized polyimide (PI) microparticles by a reaction between benzophenone-3,3,4,4-tetracarboxylic dianhydride and 4,4′-diaminodiphenyl ether using polyvinylpyrrolidone as a dispersant in four different organic solvents, at different temperatures, with different amounts of the dispersing agent, and with different concentrations of monomers. After dispersion polymerization, PI microparticles in the size range 200-800 nm were obtained. Absorptions

at 1,775 and 1720 cm(-1), due to the C=O group of PI, and at 1375 cm-1, caused by the stretching vibration of the C-N group due to a lactam ring, were observed in the IR spectrum, which suggested the successful synthesis of PI particles. Scanning electron microscopy analysis of microparticle morphology showed that the PI particle sizes increased with increasing temperature, Roscovitine Cell Cycle inhibitor concentration of dispersant, and concentration of monomers. In addition, the thermal stability is also discussed on the basis of the results of simultaneous Differential Scanning Calorimetry Modulated TA Instruments (DSC-TA) measurement. (C) 2009 Wiley Periodicals, Inc. J Appl Polym Sci 113: 3671-3675, 2009″
“The pathogenesis of evolution from episodic Selleckchem CH5424802 migraine (EM) to chronic migraine (CM) has not yet been clearly determined. Some studies revealed that dysfunction of the brainstem may play a role. We aimed to determine

the brainstem H-1-MR spectroscopic (MRS) findings in episodic and chronic migraine. We recruited patients with EM, CM and controls. Patients with CM were divided into subgroups with and without medication overuse (MO). The H-1-MRS metabolite ratios at the periaqueductal gray (PAG) and bilateral dorsal pons were measured and compared with those in controls. A total of 19 patients with EM, 53 patients with CM (with MO n = 30, without MO n = 23) and 16 control subjects completed the study. Patients with EM had the highest N-acetylaspartate (NAA)/creatine (Cr) ratio at the dorsal pons (right, P = 0.014; left, P = 0.034) in comparison with those of CM and controls. The latter two groups did not differ. Among migraine patients, NAA/Cr ratios at dorsal pons were inversely correlated with headache frequency (right, r = -0.350, P = 0.004; left, r = -0.284, P = 0.019) and intensity (right, r = -0.286, P = 0.019; left, r = -0.244, P = 0.045), but not disease duration.

“
“Landscape transformation by humans is virtually ubiquitous, with several suggestions

being made that the world’s biomes should now be classified according to the extent and nature of this transformation. Even those areas that are buy H 89 thought to have a relatively limited human footprint have experienced substantial biodiversity change. This is true of both marine and terrestrial systems of southern Africa, a region of high biodiversity and including several large conservation areas. Global change drivers have had substantial effects across many levels of the biological hierarchy as is demonstrated in this review, which focuses on terrestrial systems. Interactions among drivers, such as between climate change and invasion, and between changing fire regimes and invasion, are complicating attribution of change effects and management thereof. Likewise CO(2) fertilization is having a much larger impact on terrestrial systems than perhaps commonly acknowledged. Temporal

changes in biodiversity, and the seeming failure of institutional attempts to address PLX4032 them, underline a growing polarization of world views, which is hampering efforts to address urgent conservation needs.”
“Pure titania (TiO2) polycrystalline thin films in rutile, anatase and mixed phase have been grown on amorphous glass substrates by pulsed laser deposition method at various oxygen gas pressure. Wettability investigations have been carried out on these films. Consistent with our previous report

[J. Phys. D: Appl. Phys. 41, 155308 (2008)] it has been observed that for nearly same surface roughness large contact angle or superhydrophobicity is present when sample has a pure single phase and lower contact angle or hydrophobicity when mixed phases selleck inhibitor were present. Structural characterizations suggest that in addition to roughness, pure phase film surface associated with hydrophobic sites and mixed phase film surface show association of both hydrophobic and hydrophilic sites, which might be inducing specific wetting character. UV treatment induces superhydrophilicity in the films. It was observed that UV irradiation causes nonequilibrium state on the TiO2 surface, leading to changes in the electron density, which in turn produces decrement in the crystallinity and lattice expansion. Reversible changes in the wetting state on the pure phase surfaces were observed to be faster than those on the mixed phase surfaces. We tried to establish the possible relation between crystalline phases, chemical nature of surface on reversible wettability besides the main governing parameter viz. surface roughness. (C) 2011 American Institute of Physics. [doi: 10.1063/ 1.3594695]“
“Various protocols have been developed and used for DNA extraction in grapevine.

“
“Dehiscence of median sternotomy wounds remains a clinical problem. Wall forces in thin-walled pressure vessels can be calculated by membrane stress theory. An ellipsoid pressure vessel model of sternal forces is presented together with its application for optimal wire placement in the sternum. Sternal forces were calculated by computational simulation using an ellipsoid chest wall model. Sternal forces were correlated with different sternal thicknesses and radio-density as measured by computerized tomography (CT) scans of the sternum. A comparison of alternative placement of trans-sternal wires located either at the levels

JPH203 order of the costal cartilages or the intercostal spaces was made. The ellipsoid pressure vessel model shows that higher levels of stress are operative at increasing chest diameter (P < 0.001). CT scans show that the thickness of the sternal body is on average 3 mm and 30% thicker

(P < 0.001) and 53% more radio-dense (P < 0.001) at the costal cartilage levels when compared with adjacent intercostal spaces. This results in a decrease of average sternal stress from 438 kPa at the intercostal space level to 338 kPa at the costal cartilage level (P = 0.003). Biomechanical modelling suggests that placement of trans-sternal wires at the thicker bone and more radio-dense level of the costal cartilages will result in reduced stress.”
“Objective. Evaluate the costs and benefits of the Boston Children’s Hospital Community Asthma Initiative (CAI) program through reduction Autophagy Compound Library molecular weight of Emergency Department (ED) visits and hospitalizations and quality of life (QOL) for patients and their families due to reduced missed school days and work days. Methods. Cost-benefit analysis was used to determine an adjusted Return on Investment (ROI)

for all 102 patients enrolled in the CAI program in the calendar year 2006 after controlling for changes in a comparable population without CAI intervention. A societal ROI (SROI) was also computed by including additional indirect benefits due to reduced missed Epoxomicin molecular weight school days for patients and work days for caregivers. Results. Adjusted cost savings from fewer ED visits and hospitalizations resulted in an adjusted ROI of 1.33 (adjusted Net Present Value, (NPV) of savings = $83,863) during the first 3 years after controlling for factors other than the CAI intervention. When benefits due to reduced missed school days and missed work days were added to adjusted cost savings, the SROI increased to 1.85 (Societal NPV of savings = $215,100). Conclusions. Multidisciplinary, coordinated disease management programs offer the opportunity to prevent costly complications and hospitalizations for chronic diseases, while improving QOL for patients and families.

The increase in extracellular glutamate levels induced

by A beta Os was blocked by the sodium channel blocker tetrodotoxin (TTX), by the NMDAR blocker (+)-5-methyl-10,11-dihydro-5H-dibenzo[a, d] cyclohepten-5,10-imine maleate (MK-801) and by removal of Ca(2+) from the extracellular medium, indicating dependence on excitatory neuronal activity. A beta Os enhanced the Selleckchem Cilengitide release of pre-synaptic vesicles labeled by FM1-43 as well as spontaneous post-synaptic activity measured by whole-cell patch-clamp. Activation of inhibitory GABA(A) receptors by taurine blocked the increase in extracellular glutamate levels, suggesting that selective pharmacological inhibition of neuronal activity can counteract the impact of A beta Os on glutamate dyshomeostasis. Results reveal a novel mechanism

by which A beta oligomers promote abnormal release of glutamate from hippocampal neurons, which may contribute to dysregulation of excitatory signaling in the brain.”
“Background: Increased consumption of n-3 (omega-3) long-chain polyunsaturated GW786034 fatty acids (LC PUFAs), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may maintain cognitive function in later life.

Objective: We tested the hypothesis that n-3 LC PUFA supplementation would benefit cognitive function in cognitively healthy older people.

Design: At total of 867 cognitively healthy adults, aged 70-79 y, from selleck 20 general practices in England and Wales were randomly assigned into a double-blind controlled trial of daily capsules providing 200 mg EPA plus 500 mg DHA or olive oil for 24 mo. Treatment-allocation codes were obtained from a central computerized randomization service. Trained research nurses administered a battery of cognitive tests, including the primary outcome, the California Verbal Learning Test (CVLT), at baseline and 24 mo. Intention-to-treat

analysis of covariance, with adjustment for baseline cognitive scores, age, sex, and age at leaving full-time education, included 748 (86%) individuals who completed the study.

Results: The mean age of participants was 75 y; 55% of the participants were men. Withdrawals and deaths were similar in active (n = 49 and n = 9, respectively) and placebo (n = 53 and n = 8, respectively) arms. Mean (+/- SD) serum EPA and DHA concentrations were significantly higher in the active arm than in the placebo arm at 24 mo (49.9 +/- 2.7 mg EPA/L in the active arm compared with 39.1 +/- 3.1 mg EPA/L, in the placebo arm; 95.6 +/- 3.1 mg DHA/L in the active arm compared with 70.7 +/- 2.9 mg DHA/L in the placebo arm). There was no change in cognitive function scores over 24 mo, and intention-to-treat analysis showed no significant differences between trial arms at 24 mo in the CVLT or any secondary cognitive outcome.

Conclusions: Cognitive function did not decline in either study arm over 24 mo.

The temperature dependence of the rate was studied. A possible mechanism consistent with the experimental data is proposed. (C) 2011 Wiley Periodicals, Inc. J Appl buy IPI-145 Polym Sci 121: 1299-1303, 2011″
“Radiofrequency. ablation (RFA), usually performed under percutaneous ultrasound guidance, is considered the gold standard among minimally invasive therapies. On the strength of some recent randomized trials, its indications include operable patients with small hepatocellular carcinoma and inoperable patients with more advanced disease also in combination with other therapies. RFA has lower

complication rates and costs less than surgery.”
“Distinct ecotypes of the snail Littorina saxatilis, each linked to a specific shore microhabitat, form a mosaic-like pattern with narrow hybrid zones in between, over which gene flow is

10-30% of within-ecotype gene flow. Multi-locus comparisons cluster populations by geographic affinity independent of ecotype, while loci under selection group populations by ecotype. The repeated occurrence of partially reproductively isolated ecotypes and the Ro-3306 cost conflicting patterns in neutral and selected genes can either be explained by separation in allopatry followed by secondary overlap and extensive introgression that homogenizes neutral differences evolved under allopatry, or by repeated evolution in parapatry, or in sympatry, with the same ecotypes appearing in each local site. Data from Spain, the UK and Sweden give stronger support for a non-allopatric model of ecotype formation than for an allopatric model. Several different non-allopatric mechanisms can, however, explain the repeated evolution of the ecotypes: (i) parallel evolution by new mutations

in different populations; (ii) evolution from standing genetic variation; and (iii) evolution in concert with rapid spread of new positive mutations among populations inhabiting similar environments. These models make different predictions that can be tested using comprehensive phylogenetic information combined with candidate loci sequencing.”
“Density (rho), viscosity (eta), check details and speed of ultrasound (U) (2 MHz) of pure solvents (chloroform, THF, and 1,4-dioxane) and solutions of epoxy acrylate of 9,9′-bis(4-hydroxy phenyl) anthrone-10 (EAAN) have been investigated at 303, 308, and 313 K. Specific acoustical impedance (Z), isentropic compressibility (kappa(s)), intermolecular free path length (L(f)), classical absorption coefficient (alpha/f(2))(cl), and viscous relaxation time (tau) have been determined from rho, eta, and U data and are correlated with concentration. Z, (alpha/f(2))(cl), and tau increased with C and decreased with T, while kappa(s) and L(f) decreased with C and increased with T in the solvent systems studied. A fairly good to excellent correlation between a given parameter and concentration is observed in solvent systems studied.

We compared the effectiveness, efficiency, buy BEZ235 and costliness of the 2 methods.

Results: Comparing the culture determination methods revealed that the identification sensitivity, specificity, and positive and negative

predictive values were 100%, 100%, 100% and 100%, respectively, for the FISH method and 98.5%, 100%, 100% and 98.5%, respectively, for the PCR method. The FISH method took approximately 3 hours to complete per sample, whereas PCR took approximately 4 hours. S aureus was differentiated from CoNS via the FISH method 1 hour faster than via PCR identification.

Conclusion: Although the FISH and PCR methods both allow for the rapid and reliable identification of S aureus in clinical specimens, FISH is more appropriate for testing a few specimens, whereas PCR is more appropriate for testing a large number of specimens at a lower cost.”
“OBJECTIVE: Neonatal asphyxia may have severe consequences in term newborns. Our purpose was to identify possible risk factors of severe acidosis during pregnancy and labor.

METHODS:

In a case-control study from January 2003 to December 2008 in three university perinatal centers (two French and one Canadian hospitals), we analyzed 226 women with term pregnancies complicated by severe neonatal acidosis (umbilical artery pH less than 7.00). Cases were individually matched with controls with a normal acid-base status (pH 7.15 or greater) paired by parity. Groups were compared for differences in maternal, obstetric, and fetal characteristics. Univariable and logistic conditional

5-Fluoracil in vitro regression were used to identify possible risk factors.

RESULTS: Among 46,722 births after 22 weeks, 6,572 preterm births and 829 stillbirths or terminations of pregnancy were excluded. From the 39,321 live term births, 5.30% of pH values were unavailable. Severe acidosis complicated 0.63% of 37,235 term structurally normal pregnancies. By using multivariate conditional regression, maternal age 35 years or older (35.0% compared with selleckchem 15.5%; odds ratio [OR] 5.58, 95% confidence interval [CI] 2.51-12.40), prior neonatal death (3.5% compared with 0%), prior cesarean delivery (24.7% compared with 6.6%; OR 4.08, 95% CI 1.71-9.72) even after excluding cases of uterine rupture, general anesthesia (8.4 compared with 0.9%; OR 8.04, 95% CI 1.26-50.60), thick meconium (6.4% compared with 2.8%; OR 5.81, 95% CI 1.72-19.66), uterine rupture (4.4% compared with 0%), and abnormal fetal heart rate (66.1% compared with 19.8%; OR 8.77, 95% CI 3.72-20.78) were independent risk factors of severe neonatal acidosis.

CONCLUSION: Prior cesarean delivery, maternal age 35 years or older, prior neonatal death, general anesthesia, thick meconium, uterine rupture, and abnormal fetal heart rate are independent risk factors of severe neonatal acidosis. (Obstet Gynecol 2011;118:818-23) DOI: 10.1097/AOG.

PCB 9 was cytotoxic at 5 mu M within 5 min of exposure, and the toxicity increased

with time and concentration. None of the other congeners showed consistent cytotoxicity. The cytotoxicity was roughly correlated Selleck A1331852 with elevations in cellular ROS levels, but not with changes in intracellular calcium. To the best of our knowledge, toxicity of lower chlorinated, more volatile congeners such as PCB 9 has not been previously studied. These observations may be taken to explain the elevated risk of cardiovascular disease previously reported among residents living near to hazardous waste sites containing PCBs. (c) 2011 Wiley Periodicals, Inc. Environ Toxicol, 2012.”
“Objective. Laparoscopic techniques for placement of peritoneal dialysis catheters are becoming increasingly popular. This study describes an one-port laparoscopic technique for insertion of peritoneal dialysis learn more catheters. Material and methods. Eighteen consecutive chronic renal failure patients underwent laparoscopic placement of Swan-neck catheters. All patients were eligible to receive local

infiltration anaesthesia and none had had a previous peritoneal catheter placed. Videoscopic monitoring was performed via a peel-away sheath through an incision near the umbilicus; a 16 Fr peel-away sheath was then inserted towards the bladder and rectum. A Swan-neck catheter was passed through the peel-away sheath into the true pelvis. A subcutaneous tunnel was created and a point in left lower quadrant was selected as the exit site of

the catheter. Results. All the catheters were successfully placed and the mean time of operation was 26.5 min (range 14-35 min). The patients were discharged 2-4 Pevonedistat cell line days following the operation. During a mean follow-up period of 10.6 months (range 6-18 months), there were no catheter-related complications, such as catheter migration, dialysate leakage, exit-site infection and bacterial peritonitis. Conclusions. One-port laparoscopic technique is a simple, safe and effective method for placement of peritoneal dialysis catheters.”
“AimTo assess the diagnostic accuracy of the ultrasonographic discrimination of benign adnexal masses.

MethodsThis was a prospective study, evaluating 245 consecutive cases using real-time gray-scale ultrasonography in a tertiary education hospital.

ResultsDiagnostic accuracy was high for simple cysts and solid masses as -values of 0.824 and 0.816 and accuracy was moderate for endometriomas, dermoid cysts and cystadenomas as -values of 0.758, 0.689 and 0.627, respectively, and low for hemorrhagic cysts as a -value of 0.587. A logistic regression model was developed using ultrasonographic characteristics of the adnexal masses.

The authors,

journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. All the included studies were follow-up studies; eight studies used prospective data collection, and five studies collected the study data retrospectively. No randomized controlled trials were found. Nine of the 13 included papers used a propensity-score-matched comparison of the survival of bilateral mammary artery graft [or, bilateral internal thoracic artery ( BITA) graft] patients vs single mammary artery graft [or, single internal thoracic artery (SITA) graft] patients. These studies consistently showed an enhanced survival of BITA patients compared with propensity-score-matched SITA patients.

Three of the 13 included papers used Cox proportional hazards regression analysis to compare survival of BITA vs SITA patients; one larger study showed better crude Lapatinib Protein Tyrosine Kinase inhibitor survival of BITA patients, but did not identify BITA grafts as independent predictor of enhanced survival. The remaining two studies also did not identify BITA grafts as independent predictor of enhanced survival. One study only presented crude survival estimates of BITA vs SITA patients and therefore was of limited informative value. We conclude that the use of BITA grafts seems to offer a long-term survival benefit compared with a SITA graft for patients undergoing coronary artery bypass grafting surgery. Although randomized evidence is lacking, observational evidence supporting this hypothesis

is mounting.”
“The study compares outcomes for patients with frozen embryos who had frozen-thawed embryo transfer (FET) timed to their natural ovulation cycle versus cycles JAK inhibitor in which endometrial timing was programmed with oestrogen and progesterone. A total of 1205 patients undergoing 1677 FET cycles between 1 January 2000 and 31 December 2006 were analysed. Comparisons were made for patients undergoing modified natural versus programmed FET cycles, as well as between patients using their own eggs for frozen embryos versus those using donor-egg-derived embryos. Clinical pregnancy (gestational Selleckchem ACY-738 sac oil 7 week ultrasound) rates (CPR), as well as miscarriage rates, were significantly higher in programmed FET cycles in patients using their own eggs (106/262, 40.5% per embryo transfer, P = 0.015) However, there was not a difference in delivered pregnancies between cycle types in own egg patients (natural cycle delivery rate 245/862, 28.4%; programmed cycle delivery rate 77/262, 29.4%). Furthermore, CPR were not different in natural (38/129, 29.5%) versus programmed cycles (144/424, 34.0%) for ovum donor recipients, nor were delivered pregnancy rates different in natural (33/129, 25.6%) versus programmed cycles (114/424, 26.9%) for ovum donor recipients. In conclusion, there is no significant difference in delivery rates for FET in natural (278/991, 28.1%) versus programmed (191/686, 27.8%) cycles using both own embryos and donor-egg-derived embryos.

ObjectivesWe aimed to describe the evolution of total IgE and specific IgE responses to house-dust mite (HDM) allergens and Ascaris in a birth cohort (Risk Factors for Asthma and Allergy in the Tropics, FRAAT), analyzing their relationships with PKC412 datasheet wheezing.

MethodsTotal and specific IgE were measured by ImmunoCap in mothers and children at four different time points (S1-S4) between 0 and 42months. Parasite infection was evaluated by stool examination.

ResultsMaternal total IgE (aOR: 2.43, 95% CI: 1.09-5.43; p=0.03) and socio-demographic factors were associated with high cord blood (CB) total IgE. High CB total IgE was positively associated

with higher Blomia tropicalis and Ascaris-specific IgE values during lifetime, but protected from recurrent wheezing (aOR: 0.26, 95% CI: 0.08-0.88, p=0.03). Prevalence rates of IgE sensitization

were high; at around 3yr old, they were 33.3, 18.6, and 26.5% for B.tropicalis, Dermatophagoides pteronyssinus, Selleckchem Linsitinib and Ascaris, respectively. Indicators of unhygienic conditions were risk factors for HDM and Ascaris sensitization in children. A weak statistical association between B.tropicalis-specific IgE and ever wheezing was found (aOR: 1.47 95% CI: 1.00-2.28, p=0.05).

ConclusionsIn a socioeconomically deprived community from the tropics, sensitization to HDM allergens was very frequent at early life, especially to B.tropicalis. In contrast to expected according to the hygiene hypothesis, unhygienic/poverty conditions were risk factors for allergen sensitization. High CB total IgE levels were a risk factor for allergen sensitization but protected from recurrent wheezing.

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“Background and objective: Roflumilast, an oral, selective phosphodiesterase

4 inhibitor, has been shown to reduce exacerbations and improve pulmonary function in patients with COPD. This study examined the efficacy, safety and tolerability of roflumilast in Asian patients with COPD.

Methods: Patients with COPD were randomized 1:1 to enter a 12-week treatment period and receive BMS-777607 purchase either oral roflumilast, 500 mu g once daily, or placebo, following a single-blind, 4-week baseline period in which all patients received placebo. The primary end point was mean change in FEV(1) from baseline to each postran-domization visit during the treatment period. Other spirometric lung function measurements were evaluated as secondary end points. COPD exacerbations were monitored. Safety was assessed from clinical laboratory tests, vital signs, physical examination (including electrocardiogram) and monitoring of adverse events (AEs).

Results: Of 551 patients recruited, 410 were randomized and received at least one dose of study medication (roflumilast, n = 203; placebo, n = 207).