A pragmatic randomized trial comparing tablet computer informed consent to traditional paper-based methods for an osteoporosis study

AbstractObjectiveMethods to improve informed consent efficiency and effectiveness are needed for pragmatic clinical trials. We compared informed consent using a tablet computer to a paper approach to assess comprehension and satisfaction of patients and clinic staff for a future osteoporosis clinical trial.MethodsNine community-based practices identified and recruited patients to compare the informed consent processes (tablet vs. paper) in a mock osteoporosis clinical trial. The tablet informed consent included an animation summarizing the trial, complete informed consent document, and questions to assess and reinforce comprehension of the study. Participants were women age ≥55 years with ≥1 year of alendronate use. We surveyed participants to assess comprehension and satisfaction and office staff for satisfaction and perceived time demands.ResultsThe nine practices enrolled 33 participants. There was not a significant difference in comprehension between the tablet vs. paper informed consent [mean (SD) tablet: 12.2 (1.0) vs. paper: 11.4 (1.7)]. Office staff preferred the tablet to the paper informed consent for identifying potential study participants (two-sided t-test p = 0.02) despite an increased perceived time spent to complete the tablet process [tablet: 28.3 min (SD 16.3) vs. paper: 19.0 min (SD 6.9); p = 0.08].ConclusionsAlthough, there were no significant differences in participant satisfaction and comprehension with the tablet informed consent compared to a paper informed consent, patients and office staff trended towards greater satisfaction with the tablet informed consent. Larger studies are needed to further evaluate the utility of electronic informed consent in pragmatic clinical trials

Effects of 59Fe, 65Zn and of three soil types on dry matter yield, chemical composition and nitrogen fixation in Phaseolus vulgaris L. cv. carioca

The aim of this work was to study in greenhouse conditions the effects of two levels of iron and zinc on yield and chemical composition of common bean (Phaseolus vulgaris L.) and on atmospheric nitrogen fixation, in three soils, classified as Terra Roxa Estruturada (TRE), Latossol Vermelho Escuro (LVE), and Podzolico Vermelho Amarelo (PVA). The coefficient of utilization of these micronutrients by this crop and its distribution in above-ground parts and roots were also assessed. The rates for iron were 1.5 and 3.0 ppm, and for zinc, 2.5 and 5.0 ppm. It was applied 7.5 µCi of 59Fe/kg of soil with the lower rate of the stable iron, and 5.0 and 10.0 µCi of Zn/kg of soil in the pots corresponding to the lower and higher rate of the stable zinc, respectively. The plants were harveste at the age of 60 days and nitrogen, phosphorus, potassium, iron and zinc contents were determined. Immediately after harvest, symbiotic nitrogen fixation was assessed, using the acetylene reduction method. The detection of 59Fe and 65zn radioactivity were carried out on nitric percloric extract, by gamma ray spectrometry. The behavior of common bean presented high variation among the three soils, for all the variables. There was no influence of treatments of iron and zinc on dry matter of above ground part and root and also on the weight and number of nodules. The rate of 3.0 ppm of iron decreased the capacity of nodules to fix atmospheric nitrogen in relation to rate of 1.5 ppm, while the rate of 5.0 ppm of zinc increased this capacity, in relation to the rate of 2.5 ppm. There was significative effect of treatments on nitrogen, potassium and zinc contents in above ground part and on nitrogen and zinc contents in the root. The absorption of zinc from the fertilizer and the percentagem of zinc in the plant derived from fertilizer were diretly influenced by rate of zinc The higher coefficient of utilization of zinc from the fertilizer was 4.0%.No presente trabalho, conduzido em casa de vegetação, procuramos estudar os efeitos dos micronutrientes ferro e zinco na produção de materia seca, composição química do feijoeiro (Phaseolus vulgaris L.) e na fixação do nitrogênio atmosférico, em três solos, classificados como Terra Roxa Estruturada (TRE), Latossol Vermelho Escuro (LVE) e Podzólico Vermelho Amarelo (PVA). Procuramos também determinar os índices de aproveitamento destes micronutrientes pelo feijoeiro e sua distribuição na parte aérea e na raiz. O delineamento experimental foi um fatorial 3x7, sendo três solos e sete tratamentos por solo, com três repetições. Nos tratamentos, foram utilizados duas doses de ferro e duas doses de zinco em separado ou combinando as doses menores e maiores destes micronutrientes (Fe1Zn1, Fe2Zn2). As doses de ferro foram 1,5 e 3,0 ppm e as de zinco foram 2,5 e 5,0 ppm. Foram aplicados 7,5 µCi de 59Fe/kg de solo nos vasos correspondentes à dose menor de ferro e 5,0 e 10,0 µCi de 65Zn/kg de solo nos vasos correspondentes respectivamente à dose menor e maior de zinco. Todos os tratamentos receberam uma adubação básica. O comportamento do feijoeiro apresentou grande variação entre os três tipos de solos, para todas as variáveis. Não houve influência dos tratamentos de ferro e zinco na produção de parte aérea e raiz e nem no peso e numero dos nodulos. A dose de 3,0 ppm de ferro diminuiu a capacidade dos nódulos de fixarem nitrogênio atmosférico em relação à dose de 1,5 ppm enquanto que a dose de 5,0 ppm de zinco aumentou esta capacidade, em relação à dose de 2,5 ppm. Houve um efeito significativo dos tratamentos na concentração de nitrogênio, potássio, ferro e zinco na parte aérea e na concentração de nitrogênio, e zinco na raiz. A absorção de zinco dos fertilizantes e a percentagem do zinco na planta proveniente do adubo foram influenciadas diretamente pelas doses de zinco. O maior coeficiente de aproveitamento do zinco do adubo foi de 4,0%

Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation

DNA methylation quantitative trait locus (mQTL) analyses on 32,851 participants identify genetic variants associated with DNA methylation at 420,509 sites in blood, resulting in a database of >270,000 independent mQTLs.Characterizing genetic influences on DNA methylation (DNAm) provides an opportunity to understand mechanisms underpinning gene regulation and disease. In the present study, we describe results of DNAm quantitative trait locus (mQTL) analyses on 32,851 participants, identifying genetic variants associated with DNAm at 420,509 DNAm sites in blood. We present a database of >270,000 independent mQTLs, of which 8.5% comprise long-range (trans) associations. Identified mQTL associations explain 15-17% of the additive genetic variance of DNAm. We show that the genetic architecture of DNAm levels is highly polygenic. Using shared genetic control between distal DNAm sites, we constructed networks, identifying 405 discrete genomic communities enriched for genomic annotations and complex traits. Shared genetic variants are associated with both DNAm levels and complex diseases, but only in a minority of cases do these associations reflect causal relationships from DNAm to trait or vice versa, indicating a more complex genotype-phenotype map than previously anticipated.Molecular Epidemiolog

Alendronic Acid Produces Greater Effects Than Risedronic Acid On Bone Density And Turnover In Postmenopausal Women With Osteoporosis: Results Of Facts1-international

Background: The objective of the study was to evaluate the effects of alendronic acid once weekly relative to risedronic acid once weekly on bone mineral density (BMD), markers of bone turnover and tolerability in the treatment of osteoporosis in postmenopausal women. Methods: This was a randomised, double-masked, double-dummy multicentre international study (75 centres in 27 countries in Europe, the Americas and Asia-Pacific). A total of 1303 women were screened and 936 with low bone density (T-score ≤-2.0 at the spine, hip trochanter, total hip or femoral neck) were randomised; 91% (n = 854) completed the study. Patients were randomised to treatment with either active alendronic acid 70mg weekly (Fosamax®) and placebo identical to risedronic acid weekly or active risedronic acid 35mg weekly (Actonel®) and placebo identical to alendronic acid weekly for 12 months. The primary efficacy endpoint was the percentage change from baseline in hip trochanter BMD at 12 months. Secondary endpoints included the percentage change from baseline in lumbar spine, total hip and femoral neck BMD; biochemical markers of bone turnover (including serum bone-specific alkaline phosphatase [BSAP] and urinary type I collagen N-telopeptides [NTx]); and safety and tolerability as assessed by reporting of adverse experiences. Results: Alendronic acid produced greater increases in BMD than did risedronic acid at 12 months at all sites measured. Mean percentage increases from baseline in hip trochanter BMD at month 12 were 3.56% and 2.71% in the alendronic acid and risedronic acid groups, respectively (treatment difference [95% CI]: 0.83% [0.22, 1.45; p = 0.008]). Mean percentage increases from baseline were greater with alendronic acid than risedronic acid at the lumbar spine, total hip and femoral neck BMD at month 12 (p = 0.002, p < 0.001, p = 0.039, respectively). Increases in BMD with alendronic acid compared with risedronic acid were also significantly greater at 6 months at the trochanter and total hip. There was a greater reduction in bone turnover with alendronic acid compared with risedronic acid: NTx decreased 58% with alendronic acid compared with 47% with risedronic acid at 12 months (p < 0.001); and BSAP decreased 45% with alendronic acid compared with 34% with risedronic acid at 12 months (p < 0.001). Overall tolerability and upper gastrointestinal tolerability were similar for both agents. Conclusions: Alendronic acid once weekly produced greater BMD increases at both hip and spine sites and greater reductions in bone turnover relative to risedronic acid once weekly. Both agents were well tolerated with no significant difference in upper gastrointestinal adverse experiences. Clinicians should consider these results when making treatment decisions for postmenopausal women with osteoporosis. © 2006 Adis Data Information BV. All rights reserved.2626374McClung, M.R., Bisphosphonates in osteoporosis: Recent clinical experience (2000) Exp Opin Pharmacother, 1, pp. 225-238Wasnich, R.D., Miller, P.D., Antifracture efficacy of antiresorptive agents are related to changes in bone density (2000) J Clin Endocrinol Metab, 85, pp. 231-236Hochberg, M.C., Greenspan, S., Wasnich, R.D., Changes in bone density and turnover explain the reductions in incidence of nonvertebral fractures that occur during treatment with antiresorptive agents (2002) J Clin Endocrinol Metab, 87, pp. 1586-1592Hochberg, M.C., Ross, P.D., Black, D., Larger increases in bone mineral density during alendronate therapy are associated with a lower risk of new vertebral fractures in women with postmenopausal osteoporosis (1999) Arthritis Rheum, 42, pp. 1246-1254. , Fracture Intervention Trial Research GroupBauer, D.C., Black, D.M., Garnero, P., Change in bone turnover and hip, nonspine, and vertebral fracture in alendronate-treated women: The Fracture Intervention Trial (2004) J Bone Miner Res, 19, pp. 1250-1258Cummings, S.R., Karpf, D.B., Harris, F., Improvement in spine bone density and reduction in risk of vertebral fractures during treatment with antiresorptive drugs (2002) Am J Med, 112, pp. 281-289Li, Z., Meredith, M.P., Hoseyni, M.S., A method to assess the proportion of treatment effect explained by a surrogate endpoint (2001) Stat Med, 20, pp. 3175-3188Marcus, R., Wong, M., Heath III, H., Antiresorptive treatment of postmenopausal osteoporosis: Comparison of study designs and outcomes in large clinical trials with fracture as an endpoint (2002) Endocr Rev, 23, pp. 16-37Delmas, P.D., Seeman, E., Changes in bone mineral density explain little of the reduction in vertebral or nonvertebral fracture risk with anti-resorptive therapy (2004) Bone, 34, pp. 599-604Miller, P.D., Hochberg, M.C., Wehren, L.E., How useful are measures of BMD and bone turnover? (2005) Curr Med Res Opin, 21, pp. 545-553Cummings, S.R., Black, D.M., Thompson, D.E., Alendronate reduces the risk of vertebral fractures in women without preexisting vertebral fractures: Results from the Fracture Intervention Trial (1998) JAMA, 280, pp. 2077-2082Liberman, U.A., Weiss, S.R., Broll, J., Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis (1995) N Engl J Med, 333, pp. 1437-1443Garnero, P., Shih, W.J., Gineyts, E., Comparison of new biochemical markers of bone turnover in late postmenopausal osteoporotic women in response to alendronate treatment (1994) J Clin Endocrinol Metab, 79, pp. 1693-1700Bone, H.G., Hosking, D., Devogelaer, J.-P., Ten years' experience with alendronate for osteoporosis in postmenopausal women (2004) N Engl J Med, 350, pp. 1189-1199Cranney, A., Wells, G., Willan, A., Meta-analyses of therapies for postmenopausal osteoporosis: II. Meta-analysis of alendronate for the treatment of postmenopausal women (2002) Endocr Rev, 23, pp. 508-516Ḧauselmann, H.J., Rizzoli, R., A comprehensive review of treatments for postmenopausal osteoporosis (2003) Osteoporos Int, 14, pp. 2-12Levis, S., Quandt, S.A., Thompson, D., Alendronate reduces the risk of multiple symptomatic fractures: Results from the Fracture Intervention Trial (2002) J Am Geriatr Soc, 50, pp. 409-415Black, D.M., Thompson, D.E., Bauer, D.C., Fracture risk reduction with alendronate in women with osteoporosis: The Fracture Intervention Trial (2000) J Clin Endocrinol Metab, 85, pp. 4118-4124. , FIT Research GroupPols, H.A.P., Felsenberg, D., Hanley, Multinational, placebo controlled, randomized trial of the effects of alendronate on bone density and fracture risk in postmenopausal women with low bone mass: Results of the FOSIT study (1999) Osteoporos Int, 9, pp. 461-468Harris, S.T., Watts, N.B., Genant, H.K., Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: A randomized controlled trial (1999) JAMA, 282, pp. 1344-1352. , Vertebral Efficacy with Risedronate Therapy (VERT) Study GroupCranney, A., Guyatt, G., Griffith, L., Meta-analyses of therapies for postmenopausal osteoporosis: IX. Summary of meta-analysis of therapies for postmenopausal women (2002) Endocr Rev, 23, pp. 570-577Kanis, J.A., Oden, A., Johnell, O., Uncertain future of trials in osteoporosis (2002) Osteoporos Int, 13, pp. 443-449McAlister, F.A., Laupacis, A., Wells, G.A., Users' guides to the medical literature: XIX. Applying clinical trial results. B. Guidelines for determining whether a drug is exerting (more than) a class effect (1999) JAMA, 282, pp. 1371-1377Bucher, H.C., Guyatt, G.H., Cook, D.J., Users' guides to the medical literature: XIX. Applying clinical trial results. A. How to use an article measuring the effect of an intervention on surrogate endpoints: Evidence-Based Medicine Working Group (1999) JAMA, 282, pp. 771-778Hosking, D., Adami, S., Felsenberg, D., Comparison of change in bone resorption and bone mineral density with once weekly alendronate and daily risedronate (2003) Curr Med Res Opin, 19, pp. 383-394Rosen, C., Hochberg, M., Bonnick, S., Treatment with once-weekly alendronate 70mg compared to once-weekly risedronate 35mg in women with postmenopausal osteoporosis: A randomized, double-blind study (2005) J Bone Miner Res, 20, pp. 141-151Khosla, S., Surrogates for fracture endpoints in clinical trials (2003) J Bone Miner Res, 18, pp. 1146-1149Cummings, S.R., Black, D.M., Nevitt, M.C., Bone density at various sites for prediction of hip fractures (1993) Lancet, 341, pp. 72-75Eastell, R., Barton, I., Hannon, R.A., Relationship of early changes in bone resorption to the reduction in fracture risk with risedronate (2003) J Bone Miner Res, 18, pp. 1051-1056Epstein, S., The roles of BMD, turnover, and other properties in reducing fracture risk during antiresorptive therapy (2005) Mayo Clin Proc, 80, pp. 379-388Watts, N.B., Cooper, C., Lindsay, R., Relationship between changes in bone mineral density and vertebral fracture risk associated with risedronate: Greater increases in bone mineral density do not relate to greater decreases in fracture risk (2004) J Clin Densitom, 7, pp. 255-261Bonnick, S.L., Johnston, C.C., Kleerekoper, M., The importance of precision in bone density measurements (2001) J Clin Densitom, 4, pp. 105-110Chestnut III, C.H., Rosen, C.J., Reconsidering the effects of antiresorptive therapies in reducing osteoporotic fracture (2001) J Bone Miner Res, 16, pp. 2163-217

Geomorphology and earth system science

Earth system science is an approach to obtain a scientific understanding of the entire Earth system on a global scale by describing how its component parts and their interactions have evolved, how they function, and how they may be expected to continue to evolve on all time-scales. The aim of this review is to introduce some key examples showing the role of earth surface processes, the traditional subject of geomorphology, within the interacting Earth system. The paper considers three examples of environmental systems in which geomorphology plays a key role: (i) links between topography, tectonics, and atmospheric circulation; (ii) links between geomorphic processes and biogeochemical cycles; and (iii) links between biological processes and the earth’s surface. Key research needs are discussed, including the requirement for better opportunities for interdisciplinary collaboration, clearer mathematical frameworks for earth system models, and more sophisticated interaction between natural and social scientists