Hill A.P.,Medicines Research Center |
Redman A.M.,Moore Research |
Sneddon H.F.,Medicines Research Center
Green Chemistry | Year: 2015
Further to the introduction of solvent and reagent guides at GSK, the reagent guide methodology has been adapted to score common acids and bases for use in situations where the chemistry is tolerant of a number of options. The pKa of each acid and base, and information as to whether they are generally recognised as safe are included to enhance the utility of such guides. © 2015 The Royal Society of Chemistry.
Donohue J.F.,University of North Carolina at Chapel Hill |
Worsley S.,Respiratory Medicines Development Center |
Zhu C.-Q.,GSK |
Hardaker L.,Global Clinical Safety and Pharmacovigilance |
Church A.,Moore Research
Respiratory Medicine | Year: 2015
Background Umeclidinium (UMEC; long-acting muscarinic antagonist [LAMA])/vilanterol (VI; long-acting beta2-agonist [LABA]) and fluticasone propionate/salmeterol (FP/SAL) (inhaled corticosteroid/LABA) are approved maintenance therapies for chronic obstructive pulmonary disease (COPD). Two studies compared efficacy and safety of UMEC/VI with FP/SAL in patients with moderate-to-severe COPD with no exacerbations in the previous year. Methods In these 12-week, multicenter, double-blind, parallel-group, double-dummy trials, randomized (1:1) patients received once-daily UMEC/VI 62.5/25 mcg or twice-daily FP/SAL 250/50 mcg (DB2114930 n = 353 and 353; DB2114951 n = 349 and 348, respectively; intent-to-treat). Endpoints included 0-24 h weighted mean (wm) forced expiratory volume in 1 s (FEV1) (Day 84; primary), trough FEV1 (Day 85; secondary), other lung function endpoints, dyspnea, quality of life (QoL) and safety. Results UMEC/VI demonstrated statistically significant, clinically meaningful improvements in lung function measures versus FP/SAL. For 0-24 h wmFEV1 (Day 84), improvements with UMEC/VI versus FP/SAL were 74 mL (95% confidence interval [CI]: 38-110; DB2114930) and 101 mL (63-139; DB2114951) (both p < 0.001). Trough FEV1 improvements were 82 mL (45-119) and 98 mL (59-137) (both p < 0.001) for UMEC/VI versus FP/SAL, respectively. Both treatments demonstrated similar, clinically meaningful improvements from baseline in dyspnea (Transition Dyspnea Index focal score >1 unit) and QoL (St George's Respiratory Questionnaire Total score >4-unit decrease) in both studies with no statistical differences between treatments. Adverse event rates were similar: 26 and 30% UMEC/VI; 27 and 31% FP/SAL. Conclusions Once-daily UMEC/VI 62.5/25 mcg over 12 weeks resulted in statistically significant, clinically meaningful improvements in lung function versus twice-daily FP/SAL 250/50 mcg in patients with moderate-to-severe COPD with infrequent exacerbations. Both treatments improved dyspnea and QoL. Clinical trial registration DB2114930/NCT01817764; DB2114951/NCT01879410. © 2015 The Authors.
Keyser T.L.,U.S. Department of Agriculture |
Brown P.M.,Moore Research
Forest Ecology and Management | Year: 2014
As the focus of forest management on many public lands shifts away from timber production and extraction to habitat, restoration, and diversity-related objectives, it is important to understand the long-term effects that previous management activities have on structure and composition to better inform current management decisions. In this paper, we analyzed 40years of growth data to quantify (1) the long-term response of yellow-poplar to thinning across an age and site quality gradient, and (2) the longevity of any growth response yellow-poplar may have to thinning throughout the southern Appalachian Mountains. Between 1960 and 1963, 134-0.1ha plots were established across an age and site quality gradient in yellow-poplar (Liriodendron tulipifera L.) stands throughout the southern Appalachian Mountains. All plots were thinned from below, with post-thinning relative density categorized into three classes: low (relative density <0.25), moderate (relative density ≥0.25 but <0.35), and high (relative density ≥0.35 but <0.60). Using plot-level annual basal area increment (BAI; cm2 yr-1) chronologies reconstructed from tree cores, average annual BAI was calculated for 10years prior to thinning (BAIpre) and each following 10year period thereafter (BAIpost).Site index and age at the time of thinning had a positive effect on BAIpost. During the first 10year period following thinning, annual BAI (at a site index=32.3m and age=43) averaged (SE) 33.7 (1.6), 26.3 (1.3), and 21.6 (1.1) cm2 yr-1 in the low, moderate, and high density classes, respectively. Significant differences between low and moderate and low and high density classes remained throughout the duration of the study. During the 10years post-thinning the ratio of BAIpost to BAIpre (RBAI) was >1.0 in 92%, 86%, and 57% of plots in the low, moderate, and high density classes, respectively indicating an overall increase in growth relative to pre-thinning growth rates. By the fourth decade post-thinning the percentage of stands containing trees that possessed RBAI values >1.0 had fallen; however trees in 71% of the plots in the low density class continued to experience growth rates greater than those prior to thinning. We conclude the increase in growth is short-lived when density is reduced to moderate and high levels whereas the response of trees to more intense thinnings is long-lasting. © 2013.
Tang L.,Moore Research |
Thakuriah P.V.,University of Illinois at Chicago
Transportation Research Part C: Emerging Technologies | Year: 2012
In this paper, using longitudinal data on route level monthly average weekday ridership in the entire Chicago Transit Authority (CTA) bus system from January 2002 through December 2010, we evaluate the ridership effects of the CTA real-time bus information system. This bus information system is called CTA Bus Tracker and was incrementally implemented on different CTA bus routes from August 2006 to May 2009. To take account of other factors that might affect bus ridership, we also include data on unemployment levels, gas prices, local weather conditions, transit service attributes, and socioeconomic characteristics during the study period. This combined longitudinal data source enables us to implement a quasi-experimental design with statistical controls to examine changes in monthly average weekday ridership, before and after the Bus Tracker system was implemented, on each bus route. Based on a linear mixed model, we found that the provision of Bus Tracker service does increase CTA bus ridership, although the average increase is modest. Further, the study findings suggest that there are temporal variations of the ridership effects among the routes, with the " winning" routes more likely to have the technology implemented in the later phases of the overall " roll-out" period. However, the results are less conclusive regarding geographical variations in the effects of Bus Tracker. © 2012 Elsevier Ltd.
Yilmaz Y.,Marmara University |
Younossi Z.M.,Moore Research
Clinics in Liver Disease | Year: 2014
Obesity is strongly associated with the prevalence of nonalcoholic fatty liver disease (NAFLD) in adult and pediatric populations. Nutrition, physical activity, and behavioral modifications are critical components of the treatment regimen for all obese patients with NAFLD. Bariatric surgeries that affect or restrict the flow of food through the gastrointestinal tract may improve liver histology in morbidly obese patients with nonalcoholic steatohepatitis (NASH), although randomized clinical trials and quasi-randomized clinical studies are lacking. Early detection of NASH and hepatic fibrosis using noninvasive biochemical and imaging markers that may replace liver biopsy is the current challenge. © 2014 Elsevier Inc.
Margolis D.A.,Moore Research |
Boffito M.,St Stephens Center |
Boffito M.,Imperial College London
Current Opinion in HIV and AIDS | Year: 2015
Purpose of review Long-acting antiretroviral (ARV) agents are currently under development for the treatment of chronic HIV infection. This review focuses on data recently produced on injectable ARVs for patients living with HIV/AIDS and on the patients' perspectives on the use of these agents. Recent findings Crystalline nanoparticle formulations of the nonnucleoside reverse transcriptase inhibitor rilpivirine (TMC278) and of the HIV-1 integrase strand transfer inhibitor cabotegravir (GSK1265744) have progressed into phase II clinical trials as injectable maintenance therapy for patients living with HIV/AIDS with an undetectable viral load. Summary Phase II studies evaluating the coadministration of rilpivirine and cabotegravir intramuscularly to HIVinfected individuals with an undetectable viral load are currently underway. Rilpivirine and cabotegravir are characterized by different mechanisms of action against HIV and a favorable drug interaction profile, providing a rationale for coadministration. The high potency and low daily dosing requirements of oral cabotegravir and rilpivirine facilitate long-acting formulation development. Intramuscular dosing is preceded by an oral lead-in phase to assess safety and tolerability in individual participants. In addition to assessing the safety of injectable therapies in ongoing studies, it will be important to evaluate whether differences in drug adherence between injectable and oral therapies lead to different virologic outcomes, including rates of virologic failure and the emergence of resistance. Long-acting formulations may be associated with challenges, such as the management of adverse effects with persistent drug concentrations and the risk of virologic resistance, as drug concentrations decline following discontinuation. © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Rittmaster R.S.,Glaxosmithkline |
Rittmaster R.S.,Moore Research
Acta Oncologica | Year: 2011
Over the past two decades, many more men are diagnosed with prostate cancer then die of the disease. This increase in diagnosis has led to aggressive treatment of indolent disease in many individuals and has been the impetus for finding a means of reducing the risk of prostate cancer. In the past decade, there have been eight large trials of prostate cancer risk reduction using dietary supplements, 5αÎ±-reductase inhibitors, or anti-estrogens. The only two trials which have demonstrated efficacy are those involving 5αÎ±-reductase inhibitors: the PCPT (finasteride) and REDUCE (dutasteride). This review examines prostate cancer risk reduction, with emphasis on conclusions that can be drawn from these two landmark studies. © 2011 Informa Healthcare.
Moore Research | Date: 2011-06-01
A cellular constituent is lysed from, produced by and/or isolated from one or more bacteria from the genus Bacteroides, and the cellular constituent, a derivative thereof, and/or one or more bacteria from the genus Bacteroides, or a modified form thereof, is employed in compositions and methods for modulating an inflammatory response. Such methods include methods of treating, delaying the onset of or reducing the symptoms of one or more inflammatory conditions/diseases, including corporal or gastrointestinal inflammation, for example, Irritable Bowel Syndrome, Crohns Disease, or colitis, and/or associated diseases such diabetes, asthma, multiple sclerosis, cancer, rheumatoid arthritis, gingivitis, atopic diseases, for example, hay fever, food allergies, eczema, rhinitis, dermatitis, conjunctivitis, atopic syndrome and keratosis pelaris, ocular inflammatory disease, strokes, cardiovascular disease, depression, atherosclerosis and hypertension, and comprise administering a composition comprising one or more natural and/or modified bacteria of the genus Bacteroides, and/or a cellular constituent lysed from, produced by, or isolated from one or more natural and/or modified bacteria from the genus Bacteroides, or a derivative thereof.
Agency: NSF | Branch: Standard Grant | Program: | Phase: | Award Amount: 178.80K | Year: 2011
This Small Business Innovation Research (SBIR) Phase I project is designed to provide a new probiotic product for public consumption that will address the rising US and global obesity issue and related concurrent increase in health problems such as diabetes and heart disease. According to the Centers for Disease and Prevention, 60-65% of the adult population in the US is overweight or obese. While implementation of lifestyle change (dietary modification and increased physical activity) improves this condition, relapse with additional weight gain is well documented. Current treatments are limited and include surgery and pharmacological agents with well documented health risks. This product is designed to work within the gastrointestinal tract, decreasing the amount of energy available to the host, and providing a means to the consumer to halt weight gain and decrease the risk of relapse, with possible positive modulation of underlying risk factors which contribute to declining health and contribute to increased health care costs.
The broader/commercial impacts of this research will be to reduce the high incidence of obesity. The rising cost of health care in the US has been well documented. Much of this cost is associated with increasing obesity, an underlying factor in the development of diseases such as diabetes and heart disease, commonly associated with an increase in abdominal circumference/inflammatory processes. According to the World Health Organization, three-fourths of the world population depends upon some form of non-pharmaceutical product for health care, providing a world-wide marketing opportunity for future commercialization.
Agency: National Science Foundation | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 150.00K | Year: 2011
This Small Business Innovation Research (SBIR) Phase I project is designed to provide a new probiotic product for public consumption that will address the rising US and global obesity issue and related concurrent increase in health problems such as diabetes and heart disease. According to the Centers for Disease and Prevention, 60-65% of the adult population in the US is overweight or obese. While implementation of lifestyle change (dietary modification and increased physical activity) improves this condition, relapse with additional weight gain is well documented. Current treatments are limited and include surgery and pharmacological agents with well documented health risks. This product is designed to work within the gastrointestinal tract, decreasing the amount of energy available to the host, and providing a means to the consumer to halt weight gain and decrease the risk of relapse, with possible positive modulation of underlying risk factors which contribute to declining health and contribute to increased health care costs. The broader/commercial impacts of this research will be to reduce the high incidence of obesity. The rising cost of health care in the US has been well documented. Much of this cost is associated with increasing obesity, an underlying factor in the development of diseases such as diabetes and heart disease, commonly associated with an increase in abdominal circumference/inflammatory processes. According to the World Health Organization, three-fourths of the world population depends upon some form of non-pharmaceutical product for health care, providing a world-wide marketing opportunity for future commercialization.