Efficacy and safety of 4 weeks' treatment with combined fluticasone furoate/vilanterol in a single inhaler given once daily in COPD: a placebo-controlled randomised trial

Background: Fluticasone furoate/vilanterol (FF/VI) is a novel once-daily (OD) inhaled corticosteroid/long-acting beta(2) agonist combination in development for chronic obstructive pulmonary disease (COPD) and asthma. Trial design: A multicentre, randomised, double-blind, parallel-group, placebo-controlled study. Methods: Participants were patients with moderate-to-severe COPD treated with placebo or FF/VI 400/25 mu g OD for 4 weeks. Study objectives were to assess the safety and efficacy of FF/VI 400/25 mg OD administered for 4 weeks via a novel dry powder inhaler. Co-primary end points were change from baseline in weighted mean (wm) heart rate 0-4 h postdose at day 28 and the incidence of adverse events (AEs). Secondary end points included change from baseline in trough forced expiratory volume in one second (FEV1) (23-24 h postdose; day 29) and wm FEV1 (0-4 h postdose; day 28). Patients were randomised to receive FF/VI 400/25 mg or placebo in a 2: 1 ratio; all patients and investigators were blinded to active or placebo treatment. Results: 60 patients (mean age 64 years) were randomised (FF/VI: n=40; placebo: n=20), and all contributed data to the analysis. Mean screening post-bronchodilator FEV1 per cent predicted was comparable between groups (FF/VI: 58.5%; placebo: 60.1%). The wm heart rate 0-4 h postdose was similar between groups (difference: 0.6 beats per minute; 95% CI -3.9 to 5.1). More on-treatment AEs were reported in the FF/VI group (68%) compared with the placebo group (50%). The most common drug-related AEs in the FF/VI group were oral candidiasis (8%) and dysphonia (5%). There were no clinically relevant effects on laboratory values, including glucose and potassium, or on vital signs or ECGs/Holters. The FF/VI group had statistically greater improvements compared with placebo in trough FEV1 (mean difference 183 ml) and 0-4 h postdose wm FEV1 (mean difference 236 ml). Conclusion: FF/VI has a good safety and tolerability profile and improves lung function compared with placebo in patients with COPD. Trial registration number: clinical trials. gov-NCT00731822

Efficacy and safety of 4 weeks' treatment with combined fluticasone furoate/vilanterol in a single inhaler given once daily in COPD: a placebo-controlled randomised trial

Background. Fluticasone furoate/vilanterol (FF/VI) is a novel once-daily (OD) inhaled corticosteroid/long-acting β2 agonist combination in development for chronic obstructive pulmonary disease (COPD) and asthma. Trial design. A multicentre, randomised, double-blind, parallel-group, placebo-controlled study. Methods. Participants were patients with moderate-to-severe COPD treated with placebo or FF/VI 400/25 μg OD for 4 weeks. Study objectives were to assess the safety and efficacy of FF/VI 400/25 μg OD administered for 4 weeks via a novel dry powder inhaler. Co-primary end points were change from baseline in weighted mean (wm) heart rate 0–4 h postdose at day 28 and the incidence of adverse events (AEs). Secondary end points included change from baseline in trough forced expiratory volume in one second (FEV1) (23–24 h postdose; day 29) and wm FEV1 (0–4 h postdose; day 28). Patients were randomised to receive FF/VI 400/25 μg or placebo in a 2:1 ratio; all patients and investigators were blinded to active or placebo treatment. Results. 60 patients (mean age 64 years) were randomised (FF/VI: n=40; placebo: n=20), and all contributed data to the analysis. Mean screening post-bronchodilator FEV1 per cent predicted was comparable between groups (FF/VI: 58.5%; placebo: 60.1%). The wm heart rate 0–4 h postdose was similar between groups (difference: 0.6 beats per minute; 95% CI −3.9 to 5.1). More on-treatment AEs were reported in the FF/VI group (68%) compared with the placebo group (50%). The most common drug-related AEs in the FF/VI group were oral candidiasis (8%) and dysphonia (5%). There were no clinically relevant effects on laboratory values, including glucose and potassium, or on vital signs or ECGs/Holters. The FF/VI group had statistically greater improvements compared with placebo in trough FEV1 (mean difference 183 ml) and 0–4 h postdose wm FEV1 (mean difference 236 ml). Conclusion. FF/VI has a good safety and tolerability profile and improves lung function compared with placebo in patients with COPD.publishedVersio

CD8(+) T-Cell Responses to Trypanosoma cruzi Are Highly Focused on Strain-Variant trans-Sialidase Epitopes

CD8(+) T cells are crucial for control of a number of medically important protozoan parasites, including Trypanosoma cruzi, the agent of human Chagas disease. Yet, in contrast to the wealth of information from viral and bacterial infections, little is known about the antigen specificity or the general development of effector and memory T-cell responses in hosts infected with protozoans. In this study we report on a wide-scale screen for the dominant parasite peptides recognized by CD8(+) T cells in T. cruzi–infected mice and humans. This analysis demonstrates that in both hosts the CD8(+) T-cell response is highly focused on epitopes encoded by members of the large trans-sialidase family of genes. Responses to a restricted set of immunodominant peptides were especially pronounced in T. cruzi–infected mice, with more than 30% of the CD8(+) T-cell response at the peak of infection specific for two major groups of trans-sialidase peptides. Experimental models also demonstrated that the dominance patterns vary depending on the infective strain of T. cruzi, suggesting that immune evasion may be occurring at a population rather than single-parasite level

Imaging of Repaired Rotator Cuff

info:eu-repo/semantics/publishedVersio

Murine and related chapparvoviruses are nephro-tropic and produce novel accessory proteins in infected kidneys.

Mouse kidney parvovirus (MKPV) is a member of the provisional genus Chapparvovirus that causes renal disease in immune-compromised mice, with a disease course reminiscent of polyomavirus-associated nephropathy in immune-suppressed kidney transplant patients. Here we map four major MKPV transcripts, created by alternative splicing, to a common initiator region, and use mass spectrometry to identify "p10" and "p15" as novel chapparvovirus accessory proteins produced in MKPV-infected kidneys. p15 and the splicing-dependent putative accessory protein NS2 are conserved in all near-complete amniote chapparvovirus genomes currently available (from mammals, birds and a reptile). In contrast, p10 may be encoded only by viruses with >60% amino acid identity to MKPV. We show that MKPV is kidney-tropic and that the bat chapparvovirus DrPV-1 and a non-human primate chapparvovirus, CKPV, are also found in the kidneys of their hosts. We propose, therefore, that many mammal chapparvoviruses are likely to be nephrotropic

The Social Studies Curriculum in Atlanta Public Schools During the Desegregation Era

This historical investigation explores how teachers, students, and education officials viewed the social studies curriculum in the local context of Atlanta, and the broader state of Georgia, during the post-Civil Rights era, when integration was a court-ordered reality in the public schools. During the desegregation era, Atlanta schools were led by Atlanta Public Schools (APS) Superintendent, Dr. Alonzo Crim. Brought to Atlanta as part of a desegregation compromise, Dr. Crim became APS\u27s first African American superintendent. In particular, the authors investigate how national social studies movements, such as Man: A Course of Study (MACOS), inquiry-based learning, co-curriculum activities, and standards movements, adapted to fit this Southeastern locale, at a time when schools were struggling to desegregate. Local curriculum documents written in the 1970s reveal a traditional social studies curriculum. By the 1980s, APS\u27s social studies curriculum guides broadened to include a stronger focus on an enacted community—inside the classroom and around the world. In oral history interviews, however, former teachers, students, and school officials presented contrasting perspectives of how the social studies curriculum played out in the reality of Atlanta\u27s public schools during the desegregation era

Linking Adult Reproduction and Larval Density of Invasive Carp in a Large River

Identifying how temporal variation in the environment affects reproductive success of invasive alien species will aid in predicting future establishment and tracking dynamics of established populations. Asian carp Hypophthalmichthys spp. have become a nuisance in recent years in the Mississippi River basin. Their populations are apparently expanding, indicating favorable conditions for reproduction. During 2004 and 2005, we quantified mean density of Asian carp larvae, mean monthly gonadosomatic index (GSI) of adult males and females, and number of eggs within mature females in the lower Illinois River, a major tributary of the Mississippi River. A flood (water velocity ≥ 0.7 m/s) and drought (\u3c0.2 m/s) occurred during apparent spawning in 2004 and 2005, respectively. During 2004, Asian carp larvae were found during 32% of sampling weeks; mean GSI and fecundity were relatively low for adults, probably reflecting partially spawned individuals and perhaps low reproductive investment. During the drought of 2005, larval stages were present during only one (5%) of the sampling weeks, whereas mean GSI and fecundity of adults were high through summer. Females resorbed their eggs instead of spawning during this year. Spawning conditions during low water periods appear to be unsuitable for Asian carps, inhibiting adult spawning and yielding few larvae. Spawning conditions during 2004 were better but still yielded low densities of larvae relative to native fishes. Reproduction in the lower Illinois River appears to be linked to river flow and its impact on adult spawning decisions, but conditions for strong year-class production (i.e., high larval densities) may be rarer than previously expected