A long-term clinical trial on the efficacy and safety profile of doxofylline in Asthma: The LESDA study.

Doxofylline, an oral methylxanthine with bronchodilator and anti-inflammatory activities, offers a promising alternative to theophylline due to its superior efficacy/safety profile. No long-term studies on the efficacy and safety of doxofylline are currently available in asthma. The aim of the Long-term clinical trial on the Efficacy and Safety profile of Doxofylline in Asthma (LESDA) study was to investigate the safety and efficacy profile of doxofylline administered for one year in asthmatic patients. LESDA was a multicenter, open-label, Phase III, clinical trial in which adult asthmatic patients received the same treatment (oral doxofylline 400 mg t.i.d.) for one year. Efficacy was assessed through periodic pulmonary function tests and by having the subjects keep monthly records of asthma events rates and use of salbutamol as rescue medication. The rate of adverse events (AEs) was recorded during the study. Three-hundred nine patients were screened and allocated in the study. Doxofylline significantly improved the change from baseline in forced expiratory volume in 1 s (FEV1) (+16.90 ± 1.81%, P < 0.001 vs. baseline). Doxofylline also significantly improved the rate of asthma events (events/day: -0.57 ± 0.18, P < 0.05 vs. baseline) and the use of salbutamol as rescue medication (puffs/day: -1.48 ± 0.25, P < 0.01 vs. baseline). The most common AEs were nausea (14.56%), headache (14.24%), insomnia (10.68%), and dyspepsia (10.03%). There were neither serious AEs nor deaths during or shortly after the study. Concluding, doxofylline is effective and well tolerated when administered chronically in asthmatic patients

Impact of doxofylline compared to theophylline in asthma: A pooled analysis of functional and clinical outcomes from two multicentre, double-blind, randomized studies (DOROTHEO 1 and DOROTHEO 2)

Abstract This pooled analysis of double-blind, randomized, placebo-controlled trials aimed to investigate the impact of DOxofylline compaRed tO THEOphylline (DOROTHEO 1 and DOROTHEO 2 studies) on functional and clinical outcomes in asthma. Asthmatic patients ≥16 years of age with forced expiratory volume in 1 s (FEV1) ≥50% and  0.05) increase the risk of AEs compared to placebo, conversely in patients treated with theophylline 250 mg the risk of AEs was significantly (

Spatial description of hake-directed fishing activity off the west coast of South Africa

Historically, the two species of Cape hakes Merluccius capensis and M. paradoxus off South Africa were commercially exploited exclusively by demersal trawling. In 1994, hake-directed demersal longline was introduced on an experimental basis, and in 1998 was initiated as a commercial fishing sector. The effect of a combined fleet composed of both trawlers and longliners on the Cape hake resource is not fully understood. Analysis of fishing intensity and catch-rate data revealed that the highest catch rates were found around the 400m and 500m isobaths for the trawl and longline fisheries respectively. Catch rates from both fishing sectors were also noted to be higher over sediments with a sand component. Differences between areas of the highest fishing intensity and highest catch rates were noted. In addition to other factors, it is suggested that a ‘friction of distance’ effect applies — vessels will trade-off higher catch rates with the increased costs associated with fishing in deeper waters

Two Regional Mental Health Treatment Facilities

One of the major social programs of the 1960s was the development of community mental health centers. As with most early attempts at evaluation, the results were pessimistic. This article reanalyzes one of the earliest, and best-known, evaluations of a community-based treatment facility. Following the conceptual framework of Campbell and his associates, it was found that the various threats to the validity of the findings indicate a consistent and systematic bias against detecting a positive effect for the new mental health center. In light of recent federal legislation mandating formal evaluations, appropriate procedures are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68090/2/10.1177_0193841X7900300403.pd

Reasoning with heuristics

Which rules should guide our reasoning? Human reasoners often use reasoning shortcuts, called heuristics, which function well in some contexts but lack the universality of reasoning rules like deductive implication or inference to the best explanation. Does it follow that human reasoning is hopelessly irrational? I argue: no. Heuristic reasoning often represents human reasoners reaching a local rational maximum, reasoning more accurately than if they try to implement more “ideal” rules of reasoning. I argue this is a genuine rational achievement. Our ideal rational advisors would advise us to reason with heuristic rules, not more complicated ideal rules. I argue we do not need a radical new account of epistemic norms to make sense of the success of heuristic reasoning

Discovery of Sexual Dimorphisms in Metabolic and Genetic Biomarkers

Metabolomic profiling and the integration of whole-genome genetic association data has proven to be a powerful tool to comprehensively explore gene regulatory networks and to investigate the effects of genetic variation at the molecular level. Serum metabolite concentrations allow a direct readout of biological processes, and association of specific metabolomic signatures with complex diseases such as Alzheimer's disease and cardiovascular and metabolic disorders has been shown. There are well-known correlations between sex and the incidence, prevalence, age of onset, symptoms, and severity of a disease, as well as the reaction to drugs. However, most of the studies published so far did not consider the role of sexual dimorphism and did not analyse their data stratified by gender. This study investigated sex-specific differences of serum metabolite concentrations and their underlying genetic determination. For discovery and replication we used more than 3,300 independent individuals from KORA F3 and F4 with metabolite measurements of 131 metabolites, including amino acids, phosphatidylcholines, sphingomyelins, acylcarnitines, and C6-sugars. A linear regression approach revealed significant concentration differences between males and females for 102 out of 131 metabolites (p-values<3.8 x 10(-4); Bonferroni-corrected threshold). Sex-specific genome-wide association studies (GWAS) showed genome-wide significant differences in beta-estimates for SNPs in the CPS1 locus (carbamoyl-phosphate synthase 1, significance level: p<3.8 x 10(-10); Bonferroni-corrected threshold) for glycine. We showed that the metabolite profiles of males and females are significantly different and, furthermore, that specific genetic variants in metabolism-related genes depict sexual dimorphism. Our study provides new important insights into sex-specific differences of cell regulatory processes and underscores that studies should consider sex-specific effects in design and interpretation

New Faculty on the Block: Issues of Stress and Support

The research reported investigated the experiences of new faculty in their first three years of employment in higher education administration programs. New faculty face stress relative to work-life integration, issues pertaining to gender or color, teaching responsibilities, and unclear expectations. The findings of this study highlight the role of graduate school socialization and identification as a chosen student targeting a faculty position as an influence on new faculty and their acclimation during their first years. Implications include the need for intentional mentoring, inclusive support for all students seeking faculty roles, and the need for specificity on the part of hiring committees and new departments regarding expectations. Key to new faculty success is obtaining a sense of work-life integration